{"paper_id":"1566fe5d-0ef8-4f2d-82c1-0650c67dd574","body_text":"Low-dose Aspirin Delays the Onset of Pre-eclampsia in an Unselected Population of Ivf/icsi Pregnancies by Almost 4 Weeks | 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 Low-dose Aspirin Delays the Onset of Pre-eclampsia in an Unselected Population of Ivf/icsi Pregnancies by Almost 4 Weeks Edward Anabila Agana, Charles Mawunyo Senaya, John Jude Kwaku Annan, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8181675/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Pre-eclampsia, a leading cause of maternal and perinatal mortality, presents with increased frequency and severity in pregnancies conceived via assisted reproductive technology (ART). The distinction between early-onset (< 34 weeks) and late-onset (≥ 34 weeks) pre-eclampsia is life-threatening, as the former is associated with substantially greater morbidity. While low-dose aspirin (LDA) is recommended for prevention in high-risk groups, its specific impact on the timing of disease onset in in-vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) pregnancies, particularly in regions like sub-Saharan Africa, remains insufficiently characterised. The study aimed to compare the gestational age at onset of pre-eclampsia between IVF/ICSI pregnancies with and without LDA prophylaxis in Kumasi, Ghana. Methods A prospective cohort study was conducted at four specialist ART centres in Kumasi from August 2024 to February 2025. One hundred women with ongoing singleton or multiple pregnancies conceived via IVF/ICSI were recruited at or beyond 20 weeks of gestation and followed until delivery. Participants were allocated into two groups of 50, based on their use of LDA: an exposed group that received aspirin and a non-exposed (control) group. The primary outcome was the gestational age at diagnosis of pre-eclampsia, defined according to the 2021 International Society for the Study of Hypertension in Pregnancy (ISSHP) criteria. Results The use of LDA was associated with a profound shift in the clinical presentation of pre-eclampsia. The mean gestational age at diagnosis was significantly later in the aspirin group (36w + 5d) compared to the non-aspirin group (32w + 6d), representing a delay of nearly four weeks. Most outstandingly, there was a complete absence of early-onset pre-eclampsia in the aspirin group (0%), whereas 47.1% of pre-eclampsia cases in the non-aspirin group occurred before 34 weeks of gestation. This indicates that aspirin not only delayed the onset of the disease but also effectively prevented its most severe, early-gestation phenotype in this cohort. Conclusion Low-dose aspirin prophylaxis in IVF/ICSI pregnancies results in a clinically meaningful delay in the onset of pre-eclampsia. Its primary benefit appears to be the prevention of the more dangerous early-onset form of the disease, thereby modifying its clinical course towards a more manageable, near-term presentation. These findings underscore the critical importance of implementing routine LDA prophylaxis in this high-risk obstetric population to improve maternal and perinatal outcomes. Pre-eclampsia in-vitro fertilisation/intracytoplasmic sperm injection Low-dose aspirin Assisted reproductive technology Gestational Age Early-Onset Pre-eclampsia Figures Figure 1 Background Hypertensive disorders of pregnancy (HDP) represent a formidable challenge to global maternal health, accounting for an estimated 14% of maternal deaths worldwide ( 1 ). Pre-eclampsia, the most severe manifestation of HDP, is a multisystem disorder that complicates 2–8% of pregnancies and is directly responsible for over 70,000 maternal and 500,000 foetal deaths annually ( 1 ). The burden of this condition is disproportionately borne by low- and middle-income countries, particularly in sub-Saharan Africa, where the pooled incidence of pre-eclampsia is estimated to be as high as 13% ( 2 ). In Ghana, HDP is the second leading direct cause of maternal mortality, trailing only obstetric haemorrhage. Institutional data from the country's largest referral centres, Korle-Bu Teaching Hospital (KBTH) and Komfo Anokye Teaching Hospital (KATH), consistently place HDP among the top two causes of maternal death over the past decade, with prevalence rates of HDP reported as high as 21.4% in some cohorts ( 3 ). Beyond mortality, pre-eclampsia is a major contributor to severe maternal morbidity and adverse perinatal outcomes, including preterm birth, intrauterine growth restriction (IUGR), and neonatal intensive care unit (NICU) admissions ( 4 ). A growing body of evidence has firmly established that pregnancies conceived through assisted reproductive technology (ART), such as in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI), carry a significantly higher risk of pre-eclampsia compared to spontaneously conceived pregnancies ( 5 ). Meta-analyses have quantified this risk, showing that ART pregnancies are associated with an approximately 1.7 to 2-fold increased odds of developing hypertensive disorders ( 6 ). This elevated risk has prompted leading international bodies, including the International Society for the Study of Hypertension in Pregnancy (ISSHP) and the Society of Obstetricians and Gynaecologists of Canada (SOGC), to classify ART conception as a high-risk factor for pre-eclampsia, warranting prophylactic intervention ( 7 ). The increased susceptibility of ART pregnancies to pre-eclampsia is not merely an association with underlying subfertility but is linked to the ART procedures themselves. The pathophysiology is thought to be multifactorial, involving mechanisms that disrupt the critical early stages of placentation ( 8 ). The conventional two-stage model of pre-eclampsia posits that the disorder originates from defective trophoblastic invasion of maternal spiral arteries, leading to placental hypoperfusion (Stage 1). This ischemic placenta then releases anti-angiogenic and pro-inflammatory factors into the maternal circulation, causing systemic endothelial dysfunction and clinical syndrome of hypertension and end-organ damage (Stage 2) ( 9 ). In ART pregnancies, several factors can exacerbate this process. Ovarian stimulation protocols can create a hyperoestrogenic state that may impair endometrial receptivity, while the manipulation of gametes and embryos may introduce epigenetic modifications affecting placental development ( 10 ). A particularly compelling mechanism involves the absence of the corpus luteum in programmed frozen embryo transfer (FET) and donor oocyte cycles. The corpus luteum is the primary source of the hormone relaxin in early pregnancy, a potent vasodilator crucial for the maternal cardiovascular adaptations required to accommodate pregnancy, such as increased arterial compliance ( 11 ). Its absence in these ART cycles leads to impaired vascular remodelling, creating a physiological predisposition to hypertension from the outset ( 11 ). Momentously, pre-eclampsia is not a monolithic entity. It is increasingly understood as a syndrome with at least two distinct clinical phenotypes: early-onset pre-eclampsia diadnosis < 34 weeks of gestation) and late-onset pre-eclampsia (diagnosis ≥ 34 weeks). This distinction is of profound clinical importance. Early-onset pre-eclampsia is a severe, aggressive disease primarily driven by profound placental dysfunction and malperfusion. It is strongly associated with foetal growth restriction and is responsible for a disproportionate share of adverse maternal and perinatal outcomes, including a 5- to 10-fold increased risk of future maternal cardiovascular disease ( 12 ). In contrast, late-onset pre-eclampsia is more common, typically less severe, and thought to be related to the interaction of a normally ageing placenta with underlying maternal constitutional factors, resulting in better outcomes ( 12 ). Preventing the early-onset form of the disease is therefore a primary goal of modern obstetrics. Low-dose aspirin (LDA) has emerged as the most effective pharmacological intervention for the prevention of pre-eclampsia in high-risk women. Its mechanism of action involves the inhibition of thromboxane A2 synthesis, which promotes vasodilation and improves placental perfusion, thereby targeting the root cause of placental-mediated pre-eclampsia ( 13 ). Evidence from landmark randomised controlled trials has demonstrated that the primary benefit of LDA is its ability to prevent the more dangerous preterm (early-onset) form of the disease. The ASPRE trial, for instance, found that 150 mg of aspirin initiated in the first trimester reduced the incidence of preterm pre-eclampsia by 62% in a high-risk population ( 14 ). Similarly, the ASPIRIN trial, conducted in low- and middle-income countries, reported a significant reduction in early preterm delivery (< 34 weeks) due to hypertensive disorders among women on LDA ( 15 ). This suggests that aspirin's main utility lies in its capacity to modify the disease course away from its most severe phenotype. Notwithstanding the strong evidence and international guidelines, anecdotal reports from Kumasi, Ghana, suggested that aspirin was not being routinely prescribed in ART pregnancies, and there was a lack of local data on its effectiveness in this specific high-risk group. Given the high cost and emotional investment associated with IVF/ICSI, preventing severe complications like early-onset pre-eclampsia is of paramount importance. A 2019 Cochrane review confirmed that aspirin prophylaxis reduces the risk of proteinuric pre-eclampsia, preterm birth, and perinatal mortality, making it a cost-effective and accessible intervention with the potential for significant impact in the Ghanaian context ( 16 ). Therefore, the current study aimed to compare the gestational age at onset of pre-eclampsia between IVF/ICSI pregnancies on aspirin and those not on aspirin in Kumasi, to determine if LDA can delay the onset and mitigate the severity of the disease in this uniquely vulnerable population. Methodology Study Design A prospective cohort study was conducted to compare the incidence and onset of pre-eclampsia between aspirin users and non-users. The exposure of interest was the use of low-dose aspirin (LDA). The exposed group consisted of women with ongoing pregnancies conceived through IVF/ICSI who were on LDA, while the unexposed (control) group comprised women with IVF/ICSI pregnancies who were not on aspirin. The design allows for the direct calculation and comparison of incidence rates and to assess the temporal relationship between aspirin exposure and the onset of pre-eclampsia. Study Site The study was carried out across four private Assisted Reproductive Technology (ART) centres in Kumasi, Ghana: Trustcare Specialist Hospital and Fertility Centre, Ruma Specialist Hospital and Fertility Centre, Hallmark Medicals, and Oak Specialist Hospital. These facilities specialise in fertility treatments and also provide antenatal and delivery services, making them ideal sites for recruiting a concentrated population of women who have conceived via IVF or ICSI. Study Population The study population included all women with ongoing pregnancies at or beyond 20 weeks of gestation who were conceived through IVF or ICSI at the participating centres. Participants were followed from the time of recruitment until delivery. Women were categorised into the exposed or unexposed groups based on their documented use of LDA for pre-eclampsia prophylaxis beyond 12 weeks of gestation. Selection Criteria Inclusion Criteria The study included women with ongoing IVF/ICSI pregnancies at 20 weeks of gestation or beyond who provided written informed consent to participate. Exclusion Criteria Women were excluded if they declined to provide consent at any point during the study or if their pregnancy was terminated at or beyond 20 weeks for reasons of lethal foetal anomalies. Sample Size Calculation The sample size was calculated using the StatCalc function in Epi Info (version 7.2.5.0). The calculation was based on a prior study by Lambers et al. (2009), which reported an incidence of hypertensive complications of 3.6% in an aspirin group versus 26.9% in a placebo group ( 17 ). To detect a similar difference with a 95% confidence level and 80% statistical power, assuming a 1:1 ratio of exposed to unexposed participants, a sample size of 90 was required. This was adjusted to 100 participants (50 per group) to account for a potential 10% loss to follow-up. Sampling and Sampling Techniques During the study period from August 2024 to February 2025, a total of 243 women who conceived via IVF/ICSI were identified. From this pool, participants were enrolled using a consecutive sampling method. To ensure balanced groups, eligible women were allocated alternately into the aspirin and non-aspirin cohorts until the target sample size of 50 participants in each group was reached. If a potential participant declined consent, the next eligible woman meeting the criteria was recruited to maintain the sampling sequence and minimise selection bias. The rate limiting step in the selection of participants was the aspirin group because there were much less women on aspirin than those not on aspirin. Any time a participant on aspirin was encounted and selected, the next available women not on aspirin was also selected and this cycle was then repeated until the sample size of 100 was obtained. Source: Author’s Construct (2025) Data Collection