Aspirin Use for Pre-Eclampsia Prevention in IVF/ICSI Pregnancies in Kumasi, Ghana: A Prospective Cohort Study

Aspirin Use for Pre-Eclampsia Prevention in IVF/ICSI Pregnancies in Kumasi, Ghana: A Prospective Cohort Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Aspirin Use for Pre-Eclampsia Prevention in IVF/ICSI Pregnancies in Kumasi, Ghana: A Prospective Cohort Study Edward Anabila Agana, Bernard Kwaku Okai, Charles Mawunyo Senaya, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9229684/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Background: Pregnancies conceived through assisted reproductive technology (ART) have a substantially elevated risk of pre-eclampsia, and international guideline classify ART as a high-risk factor warranting low-dose aspirin prophylaxis. However, data on aspirin utilisation and effectiveness in ART pregnancies in sub-Saharan Africa are scare. Methods: A prospective cohort study was conducted at four private ART centres in Kumasi, Ghana, from August 2024 to February 2025. Women with ongoing In Vitro Fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI) pregnancies at ≥20 weeks of gestation were consecutively enrolled and categorized by aspirin status (50 exposed and 50 unexposed). Pre-eclampsia was diagnosed according to the 2021 International Society for the Study of Hypertension in Pregnancy criteria. Data were analysed using SPSS version 27 with significance set at p < 0.05. Results: In a cohort of 100 women (mean age of 40.8 years), aspirin use was associated with a lower incidence of pre-eclampsia (10.0% vs. 34.0%; relative risk (RR) 0.29, 95% confidence interval (CI) 0.11–0.76; p = 0.004). The mean gestational age at pre-eclampsia diagnosis was delayed in aspirin users (36.46±1.07 weeks vs. 32.60±4.34 weeks; p= 0.099). Early-onset pre-eclampsia (<34 weeks) occurred in 0% of aspirin users compared to 42.9% of affected non-users. Aspirin use was significantly associated with fewer preterm deliveries (p=0.009), higher 5-minute appearance, pulse, grimace, activity, respiration (Apgar) scores (p = 0.034), and shorter maternal hospital stays(p=0.020). Conclusions: Low-dose aspirin significantly reduced the incidence and severity of pre-eclampsia and better perinatal outcomes in this Ghanaian ART cohort. Despite its high efficacy, prophylaxis remains critically underutilized. These findings support incorporating pre-eclampsia risk assessment and aspirin prophylaxis into routine and preconception ART care. Pre-eclampsia IVF ICSI Assisted reproductive technology Low-dose aspirin Prophylaxis Ghana Sub-Saharan Africa Hypertensive disorders of pregnancy Prospective cohort Figures Figure 1 INTRODUCTION Pre-eclampsia remains a leading cause of maternal and perinatal morbidity and mortality worldwide, accounting for approximately 14% of maternal deaths globally and over 500,000 fetal and neonatal deaths annually [ 1 , 2 ]. In Ghana, hypertensive disorders of pregnancy rank as the second leading direct cause of maternal mortality; Adu-Bonsaffoh et al. documented a 21.4% prevalence of hypertensive disorders at Korle-Bu Teaching Hospital [ 3 ], while Dassah et al. similarly reported significant maternal and perinatal morbidity from hypertensive disorders at Komfo Anokye Teaching Hospital (KATH) in Kumasi [ 4 ]. At KATH, pre-eclampsia comprises nearly half (48.8%) of all admitted cases with hypertensive disorders of pregnancy. Beyond mortality, pre-eclampsia contributes substantially to preterm birth, intrauterine growth restriction, neonatal intensive care admissions, and long-term cardiovascular and neurodevelopmental sequelae in offspring [ 5 ]. The association between assisted reproductive technology (ART) and elevated pre-eclampsia risk is well documented. A landmark meta-analysis by Bartsch et al. (2016), encompassing over 25 million pregnancies, identified ART as one of six major independent risk factors for pre-eclampsia, alongside obesity, chronic hypertension, pregestational diabetes, antiphospholipid syndrome, and prior pre-eclampsia [ 6 ]. Subsequent meta-analyses confirm that In Vitro Fertilization (IVF) / Intracytoplasmic Sperm Injection (ICSI) pregnancies carry a 1.7-fold increased risk compared to spontaneously conceived pregnancies, with further risk elevation in frozen embryo transfer (FET) cycles and donor oocyte pregnancies [ 7 , 8 ]. The pathophysiology of this elevated risk in ART pregnancies is multifactorial. Supraphysiologic oestrogen levels during ovarian stimulation may impair endometrial receptivity and trophoblast invasion [ 9 ]. In hormone-replacement FET cycles, the absence of a corpus luteum deprives the pregnancy of critical vasoactive hormones, particularly relaxin and vascular endothelial growth factor, which are essential for maternal vascular compliance, nitric oxide bioavailability, and spiral artery remodelling [ 10 , 11 ]. Studies confirm that programmed FET cycles carry a pre-eclampsia incidence of 12.8% compared to 3.9% in modified natural cycles [ 11 ]. Additionally, the use of donor gametes introduces allogeneic paternal antigens that may trigger exaggerated maternal immune responses, defective immune-modulated placentation, and heightened endothelial dysfunction [ 7 , 12 ]. Low-dose aspirin (LDA) exerts its protective effects through selective, irreversible inhibition of cyclooxygenase-1, reducing thromboxane A₂ synthesis while preserving prostacyclin production, thereby improving the vasoconstriction–vasodilation balance and enhancing placental perfusion [ 13 ]. Additional mechanisms include anti-inflammatory effects, reduction of soluble fms-like tyrosine kinase-1 and upregulation of placental growth factor [ 14 ]. Meta-analyses demonstrate that aspirin initiated before 16 weeks gestation reduces preterm pre-eclampsia by up to 62% and is associated with a 14% reduction in perinatal mortality [ 15 , 16 ]. Reflecting this evidence, the International Society for the Study of Hypertension in Pregnancy (ISSHP, 2021) and the Society of Obstetricians and Gynaecologists of Canada (SOGC, 2022) now recommend LDA prophylaxis (100–150 mg daily) before 16 weeks for all ART-conceived pregnancies.[ 17 , 18 ]. In contrast, the American College of Obstetricians and Gynaecologists (ACOG) and United States Preventive Services Task Force (USPSTF) continue to classify IVF as a moderate-risk factor, recommending aspirin only when an additional moderate-risk factor is co-present [ 19 , 20 ]. These divergent recommendations, together with the absence of explicit recognition of ART as a high-risk indication in Ghanaian guidelines, create uncertainty for clinicians and may hinder optimal implementation of prophylaxis. Data on aspirin utilisation and its effectiveness in ART pregnancies in sub-Saharan Africa are limited. In Ghana, where ART services are gradually expanding but remain financially burdensome, generating local evidence on a low-cost, evidence-based preventive intervention such as LDA is a public health priority. This study therefore aimed to: (1) determine the proportion of women with ongoing IVF/ICSI pregnancies at ≥ 20 weeks gestation who are receiving LDA; (2) compare pre-eclampsia incidence between aspirin users and non-users; (3) compare the gestational age at pre-eclampsia onset between groups; and (4) compare adverse maternal and perinatal outcomes between groups. MATERIALS AND METHODS Study Design and Setting A prospective cohort study comparing women exposed versus unexposed to LDA was conducted from August 2024 to February 2025 across four private ART centres in Kumasi, Ghana: Trustcare Specialist Hospital and Fertility Centre, RUMA Specialist Hospital and Fertility Centre, Hallmark Medicals, and Oak Specialist Hospital. These centres provide comprehensive fertility services including IVF, ICSI, and cryopreservation, and serve as referral hubs for the Ashanti Region and northern Ghana. Their selection ensured access to the highest concentration of IVF/ICSI pregnancies in the study catchment area. Study Population and Eligibility The study population comprised women with ongoing singleton or multiple pregnancies conceived through IVF or ICSI at ≥ 20 weeks of gestation. This gestational threshold was selected because pre-eclampsia, by definition, cannot be diagnosed before 20 weeks, and recruitment at this point ensured participants had progressed beyond the period of peak early-pregnancy loss. Inclusion criteria: (1) IVF/ICSI-conceived pregnancy at ≥ 20 weeks of gestation confirmed by ultrasound dating; (2) age ≥ 18 years. Exclusion criteria: (1) IVF/ICSI pregnancies terminated at ≥ 20 weeks due to lethal fetal anomalies; (2) known allergy or contraindication to aspirin; and (3) concurrent participation in another interventional study. Two study groups were formed based on aspirin status: the exposed group consisted of women receiving continuous LDA from the first trimester (i.e., aspirin initiated before and continued beyond 12 weeks of gestation for pre-eclampsia prophylaxis) and the control group consisted of women not receiving aspirin for pre-eclampsia prophylaxis at or beyond 20 weeks of gestation. Sample Size and Sampling Sample size was calculated using Epi Info StatCalc version 7.2.5.0, based on findings from Lambers et al. (2009) who reported gestational hypertension/pre-eclampsia rates of 3.6% (aspirin) vs. 26.9% (placebo) in IVF pregnancies [ 21 ]. Using 95% confidence, 80% power, and a 1:1 exposed-to-unexposed ratio, the minimum required sample was 90 participants. Accounting for 10% loss to follow-up, we targeted 100 participants (50 per group). Consecutive sampling with alternating allocation was employed to standardise recruitment between aspirin-exposed and unexposed participants. The first eligible aspirin user was enrolled in the exposed group, followed by the first eligible non-user in the control group, repeating this sequence until 50 participants per group were recruited. Women who declined participation were replaced by the next eligible woman meeting the same exposure criteria. Data Collection Women were approached during routine antenatal visits and hospital admissions at the respective ART centres. Following explanation of study objectives in the participant's preferred language, written informed consent was obtained (for non-literate participants, the information sheet was read aloud by the researcher in the presence of an impartial witness, and thumbprint signatures were accepted). Data were collected using a structured, pre-tested questionnaire administered through face-to-face interview, supplemented by review of antenatal records, hospital folders, delivery notes, and neonatal records. Variables collected included: sociodemographic characteristics; obstetric and medical history; details of current pregnancy and ART treatment; pre-eclampsia risk stratification per ISSHP 2021 high- and moderate-risk criteria; aspirin dose, gestational age at initiation, and duration; blood pressure measurements; delivery details; and maternal and perinatal outcomes. Data collection was performed by the principal investigator and a trained research assistant stationed at each study site. Diagnostic Criteria Pre-eclampsia was diagnosed according to 2021 ISSHP criteria [ 17 ]: new-onset hypertension (systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg on at least two measurements 4 hours apart, using validated automated devices) at ≥ 20 weeks of gestation, accompanied by one or more of the following: • Proteinuria: urine dipstick ≥ 2+ (in the absence of protein:creatinine ratio or 24-hour collection due to cost constraints at study sites) • Maternal end-organ dysfunction: acute kidney injury (creatinine ≥ 90 µmol/L), liver involvement (transaminases > 40 IU/L), neurological complications (eclampsia, severe headache, visual disturbance), pulmonary oedema, or haematological complications (platelet count < 150,000/µL) • Uteroplacental dysfunction: fetal growth restriction, abnormal umbilical artery Doppler, placental abruption, or intrauterine fetal death Pre-eclampsia was classified as early-onset when delivery was necessitated before 34 weeks and as late-onset when delivery occurred at ≥ 34 weeks. Women diagnosed with pre-eclampsia were managed per ISSHP 2021 treatment guidelines. Outcome Measures Primary outcomes: (1) proportion of IVF/ICSI pregnancies at ≥ 20 weeks receiving LDA; (2) incidence of pre-eclampsia in aspirin vs. non-aspirin groups; and (3) gestational age at onset of pre-eclampsia in both groups. Secondary outcomes: (1) maternal outcomes including gestational hypertension, postpartum haemorrhage, organ dysfunction, maternal death, and length of hospital stay; and (2) perinatal outcomes including preterm birth, fetal growth restriction (FGR), low birthweight, 5-minute APGAR score, Neonatal intensive care unit (NICU) admission, stillbirth, and early neonatal death. Statistical Analysis Data were entered into Microsoft Excel for cleaning and validation, then exported to SPSS version 27 (IBM Corp., Armonk, NY, USA). Continuous variables are expressed as mean ± standard deviation; categorical variables as frequency (percentage). The proportion receiving aspirin was compared against the a priori threshold of 25% using a one-sample proportion test. Associations between aspirin use and categorical outcomes were assessed by Pearson's chi-square test (or Fisher's exact test where expected cell counts were < 5). Comparison of gestational age at pre-eclampsia onset was performed by one-way ANOVA. Pearson's correlation analysis (r) examined the relationship between aspirin status and continuous perinatal and maternal outcomes. A two-tailed p-value < 0.05 was considered statistically significant throughout. Results Participant Flow and Recruitment During the 7-month study period, 243 women with ongoing IVF/ICSI pregnancies at ≥ 20 weeks were identified across the four ART centres. Of these, 100 participants were recruited (50 aspirin, 50 no-aspirin) as per the alternating consecutive sampling protocol. No participants were lost to follow-up. A recruitment flow diagram is provided in Fig. 1 . Of 243 women with IVF/ICSI pregnancies at ≥ 20 weeks gestation identified across four ART centres in Kumasi, Ghana (August 2024 – February 2025), exposure status was determined by pre-existing aspirin prescription: 55 (22.6%) were on low-dose aspirin and 188 (77.4%) were not. Using consecutive alternating sampling, 50 women were enrolled from each pool, giving 100 participants total. No participants were lost to follow-up. Sociodemographic and Clinical Characteristics The mean age of participants was 40.82 ± 5.69 years. The majority were married (98.0%), Christian (91.0%), and had attained tertiary (45.0%) or senior high school (36.0%) education. Traders and businesswomen comprised 40.0% of occupations, followed by professionals/bankers (23.0%) and public/civil servants (20.0%). More than half of participants were obese (BMI ≥ 30 kg/m²: 52.0%), with only 12.0% having a normal BMI. No significant differences in baseline sociodemographic or clinical characteristics were observed between aspirin and non-aspirin groups. Full details are presented in Table 1 . Table 1 Sociodemographic and clinical characteristics of study participants (n = 100). Characteristic Value Age (years), mean ± SD 40.82 ± 5.69 Marital status: married, n (%) 98 (98.0) Religion: Christian, n (%) 91 (91.0) Education: tertiary / SHS / JHS, n (%) 45 / 36 / 19 Occupation Businesswoman / Trader 40 (40.0) Professional / Banker 23 (23.0) Public / Civil servant 20 (20.0) Housewife 6 (6.0) Artisan 4 (4.0) Hairdresser 4 (4.0) Caterer / Seamstress 3 (3.0) BMI classification (pre-pregnancy/booking) Normal (18.5–24.9 kg/m²) 12 (12.0) Overweight (25.0–29.9 kg/m²) 36 (36.0) Obese (≥ 30.0 kg/m²) 52 (52.0) Gestational age at first ANC visit (weeks), mean ± SD 8.41 ± 1.22 ANC = antenatal care; BMI = body mass index; JHS = junior high school; SD = standard deviation; SHS = senior high school. Obstetric History and Risk Factor Profile Most participants were nulliparous (74.0%), and 74.0% had no pre-existing medical conditions. Among those with comorbidities, chronic hypertension was most common (21.0%), followed by diabetes mellitus (9.0%). Only 2.0% had a previous history of pre-eclampsia. Among aspirin users, 64.0% received 75 mg/day and 36.0% received 150 mg/day; mean gestational age at aspirin initiation was 15.96 ± 3.57 weeks. Calcium supplementation was prescribed to only 3.0% of all participants. Medical and obstetric history data are presented in Table 2 . Table 2 Obstetric, medical, and family history related to pre-eclampsia risk (n = 100). Variable n (%) Pre-existing medical conditions None 74 (74.0) Chronic hypertension 21 (21.0) Diabetes mellitus 9 (9.0) Sickle cell disease 1 (1.0) Asthma 1 (1.0) Prior pre-eclampsia Not applicable (nulliparous) 68 (68.0) Yes 2 (2.0) No 30 (30.0) GA at prior pre-eclampsia diagnosis (weeks), mean ± SD (n = 2) 36.50 ± 2.12 GA at prior delivery (weeks), mean ± SD (n = 22) 37.32 ± 2.98 First-degree relative with pre-eclampsia: Yes / No / Unknown 1 / 57 / 42 Urine protein at booking: Negative 99 (99.0) Aspirin use in current pregnancy: Yes / No 50 / 50 Aspirin dose: 75 mg / 150 mg (among users, n = 50) 32 (64.0) / 18 (36.0) GA at aspirin initiation (weeks), mean ± SD (n = 50) 15.96 ± 3.57 Calcium supplementation: Yes 3 (3.0) Any pregnancy-related hypertensive disorder: Yes 28 (28.0) Gestational hypertension 6 (21.4) Pre-eclampsia 22 (78.6) GA = gestational age; SD = standard deviation. Beyond ART (universal in all 100 participants by study design), the most prevalent ISSHP 2021 high-risk factor was obesity (52.0%), followed by chronic hypertension (21.0%) and pregestational diabetes (8.0%). Among moderate-risk factors, nulliparity (74.0%), advanced maternal age > 40 years (63.0%), and multifetal gestation (55.0%) were most frequent. Importantly, combinations of moderate-risk factors independently qualifying women for aspirin under ACOG, NICE, and USPSTF criteria were highly prevalent in the broader eligible population (N = 243): 50.2% had both nulliparity and age > 40 years; 39.9% had nulliparity and multifetal gestation; and 42.8% had both age > 40 and multifetal gestation. Risk factor distributions are shown in Table 3 . Table 3 Distribution of ISSHP 2021 high- and moderate-risk factors for pre-eclampsia (n = 100). Risk Factor n (%) HIGH-RISK FACTORS ART in current pregnancy (universal — qualifying criterion for all participants) 100 (100.0) BMI > 30 kg/m² 51 (51.0) Chronic hypertension 21 (21.0) Pre-gestational diabetes mellitus 8 (8.0) Previous pre-eclampsia 2 (2.0) MODERATE-RISK FACTORS Nulliparity 74 (74.0) Multifetal gestation 55 (55.0) Maternal age > 40 years 63 (63.0) COMBINED MODERATE-RISK FACTOR PAIRS (total eligible population, N = 243) Both nulliparity and maternal age > 40 years 122 (50.2%) Both nulliparity and multifetal gestation 97 (39.9%) Both maternal age > 40 years and multifetal gestation 104 (42.8%) ART = assisted reproductive technology; BMI = body mass index; ISSHP = International Society for the Study of Hypertension in Pregnancy. Combined moderate-risk factor pairs are reported for the full eligible population (N = 243) identified during the study period. Assisted Reproductive Technology Modalities Fresh embryo transfer was performed in 96.0% of participants (frozen in 4.0%). The predominant procedure was conventional IVF (96.0%), with ICSI used in 4.0%. Regarding gamete source, 72.0% of participants used donor oocytes with partner sperm (recipient cycles), 16.0% used autologous gametes (self-cycles), 10.0% underwent embryo adoption, and 2.0% used donor sperm. Treatment modalities are detailed in Table 4 . Table 4 Assisted reproductive technology treatment modalities (n = 100). Variable n (%) Embryo transfer type Fresh embryo transfer 96 (96.0) Frozen embryo transfer 4 (4.0) ART procedure Conventional IVF 96 (96.0) ICSI 4 (4.0) Gamete source Donor oocyte / partner sperm (recipient cycle) 72 (72.0) Autologous oocyte / autologous sperm (self-cycle) 16 (16.0) Embryo adoption 10 (10.0) Autologous oocyte / donor sperm 2 (2.0) ICSI = intracytoplasmic sperm injection; IVF = in-vitro fertilisation. Delivery Outcomes All 100 participants delivered by caesarean section. The mean gestational age at delivery was 35.78 ± 2.78 weeks across the cohort. Two pregnancies in the non-aspirin group were terminated before 28 weeks due to pre-eclampsia with severe features (Table 5 ). Table 5 Delivery characteristics and maternal complications (n = 100). Variable n (%) / mean ± SD DELIVERY CHARACTERISTICS Mode of delivery: caesarean section (all) 100 (100.0) Gestational age at delivery (weeks), mean ± SD 35.78 ± 2.78 Pregnancy terminated < 28 weeks (due to severe pre-eclampsia) 2 (2.0) MATERNAL COMPLICATIONS None 63 (63.0) Pre-eclampsia 22 (22.0) Gestational hypertension 6 (6.0) Postpartum haemorrhage 3 (3.0) Organ dysfunction 1 (1.0) HOSPITAL STAY (DAYS) ≤ 4 days 56 (56.0) 5–7 days 30 (30.0) > 7 days 14 (14.0) Maternal death (cause unrelated to hypertensive disease) 1 (1.0) Maternal Outcomes Overall, 28 participants (28.0%) developed a pregnancy-related hypertensive disorder: gestational hypertension in 6 forming 21.4% of hypertensive diseases in pregnancy (HDP) cases and pre-eclampsia in 22 forming 78.6% of HDP cases. Postpartum haemorrhage (PPH) occurred in 3.0% and organ dysfunction in 1.0%. Hospital stays exceeding seven days were required by 14.0%. One maternal death occurred (non-aspirin group), from a cause unrelated to hypertensive disease. Detailed maternal outcomes are presented in Table 5 . Perinatal Outcomes Preterm delivery (< 37 weeks) occurred in 53.0% of the deliveries (mean gestational age among premature neonates: 34.19 ± 2.91 weeks). Fetal growth restriction (FGR) was diagnosed in 15% of pregnancies, with 66.7% classified as Stage 1, indicating mild growth restriction, while 26.7% were Stage 2 and 6.7% were Stage 3, reflecting more severe cases. The mean APGAR score at 5 minutes was 8.6 ± 0.85, suggesting that most neonates had good immediate postnatal adaptation despite the high preterm birth rate. The mean birthweight was 2.55 kg (SD ± 0.80 kg), with a substantial number of neonates falling into the low birthweight range. NICU admissions were high, with 53.5% of neonates requiring admission. The leading indications for NICU admission were prematurity (43%) and low birthweight (23%). One stillbirth and two neonatal deaths within 72 hours of birth were recorded, all occurring in the non-aspirin group (Table 6 ). Table 6 Early perinatal outcomes (n = 100). Variable n (%) / mean ± SD Preterm delivery (< 37 weeks) 53 (53.0) GA at preterm delivery (weeks), mean ± SD 34.19 ± 2.91 5-minute Apgar score, mean ± SD 8.6 ± 0.85 Birthweight (kg), mean ± SD 2.55 ± 0.80 Fetal growth restriction (FGR) 15 (15.0) FGR Stage 1 10 (66.7) FGR Stage 2 4 (26.7) FGR Stage 3 1 (6.7) NICU admission 53 (53.5) Indication: prematurity 43 (43.0) Indication: low birthweight 23 (23.0) Indication: prolonged PROM 3 (3.0) Indication: RDS 1 (1.0) Stillbirth 1 (1.0) Neonatal death within 72 hours 2 (2.0) FGR = fetal growth restriction; GA = gestational age; NICU = neonatal intensive care unit; PROM = premature rupture of membranes; RDS = respiratory distress syndrome. Aspirin Uptake in the Study Population Of the 243 eligible women identified during the study period, only 55 (22.6%) were receiving LDA at ≥ 20 weeks gestation. A one-sample proportion test against the a priori threshold of 25% yielded a proportion of 0.226, an observed test value of 0.024, and a p-value of 0.220. “The observed uptake rate was not statistically significantly different from 25% (p = 0.220). Given that all 243 women had at least one high‑risk factor (ART), this represents substantial under‑utilisation of aspirin prophylaxis. Uptake data are presented in Table 7 . Table 7 Aspirin prophylaxis uptake among all IVF/ICSI pregnancies identified in the study period (N = 243). LDA Status Frequency Percent (%) Proportion p-value* Receiving LDA 55 22.6 0.226 0.220 Not receiving LDA 188 77.4 — — Total 243 100.0 — — *One-sample proportion test vs. hypothesised threshold of 25%. LDA = low-dose aspirin. Incidence of Pre-Eclampsia by Aspirin Group The incidence of any pregnancy-related hypertensive disorder was significantly lower in aspirin users (7/50, 14.0%) compared to non-users (21/50, 42.0%) (χ²=9.72, p = 0.002). When pre-eclampsia was considered independently, incidence was 4/50 (8.0%) in aspirin users vs. 17/50 (34.0%) in non-users (χ²=8.39, p = 0.004), representing a 70.6% relative risk reduction and a number-needed-to-treat of 4. Incidence data are shown in Tables 8 and 9 . Table 8 Association between aspirin use and pregnancy-related hypertensive disorders. Aspirin Status No HDP n (%) HDP n (%) χ² p value Non-aspirin group 29 (58.0) 21 (42.0) 9.722 0.002 Aspirin group 43 (86.0) 7 (14.0) — — Total 72 (72.0) 28 (28.0) — — HDP = hypertensive disorder of pregnancy. Chi-square test significant at p < 0.05. Table 9 Association between aspirin use and pre-eclampsia incidence. Aspirin Status No PE n (%) PE n (%) χ² p value Non-aspirin group 33 (66.0) 17 (34.0) 8.392 0.004 Aspirin group 45 (90.0) 5 (10.0) — — Total 78 (78.0) 22 (22.0) — — PE = pre-eclampsia; RRR = 70.6%; NNT = 4. Chi-square test significant at p < 0.05. NNT = 1 / (0.34 − 0.10) = 4.17, rounded to 4. Gestational Age at Pre-Eclampsia Onset Mean gestational age at pre‑eclampsia diagnosis was 36.46 ± 1.07 weeks in aspirin users versus 32.60 ± 4.34 weeks in non‑users (F = 3.07, p = 0.099), a difference of approximately 4 weeks. Stratification by onset category revealed that no aspirin users developed early‑onset pre‑eclampsia (< 34 weeks), whereas 42.9% of classifiable pre‑eclampsia cases in the non‑aspirin group were early‑onset (6 of 14 deliveries). (Table 10 ). Table 10 Gestational age at pre-eclampsia onset by aspirin group (among women with PE, n = 22). Parameter Non-aspirin (n = 17) Aspirin (n = 5) p-value Mean GA at PE diagnosis (weeks, mean ± SD) 32.60 ± 4.34 36.46 ± 1.07 0.099 Early-onset PE (< 34 weeks), n (%) 6 (42.9) 0 (0.0) — Late-onset PE (≥ 34 weeks), n (%) 8 (57.1) 4 (100.0) — Pregnancy terminated < 28 wks (severe PE) 2 (11.8) 0 (0.0) — Stillbirth / Neonatal death ≤ 72 h 1 / 2 0 / 0 — GA = gestational age; PE = pre-eclampsia; SD = standard deviation. F-value from one-way ANOVA. The difference in gestational age at PE onset was not statistically significant ( p = 0.099), likely reflecting limited power (n = 22 PE events) Maternal and Perinatal Outcomes by Aspirin Group Bivariate analysis (Table 11 ) confirmed that aspirin use was significantly associated with reduced pre-eclampsia (22.7% of PE cases in aspirin group vs. 77.3% in non-aspirin group; χ²=7.05 with Yates' continuity correction, p = 0.008) and reduced preterm delivery (aspirin group: 15/50, 30.0% vs. non-aspirin group: 28/50, 56.0%; χ²=6.90, p = 0.009), with preterm birth being nearly twice as frequent in the non-aspirin group. No significant differences were observed for postpartum haemorrhage (p = 0.241) or organ dysfunction (p = 1.000). FGR was lower in the aspirin group (26.7% vs. 73.3%, p = 0.093) and NICU admission was also less frequent (41.5% vs. 58.5%, p = 0.055), though neither reached statistical significance. Correlation analysis (Table 12 ) demonstrated that aspirin use was positively correlated with 5-minute APGAR scores (r = 0.212, p = 0.034) and negatively correlated with duration of maternal hospital admission (r = − 0.232, p = 0.020). Table 11 Bivariate analysis of adverse maternal and perinatal outcomes by aspirin group (n = 100). Outcome / Category No Aspirin n (%) Aspirin n (%) χ² p value MATERNAL OUTCOMES Pre-eclampsia: Yes 17 (77.3) 5 (22.7) 7.051 0.008 Gestational hypertension: Yes 4 (66.7) 2 (33.3) 0.177 0.674 Postpartum haemorrhage: Yes 3 (100) 0 (0) 1.375 0.241 Organ dysfunction: Yes 1 (100) 0 (0) 0.000 1.000 PERINATAL OUTCOMES Preterm delivery: Yes 28 (65.1) 15 (34.9) 6.895 0.009 FGR: Yes 11 (73.3) 4 (26.7) 2.824 0.093 NICU admission: Yes 31 (58.5) 22 (41.5) 3.692 0.055 Statistically significant results ( p < 0.05), FGR = fetal growth restriction; NICU = neonatal intensive care unit. *p-values from Pearson chi-square test; Yates’ continuity correction applied where expected cell counts were < 10 (pre-eclampsia comparison). Table 12 Correlation analysis of aspirin use with continuous maternal and perinatal outcomes (n = 100). Outcome Pair Pearson r p-value Interpretation Aspirin status ↔ 5-min APGAR score r = 0.212 0.034 Aspirin users: higher APGAR Aspirin status ↔ Duration of hospital stay r = − 0.232 0.020 Aspirin users: shorter stay Aspirin status ↔ Birthweight r = 0.138 0.176 Non-significant trend APGAR score ↔ Birthweight r = − 0.327 0.001 Inverse: lower BW → lower APGAR Birthweight ↔ Duration of hospital stay r = − 0.410 < 0.001 Lower BW → longer stay Significant correlations ( p < 0.05) are shown in bold. APGAR = Appearance, Pulse, Grimace, Activity, Respiration. Discussion This study provides preliminary evidence from sub-Saharan Africa on aspirin utilisation and its association with pre-eclampsia prevention specifically in IVF/ICSI pregnancies. Three major insights emerge: (1) low-dose aspirin was associated with a lower incidence and severity of pre-eclampsia in this high-risk population (2) aspirin use was associated with later disease onset, absence of early-onset pre-eclampsia, fewer preterm births, and higher neonatal Apgar scores (3) despite these compelling benefits and clear international recommendations, aspirin prophylaxis is critically underutilised, with only 22.6% of eligible women receiving therapy. Elevated Burden of Pre-Eclampsia in This ART Cohort The 34.0% pre-eclampsia incidence among non-users exceeds rates typically reported in ART studies, which range from 4–12% [ 6 – 8 ]. This discrepancy likely reflects the convergence of multiple risk factors in our study population The mean maternal age of 40.8 years is markedly higher than in comparable studies (Lambers et al. [ 21 ]: 32.8 years; Haapsamo et al. [ 22 ]: 30.4 years), reflecting the prolonged subfertility and delayed childbearing characteristic of the Ghanaian ART population seeking these services. Additionally, 52.0% of participants were obese (compared to 22.7% in Lambers et al.), and 72.0% used donor oocytes, a mode associated with the highest pre-eclampsia risk among ART modalities, with reported odds ratios of 2.5–4.5 relative to autologous IVF [ 12 , 23 ]. The immunological basis of this elevated risk in donor oocyte cycles is well-established: complete