Procedure Potential participants were approached during their routine antenatal visits. After a thorough explanation of the study's purpose and procedures, written informed consent was obtained. Data were collected by the principal investigator and trained research assistants using a structured questionnaire. Additional information was extracted from participants' antenatal records, hospital folders, and newborn medical records. Pre-eclampsia was diagnosed and managed according to the 2021 ISSHP guidelines. Data points collected included sociodemographic characteristics, medical and obstetric history, details of the ART treatment, risk factors for pre-eclampsia, and all maternal and perinatal outcomes until delivery. Outcome Measurements The primary outcome was the gestational age at the onset of pre-eclampsia. This was measured as the number of completed weeks of gestation at the time of diagnosis. Cases were further categorised as early-onset (< 34 weeks) or late-onset (≥ 34 weeks) pre-eclampsia. Data Analysis and Management Data were first entered into Microsoft Excel for cleaning and validation and subsequently exported to the STATA version 17 for analysis. Descriptive statistics, including means, standard deviations, frequencies, and percentages, were used to summarise participant characteristics. The comparison of mean gestational age at onset between the two groups was performed using an analysis of variance (ANOVA). The association between aspirin use and the categorical outcome of early- versus late-onset pre-eclampsia was assessed using the chi-square test. A p-value of less than 0.05 was considered statistically significant for all inferential analyses. Ethical considerations Ethical approval for the study was granted by the Committee on Human Research, Publications, and Ethics (CHRPE) of Kwame Nkrumah University of Science and Technology (KNUST) (Registration number: CHRPE/AP/1334/24). Permission was also obtained from the management of each participating ART centre. All participants provided written informed consent before enrolment. To ensure confidentiality, all data were anonymised using study codes, and electronic data were stored on a password-protected computer accessible only to the research team. The study was non-interventional and posed no direct physical risk to participants, with all financial costs borne by the principal investigator. Results Socio-demographic and clinical characteristics of study participants The socio-demographic and clinical characteristics of the study participants indicate that the majority were married (98%), with only 2% being single. Most respondents were Christians (90.91%), while Muslims constituted 9.09% of the study population. The mean age of participants was 40.82 ± 5.69 years, with nearly equal age distribution 49% were aged 41 years or below, 51% were older than 41 years. In terms of educational attainment, 45% had tertiary education, 36% completed senior high school (SHS), and 19% had junior high school (JHS) education. A wide variety of occupations were reported, although traders formed the largest group (31%), followed by professionals (21%) and public or civil servants (20%). Other occupations such as artisans (4%), hairdressers (4%), businesswomen (9%), housewives (6%), caterers (2%), bankers (2%), and seamstresses (1%) were also represented. Regarding body mass index (BMI), more than half of the participants were obese (52%), 36% were overweight, and only 12% had a normal BMI, suggesting a high prevalence of excess weight among the study population. Table 1 Socio-demographic and Clinical Characteristics of Study Participants Variable Frequency (n) Percentage (%) Marital status Single 2 2.00 Married 98 98.00 Religion Christianity 91 91.00 Muslim 9 9.00 Age in years (N = 100) x̄±SD = 40.82 ± 5.69 =<41 49 49.00 > 41 51 51.00 Highest level of Education JHS 19 19.00 SHS 36 36.00 Tertiary 45 45.00 Occupation Artisan 4 4.00 Banker 2 2.00 Businesswoman 9 9.00 Caterer 2 2.00 Hairdresser 4 4.00 Housewife 6 6.00 Professional 21 21.00 Public/civil servant 20 20.00 Seamstress 1 1.00 Trader 31 31.00 BMI Level Normal (18.5–24.9) 12 12.00 Overweight (25-29.9) 36 36.00 Obese ( > = 30) 52 52.00 Source: Field Data, 2025. Demographics by status of aspirin intake The demographic and clinical characteristics of the 100 participants, categorised by aspirin intake, are presented in Table 2 . Generally, the two groups were well-matched across most sociodemographic variables, including marital status, religion, age, education level, and BMI, with no statistically significant differences observed. The mean age for both the non-aspirin (40.2 years) and aspirin (41.4 years) groups was high. In terms of education, a majority of the non-aspirin group had completed tertiary education (52%), whereas the largest proportion of the aspirin group had completed Senior High School (42%). The occupational landscape also varied; professionals constituted the largest segment of the non-aspirin group (26%), while traders were the most common occupation in the aspirin group (42%). A significant clinical finding was the high prevalence of obesity across both cohorts. Nearly half of the non-aspirin group (46%) and a majority of the aspirin group (58%) were classified as obese, with a BMI of 30 kg/m² or higher. Despite these variations in distribution, the lack of statistically significant p-values across all categories (p > 0.05) confirms that the two groups were demographically comparable at baseline, which is crucial for attributing differences in outcomes to the intervention (aspirin use) rather than to confounding demographic factors. Table 2 Demographics by Status of Aspirin Intake Aspirin Intake X 2 p-value Variables No n(%) Yes n(%) Marital status 0.510 0.475 Single 2( 4 ) 0(0) Married 48(96) 50(100) Religion 0.534 0.465 Christianity 44(88) 47(94) Muslim 6( 12 ) 3( 6 ) Age 40.23 ± 5.58 41.38 ± 5.79 0.992 0.324 Highest level of Education 2.142 0.343 JHS 9( 18 ) 10(20) SHS 15(30) 21(42) Tertiary 26(52) 19(38) Occupation 13.760 0.131 Artisan 1( 2 ) 3( 6 ) Banker 2( 4 ) 0(0) Businesswoman 6( 12 ) 3( 6 ) Caterer 0(0) 2( 4 ) Hairdresser 3( 6 ) 1( 2 ) Housewife 4( 8 ) 2( 4 ) Professional 13(26) 8( 16 ) Public/civil servant 10(20) 10(20) Seamstress 1( 2 ) 0(0) Trader 10(20) 21(42) BMI Level 29.98 ± 5.73 31.12 ± 5.53 1.692 0.429 Normal (18.5–24.9) 6( 12 ) 6( 12 ) Overweight (25-29.9) 21(42) 15(30) Obese ( > = 30) 23(46) 29(58) Source: Field Data, 2025. Past obstetric, medical and family history A breakdown of the participants' medical histories revealed significant differences between the groups in the Table 3 below. Women in the aspirin group had a significantly higher prevalence of pre-existing chronic hypertension (34% vs. 8%, p = 0.002) and diabetes mellitus (16% vs. 2%, p = 0.036) compared to the non-aspirin group. 1 This suggests that the prescription of aspirin was appropriately targeted toward women with established high-risk factors for pre-eclampsia. Consequently, a significantly lower proportion of women in the aspirin group developed a hypertensive disorder during the current pregnancy (14% vs. 42%, p < 0.001). Table 3 Past Obstetric, Medical and Family History Aspirin Chi-square p-value Variables No n(%) Yes n(%) Medical disorders you have been diagnosed with 11.694 < 0.001 No 5( 10 ) 21(42) Yes 45(90) 29(58) Asthma < 0.001 1.000 No 50(100) 49(98) Yes 0(0) 1( 2 ) Chronic hypertension 8.680 0.002 8.680 No 46(92) 33(66) Yes 4( 8 ) 17(34) Diabetes mellitus 4.396 0.036 No 49(98) 42(84) Yes 1( 2 ) 8( 16 ) Sickle cell disease < 0.001 1.000 No 50(100) 49(98) Yes 0(0) 1( 2 ) Diagnosed with pre-eclampsia in a previous pregnancy? 3.075 0.215 Not applicable 30(60) 38(76) Yes 1( 2 ) 1( 2 ) No 19(38) 11(22) Gestational age at delivery in the previous pregnancy 37w ± 4w 38 -0.804 0.431 First degree relation ever had pre-eclampsia 1.018 0.601 Yes 0(0) 1( 2 ) No 29(58) 28(56) Don't know 21(42) 21(42) The urine protein at booking < 0.001 1.000 Negative 50(100) 49(98) 1+ 0(0) 1( 2 ) Dose of Aspirin 75mg - 32(64) - - 150mg - 18(36) Is the patient currently on calcium treatment? - < 0.001 1.000 No 48(96) 49(98) Yes 2( 4 ) 1( 2 ) What dose of calcium is the patient on? 1g 2(100) 1(100) - - Patient diagnosed with any pregnancy-related hypertensive disorder in this pregnancy? - 8.383 < 0.001 No 29(58) 43(86) Yes 21(42) 7( 14 ) The type of pregnancy-related hypertensive disorder diagnosed. 0.233 0.629 Gestational hypertension 5(23.8) 3(42.9) Pre-eclampsia 16(76.2) 4(57.1) Source: Field Data, 2025. Current pregnancy The Table 4 below indicates the current pregnancy, both groups had a similar mean gestational age at booking (approximately 8weeks 4 days). For those in the aspirin group, the medication was initiated at a mean gestational age of 16 weeks 1 day ± 4 weeks. A key discovery was the statistically significant difference in the gestational age at which a hypertensive disorder was diagnosed: 32w + 6d in the non-aspirin group versus 36w + 5d in the aspirin group (p = 0.039). Table 4 Current Pregnancy Aspirin Chi-square p-value No n(%) Yes n(%) Gestational age at booking 8w4d ± 1w 8w5d ± 1w 5d -0.410 0.683 Gestational age at which Aspirin was started - 16w1d ± 4w - Gestational age at which the diagnosis made 32w6d ± 4d 36w + 5d ± 2w -2.195 0.039 Is the patient on anti-hypertensive medication 0.008 0.931 No 27(56.3) 29(59.2) Yes 21(43.8) 20(40.8) On blood pressure medication 2.992 0.084 No 39(78) 30(60) Yes 11(22) 20(40) Methyldopa 0.903 0.342 No 41(82) 36(72) Yes 9( 18 ) 14(28) Nifedipine 0.391 0.532 No 30(60) 34(68) Yes 20(40) 16(32) Hydralazine 0.51 0.475 No 48(96) 50(100) Yes 2( 4 ) 0(0) Source: Field Data, 2025. Details of fertility treatment modalities An analysis of the fertility treatments undertaken by the cohort reveals a profile heavily skewed towards modalities known to confer a high a priori risk for pre-eclampsia in Table 5 below. The vast majority of participants in both the non-aspirin and aspirin groups underwent fresh embryo transfer (98% and 94%, respectively), with only a small fraction receiving a frozen embryo transfer (2% and 6%, respectively). Similarly, conventional IVF was the predominant treatment modality (94% and 98%, respectively) compared to ICSI. The most notable finding relates to the source of gametes. A striking majority of pregnancies were conceived using donor oocytes, with 68% of the non-aspirin group and 76% of the aspirin group utilising donor egg/self-sperm cycles. In contrast, autologous cycles using self-egg and self-sperm were far less common, constituting only 18% and 14% of the groups, respectively. These distributions in treatment characteristics were statistically similar between the aspirin and non-aspirin cohorts (p > 0.05 for all comparisons), indicating that the baseline risk for placental-mediated disease conferred by the ART procedures themselves was comparable across both groups. Table 5 Details of Fertility Treatment Aspirin Chi-square p-value No n(%) Yes n(%) The type of embryo transfers the patient underwent 0.26 0.61 Fresh embryo transfer 49(98) 47(94) Frozen embryo transfer 1( 2 ) 3( 6 ) What type of ART treatment did the patient undergo? 0.26 0.61 Conventional IVF 47(94) 49(98) ICSI 3( 6 ) 1( 2 ) The type of gametes was used 4.072 0.254 Donor egg/self-sperm 34(68) 38(76) Self-egg/self-sperm 9( 18 ) 7( 14 ) Gestational surrogate/Embryo adoption 7( 14 ) 3( 6 ) Self-egg/Donor sperm 0(0) 2( 4 ) Source: Field Data, 2025. Gestational age at diagnosis between aspirin users and non-users among women with pre-eclampsia The mean gestational age at which pre-eclampsia was diagnosed differed markedly between the two cohorts. As shown in Fig. 1 and Table 6 , women in the non-aspirin group developed pre-eclampsia at an average gestational age of 32w6d ± 4w. In contrast, women in the aspirin group developed the condition significantly later, at an average gestational age of 36w + 5d ± 2 w. This represents a delay in the clinical onset of the disease by nearly four weeks. While this difference was substantial from a clinical perspective, it did not reach the conventional threshold for statistical significance, likely due to the limited number of pre-eclampsia events in the cohort. Table 6 Comparison of Gestational Age at Delivery Between Aspirin Users and Non-users Among Women Diagnosed with Pre-eclampsia Variable Average Score F-value p-value Aspirin Intake 3.068 0.099 No 32w6d ± 4w Yes 36w5d ± 2w Source: Field Data, 2025. Association between aspirin use and onset of pre-eclampsia (< 34 weeks vs. ≥34 weeks) To further investigate the impact of aspirin on the clinical phenotype of pre-eclampsia, cases were stratified into early-onset (diagnosis < 34 weeks of gestation) and late-onset (diagnosis ≥ 34 weeks of gestation). The results of this analysis, presented in Table 5 , revealed a finding with possibly clinical significance even though it was not statistically significant (p = 0.316). Among the women in the non-aspirin group who developed pre-eclampsia, 47.1% (8 out of 17 evaluable cases) were diagnosed before 34 weeks, representing the more severe, early-onset form of the disease. In stark contrast, among women in the aspirin group, there were zero cases of early-onset pre-eclampsia (0%). All cases of pre-eclampsia that occurred in the aspirin group were of the late-onset type. This finding demonstrates that aspirin use was associated with a complete prevention of the early-onset phenotype of pre-eclampsia in this study population (Table 7 ). Table 7 Association Between Aspirin Use and Onset of Pre-eclampsia (< 34 weeks vs. ≥34 weeks) Variable < 34 Weeks ≥ 34 Weeks Chi-Sq p-value Aspirin Intake 1.004 0.316 No 8 (47.1%) 9 (52.9%) Yes 0 (0%) 5 (100%) Source: Field Data, 2025. Discussion Clinical significance of delayed onset and phenotypic modification of pre-eclampsia One discovery of the study is a delay in the onset of pre-eclampsia with a fundamental modification of its clinical phenotype, shifting the disease from its severe, early-onset form to a more manageable, near-term presentation. The observation that the mean gestational age at diagnosis was delayed from 32w + 6d in the non-aspirin group to 36w + 5d in the aspirin group carries immense clinical weight. A diagnosis at 32 weeks often necessitates iatrogenic preterm delivery, exposing the neonate to significant risks of morbidity and mortality associated with prematurity, including respiratory distress syndrome, intraventricular haemorrhage, and prolonged NICU stays. Shifting the onset to beyond 36 weeks alters the clinical scenario, enabling the pregnancy to progress to near-term or term, which significantly improves neonatal outcomes. While the difference in mean gestational age did not achieve statistical significance (p = 0.099), this is likely a reflection of the study's limited statistical power due to the small number of pre-eclampsia events (n = 22) rather than an absence of a true effect. In this context, the magnitude of the clinical effect, a four-week delay, should not be understated and is arguably of greater importance than a statistical threshold. In addition, there is a complete absence of early-onset pre-eclampsia (< 34 weeks) in the aspirin group, compared to a 47.1% rate among those who developed pre-eclampsia in the non-aspirin group. This result moves beyond a simple delay in onset to suggest a true modification of the disease phenotype. As established in literature, early- and late-onset pre-eclampsia are considered distinct pathophysiological entities. Early-onset disease is a severe placentopathy rooted in defective spiral artery remodelling, whereas late-onset disease is more related to maternal constitutional factors ( 12 ). Aspirin's primary mechanism is to improve placental perfusion by correcting the imbalance between thromboxane and prostacyclin. It is therefore biologically plausible that its main effect would be to counteract the pathological processes of defective placentation that drive the early-onset form of the disease. This provides strong clinical support for this mechanistic hypothesis, suggesting that aspirin effectively neutralises the pathway leading to the most severe form of pre-eclampsia. These results are consistent with and build upon the findings of major international trials. The ASPRE trial, which administered 150 mg of aspirin to a high-risk population, reported a 63% reduction in the incidence of preterm pre-eclampsia ( 14 ). The current study, though observational, observed an even more pronounced effect (a 100% reduction in early-onset cases) within a uniquely high-risk ART population. This may suggest that ART pregnancies, which are predisposed to placental dysfunction from conception, are particularly responsive to an intervention that targets placentation. Similarly, the ASPIRIN trial demonstrated a significant reduction in deliveries before 34 weeks due to hypertensive disorders in women receiving LDA ( 15 ). The findings from our cohort provide a clear mechanistic explanation for this outcome: by preventing early-onset pre-eclampsia, aspirin obviates the need for iatrogenic preterm delivery, which is the primary management for this severe condition. Our results also fall in line with local Ghanaian data from Owusu, (2022), who similarly reported that women on LDA who developed pre-eclampsia predominantly had the late-onset form, whereas those not on aspirin were more likely to have early-onset disease, reinforcing the consistency of this effect within the local context ( 18 ). Conclusion The current study reveals a new and crucial insight into the utility of low-dose aspirin in ART pregnancies. The demonstration that aspirin's benefit extends beyond merely reducing the overall incidence of pre-eclampsia; its most powerful effect may be the modification of the disease phenotype. The complete prevention of early-onset pre-eclampsia in the aspirin group strengthens the understanding of how aspirin mitigates pregnancy risk, suggesting it directly counteracts the severe placental pathology that drives early-onset disease. This provides strong evidence that routine aspirin prophylaxis is a powerful tool to prevent the most devastating maternal and perinatal complications associated with pre-eclampsia in the uniquely vulnerable ART population. Although the study provides convincing observational evidence, a larger, multi-centre randomised controlled trial is warranted within the Ghanaian population to definitively confirm these findings. Such a study should be powered to compare the efficacy of different aspirin dosages (e.g., 81 mg vs. 150 mg) specifically for the prevention of early-onset pre-eclampsia in ART pregnancies. Further research should also explore the long-term neonatal outcomes of infants born to mothers who received aspirin prophylaxis in this situation. Limitations of the study As a non-randomised, observational study, it is susceptible to selection bias and unmeasured confounding variables that could have influenced the outcomes. The sample size, while adequate for the overall cohort, resulted in a small number of pre-eclampsia events, which limited the statistical power for some analyses, such as the comparison of mean gestational age at onset. The study was conducted in private ART centres in a single city, which may limit the generalizability of the findings to the broader population of pregnant women in Ghana. Abbreviations ART Assisted Reproductive Technology ASPRE Aspirin for Evidence–Based Preeclampsia Prevention (Trial) ASPIRIN Aspirin Supplementation for Pregnancy Indicated Risk Improvement in Nulliparas (Trial) BMI Body Mass Index CHRPE Committee on Human Research, Publications, and Ethics DBP Diastolic Blood Pressure FET Frozen Embryo Transfer GA Gestational Age HDP Hypertensive Disorders of Pregnancy ICSI Intracytoplasmic Sperm Injection IUGR Intrauterine Growth Restriction IVF In Vitro Fertilisation ISSHP International Society for the Study of Hypertension in Pregnancy JHS Junior High School KATH Komfo Anokye Teaching Hospital KBTH Korle–Bu Teaching Hospital LDA Low–Dose Aspirin LMIC Low–and Middle–Income Countries NICU Neonatal Intensive Care Unit PE Pre–eclampsia SBP Systolic Blood Pressure SHS Senior High School Declarations a. Ethical approval and consent to participant This study received ethical approval from the Committee on Human Research, Publications, and Ethicsof the Kwame Nkrumah University of Science and Technology, with reference number (CHRPE/AP/1334/24) . b. Availability of data and materials Not applicable d. Competing of interest The authors declare no conflict of interest. e. Funding Source No funding was received for this study. f. Acknowledgements The author extends gratitude to all participants who participate in this study. g. Consent for Publication Not applicable h. Authors’ contribution EAA: write-up, review and editing. CMS: review and editing, JJKA: review and editing. FJMKD: review and editing. RMKD: review and editing. RKA- editing, ETD: review and editing, ATO: review and editing. All authors approved the version to be published and agreed to be accountable for all aspects of the work. References Wang W, Xie X, Yuan T, Wang Y, Zhao F, Zhou Z, et al. Epidemiological trends of maternal hypertensive disorders of pregnancy at the global, regional, and national levels: a population-based study. BMC Pregnancy Childbirth. 2021;21(1):364. Jikamo B, Adefris M, Azale T, Alemu K. Incidence, trends and risk factors of preeclampsia in sub-Saharan Africa: a systematic review and meta-analysis. PAMJ-One Health. 2023;11(1):1–54. Adu-Bonsaffoh K, Ntumy MY, Obed SA, Seffah JD. Perinatal outcomes of hypertensive disorders in pregnancy at a tertiary hospital in Ghana. BMC Pregnancy Childbirth. 2017;17(1):388. Patel AJ, Patel BS, Shah AC, Jani SK. Maternal and perinatal outcome in severe pre-eclampsia and eclampsia: a study of 120 cases at a tertiary health care centre in Western India. Int J Reprod Contracept Obstet Gynecol. 2021;10(3):1011–7. Almasi-Hashiani A, Omani-Samani R, Mohammadi M, Amini P, Navid B, Alizadeh A, et al. Assisted reproductive technology and the risk of preeclampsia: an updated systematic review and meta-analysis. BMC Pregnancy Childbirth. 2019;19(3):149. Chih HJ, Elias FTS, Gaudet L, Velez MP. Assisted reproductive technology and hypertensive disorders of pregnancy: systematic review and meta-analyses. BMC Pregnancy Childbirth. 2021 June 28;21(5):449. Magee LA, Brown MA, Hall DR, Gupte S, Hennessy A, Karumanchi SA, et al. The 2021 International Society for the Study of Hypertension in Pregnancy classification, diagnosis & management recommendations for international practice. Pregnancy Hypertens. 2022;27(5):148–69. Bisson C, Dautel S, Patel E, Suresh S, Dauer P, Rana S. Preeclampsia pathophysiology and adverse outcomes during pregnancy and postpartum. Front Med. 2023;10(3):114–70. Phipps EA, Thadhani R, Benzing T, Karumanchi SA. Pre-eclampsia: pathogenesis, novel diagnostics and therapies. Nat Rev Nephrol. 2019;15(5):275–89. Cao X, Gao C, Su M, Zhang D, Zhao F, Li W, et al. Impact of different endometrial preparation protocols on pregnancy outcomes in patients at high risk for ovarian hyperstimulation syndrome: a propensity score matched retrospective cohort study. BMC Pregnancy Childbirth. 2025;25(1):449. von Versen-Höynck F, Schaub AM, Chi YY, Chiu KH, Liu J, Lingis M, et al. Increased Preeclampsia Risk and Reduced Aortic Compliance With In Vitro Fertilisation Cycles in the Absence of a Corpus Luteum. Hypertension. 2019;73(3):640–9. Roberts JM, Rich-Edwards JW, McElrath TF, Garmire L, Myatt L. SUBTYPES OF PREECLAMPSIA: RECOGNITION AND DETERMINING CLINICAL USEFULNESS. Hypertens Dallas Tex 1979. 2021;77(5):1430–41. Xu T, Zhou F, Deng C, Huang G, Li J, Wang X. Low-Dose Aspirin for Preventing Preeclampsia and Its Complications: A Meta‐Analysis. J Clin Hypertens. 2015;17(7):567–73. Rolnik DL, Wright D, Poon LC, O’Gorman N, Syngelaki A, de Paco Matallana C, et al. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. N Engl J Med. 2017;377(7):613–22. Hoffman MK, Goudar SS, Kodkany BS, Metgud M, Somannavar M, Okitawutshu J, et al. 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 Lond Engl. 2020;395(10):285–93. Duley L, Meher S, Hunter KE, Seidler AL, Askie LM. Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev. 2019;2019(10):CD004659. Lambers MJ, Groeneveld E, Hoozemans DA, Schats R, Homburg R, Lambalk CB, et al. Lower incidence of hypertensive complications during pregnancy in patients treated with low-dose aspirin during in vitro fertilisation and early pregnancy. Hum Reprod. 2009;24(10):2447–50. Owusu YG, LOW DOSE ASPIRIN PROPHYLAXIS USE AMONG PRE-ECLAMPTIC/ECLAMPTIC WOMEN WITH HISTORY-BASED RISK FACTOR(S). IN A TERTIARY HOSPITAL IN GHANA [Internet] [Academic]. [Ghana]: Ghana College of Physicians and Surgeons; 2022 [cited 2025 Oct 17]. Available from: https://repository.gcps.edu.gh/handle/123456789/39 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. 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14:59:25\",\"extension\":\"html\",\"order_by\":7,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"acdc-reference\",\"size\":134388,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"earlyproof.html\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-8181675/v1/7ac8161302380bff6963102f.html\"},{\"id\":97271026,\"identity\":\"423a9da5-1522-4eaf-ad09-2cbf34c11470\",\"added_by\":\"auto\",\"created_at\":\"2025-12-02 14:59:25\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":26386,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eAverage Gestational Age and Incidence of Pre-Eclampsia by Aspirin Status\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eSource: Field Data, 2025.