allogeneic mismatch between maternal and fetal tissues triggers an exaggerated maternal immune response and defective immune-modulated placentation, contributing to endothelial dysfunction and hypertension [ 24 , 25 ]. In our setting, donor oocyte cycles predominate due to advanced maternal age and diminished ovarian reserve, creating a convergence of age-related, metabolic, and immunological risk factors that substantially amplify pre-eclampsia susceptibility beyond that observed in typical IVF cohorts from Europe or North America. Effectiveness of Aspirin Prophylaxis The 70.6% relative risk reduction (34.0% → 8.0%) observed in our study exceeds the 18–25% reduction typically reported in broad meta-analyses of aspirin for pre-eclampsia prevention [ 16 , 26 ]. This enhanced effect size likely reflects the 'high-risk, high-benefit' paradigm: in a population with extremely high baseline risk, the absolute risk reduction and consequently the observed relative reduction is maximised. The number‑needed‑to‑treat of 4 compares favourably with other established obstetric preventive interventions and underscores the potential value of systematically implementing aspirin prophylaxis in ART pregnancies. These findings align with, and in important ways corroborate, the landmark randomised controlled trial by Lambers et al. (2009), which reported hypertensive complication rates of 3.6% (aspirin) vs. 26.9% (placebo) in IVF pregnancies [ 21 ], the only prior RCT specifically in ART populations. Our observational study, conducted in a real-world, resource-limited setting, suggests that aspirin’s protective effect is maintained and possibly enhanced. These findings support the external validity of clinical guidelines recommending routine aspirin in ART pregnancies The complete elimination of early-onset pre-eclampsia (< 34 weeks) among aspirin users versus 42.9% of pre-eclampsia cases in non-users occurring before 34 weeks is particularly striking. Early-onset pre-eclampsia is associated with significantly greater maternal morbidity (severe features, eclampsia, HELLP syndrome), higher rates of indicated preterm birth, and worse long-term cardiovascular outcomes for both mother and child [ 27 , 28 ]. The ASPRE trial similarly demonstrated that 150 mg aspirin reduced preterm pre-eclampsia by 62%, with the most pronounced protection for cases requiring delivery before 34 weeks [ 29 ]. Our data strongly suggest that aspirin's mechanistic effect on spiral artery remodelling during early placentation primarily prevents the placenta-driven, early-onset disease phenotype. This study also found a significant association between aspirin use and reduced preterm delivery overall (aspirin group: 15/50, 30.0% vs. non-aspirin group: 28/50, 56.0%; χ²=6.90, p = 0.009), with the non-aspirin group experiencing nearly double the preterm delivery rate, consistent with the ASPIRIN trial demonstrating an 11% reduction in preterm delivery before 37 weeks with LDA in low- and middle-income countries [ 30 ]. The positive correlation between aspirin use and 5-minute APGAR scores (r = 0.212, p = 0.034) further suggests that the delay in disease onset and reduction in iatrogenic preterm delivery translated into improved neonatal vitality at birth. Similarly, the negative correlation between aspirin use and maternal hospital stay duration (r = − 0.232, p = 0.020) reflects the clinical consequence of less severe disease and fewer complications in the aspirin-treated group. The Implementation Gap Despite the unequivocal evidence and the 2021 ISSHP reclassification of ART as a high-risk factor mandating aspirin prophylaxis [ 17 ], only 22.6% of eligible women in our catchment population received LDA. Despite strong evidence and the 2021 ISSHP reclassification reclassification of ART as a high-risk factor mandating aspirin prophylaxis [ 17 ], only 22.6% of eligible women in our catchment population received LDA. This figure aligns with studies from high-income countries reporting aspirin utilisation rates of 24–29% in high-risk pregnancies [ 31 ], collectively suggests that underutilisation is a global problem. This figure aligns with studies from high-income countries reporting aspirin utilisation rates of 24–29% in high-risk pregnancies [ 31 ], collectively suggests that underutilisation is a global problem not limited to resource-limited settings. To our knowledge, no prior Ghanaian study has specifically examined aspirin utilisation rates in ART pregnancies, underscoring both the novelty and urgency of the present findings. Our study reveals that the implementation gap is even wider than these figures suggest. Beyond ART as a qualifying high-risk factor, 50.2% of our broader cohort had both nulliparity and advanced maternal age, two moderate-risk factors that independently satisfy criteria for aspirin initiation under ACOG, NICE, and USPSTF guidelines [ 19 , 20 , 32 ]. Yet aspirin utilisation in this subgroup was similarly low, indicating that the problem represents not merely a failure to recognise ART as a risk factor, but fundamental deficiencies in systematic pre-eclampsia risk screening and preventive implementation across antenatal care more broadly. Several barriers likely contribute to this implementation gap. First, awareness of updated ISSHP and SOGC guidelines may be limited among Ghanaian obstetricians and fertility specialists, many of whom trained prior to the 2021 reclassification. Second, the absence of explicit recognition of ART as a high-risk factor in Ghana's national standard treatment guidelines creates ambiguity and perpetuates outdated practices. Third, the perception of aspirin as an intervention rather than standard prophylaxis may lead to selective prescribing only to women perceived as 'very high risk', rather than the universal application that the evidence supports. Fourth, concerns about aspirin safety in pregnancy, though largely unfounded at low prophylactic doses, persist among some clinicians and patients. Aspirin Dose and Timing The mean gestational age at aspirin initiation in our study was 15.96 ± 3.57 weeks. While the mean falls within the recommended < 16-week window, the standard deviation of 3.57 weeks indicates that a substantial proportion of women-initiated aspirin beyond this threshold, further limiting the potential for maximal protection. Had initiation been uniformly achieved at 11–14 weeks, the protective effect observed may have been even greater. Robust evidence from Roberge et al. demonstrates that earlier initiation is associated with greater risk reduction, with each week of delay attenuating the prophylactic benefit [ 33 ]. The ideal timing of 11–14 weeks, coinciding with first-trimester screening, was achieved in only a minority of participants, representing a missed optimisation opportunity. Regarding dose, 64.0% of aspirin users received 75 mg/day and 36.0% received 150 mg/day. The 2021 ISSHP guidelines recommend 150 mg nightly based on the ASPRE trial demonstrating superior efficacy of 150 mg over lower doses for preterm pre-eclampsia prevention [ 17 , 29 ]. A meta-analysis by van Doorn et al. confirmed a 62% reduction in preterm pre-eclampsia with ≥ 150 mg but no significant reduction at lower doses [ 34 ]. The predominant use of 75 mg in our cohort, while providing some benefit, likely represents a suboptimal dosing strategy that may have attenuated the observed treatment effect. Optimal dosing should be a focus of future guidance and audit activities. Recommendations Based on these findings and the convergent evidence base, we advance four actionable recommendations: Universal aspirin prophylaxis may be considered for all ART pregnancies. Emerging evidence suggests that pregnancies conceived through IVF or ICSI may benefit from low-dose aspirin (150 mg nightly), initiated between 12 and 16 weeks’ gestation, even in the absence of additional pre-eclampsia risk factors. The NNT of 4 reported here compares exceptionally favourably with most other established preventive interventions in obstetrics. 2. Integration of pre-eclampsia prevention into ART counselling. Preconception and first-trimester counselling must explicitly address the elevated pre-eclampsia risk and documented benefits of aspirin. This discussion should be documented and communicated to antenatal care providers to ensure continuity of prophylaxis throughout pregnancy. 3. Urgent national guideline revision. The Society of Obstetricians and Gynaecologists of Ghana (SOGOG), the Fertility Society of Ghana (FERSOG), and the National Standard Treatment Guidelines Working Group should revise existing guidelines to explicitly recognise ART as an independent high-risk factor and recommend routine aspirin prophylaxis at 150 mg nightly from 12 to 36 weeks. 4. Health system implementation strategies. Clinical decision support tools, protocolised order sets, and audit-feedback cycles should be deployed to systematically identify eligible women and ensure aspirin prescription at the first antenatal visit after ART conception. Strengths and Limitations Several limitations must be acknowledged. First, the sample size (n = 100), while adequately powered for the primary outcomes, was insufficient for multivariable adjustment and subgroup analyses, including comparisons of 75 mg vs. 150 mg aspirin and fresh vs. frozen embryo transfer subgroups. Second, the observational design precludes causal inference; unmeasured confounders (e.g., health-seeking behaviour, nutritional status) may have influenced both aspirin prescription and outcomes. Third, proteinuria quantification relied on urine dipstick rather than protein: creatinine ratio, potentially causing some misclassification. Fourth, aspirin adherence was based on patient report and prescription records and was not objectively verified using pill counts or pharmacy refill data. Fifth, long-term neonatal follow-up was not performed, precluding assessment of neurodevelopmental outcomes. Finally, the study was conducted exclusively in private fertility centres; generalisability to public-sector ART services in Ghana may be limited. Future research priorities include: (1) a large, adequately powered randomised controlled trial comparing 75 mg versus 150 mg aspirin in ART populations; (2) comparative effectiveness studies by ART modality (fresh/frozen transfer, autologous/donor gametes); (3) implementation science research to identify effective strategies for improving guideline adherence in low-resource settings; and (4) cost-effectiveness analysis of universal aspirin prophylaxis in ART pregnancies in sub-Saharan Africa. Conclusions This study provides important preliminary evidence from a sub-Saharan African setting that low-dose aspirin use was associated with a significantly lower incidence and severity of pre-eclampsia in IVF/ICSI pregnancies, later disease onset, and improved perinatal outcomes. The magnitude of benefit, a 70.6% relative risk reduction with a number-needed-to-treat of 4, reflects the very high baseline risk in this cohort characterised by advanced maternal age, obesity, and high-prevalence donor oocyte cycles. However, the critical underutilisation of this safe, inexpensive, and highly effective intervention at only 22.6% uptake represents a major evidence-to-practice gap and a missed opportunity to prevent substantial maternal and perinatal morbidity. Bridging this implementation gap requires concerted action at multiple levels: individual clinicians must update practice in accordance with current international guidelines; professional societies must provide clear, context-adapted recommendations for the Ghanaian setting; and health systems must implement systematic screening and prophylaxis protocols within ART care pathways. For the hundreds of Ghanaian women who undergo IVF/ICSI annually, and for the thousands more across Africa where ART is expanding rapidly, ensuring routine access to aspirin prophylaxis is not merely a matter of guideline adherence but an essential component of equitable, evidence-based reproductive healthcare. Abbreviations ACOG American College of Obstetricians and Gynecologists ANC Antenatal Care APGAR Appearance, Pulse, Grimace, Activity, Respiration ART Assisted Reproductive Technology BMI Body Mass Index BP Blood Pressure CI Confidence Interval FET Frozen Embryo Transfer FGR Fetal Growth Restriction GA Gestational Age HDP Hypertensive Disorders of Pregnancy ICSI Intracytoplasmic Sperm Injection ISSHP International Society for the Study of Hypertension in Pregnancy IVF In Vitro Fertilisation JHS Junior High School KATH Komfo Anokye Teaching Hospital LDA Low-Dose Aspirin NICE National Institute for Health and Care Excellence NICU Neonatal Intensive Care Unit PROM Premature Rupture of Membranes RDS Respiratory Distress Syndrome RR Relative Risk SD Standard Deviation SHS Senior High School SOGC Society of Obstetricians and Gynaecologists of Canada SPSS Statistical Package for the Social Sciences STROBE Strengthening the Reporting of Observational Studies in Epidemiology USPSTF United States Preventive Services Task Force Declarations Ethics approval and consent to participate Ethical approval was obtained from the Committee on Human Research, Publications and Ethics (CHRCLCL) of Kwame Nkrumah University of Science and Technology, Kumasi (protocol ID: CHRPE/AP/1334/24. All study participants provided written informed consent and the research was conducted in accordance with the Declaration of Helsinki. Consent for publication All authors have read and approved the final manuscript and consent to its publication Competing interests The authors declare no competing interests. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Author Contribution EAA designed the study with support from MYA. Data collection, validation and analysis were done by BKO, AAK and CMS. AKD, RMKD, WMB, and WKA drafted the manuscript, and all authors reviewed it for intellectual content. All authors read, reviewed, and approved the final version of the manuscript. Acknowledgements We are profoundly grateful to the women who participated in this study. We acknowledge the invaluable contributions of the medical directors, fertility specialists, embryologists, and nursing staff at Trustcare Specialist Hospital and Fertility Centre, RUMA Specialist Hospital and Fertility Centre, Hallmark Medicals, and Oak Specialist Hospital, Kumasi. We thank the Committee on Human Research, Publications and Ethics (CHRPE) of KNUST for thorough ethical oversight. Special appreciation is extended to research assistants at each study site for ensuring complete participant follow-up. Data Availability The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request References Say L, Chou D, Gemmill A, Tunçalp Ö, Moller AB, Daniels J, Gülmezoglu AM. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health. 2014;2(6):e323–33. 10.1016/S2214-109X(14)70227-X . 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Rolnik DL, Wright D, Poon LC, O'Gorman N, Syngelaki A, de Paco Matallana C, Akolekar R, Cicero S, Janga D, Singh M, Molina FS, Persico N, Jani JC, Plasencia W, Papaioannou G, Tenenbaum-Gavish K, Meiri H, Gizurarson S, Maclagan K, Nicolaides KH. Aspirin versus placebo in pregnancies at high risk for preterm pre-eclampsia. N Engl J Med. 2017;377(7):613–22. 