\\u003c/strong\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-8181675/v1/cbd8fccacbfbb6562a59ef86.png\"},{\"id\":98733208,\"identity\":\"4cf42166-da61-43bb-aacc-c2582578f10a\",\"added_by\":\"auto\",\"created_at\":\"2025-12-22 05:54:42\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":2097842,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-8181675/v1/9e0609d0-be43-441f-90aa-5810396a84f7.pdf\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"\\u003cp\\u003eLow-dose Aspirin Delays the Onset of Pre-eclampsia in an Unselected Population of Ivf/icsi Pregnancies by Almost 4 Weeks\\u003c/p\\u003e\",\"fulltext\":[{\"header\":\"Background\",\"content\":\"\\u003cp\\u003eHypertensive disorders of pregnancy (HDP) represent a formidable challenge to global maternal health, accounting for an estimated 14% of maternal deaths worldwide (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e). Pre-eclampsia, the most severe manifestation of HDP, is a multisystem disorder that complicates 2\\u0026ndash;8% of pregnancies and is directly responsible for over 70,000 maternal and 500,000 foetal deaths annually (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e). The burden of this condition is disproportionately borne by low- and middle-income countries, particularly in sub-Saharan Africa, where the pooled incidence of pre-eclampsia is estimated to be as high as 13% (\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e). In Ghana, HDP is the second leading direct cause of maternal mortality, trailing only obstetric haemorrhage. Institutional data from the country's largest referral centres, Korle-Bu Teaching Hospital (KBTH) and Komfo Anokye Teaching Hospital (KATH), consistently place HDP among the top two causes of maternal death over the past decade, with prevalence rates of HDP reported as high as 21.4% in some cohorts (\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e). Beyond mortality, pre-eclampsia is a major contributor to severe maternal morbidity and adverse perinatal outcomes, including preterm birth, intrauterine growth restriction (IUGR), and neonatal intensive care unit (NICU) admissions (\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cp\\u003eA growing body of evidence has firmly established that pregnancies conceived through assisted reproductive technology (ART), such as in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI), carry a significantly higher risk of pre-eclampsia compared to spontaneously conceived pregnancies (\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e). Meta-analyses have quantified this risk, showing that ART pregnancies are associated with an approximately 1.7 to 2-fold increased odds of developing hypertensive disorders (\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e). This elevated risk has prompted leading international bodies, including the International Society for the Study of Hypertension in Pregnancy (ISSHP) and the Society of Obstetricians and Gynaecologists of Canada (SOGC), to classify ART conception as a high-risk factor for pre-eclampsia, warranting prophylactic intervention (\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cp\\u003eThe increased susceptibility of ART pregnancies to pre-eclampsia is not merely an association with underlying subfertility but is linked to the ART procedures themselves. The pathophysiology is thought to be multifactorial, involving mechanisms that disrupt the critical early stages of placentation (\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e). The conventional two-stage model of pre-eclampsia posits that the disorder originates from defective trophoblastic invasion of maternal spiral arteries, leading to placental hypoperfusion (Stage 1). This ischemic placenta then releases anti-angiogenic and pro-inflammatory factors into the maternal circulation, causing systemic endothelial dysfunction and clinical syndrome of hypertension and end-organ damage (Stage 2) (\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e). In ART pregnancies, several factors can exacerbate this process. Ovarian stimulation protocols can create a hyperoestrogenic state that may impair endometrial receptivity, while the manipulation of gametes and embryos may introduce epigenetic modifications affecting placental development (\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e). A particularly compelling mechanism involves the absence of the corpus luteum in programmed frozen embryo transfer (FET) and donor oocyte cycles. The corpus luteum is the primary source of the hormone relaxin in early pregnancy, a potent vasodilator crucial for the maternal cardiovascular adaptations required to accommodate pregnancy, such as increased arterial compliance (\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e). Its absence in these ART cycles leads to impaired vascular remodelling, creating a physiological predisposition to hypertension from the outset (\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cp\\u003eMomentously, pre-eclampsia is not a monolithic entity. It is increasingly understood as a syndrome with at least two distinct clinical phenotypes: early-onset pre-eclampsia diadnosis\\u0026thinsp;\\u0026lt;\\u0026thinsp;34 weeks of gestation) and late-onset pre-eclampsia (diagnosis\\u0026thinsp;\\u0026ge;\\u0026thinsp;34 weeks). This distinction is of profound clinical importance. Early-onset pre-eclampsia is a severe, aggressive disease primarily driven by profound placental dysfunction and malperfusion. It is strongly associated with foetal growth restriction and is responsible for a disproportionate share of adverse maternal and perinatal outcomes, including a 5- to 10-fold increased risk of future maternal cardiovascular disease (\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e). In contrast, late-onset pre-eclampsia is more common, typically less severe, and thought to be related to the interaction of a normally ageing placenta with underlying maternal constitutional factors, resulting in better outcomes (\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e). Preventing the early-onset form of the disease is therefore a primary goal of modern obstetrics.\\u003c/p\\u003e\\u003cp\\u003eLow-dose aspirin (LDA) has emerged as the most effective pharmacological intervention for the prevention of pre-eclampsia in high-risk women. Its mechanism of action involves the inhibition of thromboxane A2 synthesis, which promotes vasodilation and improves placental perfusion, thereby targeting the root cause of placental-mediated pre-eclampsia (\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e). Evidence from landmark randomised controlled trials has demonstrated that the primary benefit of LDA is its ability to prevent the more dangerous preterm (early-onset) form of the disease. The ASPRE trial, for instance, found that 150 mg of aspirin initiated in the first trimester reduced the incidence of preterm pre-eclampsia by 62% in a high-risk population (\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e). Similarly, the ASPIRIN trial, conducted in low- and middle-income countries, reported a significant reduction in early preterm delivery (\\u0026lt;\\u0026thinsp;34 weeks) due to hypertensive disorders among women on LDA (\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e). This suggests that aspirin's main utility lies in its capacity to modify the disease course away from its most severe phenotype.\\u003c/p\\u003e\\u003cp\\u003e Notwithstanding the strong evidence and international guidelines, anecdotal reports from Kumasi, Ghana, suggested that aspirin was not being routinely prescribed in ART pregnancies, and there was a lack of local data on its effectiveness in this specific high-risk group. Given the high cost and emotional investment associated with IVF/ICSI, preventing severe complications like early-onset pre-eclampsia is of paramount importance. A 2019 Cochrane review confirmed that aspirin prophylaxis reduces the risk of proteinuric pre-eclampsia, preterm birth, and perinatal mortality, making it a cost-effective and accessible intervention with the potential for significant impact in the Ghanaian context (\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e). Therefore, the current study aimed to compare the gestational age at onset of pre-eclampsia between IVF/ICSI pregnancies on aspirin and those not on aspirin in Kumasi, to determine if LDA can delay the onset and mitigate the severity of the disease in this uniquely vulnerable population.\\u003c/p\\u003e\"},{\"header\":\"Methodology\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eStudy Design\\u003c/h2\\u003e\\u003cp\\u003eA prospective cohort study was conducted to compare the incidence and onset of pre-eclampsia between aspirin users and non-users. The exposure of interest was the use of low-dose aspirin (LDA). The exposed group consisted of women with ongoing pregnancies conceived through IVF/ICSI who were on LDA, while the unexposed (control) group comprised women with IVF/ICSI pregnancies who were not on aspirin. The design allows for the direct calculation and comparison of incidence rates and to assess the temporal relationship between aspirin exposure and the onset of pre-eclampsia.\\u003c/p\\u003e\\u003c/div\\u003e\\n\\u003ch3\\u003eStudy Site\\u003c/h3\\u003e\\n\\u003cp\\u003eThe study was carried out across four private Assisted Reproductive Technology (ART) centres in Kumasi, Ghana: Trustcare Specialist Hospital and Fertility Centre, Ruma Specialist Hospital and Fertility Centre, Hallmark Medicals, and Oak Specialist Hospital. These facilities specialise in fertility treatments and also provide antenatal and delivery services, making them ideal sites for recruiting a concentrated population of women who have conceived via IVF or ICSI.\\u003c/p\\u003e\\n\\u003ch3\\u003eStudy Population\\u003c/h3\\u003e\\n\\u003cp\\u003eThe study population included all women with ongoing pregnancies at or beyond 20 weeks of gestation who were conceived through IVF or ICSI at the participating centres. Participants were followed from the time of recruitment until delivery. Women were categorised into the exposed or unexposed groups based on their documented use of LDA for pre-eclampsia prophylaxis beyond 12 weeks of gestation.\\u003c/p\\u003e\\n\\u003ch3\\u003eSelection Criteria\\u003c/h3\\u003e\\n\\u003cdiv id=\\\"Sec7\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eInclusion Criteria\\u003c/h2\\u003e\\u003cp\\u003eThe study included women with ongoing IVF/ICSI pregnancies at 20 weeks of gestation or beyond who provided written informed consent to participate.\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec8\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eExclusion Criteria\\u003c/h2\\u003e\\u003cp\\u003eWomen were excluded if they declined to provide consent at any point during the study or if their pregnancy was terminated at or beyond 20 weeks for reasons of lethal foetal anomalies.\\u003c/p\\u003e\\u003c/div\\u003e\\n\\u003ch3\\u003eSample Size Calculation\\u003c/h3\\u003e\\n\\u003cp\\u003eThe sample size was calculated using the StatCalc function in Epi Info (version 7.2.5.0). The calculation was based on a prior study by Lambers et al. (2009), which reported an incidence of hypertensive complications of 3.6% in an aspirin group versus 26.9% in a placebo group (\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e). To detect a similar difference with a 95% confidence level and 80% statistical power, assuming a 1:1 ratio of exposed to unexposed participants, a sample size of 90 was required. This was adjusted to 100 participants (50 per group) to account for a potential 10% loss to follow-up.\\u003c/p\\u003e\\n\\u003ch3\\u003eSampling and Sampling Techniques\\u003c/h3\\u003e\\n\\u003cp\\u003eDuring the study period from August 2024 to February 2025, a total of 243 women who conceived via IVF/ICSI were identified. From this pool, participants were enrolled using a consecutive sampling method. To ensure balanced groups, eligible women were allocated alternately into the aspirin and non-aspirin cohorts until the target sample size of 50 participants in each group was reached. If a potential participant declined consent, the next eligible woman meeting the criteria was recruited to maintain the sampling sequence and minimise selection bias. The rate limiting step in the selection of participants was the aspirin group because there were much less women on aspirin than those not on aspirin. Any time a participant on aspirin was encounted and selected, the next available women not on aspirin was also selected and this cycle was then repeated until the sample size of 100 was obtained.\\u003c/p\\u003e\\u003cp\\u003e\\u003c/p\\u003e\\u003cdiv id=\\\"Sec11\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eSource: Author\\u0026rsquo;s Construct (2025)\\u003c/h2\\u003e\\u003cdiv id=\\\"Sec12\\\" class=\\\"Section3\\\"\\u003e\\u003ch2\\u003eData Collection Procedure\\u003c/h2\\u003e\\u003cp\\u003e Potential participants were approached during their routine antenatal visits. After a thorough explanation of the study's purpose and procedures, written informed consent was obtained. Data were collected by the principal investigator and trained research assistants using a structured questionnaire. Additional information was extracted from participants' antenatal records, hospital folders, and newborn medical records. Pre-eclampsia was diagnosed and managed according to the 2021 ISSHP guidelines. Data points collected included sociodemographic characteristics, medical and obstetric history, details of the ART treatment, risk factors for pre-eclampsia, and all maternal and perinatal outcomes until delivery.\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec13\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eOutcome Measurements\\u003c/h2\\u003e\\u003cp\\u003eThe primary outcome was the gestational age at the onset of pre-eclampsia. This was measured as the number of completed weeks of gestation at the time of diagnosis. Cases were further categorised as early-onset (\\u0026lt;\\u0026thinsp;34 weeks) or late-onset (\\u0026ge;\\u0026thinsp;34 weeks) pre-eclampsia.\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec14\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eData Analysis and Management\\u003c/h2\\u003e\\u003cp\\u003eData were first entered into Microsoft Excel for cleaning and validation and subsequently exported to the STATA version 17 for analysis. Descriptive statistics, including means, standard deviations, frequencies, and percentages, were used to summarise participant characteristics. The comparison of mean gestational age at onset between the two groups was performed using an analysis of variance (ANOVA). The association between aspirin use and the categorical outcome of early- versus late-onset pre-eclampsia was assessed using the chi-square test. A p-value of less than 0.05 was considered statistically significant for all inferential analyses.