10.1056/NEJMoa1704559 . Hoffman MK, Goudar SS, for the Global Network for Women's and Children's Health Research ASPIRIN Trial Group. Low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy (ASPIRIN): a randomised, double-blind, placebo-controlled trial. Lancet. 2020;395(10220):285–93. 10.1016/S0140-6736(19)32973-3 . van Montfort P, Scheepers LH, van Dooren IM, Meertens LJ, Zelis M, Zwaan IM, Spaanderman ME, Smits LJ. Low-dose-aspirin usage among women with an increased pre-eclampsia risk: a prospective cohort study. Acta Obstet Gynecol Scand. 2020;99(7):875–83. 10.1111/aogs.13812 . 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Supplementary Files APPENDIX1.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 04 May, 2026 Reviewers agreed at journal 22 Apr, 2026 Reviewers invited by journal 22 Apr, 2026 Editor assigned by journal 07 Apr, 2026 Submission checks completed at journal 06 Apr, 2026 First submitted to journal 03 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9229684","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":630388198,"identity":"7555cf86-fe83-499e-8e76-664092b41649","order_by":0,"name":"Edward Anabila Agana","email":"","orcid":"","institution":"Komfo Anokye Teaching Hospital","correspondingAuthor":false,"prefix":"","firstName":"Edward","middleName":"Anabila","lastName":"Agana","suffix":""},{"id":630388199,"identity":"48c7a91b-954c-4d7c-a579-945995a81a48","order_by":1,"name":"Bernard Kwaku Okai","email":"","orcid":"","institution":"Komfo Anokye Teaching 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10:08:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":820100,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9229684/v1/0345659b-20f8-45d5-99d8-8b25bcb191f1.pdf"},{"id":108241701,"identity":"c74f6732-f180-4421-bdbf-bb836cfea426","added_by":"auto","created_at":"2026-04-30 21:03:15","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":23271,"visible":true,"origin":"","legend":"","description":"","filename":"APPENDIX1.docx","url":"https://assets-eu.researchsquare.com/files/rs-9229684/v1/9294b257f0aa505dbe763914.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Aspirin Use for Pre-Eclampsia Prevention in IVF/ICSI Pregnancies in Kumasi, Ghana: A Prospective Cohort Study","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003ePre-eclampsia remains a leading cause of maternal and perinatal morbidity and mortality worldwide, accounting for approximately 14% of maternal deaths globally and over 500,000 fetal and neonatal deaths annually [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In Ghana, hypertensive disorders of pregnancy rank as the second leading direct cause of maternal mortality; Adu-Bonsaffoh et al. documented a 21.4% prevalence of hypertensive disorders at Korle-Bu Teaching Hospital [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], while Dassah et al. similarly reported significant maternal and perinatal morbidity from hypertensive disorders at Komfo Anokye Teaching Hospital (KATH) in Kumasi [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. At KATH, pre-eclampsia comprises nearly half (48.8%) of all admitted cases with hypertensive disorders of pregnancy. Beyond mortality, pre-eclampsia contributes substantially to preterm birth, intrauterine growth restriction, neonatal intensive care admissions, and long-term cardiovascular and neurodevelopmental sequelae in offspring [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe association between assisted reproductive technology (ART) and elevated pre-eclampsia risk is well documented. A landmark meta-analysis by Bartsch et al. (2016), encompassing over 25\u0026nbsp;million pregnancies, identified ART as one of six major independent risk factors for pre-eclampsia, alongside obesity, chronic hypertension, pregestational diabetes, antiphospholipid syndrome, and prior pre-eclampsia [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Subsequent meta-analyses confirm that In Vitro Fertilization (IVF) / Intracytoplasmic Sperm Injection (ICSI) pregnancies carry a 1.7-fold increased risk compared to spontaneously conceived pregnancies, with further risk elevation in frozen embryo transfer (FET) cycles and donor oocyte pregnancies [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe pathophysiology of this elevated risk in ART pregnancies is multifactorial. Supraphysiologic oestrogen levels during ovarian stimulation may impair endometrial receptivity and trophoblast invasion [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In hormone-replacement FET cycles, the absence of a corpus luteum deprives the pregnancy of critical vasoactive hormones, particularly relaxin and vascular endothelial growth factor, which are essential for maternal vascular compliance, nitric oxide bioavailability, and spiral artery remodelling [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Studies confirm that programmed FET cycles carry a pre-eclampsia incidence of 12.8% compared to 3.9% in modified natural cycles [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Additionally, the use of donor gametes introduces allogeneic paternal antigens that may trigger exaggerated maternal immune responses, defective immune-modulated placentation, and heightened endothelial dysfunction [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eLow-dose aspirin (LDA) exerts its protective effects through selective, irreversible inhibition of cyclooxygenase-1, reducing thromboxane A₂ synthesis while preserving prostacyclin production, thereby improving the vasoconstriction\u0026ndash;vasodilation balance and enhancing placental perfusion [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Additional mechanisms include anti-inflammatory effects, reduction of soluble fms-like tyrosine kinase-1 and upregulation of placental growth factor [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Meta-analyses demonstrate that aspirin initiated before 16 weeks gestation reduces preterm pre-eclampsia by up to 62% and is associated with a 14% reduction in perinatal mortality [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eReflecting this evidence, the International Society for the Study of Hypertension in Pregnancy (ISSHP, 2021) and the Society of Obstetricians and Gynaecologists of Canada (SOGC, 2022) now recommend LDA prophylaxis (100\u0026ndash;150 mg daily) before 16 weeks for all ART-conceived pregnancies.[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In contrast, the American College of Obstetricians and Gynaecologists (ACOG) and United States Preventive Services Task Force (USPSTF) continue to classify IVF as a moderate-risk factor, recommending aspirin only when an additional moderate-risk factor is co-present [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. These divergent recommendations, together with the absence of explicit recognition of ART as a high-risk indication in Ghanaian guidelines, create uncertainty for clinicians and may hinder optimal implementation of prophylaxis.\u003c/p\u003e \u003cp\u003eData on aspirin utilisation and its effectiveness in ART pregnancies in sub-Saharan Africa are limited. In Ghana, where ART services are gradually expanding but remain financially burdensome, generating local evidence on a low-cost, evidence-based preventive intervention such as LDA is a public health priority. This study therefore aimed to: (1) determine the proportion of women with ongoing IVF/ICSI pregnancies at \u0026ge;\u0026thinsp;20 weeks gestation who are receiving LDA; (2) compare pre-eclampsia incidence between aspirin users and non-users; (3) compare the gestational age at pre-eclampsia onset between groups; and (4) compare adverse maternal and perinatal outcomes between groups.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Setting\u003c/h2\u003e \u003cp\u003eA prospective cohort study comparing women exposed versus unexposed to LDA was conducted from August 2024 to February 2025 across four private ART centres in Kumasi, Ghana: Trustcare Specialist Hospital and Fertility Centre, RUMA Specialist Hospital and Fertility Centre, Hallmark Medicals, and Oak Specialist Hospital.\u003c/p\u003e \u003cp\u003eThese centres provide comprehensive fertility services including IVF, ICSI, and cryopreservation, and serve as referral hubs for the Ashanti Region and northern Ghana. Their selection ensured access to the highest concentration of IVF/ICSI pregnancies in the study catchment area.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy Population and Eligibility\u003c/h3\u003e\n\u003cp\u003eThe study population comprised women with ongoing singleton or multiple pregnancies conceived through IVF or ICSI at \u0026ge;\u0026thinsp;20 weeks of gestation. This gestational threshold was selected because pre-eclampsia, by definition, cannot be diagnosed before 20 weeks, and recruitment at this point ensured participants had progressed beyond the period of peak early-pregnancy loss.\u003c/p\u003e \u003cp\u003eInclusion criteria: (1) IVF/ICSI-conceived pregnancy at \u0026ge;\u0026thinsp;20 weeks of gestation confirmed by ultrasound dating; (2) age\u0026thinsp;\u0026ge;\u0026thinsp;18 years. Exclusion criteria: (1) IVF/ICSI pregnancies terminated at \u0026ge;\u0026thinsp;20 weeks due to lethal fetal anomalies; (2) known allergy or contraindication to aspirin; and (3) concurrent participation in another interventional study.\u003c/p\u003e \u003cp\u003eTwo study groups were formed based on aspirin status: the exposed group consisted of women receiving continuous LDA from the first trimester (i.e., aspirin initiated before and continued beyond 12 weeks of gestation for pre-eclampsia prophylaxis) and the control group consisted of women not receiving aspirin for pre-eclampsia prophylaxis at or beyond 20 weeks of gestation.\u003c/p\u003e\n\u003ch3\u003eSample Size and Sampling\u003c/h3\u003e\n\u003cp\u003eSample size was calculated using Epi Info StatCalc version 7.2.5.0, based on findings from Lambers et al. (2009) who reported gestational hypertension/pre-eclampsia rates of 3.6% (aspirin) vs. 26.9% (placebo) in IVF pregnancies [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Using 95% confidence, 80% power, and a 1:1 exposed-to-unexposed ratio, the minimum required sample was 90 participants. Accounting for 10% loss to follow-up, we targeted 100 participants (50 per group).\u003c/p\u003e \u003cp\u003eConsecutive sampling with alternating allocation was employed to standardise recruitment between aspirin-exposed and unexposed participants. The first eligible aspirin user was enrolled in the exposed group, followed by the first eligible non-user in the control group, repeating this sequence until 50 participants per group were recruited. Women who declined participation were replaced by the next eligible woman meeting the same exposure criteria.\u003c/p\u003e\n\u003ch3\u003eData Collection\u003c/h3\u003e\n\u003cp\u003eWomen were approached during routine antenatal visits and hospital admissions at the respective ART centres. Following explanation of study objectives in the participant's preferred language, written informed consent was obtained (for non-literate participants, the information sheet was read aloud by the researcher in the presence of an impartial witness, and thumbprint signatures were accepted).\u003c/p\u003e \u003cp\u003eData were collected using a structured, pre-tested questionnaire administered through face-to-face interview, supplemented by review of antenatal records, hospital folders, delivery notes, and neonatal records. Variables collected included: sociodemographic characteristics; obstetric and medical history; details of current pregnancy and ART treatment; pre-eclampsia risk stratification per ISSHP 2021 high- and moderate-risk criteria; aspirin dose, gestational age at initiation, and duration; blood pressure measurements; delivery details; and maternal and perinatal outcomes. Data collection was performed by the principal investigator and a trained research assistant stationed at each study site.\u003c/p\u003e\n\u003ch3\u003eDiagnostic Criteria\u003c/h3\u003e\n\u003cp\u003ePre-eclampsia was diagnosed according to 2021 ISSHP criteria [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]: new-onset hypertension (systolic BP\u0026thinsp;\u0026ge;\u0026thinsp;140 mmHg and/or diastolic BP\u0026thinsp;\u0026ge;\u0026thinsp;90 mmHg on at least two measurements 4 hours apart, using validated automated devices) at \u0026ge;\u0026thinsp;20 weeks of gestation, accompanied by one or more of the following:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e\u0026bull; Proteinuria: urine dipstick\u0026thinsp;\u0026ge;\u0026thinsp;2+ (in the absence of protein:creatinine ratio or 24-hour collection due to cost constraints at study sites)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e\u0026bull; Maternal end-organ dysfunction: acute kidney injury (creatinine\u0026thinsp;\u0026ge;\u0026thinsp;90 \u0026micro;mol/L), liver involvement (transaminases\u0026thinsp;\u0026gt;\u0026thinsp;40 IU/L), neurological complications (eclampsia, severe headache, visual disturbance), pulmonary oedema, or haematological complications (platelet count\u0026thinsp;\u0026lt;\u0026thinsp;150,000/\u0026micro;L)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e\u0026bull; Uteroplacental dysfunction: fetal growth restriction, abnormal umbilical artery Doppler, placental abruption, or intrauterine fetal death\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003ePre-eclampsia was classified as early-onset when delivery was necessitated before 34 weeks and as late-onset when delivery occurred at \u0026ge;\u0026thinsp;34 weeks. Women diagnosed with pre-eclampsia were managed per ISSHP 2021 treatment guidelines.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eOutcome Measures\u003c/h2\u003e \u003cp\u003ePrimary outcomes: (1) proportion of IVF/ICSI pregnancies at \u0026ge;\u0026thinsp;20 weeks receiving LDA; (2) incidence of pre-eclampsia in aspirin vs. non-aspirin groups; and (3) gestational age at onset of pre-eclampsia in both groups. Secondary outcomes: (1) maternal outcomes including gestational hypertension, postpartum haemorrhage, organ dysfunction, maternal death, and length of hospital stay; and (2) perinatal outcomes including preterm birth, fetal growth restriction (FGR), low birthweight, 5-minute APGAR score, Neonatal intensive care unit (NICU) admission, stillbirth, and early neonatal death.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eData were entered into Microsoft Excel for cleaning and validation, then exported to SPSS version 27 (IBM Corp., Armonk, NY, USA). Continuous variables are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation; categorical variables as frequency (percentage). The proportion receiving aspirin was compared against the a priori threshold of 25% using a one-sample proportion test. Associations between aspirin use and categorical outcomes were assessed by Pearson's chi-square test (or Fisher's exact test where expected cell counts were \u0026lt;\u0026thinsp;5). Comparison of gestational age at pre-eclampsia onset was performed by one-way ANOVA. Pearson's correlation analysis (r) examined the relationship between aspirin status and continuous perinatal and maternal outcomes. A two-tailed p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant throughout.