\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec15\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eEthical considerations\\u003c/h2\\u003e\\u003cp\\u003e\\u003cstrong\\u003eEthical approval\\u003c/strong\\u003e\\u003cp\\u003e for the study was granted by the Committee on Human Research, Publications, and Ethics (CHRPE) of Kwame Nkrumah University of Science and Technology (KNUST) (Registration number: CHRPE/AP/1334/24). Permission was also obtained from the management of each participating ART centre. All participants provided written informed consent before enrolment. To ensure confidentiality, all data were anonymised using study codes, and electronic data were stored on a password-protected computer accessible only to the research team. The study was non-interventional and posed no direct physical risk to participants, with all financial costs borne by the principal investigator.\\u003c/p\\u003e\\u003c/p\\u003e\\u003c/div\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cdiv id=\\\"Sec17\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eSocio-demographic and clinical characteristics of study participants\\u003c/h2\\u003e\\u003cp\\u003eThe socio-demographic and clinical characteristics of the study participants indicate that the majority were married (98%), with only 2% being single. Most respondents were Christians (90.91%), while Muslims constituted 9.09% of the study population. The mean age of participants was 40.82\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;5.69 years, with nearly equal age distribution 49% were aged 41 years or below, 51% were older than 41 years. In terms of educational attainment, 45% had tertiary education, 36% completed senior high school (SHS), and 19% had junior high school (JHS) education. A wide variety of occupations were reported, although traders formed the largest group (31%), followed by professionals (21%) and public or civil servants (20%). Other occupations such as artisans (4%), hairdressers (4%), businesswomen (9%), housewives (6%), caterers (2%), bankers (2%), and seamstresses (1%) were also represented. Regarding body mass index (BMI), more than half of the participants were obese (52%), 36% were overweight, and only 12% had a normal BMI, suggesting a high prevalence of excess weight among the study population.\\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\\u003eSocio-demographic and Clinical Characteristics of Study Participants\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/caption\\u003e\\u003ccolgroup cols=\\\"3\\\"\\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\\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\\u003eFrequency (n)\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003ePercentage (%)\\u003c/p\\u003e\\u003c/th\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eMarital status\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e\\u003c/tr\\u003e\\u003c/thead\\u003e\\u003ctbody\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eSingle\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e2\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e2.00\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eMarried\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e98\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e98.00\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eReligion\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eChristianity\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e91\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e91.00\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eMuslim\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e9\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e9.00\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eAge in years (N\\u0026thinsp;=\\u0026thinsp;100)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e\\u003cp\\u003ex̄\\u0026plusmn;SD\\u0026thinsp;=\\u0026thinsp;40.82\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;5.69\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e=\\u0026lt;41\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e49\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e49.00\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u0026gt;\\u0026thinsp;41\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e51\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e51.00\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eHighest level of Education\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eJHS\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e19\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e19.00\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eSHS\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e36\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e36.00\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eTertiary\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e45\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e45.00\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eOccupation\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\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\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e4.00\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eBanker\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e2\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e2.00\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eBusinesswoman\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e9\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e9.00\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eCaterer\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e2\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e2.00\\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\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e4.00\\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\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e6.00\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eProfessional\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e21\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e21.00\\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\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e20.00\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eSeamstress\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e1\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e1.00\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eTrader\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e31\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e31.00\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eBMI Level\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eNormal (18.5\\u0026ndash;24.9)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e12\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e12.00\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eOverweight (25-29.9)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e36\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e36.00\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eObese (\\u0026thinsp;\\u0026gt;\\u0026thinsp;=\\u0026thinsp;30)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e52\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e52.00\\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\\u003cb\\u003eSource: Field Data, 2025.\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec18\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eDemographics by status of aspirin intake\\u003c/h2\\u003e\\u003cp\\u003eThe demographic and clinical characteristics of the 100 participants, categorised by aspirin intake, are presented in Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e. Generally, the two groups were well-matched across most sociodemographic variables, including marital status, religion, age, education level, and BMI, with no statistically significant differences observed. The mean age for both the non-aspirin (40.2 years) and aspirin (41.4 years) groups was high. In terms of education, a majority of the non-aspirin group had completed tertiary education (52%), whereas the largest proportion of the aspirin group had completed Senior High School (42%). The occupational landscape also varied; professionals constituted the largest segment of the non-aspirin group (26%), while traders were the most common occupation in the aspirin group (42%). A significant clinical finding was the high prevalence of obesity across both cohorts. Nearly half of the non-aspirin group (46%) and a majority of the aspirin group (58%) were classified as obese, with a BMI of 30 kg/m\\u0026sup2; or higher. Despite these variations in distribution, the lack of statistically significant p-values across all categories (p\\u0026thinsp;\\u0026gt;\\u0026thinsp;0.05) confirms that the two groups were demographically comparable at baseline, which is crucial for attributing differences in outcomes to the intervention (aspirin use) rather than to confounding demographic factors.\\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\\u003eDemographics by Status of Aspirin Intake\\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\\\" 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colname=\\\"c3\\\"\\u003e\\u003cp\\u003e21(42)\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eBMI Level\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e29.98\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;5.73\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e31.12\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;5.53\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e1.692\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.429\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eNormal (18.5\\u0026ndash;24.9)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e6(\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e6(\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eOverweight (25-29.9)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e21(42)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e15(30)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eObese (\\u0026thinsp;\\u0026gt;\\u0026thinsp;=\\u0026thinsp;30)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e23(46)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e29(58)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\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\\u003cb\\u003eSource: Field Data, 2025.\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec19\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003ePast obstetric, medical and family history\\u003c/h2\\u003e\\u003cp\\u003eA breakdown of the participants' medical histories revealed significant differences between the groups in the Table \\u003cspan refid=\\\"Tab3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e below. Women in the aspirin group had a significantly higher prevalence of pre-existing chronic hypertension (34% vs. 8%, p\\u0026thinsp;=\\u0026thinsp;0.002) and diabetes mellitus (16% vs. 2%, p\\u0026thinsp;=\\u0026thinsp;0.036) compared to the non-aspirin group.\\u003csup\\u003e1\\u003c/sup\\u003eThis suggests that the prescription of aspirin was appropriately targeted toward women with established high-risk factors for pre-eclampsia. Consequently, a significantly lower proportion of women in the aspirin group developed a hypertensive disorder during the current pregnancy (14% vs. 42%, p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.001).\\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\\u003ePast Obstetric, Medical and Family History\\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 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align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e1(\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e8(\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e)\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eSickle cell disease\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e\\u0026lt;\\u0026thinsp;0.001\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e1.000\\u003c/b\\u003e\\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\\u003e50(100)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e49(98)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\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\\u003e0(0)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e1(\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e)\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eDiagnosed with pre-eclampsia in a previous pregnancy?\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e3.075\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e0.215\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eNot applicable\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e30(60)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e38(76)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\" morerows=\\\"2\\\" rowspan=\\\"3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\" morerows=\\\"2\\\" rowspan=\\\"3\\\"\\u003e\\u0026nbsp;\\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\\u003e1(\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e1(\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e)\\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\\u003e19(38)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e11(22)\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eGestational age at delivery in the previous pregnancy\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e37w\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;4w\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e38\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e-0.804\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e0.431\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eFirst degree relation ever had pre-eclampsia\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e1.018\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e0.601\\u003c/b\\u003e\\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\\u003e0(0)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e1(\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\" morerows=\\\"2\\\" rowspan=\\\"3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\" morerows=\\\"2\\\" rowspan=\\\"3\\\"\\u003e\\u0026nbsp;\\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\\u003e29(58)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e28(56)\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eDon't know\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e21(42)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e21(42)\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eThe urine protein at booking\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e\\u0026lt;\\u0026thinsp;0.001\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e1.000\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eNegative\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e50(100)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e49(98)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e1+\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e0(0)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e1(\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e)\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eDose of Aspirin\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e75mg\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e-\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e32(64)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e-\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e-\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e150mg\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e-\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e18(36)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eIs the patient currently on calcium treatment?\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e-\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e\\u0026lt;\\u0026thinsp;0.001\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e1.000\\u003c/b\\u003e\\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\\u003e48(96)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e49(98)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\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(\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e1(\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e)\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eWhat dose of calcium is the patient on?\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e1g\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e2(100)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e1(100)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e-\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e-\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003ePatient diagnosed with any pregnancy-related hypertensive disorder in this pregnancy?\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e-\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e8.383\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e\\u0026lt;\\u0026thinsp;0.001\\u003c/b\\u003e\\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\\u003e29(58)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e43(86)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\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\\u003e21(42)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e7(\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e)\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eThe type of pregnancy-related hypertensive disorder diagnosed.\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e0.233\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e0.629\\u003c/b\\u003e\\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\\u003e5(23.8)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e3(42.9)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\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\\u003e16(76.2)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e4(57.1)\\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\\u003cb\\u003eSource: Field Data, 2025.\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec20\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eCurrent pregnancy\\u003c/h2\\u003e\\u003cp\\u003eThe Table \\u003cspan refid=\\\"Tab4\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003e below indicates the current pregnancy, both groups had a similar mean gestational age at booking (approximately 8weeks 4 days). For those in the aspirin group, the medication was initiated at a mean gestational age of 16 weeks 1 day\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;4 weeks. A key discovery was the statistically significant difference in the gestational age at which a hypertensive disorder was diagnosed: 32w\\u0026thinsp;+\\u0026thinsp;6d in the non-aspirin group versus 36w\\u0026thinsp;+\\u0026thinsp;5d in the aspirin group (p\\u0026thinsp;=\\u0026thinsp;0.039).\\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\\u003eCurrent Pregnancy\\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=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e\\u003cthead\\u003e\\u003ctr\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e\\u003cp\\u003eAspirin\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u003cp\\u003eChi-square\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c5\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u003cp\\u003ep-value\\u003c/p\\u003e\\u003c/th\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eNo\\u003c/p\\u003e\\u003cp\\u003en(%)\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eYes\\u003c/p\\u003e\\u003cp\\u003en(%)\\u003c/p\\u003e\\u003c/th\\u003e\\u003c/tr\\u003e\\u003c/thead\\u003e\\u003ctbody\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eGestational age at booking\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e8w4d\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1w\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e8w5d\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1w 5d\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e-0.410\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.683\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eGestational age at which Aspirin was started\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e-\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e16w1d\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;4w\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e-\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eGestational age at which the diagnosis made\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e32w6d\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;4d\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e36w\\u0026thinsp;+\\u0026thinsp;5d\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;2w\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e-2.195\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.039\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eIs the patient on anti-hypertensive medication\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e0.008\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e0.931\\u003c/b\\u003e\\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\\u003e27(56.3)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e29(59.2)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\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\\u003e21(43.8)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e20(40.8)\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c2\\\" namest=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eOn blood pressure medication\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e2.992\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e0.084\\u003c/b\\u003e\\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\\u003e39(78)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e30(60)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\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\\u003e11(22)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e20(40)\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eMethyldopa\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e0.903\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e0.342\\u003c/b\\u003e\\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\\u003e41(82)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e36(72)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\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\\u003e9(\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e14(28)\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eNifedipine\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e0.391\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e0.532\\u003c/b\\u003e\\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(60)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e34(68)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\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\\u003e20(40)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e16(32)\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eHydralazine\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e0.51\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e0.475\\u003c/b\\u003e\\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\\u003e48(96)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e50(100)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\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(\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e0(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\\u003cb\\u003eSource: Field Data, 2025.\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec21\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eDetails of fertility treatment modalities\\u003c/h2\\u003e\\u003cp\\u003eAn analysis of the fertility treatments undertaken by the cohort reveals a profile heavily skewed towards modalities known to confer a high a priori risk for pre-eclampsia in Table \\u003cspan refid=\\\"Tab5\\\" class=\\\"InternalRef\\\"\\u003e5\\u003c/span\\u003e below. The vast majority of participants in both the non-aspirin and aspirin groups underwent fresh embryo transfer (98% and 94%, respectively), with only a small fraction receiving a frozen embryo transfer (2% and 6%, respectively). Similarly, conventional IVF was the predominant treatment modality (94% and 98%, respectively) compared to ICSI. The most notable finding relates to the source of gametes. A striking majority of pregnancies were conceived using donor oocytes, with 68% of the non-aspirin group and 76% of the aspirin group utilising donor egg/self-sperm cycles. In contrast, autologous cycles using self-egg and self-sperm were far less common, constituting only 18% and 14% of the groups, respectively. These distributions in treatment characteristics were statistically similar between the aspirin and non-aspirin cohorts (p\\u0026thinsp;\\u0026gt;\\u0026thinsp;0.05 for all comparisons), indicating that the baseline risk for placental-mediated disease conferred by the ART procedures themselves was comparable across both groups.\\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\\u003eDetails of Fertility Treatment\\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=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e\\u003cthead\\u003e\\u003ctr\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e\\u003cp\\u003eAspirin\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u003cp\\u003eChi-square\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c5\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u003cp\\u003ep-value\\u003c/p\\u003e\\u003c/th\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eNo\\u003c/p\\u003e\\u003cp\\u003en(%)\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eYes\\u003c/p\\u003e\\u003cp\\u003en(%)\\u003c/p\\u003e\\u003c/th\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eThe type of embryo transfers the patient underwent\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e0.26\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.61\\u003c/p\\u003e\\u003c/th\\u003e\\u003c/tr\\u003e\\u003c/thead\\u003e\\u003ctbody\\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\\u003e49(98)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e47(94)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\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\\u003e1(\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e3(\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e)\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eWhat type of ART treatment did the patient undergo?