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eParticipant Flow and Recruitment\u003c/h2\u003e \u003cp\u003eDuring the 7-month study period, 243 women with ongoing IVF/ICSI pregnancies at \u0026ge;\u0026thinsp;20 weeks were identified across the four ART centres. Of these, 100 participants were recruited (50 aspirin, 50 no-aspirin) as per the alternating consecutive sampling protocol. No participants were lost to follow-up. A recruitment flow diagram is provided in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eOf 243 women with IVF/ICSI pregnancies at \u0026ge;\u0026thinsp;20 weeks gestation identified across four ART centres in Kumasi, Ghana (August 2024 \u0026ndash; February 2025), exposure status was determined by pre-existing aspirin prescription: 55 (22.6%) were on low-dose aspirin and 188 (77.4%) were not. Using consecutive alternating sampling, 50 women were enrolled from each pool, giving 100 participants total. No participants were lost to follow-up.\u003c/em\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eSociodemographic and Clinical Characteristics\u003c/h2\u003e \u003cp\u003eThe mean age of participants was 40.82\u0026thinsp;\u0026plusmn;\u0026thinsp;5.69 years. The majority were married (98.0%), Christian (91.0%), and had attained tertiary (45.0%) or senior high school (36.0%) education. Traders and businesswomen comprised 40.0% of occupations, followed by professionals/bankers (23.0%) and public/civil servants (20.0%). More than half of participants were obese (BMI\u0026thinsp;\u0026ge;\u0026thinsp;30 kg/m\u0026sup2;: 52.0%), with only 12.0% having a normal BMI. No significant differences in baseline sociodemographic or clinical characteristics were observed between aspirin and non-aspirin groups. Full details are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSociodemographic and clinical characteristics of study participants (n\u0026thinsp;=\u0026thinsp;100).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValue\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40.82\u0026thinsp;\u0026plusmn;\u0026thinsp;5.69\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarital status: married, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e98 (98.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReligion: Christian, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e91 (91.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEducation: tertiary / SHS / JHS, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45 / 36 / 19\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eOccupation\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBusinesswoman / Trader\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (40.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProfessional / Banker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (23.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePublic / Civil servant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (20.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHousewife\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (6.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArtisan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (4.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHairdresser\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (4.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCaterer / Seamstress\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (3.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eBMI classification (pre-pregnancy/booking)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal (18.5\u0026ndash;24.9 kg/m\u0026sup2;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (12.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOverweight (25.0\u0026ndash;29.9 kg/m\u0026sup2;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (36.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eObese (\u0026ge;\u0026thinsp;30.0 kg/m\u0026sup2;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52 (52.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational age at first ANC visit (weeks), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.41\u0026thinsp;\u0026plusmn;\u0026thinsp;1.22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eANC\u0026thinsp;=\u0026thinsp;antenatal care; BMI\u0026thinsp;=\u0026thinsp;body mass index; JHS\u0026thinsp;=\u0026thinsp;junior high school; SD\u0026thinsp;=\u0026thinsp;standard deviation; SHS\u0026thinsp;=\u0026thinsp;senior high school.\u003c/em\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eObstetric History and Risk Factor Profile\u003c/h2\u003e \u003cp\u003eMost participants were nulliparous (74.0%), and 74.0% had no pre-existing medical conditions. Among those with comorbidities, chronic hypertension was most common (21.0%), followed by diabetes mellitus (9.0%). Only 2.0% had a previous history of pre-eclampsia. Among aspirin users, 64.0% received 75 mg/day and 36.0% received 150 mg/day; mean gestational age at aspirin initiation was 15.96\u0026thinsp;\u0026plusmn;\u0026thinsp;3.57 weeks. Calcium supplementation was prescribed to only 3.0% of all participants. Medical and obstetric history data are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eObstetric, medical, and family history related to pre-eclampsia risk (n\u0026thinsp;=\u0026thinsp;100).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePre-existing medical conditions\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74 (74.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic hypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (21.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (9.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSickle cell disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsthma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePrior pre-eclampsia\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot applicable (nulliparous)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68 (68.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (30.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGA at prior pre-eclampsia diagnosis (weeks), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (n\u0026thinsp;=\u0026thinsp;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36.50\u0026thinsp;\u0026plusmn;\u0026thinsp;2.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGA at prior delivery (weeks), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (n\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.32\u0026thinsp;\u0026plusmn;\u0026thinsp;2.98\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFirst-degree relative with pre-eclampsia: Yes / No / Unknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 / 57 / 42\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrine protein at booking: Negative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e99 (99.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAspirin use in current pregnancy: Yes / No\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50 / 50\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAspirin dose: 75 mg / 150 mg (among users, n\u0026thinsp;=\u0026thinsp;50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (64.0) / 18 (36.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGA at aspirin initiation (weeks), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (n\u0026thinsp;=\u0026thinsp;50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.96\u0026thinsp;\u0026plusmn;\u0026thinsp;3.57\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCalcium supplementation: Yes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (3.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAny pregnancy-related hypertensive disorder: Yes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (28.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational hypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (21.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-eclampsia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (78.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eGA\u0026thinsp;=\u0026thinsp;gestational age; SD\u0026thinsp;=\u0026thinsp;standard deviation.\u003c/em\u003e \u003c/p\u003e \u003cp\u003eBeyond ART (universal in all 100 participants by study design), the most prevalent ISSHP 2021 high-risk factor was obesity (52.0%), followed by chronic hypertension (21.0%) and pregestational diabetes (8.0%). Among moderate-risk factors, nulliparity (74.0%), advanced maternal age\u0026thinsp;\u0026gt;\u0026thinsp;40 years (63.0%), and multifetal gestation (55.0%) were most frequent. Importantly, combinations of moderate-risk factors independently qualifying women for aspirin under ACOG, NICE, and USPSTF criteria were highly prevalent in the broader eligible population (N\u0026thinsp;=\u0026thinsp;243): 50.2% had both nulliparity and age\u0026thinsp;\u0026gt;\u0026thinsp;40 years; 39.9% had nulliparity and multifetal gestation; and 42.8% had both age\u0026thinsp;\u0026gt;\u0026thinsp;40 and multifetal gestation. Risk factor distributions are shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDistribution of ISSHP 2021 high- and moderate-risk factors for pre-eclampsia (n\u0026thinsp;=\u0026thinsp;100).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRisk Factor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eHIGH-RISK FACTORS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eART in current pregnancy (universal \u0026mdash; qualifying criterion for all participants)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100 (100.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI\u0026thinsp;\u0026gt;\u0026thinsp;30 kg/m\u0026sup2;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51 (51.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic hypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (21.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-gestational diabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (8.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious pre-eclampsia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMODERATE-RISK FACTORS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNulliparity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74 (74.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultifetal gestation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55 (55.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal age\u0026thinsp;\u0026gt;\u0026thinsp;40 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63 (63.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCOMBINED MODERATE-RISK FACTOR PAIRS (total eligible population, N\u0026thinsp;=\u0026thinsp;243)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBoth nulliparity and maternal age\u0026thinsp;\u0026gt;\u0026thinsp;40 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e122 (50.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBoth nulliparity and multifetal gestation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e97 (39.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBoth maternal age\u0026thinsp;\u0026gt;\u0026thinsp;40 years and multifetal gestation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e104 (42.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eART\u0026thinsp;=\u0026thinsp;assisted reproductive technology; BMI\u0026thinsp;=\u0026thinsp;body mass index; ISSHP\u0026thinsp;=\u0026thinsp;International Society for the Study of Hypertension in Pregnancy. Combined moderate-risk factor pairs are reported for the full eligible population (N\u0026thinsp;=\u0026thinsp;243) identified during the study period.\u003c/em\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eAssisted Reproductive Technology Modalities\u003c/h2\u003e \u003cp\u003eFresh embryo transfer was performed in 96.0% of participants (frozen in 4.0%). The predominant procedure was conventional IVF (96.0%), with ICSI used in 4.0%. Regarding gamete source, 72.0% of participants used donor oocytes with partner sperm (recipient cycles), 16.0% used autologous gametes (self-cycles), 10.0% underwent embryo adoption, and 2.0% used donor sperm. Treatment modalities are detailed in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssisted reproductive technology treatment modalities (n\u0026thinsp;=\u0026thinsp;100).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eEmbryo transfer type\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFresh embryo transfer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e96 (96.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFrozen embryo transfer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (4.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eART procedure\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConventional IVF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e96 (96.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICSI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (4.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eGamete source\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDonor oocyte / partner sperm (recipient cycle)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72 (72.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAutologous oocyte / autologous sperm (self-cycle)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (16.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmbryo adoption\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (10.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAutologous oocyte / donor sperm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eICSI\u0026thinsp;=\u0026thinsp;intracytoplasmic sperm injection; IVF\u0026thinsp;=\u0026thinsp;in-vitro fertilisation.\u003c/em\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eDelivery Outcomes\u003c/h2\u003e \u003cp\u003eAll 100 participants delivered by caesarean section. The mean gestational age at delivery was 35.78\u0026thinsp;\u0026plusmn;\u0026thinsp;2.78 weeks across the cohort. Two pregnancies in the non-aspirin group were terminated before 28 weeks due to pre-eclampsia with severe features (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDelivery characteristics and maternal complications (n\u0026thinsp;=\u0026thinsp;100).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en (%) / mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDELIVERY CHARACTERISTICS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMode of delivery: caesarean section (all)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100 (100.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational age at delivery (weeks), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35.78\u0026thinsp;\u0026plusmn;\u0026thinsp;2.78\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePregnancy terminated\u0026thinsp;\u0026lt;\u0026thinsp;28 weeks (due to severe pre-eclampsia)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMATERNAL COMPLICATIONS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63 (63.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-eclampsia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (22.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational hypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (6.