\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e0.26\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e0.61\\u003c/b\\u003e\\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\\u003e47(94)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e49(98)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e\\u0026nbsp;\\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\\u003e3(\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e1(\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e)\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eThe type of gametes was used\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e4.072\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003e0.254\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eDonor egg/self-sperm\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e34(68)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e38(76)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\" morerows=\\\"3\\\" rowspan=\\\"4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\" morerows=\\\"3\\\" rowspan=\\\"4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eSelf-egg/self-sperm\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e9(\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e7(\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e)\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eGestational surrogate/Embryo adoption\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e7(\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e3(\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e)\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eSelf-egg/Donor sperm\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e0(0)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e2(\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e)\\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\\u003cb\\u003eSource: Field Data, 2025.\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/div\\u003e\\u003cdiv id=\\\"Sec22\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eGestational age at diagnosis between aspirin users and non-users among women with pre-eclampsia\\u003c/h2\\u003e\\u003cp\\u003eThe mean gestational age at which pre-eclampsia was diagnosed differed markedly between the two cohorts. As shown in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e and Table\\u0026nbsp;\\u003cspan refid=\\\"Tab6\\\" class=\\\"InternalRef\\\"\\u003e6\\u003c/span\\u003e, women in the non-aspirin group developed pre-eclampsia at an average gestational age of 32w6d\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;4w. In contrast, women in the aspirin group developed the condition significantly later, at an average gestational age of 36w\\u0026thinsp;+\\u0026thinsp;5d\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;2 w. This represents a delay in the clinical onset of the disease by nearly four weeks. While this difference was substantial from a clinical perspective, it did not reach the conventional threshold for statistical significance, likely due to the limited number of pre-eclampsia events in the cohort.\\u003c/p\\u003e\\u003cp\\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\\u003eComparison of Gestational Age at Delivery Between Aspirin Users and Non-users Among Women Diagnosed with Pre-eclampsia\\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=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\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\\u003eAverage Score\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eF-value\\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\\u003e\\u003cb\\u003eAspirin Intake\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e3.068\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e0.099\\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\\u003e32w6d\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;4w\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\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\\u003e36w5d\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;2w\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003c/tr\\u003e\\u003c/tbody\\u003e\\u003c/colgroup\\u003e\\u003c/table\\u003e\\u003c/div\\u003e\\u003c/p\\u003e\\u003cp\\u003eSource: Field Data, 2025.\\u003c/p\\u003e\\u003cdiv id=\\\"Sec23\\\" class=\\\"Section3\\\"\\u003e\\u003ch2\\u003eAssociation between aspirin use and onset of pre-eclampsia (\\u0026lt;\\u0026thinsp;34 weeks vs. \\u0026ge;34 weeks)\\u003c/h2\\u003e\\u003cp\\u003eTo further investigate the impact of aspirin on the clinical phenotype of pre-eclampsia, cases were stratified into early-onset (diagnosis\\u0026thinsp;\\u0026lt;\\u0026thinsp;34 weeks of gestation) and late-onset (diagnosis\\u0026thinsp;\\u0026ge;\\u0026thinsp;34 weeks of gestation). The results of this analysis, presented in Table\\u0026nbsp;\\u003cspan refid=\\\"Tab5\\\" class=\\\"InternalRef\\\"\\u003e5\\u003c/span\\u003e, revealed a finding with possibly clinical significance even though it was not statistically significant (p\\u0026thinsp;=\\u0026thinsp;0.316). Among the women in the non-aspirin group who developed pre-eclampsia, 47.1% (8 out of 17 evaluable cases) were diagnosed before 34 weeks, representing the more severe, early-onset form of the disease. In stark contrast, among women in the aspirin group, there were zero cases of early-onset pre-eclampsia (0%). All cases of pre-eclampsia that occurred in the aspirin group were of the late-onset type. This finding demonstrates that aspirin use was associated with a complete prevention of the early-onset phenotype of pre-eclampsia in this study population (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\\u003eAssociation Between Aspirin Use and Onset of Pre-eclampsia (\\u0026lt;\\u0026thinsp;34 weeks vs. \\u0026ge;34 weeks)\\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=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\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\\u003e\\u0026lt;\\u0026thinsp;34 Weeks\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e\\u0026ge;\\u0026thinsp;34 Weeks\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003eChi-Sq\\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\\u003e\\u003cb\\u003eAspirin Intake\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e1.004\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.316\\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\\u003e8 (47.1%)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e9 (52.9%)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\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\\u003e0 (0%)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e5 (100%)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003c/tr\\u003e\\u003c/tbody\\u003e\\u003c/colgroup\\u003e\\u003c/table\\u003e\\u003c/div\\u003e\\u003c/p\\u003e\\u003cp\\u003eSource: Field Data, 2025.\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cdiv id=\\\"Sec25\\\" class=\\\"Section2\\\"\\u003e\\u003ch2\\u003eClinical significance of delayed onset and phenotypic modification of pre-eclampsia\\u003c/h2\\u003e\\u003cp\\u003eOne discovery of the study is a delay in the onset of pre-eclampsia with a fundamental modification of its clinical phenotype, shifting the disease from its severe, early-onset form to a more manageable, near-term presentation. The observation that the mean gestational age at diagnosis was delayed from 32w\\u0026thinsp;+\\u0026thinsp;6d in the non-aspirin group to 36w\\u0026thinsp;+\\u0026thinsp;5d in the aspirin group carries immense clinical weight. A diagnosis at 32 weeks often necessitates iatrogenic preterm delivery, exposing the neonate to significant risks of morbidity and mortality associated with prematurity, including respiratory distress syndrome, intraventricular haemorrhage, and prolonged NICU stays. Shifting the onset to beyond 36 weeks alters the clinical scenario, enabling the pregnancy to progress to near-term or term, which significantly improves neonatal outcomes. While the difference in mean gestational age did not achieve statistical significance (p\\u0026thinsp;=\\u0026thinsp;0.099), this is likely a reflection of the study's limited statistical power due to the small number of pre-eclampsia events (n\\u0026thinsp;=\\u0026thinsp;22) rather than an absence of a true effect. In this context, the magnitude of the clinical effect, a four-week delay, should not be understated and is arguably of greater importance than a statistical threshold.\\u003c/p\\u003e\\u003cp\\u003eIn addition, there is a complete absence of early-onset pre-eclampsia (\\u0026lt;\\u0026thinsp;34 weeks) in the aspirin group, compared to a 47.1% rate among those who developed pre-eclampsia in the non-aspirin group. This result moves beyond a simple delay in onset to suggest a true modification of the disease phenotype. As established in literature, early- and late-onset pre-eclampsia are considered distinct pathophysiological entities. Early-onset disease is a severe placentopathy rooted in defective spiral artery remodelling, whereas late-onset disease is more related to maternal constitutional factors (\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e). Aspirin's primary mechanism is to improve placental perfusion by correcting the imbalance between thromboxane and prostacyclin. It is therefore biologically plausible that its main effect would be to counteract the pathological processes of defective placentation that drive the early-onset form of the disease. This provides strong clinical support for this mechanistic hypothesis, suggesting that aspirin effectively neutralises the pathway leading to the most severe form of pre-eclampsia.\\u003c/p\\u003e\\u003cp\\u003eThese results are consistent with and build upon the findings of major international trials. The ASPRE trial, which administered 150 mg of aspirin to a high-risk population, reported a 63% reduction in the incidence of preterm pre-eclampsia (\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e). The current study, though observational, observed an even more pronounced effect (a 100% reduction in early-onset cases) within a uniquely high-risk ART population. This may suggest that ART pregnancies, which are predisposed to placental dysfunction from conception, are particularly responsive to an intervention that targets placentation. Similarly, the ASPIRIN trial demonstrated a significant reduction in deliveries before 34 weeks due to hypertensive disorders in women receiving LDA (\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e). The findings from our cohort provide a clear mechanistic explanation for this outcome: by preventing early-onset pre-eclampsia, aspirin obviates the need for iatrogenic preterm delivery, which is the primary management for this severe condition. Our results also fall in line with local Ghanaian data from Owusu, (2022), who similarly reported that women on LDA who developed pre-eclampsia predominantly had the late-onset form, whereas those not on aspirin were more likely to have early-onset disease, reinforcing the consistency of this effect within the local context (\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e).\\u003c/p\\u003e\\u003c/div\\u003e\"},{\"header\":\"Conclusion\",\"content\":\"\\u003cp\\u003eThe current study reveals a new and crucial insight into the utility of low-dose aspirin in ART pregnancies. The demonstration that aspirin's benefit extends beyond merely reducing the overall incidence of pre-eclampsia; its most powerful effect may be the modification of the disease phenotype. The complete prevention of early-onset pre-eclampsia in the aspirin group strengthens the understanding of how aspirin mitigates pregnancy risk, suggesting it directly counteracts the severe placental pathology that drives early-onset disease. This provides strong evidence that routine aspirin prophylaxis is a powerful tool to prevent the most devastating maternal and perinatal complications associated with pre-eclampsia in the uniquely vulnerable ART population.\\u003c/p\\u003e\\u003cp\\u003eAlthough the study provides convincing observational evidence, a larger, multi-centre randomised controlled trial is warranted within the Ghanaian population to definitively confirm these findings. Such a study should be powered to compare the efficacy of different aspirin dosages (e.g., 81 mg vs. 150 mg) specifically for the prevention of early-onset pre-eclampsia in ART pregnancies. Further research should also explore the long-term neonatal outcomes of infants born to mothers who received aspirin prophylaxis in this situation.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eLimitations of the study\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003col\\u003e\\u003cspan\\u003e\\u003cli\\u003e\\u003cp\\u003eAs a non-randomised, observational study, it is susceptible to selection bias and unmeasured confounding variables that could have influenced the outcomes.