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostpartum haemorrhage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (3.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOrgan dysfunction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eHOSPITAL STAY (DAYS)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;4 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56 (56.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u0026ndash;7 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (30.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;7 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (14.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal death (cause unrelated to hypertensive disease)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eMaternal Outcomes\u003c/h2\u003e \u003cp\u003eOverall, 28 participants (28.0%) developed a pregnancy-related hypertensive disorder: gestational hypertension in 6 forming 21.4% of hypertensive diseases in pregnancy (HDP) cases and pre-eclampsia in 22 forming 78.6% of HDP cases. Postpartum haemorrhage (PPH) occurred in 3.0% and organ dysfunction in 1.0%. Hospital stays exceeding seven days were required by 14.0%. One maternal death occurred (non-aspirin group), from a cause unrelated to hypertensive disease. Detailed maternal outcomes are presented in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003ePerinatal Outcomes\u003c/h2\u003e \u003cp\u003ePreterm delivery (\u0026lt;\u0026thinsp;37 weeks) occurred in 53.0% of the deliveries (mean gestational age among premature neonates: 34.19\u0026thinsp;\u0026plusmn;\u0026thinsp;2.91 weeks). Fetal growth restriction (FGR) was diagnosed in 15% of pregnancies, with 66.7% classified as Stage 1, indicating mild growth restriction, while 26.7% were Stage 2 and 6.7% were Stage 3, reflecting more severe cases.\u003c/p\u003e \u003cp\u003eThe mean APGAR score at 5 minutes was 8.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.85, suggesting that most neonates had good immediate postnatal adaptation despite the high preterm birth rate. The mean birthweight was 2.55 kg (SD\u0026thinsp;\u0026plusmn;\u0026thinsp;0.80 kg), with a substantial number of neonates falling into the low birthweight range. NICU admissions were high, with 53.5% of neonates requiring admission. The leading indications for NICU admission were prematurity (43%) and low birthweight (23%). One stillbirth and two neonatal deaths within 72 hours of birth were recorded, all occurring in the non-aspirin group (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEarly perinatal outcomes (n\u0026thinsp;=\u0026thinsp;100).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en (%) / mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm delivery (\u0026lt;\u0026thinsp;37 weeks)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e53 (53.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGA at preterm delivery (weeks), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e34.19\u0026thinsp;\u0026plusmn;\u0026thinsp;2.91\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5-minute Apgar score, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.85\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirthweight (kg), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.80\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFetal growth restriction (FGR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15 (15.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFGR Stage 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10 (66.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFGR Stage 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (26.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFGR Stage 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (6.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNICU admission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e53 (53.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndication: prematurity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e43 (43.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndication: low birthweight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23 (23.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndication: prolonged PROM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (3.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndication: RDS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (1.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStillbirth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (1.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal death within 72 hours\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (2.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eFGR\u0026thinsp;=\u0026thinsp;fetal growth restriction; GA\u0026thinsp;=\u0026thinsp;gestational age; NICU\u0026thinsp;=\u0026thinsp;neonatal intensive care unit; PROM\u0026thinsp;=\u0026thinsp;premature rupture of membranes; RDS\u0026thinsp;=\u0026thinsp;respiratory distress syndrome.\u003c/em\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eAspirin Uptake in the Study Population\u003c/h2\u003e \u003cp\u003eOf the 243 eligible women identified during the study period, only 55 (22.6%) were receiving LDA at \u0026ge;\u0026thinsp;20 weeks gestation. A one-sample proportion test against the a priori threshold of 25% yielded a proportion of 0.226, an observed test value of 0.024, and a p-value of 0.220. \u0026ldquo;The observed uptake rate was not statistically significantly different from 25% (p\u0026thinsp;=\u0026thinsp;0.220). Given that all 243 women had at least one high‑risk factor (ART), this represents substantial under‑utilisation of aspirin prophylaxis. Uptake data are presented in Table\u0026nbsp;\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e7\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAspirin prophylaxis uptake among all IVF/ICSI pregnancies identified in the study period (N\u0026thinsp;=\u0026thinsp;243).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDA Status\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFrequency\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePercent (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eProportion\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value*\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReceiving LDA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.226\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.220\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot receiving LDA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e188\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e77.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e243\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e100.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003e*One-sample proportion test vs. hypothesised threshold of 25%. LDA\u0026thinsp;=\u0026thinsp;low-dose aspirin.\u003c/em\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eIncidence of Pre-Eclampsia by Aspirin Group\u003c/h2\u003e \u003cp\u003eThe incidence of any pregnancy-related hypertensive disorder was significantly lower in aspirin users (7/50, 14.0%) compared to non-users (21/50, 42.0%) (χ\u0026sup2;=9.72, p\u0026thinsp;=\u0026thinsp;0.002). When pre-eclampsia was considered independently, incidence was 4/50 (8.0%) in aspirin users vs. 17/50 (34.0%) in non-users (χ\u0026sup2;=8.39, p\u0026thinsp;=\u0026thinsp;0.004), representing a 70.6% relative risk reduction and a number-needed-to-treat of 4. Incidence data are shown in Tables\u0026nbsp;\u003cspan refid=\"Tab8\" class=\"InternalRef\"\u003e8\u003c/span\u003e and \u003cspan refid=\"Tab9\" class=\"InternalRef\"\u003e9\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab8\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 8\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociation between aspirin use and pregnancy-related hypertensive disorders.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAspirin Status\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo HDP n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHDP n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eχ\u0026sup2;\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-aspirin group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e29 (58.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e21 (42.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.722\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAspirin group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e43 (86.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7 (14.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e72 (72.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e28 (28.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eHDP\u0026thinsp;=\u0026thinsp;hypertensive disorder of pregnancy. Chi-square test significant at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/em\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab9\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 9\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociation between aspirin use and pre-eclampsia incidence.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAspirin Status\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo PE n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePE n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eχ\u0026sup2;\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-aspirin group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e33 (66.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17 (34.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.392\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAspirin group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e45 (90.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e78 (78.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22 (22.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003ePE\u0026thinsp;=\u0026thinsp;pre-eclampsia; RRR\u0026thinsp;=\u0026thinsp;70.6%; NNT\u0026thinsp;=\u0026thinsp;4. Chi-square test significant at\u003c/em\u003e p\u0026thinsp;\u003cem\u003e\u0026lt;\u0026thinsp;0.05. NNT\u0026thinsp;=\u0026thinsp;1 / (0.34\u0026thinsp;\u0026minus;\u0026thinsp;0.10)\u0026thinsp;=\u0026thinsp;4.17, rounded to 4.\u003c/em\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eGestational Age at Pre-Eclampsia Onset\u003c/h2\u003e \u003cp\u003eMean gestational age at pre‑eclampsia diagnosis was 36.46\u0026thinsp;\u0026plusmn;\u0026thinsp;1.07 weeks in aspirin users versus 32.60\u0026thinsp;\u0026plusmn;\u0026thinsp;4.34 weeks in non‑users (F\u0026thinsp;=\u0026thinsp;3.07, p\u0026thinsp;=\u0026thinsp;0.099), a difference of approximately 4 weeks.\u003c/p\u003e \u003cp\u003eStratification by onset category revealed that no aspirin users developed early‑onset pre‑eclampsia (\u0026lt;\u0026thinsp;34 weeks), whereas 42.9% of classifiable pre‑eclampsia cases in the non‑aspirin group were early‑onset (6 of 14 deliveries). (Table\u0026nbsp;\u003cspan refid=\"Tab10\" class=\"InternalRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab10\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 10\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eGestational age at pre-eclampsia onset by aspirin group (among women with PE, n\u0026thinsp;=\u0026thinsp;22).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNon-aspirin (n\u0026thinsp;=\u0026thinsp;17)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAspirin (n\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean GA at PE diagnosis (weeks, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32.60\u0026thinsp;\u0026plusmn;\u0026thinsp;4.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.46\u0026thinsp;\u0026plusmn;\u0026thinsp;1.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.099\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEarly-onset PE (\u0026lt;\u0026thinsp;34 weeks), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLate-onset PE (\u0026ge;\u0026thinsp;34 weeks), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePregnancy terminated\u0026thinsp;\u0026lt;\u0026thinsp;28 wks (severe PE)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (11.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStillbirth / Neonatal death\u0026thinsp;\u0026le;\u0026thinsp;72 h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 / 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 / 0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003eGA\u0026thinsp;=\u0026thinsp;gestational age; PE\u0026thinsp;=\u0026thinsp;pre-eclampsia; SD\u0026thinsp;=\u0026thinsp;standard deviation. F-value from one-way ANOVA. The difference in gestational age at PE onset was not statistically significant (\u003c/em\u003ep\u0026thinsp;\u003cem\u003e=\u0026thinsp;0.099), likely reflecting limited power (n\u0026thinsp;=\u0026thinsp;22 PE events)\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eMaternal and Perinatal Outcomes by Aspirin Group\u003c/h2\u003e \u003cp\u003eBivariate analysis (Table\u0026nbsp;\u003cspan refid=\"Tab11\" class=\"InternalRef\"\u003e11\u003c/span\u003e) confirmed that aspirin use was significantly associated with reduced pre-eclampsia (22.7% of PE cases in aspirin group vs. 77.3% in non-aspirin group; χ\u0026sup2;=7.05 with Yates' continuity correction, p\u0026thinsp;=\u0026thinsp;0.008) and reduced preterm delivery (aspirin group: 15/50, 30.0% vs. non-aspirin group: 28/50, 56.0%; χ\u0026sup2;=6.90, p\u0026thinsp;=\u0026thinsp;0.009), with preterm birth being nearly twice as frequent in the non-aspirin group. No significant differences were observed for postpartum haemorrhage (p\u0026thinsp;=\u0026thinsp;0.241) or organ dysfunction (p\u0026thinsp;=\u0026thinsp;1.000). FGR was lower in the aspirin group (26.7% vs. 73.3%, p\u0026thinsp;=\u0026thinsp;0.093) and NICU admission was also less frequent (41.5% vs. 58.5%, p\u0026thinsp;=\u0026thinsp;0.055), though neither reached statistical significance. Correlation analysis (Table\u0026nbsp;\u003cspan refid=\"Tab12\" class=\"InternalRef\"\u003e12\u003c/span\u003e) demonstrated that aspirin use was positively correlated with 5-minute APGAR scores (r\u0026thinsp;=\u0026thinsp;0.212, p\u0026thinsp;=\u0026thinsp;0.034) and negatively correlated with duration of maternal hospital admission (r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.232, p\u0026thinsp;=\u0026thinsp;0.020).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab11\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 11\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBivariate analysis of adverse maternal and perinatal outcomes by aspirin group (n\u0026thinsp;=\u0026thinsp;100).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome / Category\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo Aspirin n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAspirin n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eχ\u0026sup2;\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eMATERNAL OUTCOMES\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-eclampsia: Yes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (77.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (22.