\\u003c/p\\u003e\\u003c/li\\u003e\\u003c/span\\u003e\\u003cspan\\u003e\\u003cli\\u003e\\u003cp\\u003eThe sample size, while adequate for the overall cohort, resulted in a small number of pre-eclampsia events, which limited the statistical power for some analyses, such as the comparison of mean gestational age at onset.\\u003c/p\\u003e\\u003c/li\\u003e\\u003c/span\\u003e\\u003cspan\\u003e\\u003cli\\u003e\\u003cp\\u003eThe study was conducted in private ART centres in a single city, which may limit the generalizability of the findings to the broader population of pregnant women in Ghana.\\u003c/p\\u003e\\u003c/li\\u003e\\u003c/span\\u003e\\u003c/ol\\u003e\\u003c/p\\u003e\"},{\"header\":\"Abbreviations\",\"content\":\"\\u003cdiv class=\\\"DefinitionList\\\"\\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\\\"\\u003eASPRE\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eAspirin for Evidence\\u0026ndash;Based Preeclampsia Prevention (Trial)\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eASPIRIN\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eAspirin Supplementation for Pregnancy Indicated Risk Improvement in Nulliparas (Trial)\\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\\\"\\u003eCHRPE\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eCommittee on Human Research, Publications, and Ethics\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eDBP\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eDiastolic Blood Pressure\\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\\\"\\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\\\"\\u003eIUGR\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eIntrauterine Growth Restriction\\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\\\"\\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\\\"\\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\\\"\\u003eKBTH\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eKorle\\u0026ndash;Bu 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\\u0026ndash;Dose Aspirin\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eLMIC\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eLow\\u0026ndash;and Middle\\u0026ndash;Income Countries\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv 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School\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003ea.\\u0026nbsp;\\u003c/strong\\u003e\\u003cstrong\\u003eEthical\\u0026nbsp;\\u003c/strong\\u003e\\u003cstrong\\u003eapproval and consent to participant\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis study received ethical approval from the\\u0026nbsp;Committee on Human Research, Publications, and Ethicsof the\\u0026nbsp;Kwame Nkrumah University of Science and Technology, with reference number (CHRPE/AP/1334/24)\\u003cstrong\\u003e.\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eb. Availability of data and materials\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNot applicable\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003ed. Competing of interest\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors declare no conflict of interest.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003ee. Funding Source\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNo funding was received for this study.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003ef.\\u0026nbsp;\\u003c/strong\\u003e\\u003cstrong\\u003eAcknowledgements\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe author extends gratitude to all participants who participate in this study.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eg. Consent for Publication\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNot applicable\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eh. Authors’ contribution\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eEAA: write-up, review and editing. CMS: review and editing, JJKA: review and editing. FJMKD: review and editing. RMKD: review and editing. RKA- editing, ETD: review and editing, ATO: review and editing. All authors approved the version to be published and agreed to be accountable for all aspects of the work.\\u0026nbsp;\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eWang W, Xie X, Yuan T, Wang Y, Zhao F, Zhou Z, et al. Epidemiological trends of maternal hypertensive disorders of pregnancy at the global, regional, and national levels: a population-based study. BMC Pregnancy Childbirth. 2021;21(1):364.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eJikamo B, Adefris M, Azale T, Alemu K. Incidence, trends and risk factors of preeclampsia in sub-Saharan Africa: a systematic review and meta-analysis. PAMJ-One Health. 2023;11(1):1\\u0026ndash;54.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eAdu-Bonsaffoh K, Ntumy MY, Obed SA, Seffah JD. Perinatal outcomes of hypertensive disorders in pregnancy at a tertiary hospital in Ghana. BMC Pregnancy Childbirth. 2017;17(1):388.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003ePatel AJ, Patel BS, Shah AC, Jani SK. Maternal and perinatal outcome in severe pre-eclampsia and eclampsia: a study of 120 cases at a tertiary health care centre in Western India. Int J Reprod Contracept Obstet Gynecol. 2021;10(3):1011\\u0026ndash;7.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eAlmasi-Hashiani A, Omani-Samani R, Mohammadi M, Amini P, Navid B, Alizadeh A, et al. Assisted reproductive technology and the risk of preeclampsia: an updated systematic review and meta-analysis. BMC Pregnancy Childbirth. 2019;19(3):149.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eChih HJ, Elias FTS, Gaudet L, Velez MP. Assisted reproductive technology and hypertensive disorders of pregnancy: systematic review and meta-analyses. BMC Pregnancy Childbirth. 2021 June 28;21(5):449.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eMagee LA, Brown MA, Hall DR, Gupte S, Hennessy A, Karumanchi SA, et al. The 2021 International Society for the Study of Hypertension in Pregnancy classification, diagnosis \\u0026amp; management recommendations for international practice. Pregnancy Hypertens. 2022;27(5):148\\u0026ndash;69.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eBisson C, Dautel S, Patel E, Suresh S, Dauer P, Rana S. Preeclampsia pathophysiology and adverse outcomes during pregnancy and postpartum. Front Med. 2023;10(3):114\\u0026ndash;70.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003ePhipps EA, Thadhani R, Benzing T, Karumanchi SA. Pre-eclampsia: pathogenesis, novel diagnostics and therapies. Nat Rev Nephrol. 2019;15(5):275\\u0026ndash;89.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eCao X, Gao C, Su M, Zhang D, Zhao F, Li W, et al. Impact of different endometrial preparation protocols on pregnancy outcomes in patients at high risk for ovarian hyperstimulation syndrome: a propensity score matched retrospective cohort study. BMC Pregnancy Childbirth. 2025;25(1):449.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003evon Versen-H\\u0026ouml;ynck F, Schaub AM, Chi YY, Chiu KH, Liu J, Lingis M, et al. Increased Preeclampsia Risk and Reduced Aortic Compliance With In Vitro Fertilisation Cycles in the Absence of a Corpus Luteum. Hypertension. 2019;73(3):640\\u0026ndash;9.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eRoberts JM, Rich-Edwards JW, McElrath TF, Garmire L, Myatt L. SUBTYPES OF PREECLAMPSIA: RECOGNITION AND DETERMINING CLINICAL USEFULNESS. Hypertens Dallas Tex 1979. 2021;77(5):1430\\u0026ndash;41.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eXu T, Zhou F, Deng C, Huang G, Li J, Wang X. Low-Dose Aspirin for Preventing Preeclampsia and Its Complications: A Meta‐Analysis. J Clin Hypertens. 2015;17(7):567\\u0026ndash;73.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eRolnik DL, Wright D, Poon LC, O\\u0026rsquo;Gorman N, Syngelaki A, de Paco Matallana C, et al. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. N Engl J Med. 2017;377(7):613\\u0026ndash;22.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eHoffman MK, Goudar SS, Kodkany BS, Metgud M, Somannavar M, Okitawutshu J, et al. 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 Lond Engl. 2020;395(10):285\\u0026ndash;93.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eDuley L, Meher S, Hunter KE, Seidler AL, Askie LM. Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev. 2019;2019(10):CD004659.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eLambers MJ, Groeneveld E, Hoozemans DA, Schats R, Homburg R, Lambalk CB, et al. Lower incidence of hypertensive complications during pregnancy in patients treated with low-dose aspirin during in vitro fertilisation and early pregnancy. Hum Reprod. 2009;24(10):2447\\u0026ndash;50.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eOwusu YG, LOW DOSE ASPIRIN PROPHYLAXIS USE AMONG PRE-ECLAMPTIC/ECLAMPTIC WOMEN WITH HISTORY-BASED RISK FACTOR(S). IN A TERTIARY HOSPITAL IN GHANA [Internet] [Academic]. [Ghana]: Ghana College of Physicians and Surgeons; 2022 [cited 2025 Oct 17]. Available from: \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://repository.gcps.edu.gh/handle/123456789/39\\u003c/span\\u003e\\u003cspan address=\\\"https://repository.gcps.edu.gh/handle/123456789/39\\\" targettype=\\\"URL\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":false,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":true,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Pre-eclampsia, in-vitro fertilisation/intracytoplasmic sperm injection, Low-dose aspirin, Assisted reproductive technology, Gestational Age, Early-Onset Pre-eclampsia\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-8181675/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-8181675/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eBackground\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003ePre-eclampsia, a leading cause of maternal and perinatal mortality, presents with increased frequency and severity in pregnancies conceived via assisted reproductive technology (ART). The distinction between early-onset (\\u0026lt; 34 weeks) and late-onset (≥ 34 weeks) pre-eclampsia is life-threatening, as the former is associated with substantially greater morbidity. While low-dose aspirin (LDA) is recommended for prevention in high-risk groups, its specific impact on the timing of disease onset in in-vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) pregnancies, particularly in regions like sub-Saharan Africa, remains insufficiently characterised. The study aimed to compare the gestational age at onset of pre-eclampsia between IVF/ICSI pregnancies with and without LDA prophylaxis in Kumasi, Ghana.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMethods\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eA prospective cohort study was conducted at four specialist ART centres in Kumasi from August 2024 to February 2025. One hundred women with ongoing singleton or multiple pregnancies conceived via IVF/ICSI were recruited at or beyond 20 weeks of gestation and followed until delivery. Participants were allocated into two groups of 50, based on their use of LDA: an exposed group that received aspirin and a non-exposed (control) group. The primary outcome was the gestational age at diagnosis of pre-eclampsia, defined according to the 2021 International Society for the Study of Hypertension in Pregnancy (ISSHP) criteria.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eResults\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe use of LDA was associated with a profound shift in the clinical presentation of pre-eclampsia. The mean gestational age at diagnosis was significantly later in the aspirin group (36w + 5d) compared to the non-aspirin group (32w + 6d), representing a delay of nearly four weeks. Most outstandingly, there was a complete absence of early-onset pre-eclampsia in the aspirin group (0%), whereas 47.1% of pre-eclampsia cases in the non-aspirin group occurred before 34 weeks of gestation. This indicates that aspirin not only delayed the onset of the disease but also effectively prevented its most severe, early-gestation phenotype in this cohort.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusion\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eLow-dose aspirin prophylaxis in IVF/ICSI pregnancies results in a clinically meaningful delay in the onset of pre-eclampsia. Its primary benefit appears to be the prevention of the more dangerous early-onset form of the disease, thereby modifying its clinical course towards a more manageable, near-term presentation. These findings underscore the critical importance of implementing routine LDA prophylaxis in this high-risk obstetric population to improve maternal and perinatal outcomes.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Low-dose Aspirin Delays the Onset of Pre-eclampsia in an Unselected Population of Ivf/icsi Pregnancies by Almost 4 Weeks\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-12-02 14:59:20\",\"doi\":\"10.21203/rs.3.rs-8181675/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"6a0abaee-377a-41c9-a8ea-42a028ab0a4b\",\"owner\":[],\"postedDate\":\"December 2nd, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2025-12-22T05:53:28+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2025-12-02 14:59:20\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-8181675\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-8181675\",\"identity\":\"rs-8181675\",\"version\":[\"v1\"]},\"buildId\":\"XKTyCvWXoU3ODBz1xrDgd\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}