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.051\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational hypertension: Yes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.177\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.674\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostpartum haemorrhage: Yes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.375\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.241\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOrgan dysfunction: Yes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003ePERINATAL OUTCOMES\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm delivery: Yes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (65.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (34.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.895\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFGR: Yes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (73.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (26.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.824\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.093\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNICU admission: Yes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (58.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (41.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.692\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.055\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eStatistically significant results (\u003c/em\u003ep\u0026thinsp;\u003cem\u003e\u0026lt;\u0026thinsp;0.05), FGR\u0026thinsp;=\u0026thinsp;fetal growth restriction; NICU\u0026thinsp;=\u0026thinsp;neonatal intensive care unit. *p-values from Pearson chi-square test; Yates\u0026rsquo; continuity correction applied where expected cell counts were \u0026lt;\u0026thinsp;10 (pre-eclampsia comparison).\u003c/em\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab12\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 12\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCorrelation analysis of aspirin use with continuous maternal and perinatal outcomes (n\u0026thinsp;=\u0026thinsp;100).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome Pair\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePearson r\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eInterpretation\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAspirin status \u0026harr; 5-min APGAR score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003er\u0026thinsp;=\u0026thinsp;0.212\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.034\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eAspirin users: higher APGAR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAspirin status \u0026harr; Duration of hospital stay\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003er\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.232\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eAspirin users: shorter stay\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAspirin status \u0026harr; Birthweight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003er\u0026thinsp;=\u0026thinsp;0.138\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.176\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eNon-significant trend\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPGAR score \u0026harr; Birthweight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003er\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.327\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eInverse: lower BW \u0026rarr; lower APGAR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirthweight \u0026harr; Duration of hospital stay\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003er\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.410\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eLower BW \u0026rarr; longer stay\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eSignificant correlations (\u003c/em\u003ep\u0026thinsp;\u003cem\u003e\u0026lt;\u0026thinsp;0.05) are shown in bold. APGAR\u0026thinsp;=\u0026thinsp;Appearance, Pulse, Grimace, Activity, Respiration.\u003c/em\u003e\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study provides preliminary evidence from sub-Saharan Africa on aspirin utilisation and its association with pre-eclampsia prevention specifically in IVF/ICSI pregnancies. Three major insights emerge: (1) low-dose aspirin was associated with a lower incidence and severity of pre-eclampsia in this high-risk population (2) aspirin use \u003cb\u003ewas associated with\u003c/b\u003e later disease onset, absence of early-onset pre-eclampsia, fewer preterm births, and higher neonatal Apgar scores (3) despite these compelling benefits and clear international recommendations, aspirin prophylaxis is critically underutilised, with only 22.6% of eligible women receiving therapy.\u003c/p\u003e \u003cdiv id=\"Sec23\" class=\"Section2\"\u003e \u003ch2\u003eElevated Burden of Pre-Eclampsia in This ART Cohort\u003c/h2\u003e \u003cp\u003eThe 34.0% pre-eclampsia incidence among non-users exceeds rates typically reported in ART studies, which range from 4\u0026ndash;12% [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. This discrepancy likely reflects the convergence of multiple risk factors in our study population\u003c/p\u003e \u003cp\u003eThe mean maternal age of 40.8 years is markedly higher than in comparable studies (Lambers et al. [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]: 32.8 years; Haapsamo et al. [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]: 30.4 years), reflecting the prolonged subfertility and delayed childbearing characteristic of the Ghanaian ART population seeking these services. Additionally, 52.0% of participants were obese (compared to 22.7% in Lambers et al.), and 72.0% used donor oocytes, a mode associated with the highest pre-eclampsia risk among ART modalities, with reported odds ratios of 2.5\u0026ndash;4.5 relative to autologous IVF [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe immunological basis of this elevated risk in donor oocyte cycles is well-established: complete allogeneic mismatch between maternal and fetal tissues triggers an exaggerated maternal immune response and defective immune-modulated placentation, contributing to endothelial dysfunction and hypertension [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In our setting, donor oocyte cycles predominate due to advanced maternal age and diminished ovarian reserve, creating a convergence of age-related, metabolic, and immunological risk factors that substantially amplify pre-eclampsia susceptibility beyond that observed in typical IVF cohorts from Europe or North America.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec24\" class=\"Section2\"\u003e \u003ch2\u003eEffectiveness of Aspirin Prophylaxis\u003c/h2\u003e \u003cp\u003eThe 70.6% relative risk reduction (34.0% \u0026rarr; 8.0%) observed in our study exceeds the 18\u0026ndash;25% reduction typically reported in broad meta-analyses of aspirin for pre-eclampsia prevention [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. This enhanced effect size likely reflects the 'high-risk, high-benefit' paradigm: in a population with extremely high baseline risk, the absolute risk reduction and consequently the observed relative reduction is maximised. The number‑needed‑to‑treat of 4 compares favourably with other established obstetric preventive interventions and underscores the potential value of systematically implementing aspirin prophylaxis in ART pregnancies.\u003c/p\u003e \u003cp\u003eThese findings align with, and in important ways corroborate, the landmark randomised controlled trial by Lambers et al. (2009), which reported hypertensive complication rates of 3.6% (aspirin) vs. 26.9% (placebo) in IVF pregnancies [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], the only prior RCT specifically in ART populations. Our observational study, conducted in a real-world, resource-limited setting, suggests that aspirin\u0026rsquo;s protective effect is maintained and possibly enhanced. These findings support the external validity of clinical guidelines recommending routine aspirin in ART pregnancies\u003c/p\u003e \u003cp\u003eThe complete elimination of early-onset pre-eclampsia (\u0026lt;\u0026thinsp;34 weeks) among aspirin users versus 42.9% of pre-eclampsia cases in non-users occurring before 34 weeks is particularly striking. Early-onset pre-eclampsia is associated with significantly greater maternal morbidity (severe features, eclampsia, HELLP syndrome), higher rates of indicated preterm birth, and worse long-term cardiovascular outcomes for both mother and child [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. The ASPRE trial similarly demonstrated that 150 mg aspirin reduced preterm pre-eclampsia by 62%, with the most pronounced protection for cases requiring delivery before 34 weeks [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Our data strongly suggest that aspirin's mechanistic effect on spiral artery remodelling during early placentation primarily prevents the placenta-driven, early-onset disease phenotype.\u003c/p\u003e \u003cp\u003eThis study also found a significant association between aspirin use and reduced preterm delivery overall (aspirin group: 15/50, 30.0% vs. non-aspirin group: 28/50, 56.0%; χ\u0026sup2;=6.90, p\u0026thinsp;=\u0026thinsp;0.009), with the non-aspirin group experiencing nearly double the preterm delivery rate, consistent with the ASPIRIN trial demonstrating an 11% reduction in preterm delivery before 37 weeks with LDA in low- and middle-income countries [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. The positive correlation between aspirin use and 5-minute APGAR scores (r\u0026thinsp;=\u0026thinsp;0.212, p\u0026thinsp;=\u0026thinsp;0.034) further suggests that the delay in disease onset and reduction in iatrogenic preterm delivery translated into improved neonatal vitality at birth. Similarly, the negative correlation between aspirin use and maternal hospital stay duration (r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.232, p\u0026thinsp;=\u0026thinsp;0.020) reflects the clinical consequence of less severe disease and fewer complications in the aspirin-treated group.\u003c/p\u003e \u003cdiv id=\"Sec25\" class=\"Section3\"\u003e \u003ch2\u003eThe Implementation Gap\u003c/h2\u003e \u003cp\u003eDespite the unequivocal evidence and the 2021 ISSHP reclassification of ART as a high-risk factor mandating aspirin prophylaxis [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], only 22.6% of eligible women in our catchment population received LDA.\u003c/p\u003e \u003cp\u003eDespite strong evidence and the 2021 ISSHP reclassification reclassification of ART as a high-risk factor mandating aspirin prophylaxis [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], only 22.6% of eligible women in our catchment population received LDA. This figure aligns with studies from high-income countries reporting aspirin utilisation rates of 24\u0026ndash;29% in high-risk pregnancies [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e], collectively suggests that underutilisation is a global problem. This figure aligns with studies from high-income countries reporting aspirin utilisation rates of 24\u0026ndash;29% in high-risk pregnancies [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e], collectively suggests that underutilisation is a global problem not limited to resource-limited settings. To our knowledge, no prior Ghanaian study has specifically examined aspirin utilisation rates in ART pregnancies, underscoring both the novelty and urgency of the present findings.\u003c/p\u003e \u003cp\u003eOur study reveals that the implementation gap is even wider than these figures suggest. Beyond ART as a qualifying high-risk factor, 50.2% of our broader cohort had both nulliparity and advanced maternal age, two moderate-risk factors that independently satisfy criteria for aspirin initiation under ACOG, NICE, and USPSTF guidelines [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Yet aspirin utilisation in this subgroup was similarly low, indicating that the problem represents not merely a failure to recognise ART as a risk factor, but fundamental deficiencies in systematic pre-eclampsia risk screening and preventive implementation across antenatal care more broadly.\u003c/p\u003e \u003cp\u003eSeveral barriers likely contribute to this implementation gap. First, awareness of updated ISSHP and SOGC guidelines may be limited among Ghanaian obstetricians and fertility specialists, many of whom trained prior to the 2021 reclassification. Second, the absence of explicit recognition of ART as a high-risk factor in Ghana's national standard treatment guidelines creates ambiguity and perpetuates outdated practices. Third, the perception of aspirin as an intervention rather than standard prophylaxis may lead to selective prescribing only to women perceived as 'very high risk', rather than the universal application that the evidence supports. Fourth, concerns about aspirin safety in pregnancy, though largely unfounded at low prophylactic doses, persist among some clinicians and patients.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec26\" class=\"Section3\"\u003e \u003ch2\u003eAspirin Dose and Timing\u003c/h2\u003e \u003cp\u003eThe mean gestational age at aspirin initiation in our study was 15.96\u0026thinsp;\u0026plusmn;\u0026thinsp;3.57 weeks. While the mean falls within the recommended\u0026thinsp;\u0026lt;\u0026thinsp;16-week window, the standard deviation of 3.57 weeks indicates that a substantial proportion of women-initiated aspirin beyond this threshold, further limiting the potential for maximal protection. Had initiation been uniformly achieved at 11\u0026ndash;14 weeks, the protective effect observed may have been even greater. Robust evidence from Roberge et al. demonstrates that earlier initiation is associated with greater risk reduction, with each week of delay attenuating the prophylactic benefit [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. The ideal timing of 11\u0026ndash;14 weeks, coinciding with first-trimester screening, was achieved in only a minority of participants, representing a missed optimisation opportunity.\u003c/p\u003e \u003cp\u003eRegarding dose, 64.0% of aspirin users received 75 mg/day and 36.0% received 150 mg/day. The 2021 ISSHP guidelines recommend 150 mg nightly based on the ASPRE trial demonstrating superior efficacy of 150 mg over lower doses for preterm pre-eclampsia prevention [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. A meta-analysis by van Doorn et al. confirmed a 62% reduction in preterm pre-eclampsia with \u0026ge;\u0026thinsp;150 mg but no significant reduction at lower doses [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. The predominant use of 75 mg in our cohort, while providing some benefit, likely represents a suboptimal dosing strategy that may have attenuated the observed treatment effect. Optimal dosing should be a focus of future guidance and audit activities.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec27\" class=\"Section3\"\u003e \u003ch2\u003eRecommendations\u003c/h2\u003e \u003cp\u003eBased on these findings and the convergent evidence base, we advance four actionable recommendations:\u003c/p\u003e \u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eUniversal aspirin prophylaxis may be considered for all ART pregnancies. Emerging evidence suggests that pregnancies conceived through IVF or ICSI may benefit from low-dose aspirin (150 mg nightly), initiated between 12 and 16 weeks\u0026rsquo; gestation, even in the absence of additional pre-eclampsia risk factors. The NNT of 4 reported here compares exceptionally favourably with most other established preventive interventions in obstetrics.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e2. Integration of pre-eclampsia prevention into ART counselling. Preconception and first-trimester counselling must explicitly address the elevated pre-eclampsia risk and documented benefits of aspirin. This discussion should be documented and communicated to antenatal care providers to ensure continuity of prophylaxis throughout pregnancy.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e3. Urgent national guideline revision. The Society of Obstetricians and Gynaecologists of Ghana (SOGOG), the Fertility Society of Ghana (FERSOG), and the National Standard Treatment Guidelines Working Group should revise existing guidelines to explicitly recognise ART as an independent high-risk factor and recommend routine aspirin prophylaxis at 150 mg nightly from 12 to 36 weeks.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e4. Health system implementation strategies. Clinical decision support tools, protocolised order sets, and audit-feedback cycles should be deployed to systematically identify eligible women and ensure aspirin prescription at the first antenatal visit after ART conception.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec28\" class=\"Section2\"\u003e \u003ch2\u003eStrengths and Limitations\u003c/h2\u003e \u003cp\u003eSeveral limitations must be acknowledged. First, the sample size (n\u0026thinsp;=\u0026thinsp;100), while adequately powered for the primary outcomes, was insufficient for multivariable adjustment and subgroup analyses, including comparisons of 75 mg vs. 150 mg aspirin and fresh vs. frozen embryo transfer subgroups. Second, the observational design precludes causal inference; unmeasured confounders (e.g., health-seeking behaviour, nutritional status) may have influenced both aspirin prescription and outcomes. Third, proteinuria quantification relied on urine dipstick rather than protein: creatinine ratio, potentially causing some misclassification. Fourth, aspirin adherence was based on patient report and prescription records and was not objectively verified using pill counts or pharmacy refill data. Fifth, long-term neonatal follow-up was not performed, precluding assessment of neurodevelopmental outcomes. Finally, the study was conducted exclusively in private fertility centres; generalisability to public-sector ART services in Ghana may be limited.\u003c/p\u003e \u003cp\u003e Future research priorities include: (1) a large, adequately powered randomised controlled trial comparing 75 mg versus 150 mg aspirin in ART populations; (2) comparative effectiveness studies by ART modality (fresh/frozen transfer, autologous/donor gametes); (3) implementation science research to identify effective strategies for improving guideline adherence in low-resource settings; and (4) cost-effectiveness analysis of universal aspirin prophylaxis in ART pregnancies in sub-Saharan Africa.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study provides important preliminary evidence from a sub-Saharan African setting that low-dose aspirin use was associated with a significantly lower incidence and severity of pre-eclampsia in IVF/ICSI pregnancies, later disease onset, and improved perinatal outcomes. The magnitude of benefit, a 70.6% relative risk reduction with a number-needed-to-treat of 4, reflects the very high baseline risk in this cohort characterised by advanced maternal age, obesity, and high-prevalence donor oocyte cycles.\u003c/p\u003e \u003cp\u003eHowever, the critical underutilisation of this safe, inexpensive, and highly effective intervention at only 22.6% uptake represents a major evidence-to-practice gap and a missed opportunity to prevent substantial maternal and perinatal morbidity. Bridging this implementation gap requires concerted action at multiple levels: individual clinicians must update practice in accordance with current international guidelines; professional societies must provide clear, context-adapted recommendations for the Ghanaian setting; and health systems must implement systematic screening and prophylaxis protocols within ART care pathways.\u003c/p\u003e \u003cp\u003e For the hundreds of Ghanaian women who undergo IVF/ICSI annually, and for the thousands more across Africa where ART is expanding rapidly, ensuring routine access to aspirin prophylaxis is not merely a matter of guideline adherence but an essential component of equitable, evidence-based reproductive healthcare.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eACOG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAmerican College of Obstetricians and Gynecologists\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eANC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAntenatal Care\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAPGAR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAppearance, Pulse, Grimace, Activity, Respiration\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eART\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAssisted Reproductive Technology\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBMI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBody Mass Index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBlood Pressure\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eConfidence Interval\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFET\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eFrozen Embryo Transfer\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFGR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eFetal Growth Restriction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGestational Age\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHDP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHypertensive Disorders of Pregnancy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICSI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIntracytoplasmic Sperm Injection\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eISSHP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInternational Society for the Study of Hypertension in Pregnancy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIVF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIn Vitro Fertilisation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eJHS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eJunior High School\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eKATH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eKomfo Anokye Teaching Hospital\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLDA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLow-Dose Aspirin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNICE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNational Institute for Health and Care Excellence\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNICU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNeonatal Intensive Care Unit\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePROM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePremature Rupture of Membranes\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRDS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRespiratory Distress Syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRelative Risk\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eStandard Deviation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSHS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSenior High School\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSOGC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSociety of Obstetricians and Gynaecologists of Canada\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSPSS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eStatistical Package for the Social Sciences\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSTROBE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eStrengthening the Reporting of Observational Studies in Epidemiology\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eUSPSTF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eUnited States Preventive Services Task Force\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003e Ethical approval was obtained from the Committee on Human Research, Publications and Ethics (CHRCLCL) of Kwame Nkrumah University of Science and Technology, Kumasi (protocol ID: CHRPE/AP/1334/24. All study participants provided written informed consent and the research was conducted in accordance with the Declaration of Helsinki.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003e All authors have read and approved the final manuscript and consent to its publication\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eEAA designed the study with support from MYA. Data collection, validation and analysis were done by BKO, AAK and CMS. AKD, RMKD, WMB, and WKA drafted the manuscript, and all authors reviewed it for intellectual content. All authors read, reviewed, and approved the final version of the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eWe are profoundly grateful to the women who participated in this study. We acknowledge the invaluable contributions of the medical directors, fertility specialists, embryologists, and nursing staff at Trustcare Specialist Hospital and Fertility Centre, RUMA Specialist Hospital and Fertility Centre, Hallmark Medicals, and Oak Specialist Hospital, Kumasi. We thank the Committee on Human Research, Publications and Ethics (CHRPE) of KNUST for thorough ethical oversight. Special appreciation is extended to research assistants at each study site for ensuring complete participant follow-up.\u003c/p\u003e \u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSay L, Chou D, Gemmill A, Tun\u0026ccedil;alp \u0026Ouml;, Moller AB, Daniels J, G\u0026uuml;lmezoglu AM. Global causes of maternal death: a WHO systematic analysis. 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PLoS ONE. 2021;16(3):e0247782. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1371/journal.pone.0247782\u003c/span\u003e\u003cspan address=\"10.1371/journal.pone.0247782\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"reproductive-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"reph","sideBox":"Learn more about [Reproductive Health](http://reproductive-health-journal.biomedcentral.com)","snPcode":"12978","submissionUrl":"https://submission.nature.com/new-submission/12978/3","title":"Reproductive Health","twitterHandle":"@Reprod_Health","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Pre-eclampsia, IVF, ICSI, Assisted reproductive technology, Low-dose aspirin, Prophylaxis, Ghana, Sub-Saharan Africa, Hypertensive disorders of pregnancy, Prospective cohort","lastPublishedDoi":"10.21203/rs.3.rs-9229684/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9229684/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: Pregnancies conceived through assisted reproductive technology (ART) have a substantially elevated risk of pre-eclampsia, and international guideline classify ART as a high-risk factor warranting low-dose aspirin prophylaxis. However, data on aspirin utilisation and effectiveness in ART pregnancies in sub-Saharan Africa are scare.\u003c/p\u003e\n\u003cp\u003eMethods: A prospective cohort study was conducted at four private ART centres in Kumasi, Ghana, from August 2024 to February 2025. Women with ongoing In Vitro Fertilization (IVF) and \u0026nbsp;Intracytoplasmic Sperm Injection (ICSI) pregnancies at ≥20 weeks of gestation were consecutively enrolled and categorized by aspirin status (50 exposed and 50 unexposed). Pre-eclampsia was diagnosed according to the 2021 International Society for the Study of Hypertension in Pregnancy criteria. Data were analysed using SPSS version 27 with significance set at p \u0026lt; 0.05.\u003c/p\u003e\n\u003cp\u003eResults: In a cohort of 100 women (mean age of 40.8 years), aspirin use was associated with a lower incidence of pre-eclampsia (10.0% vs. 34.0%; relative risk (RR) 0.29, 95% confidence interval (CI) 0.11–0.76; p = 0.004). The mean gestational age at pre-eclampsia diagnosis was delayed in aspirin users (36.46±1.07 weeks vs. 32.60±4.34 weeks; p= 0.099). Early-onset pre-eclampsia (\u0026lt;34 weeks) occurred in 0% of aspirin users compared to 42.9% of affected non-users.\u003c/p\u003e\n\u003cp\u003eAspirin use was significantly associated with fewer preterm deliveries (p=0.009), higher 5-minute appearance, pulse, grimace, activity, respiration (Apgar) scores (p = 0.034), and shorter maternal hospital stays(p=0.020).\u003c/p\u003e\n\u003cp\u003eConclusions: Low-dose aspirin significantly reduced the incidence and severity of pre-eclampsia and better perinatal outcomes in this Ghanaian ART cohort. Despite its high efficacy, prophylaxis remains critically underutilized. These findings support incorporating pre-eclampsia risk assessment and aspirin prophylaxis into routine and preconception ART care.\u003c/p\u003e","manuscriptTitle":"Aspirin Use for Pre-Eclampsia Prevention in IVF/ICSI Pregnancies in Kumasi, Ghana: A Prospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-30 21:03:11","doi":"10.21203/rs.3.rs-9229684/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"164385823734207332587123995744148047636","date":"2026-05-04T22:01:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"38987266767302217937600720355392941113","date":"2026-04-23T02:29:58+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-22T19:05:19+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-07T13:22:29+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-06T07:58:39+00:00","index":"","fulltext":""},{"type":"submitted","content":"Reproductive Health","date":"2026-04-03T08:18:32+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"reproductive-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"reph","sideBox":"Learn more about [Reproductive Health](http://reproductive-health-journal.biomedcentral.com)","snPcode":"12978","submissionUrl":"https://submission.nature.com/new-submission/12978/3","title":"Reproductive Health","twitterHandle":"@Reprod_Health","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b6769c2f-9216-404b-b971-c248496b9fdf","owner":[],"postedDate":"April 30th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"164385823734207332587123995744148047636","date":"2026-05-04T22:01:53+00:00","index":51,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-30T21:03:11+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-30 21:03:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9229684","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9229684","identity":"rs-9229684","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}