Maternal Haemoglobin A1C Level as a Predictor of Adverse Pregnancy Outcomes in Women with early versus late Gestational Diabetes Mellitus

Maternal Haemoglobin A1C Level as a Predictor of Adverse Pregnancy Outcomes in Women with early versus late Gestational Diabetes Mellitus | 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 Maternal Haemoglobin A1C Level as a Predictor of Adverse Pregnancy Outcomes in Women with early versus late Gestational Diabetes Mellitus Lorraine Chan, Kwok-yin Leung This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8510465/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 The objective was to evaluate the association between baseline maternal haemoglobin A1C (HbA1C) levels and adverse pregnancy outcomes in early (< 24 weeks) and late (≥ 24 weeks) gestational diabetes mellitus (GDM). Study Design This was a retrospective cohort undertaken at a public hospital in Hong Kong between 2021 and 2024. The associations between baseline HbA1C level (taken within 1–2 weeks after the diagnosis of GDM) and pregnancy outcomes were analysed using multivariate logistic regression. Results Of 1,531 women studied, 554 and 977 had early and late onset GDM, respectively. In late onset GDM, baseline HbA1C ≥ 6.0% showed associations with birth weight > 97th percentile (adjusted odds ratio [95% confidence interval = 8.2 [2.2–31.2]), large for gestational age (LGA) foetus (3.0 [1.3–6.7]), neonatal hypoglycaemia (5.7 [2.4–13.2]), hypertensive disorder (5.5 [1.7–17.8]), and insulin treatment (190.3 [21.1–1717.4]). The risk of low birth weight (< 2.5kg) followed a U-shaped distribution, with the lowest risk in the HbA1C 5.5–5.9% group (0.34 [0.15–0.78]). However, in early onset GDM, the associations were limited to neonatal hypoglycaemia (3.8 [1.5–10.0]) and insulin treatment (39.7 [7.8–200.9]). Conclusion The significance of baseline HbA1C is different between early and late-onset GDM. In contrast to baseline HbA1C levels ≥ 6.0% at late-onset GDM, that at early-onset GDM did not identify LGA and hypertensive disorders. Besides, high HbA1C levels as well as low HbA1C level (< 5%) at late onset GDM are associated with increased risk of LBW. gestational diabetes haemoglobin A1C adverse pregnancy outcomes Figures Figure 1 Background Gestational diabetes mellitus (GDM) affects 14% of pregnancies worldwide, with the highest prevalence of 27% in Southeast Asia [ 1 ]. It is defined as glucose intolerance first developed or diagnosed during pregnancy [ 2 ]. GDM increases the risk of adverse maternal and neonatal outcomes including pre-eclampsia, caesarean section, preterm birth, macrosomia, shoulder dystocia, respiratory distress, neonatal hypoglycaemia, neonatal jaundice, and rarely perinatal death [ 3 , 4 ]. Offspring born to mothers with GDM face increased risks of childhood and adulthood obesity and cardiometabolic disorders [ 5 ]. Long-term maternal complications include an increased risk of type 2 diabetes mellitus, cardiovascular disease, and metabolic syndrome later in life [ 6 ]. The prevalence of GDM has risen due to increasing maternal obesity, advanced maternal age, sedentary lifestyles [ 6 , 7 ], as well as the revised diagnostic criteria of GDM by the International Association for Diabetes in Pregnancy Study Group [ 8 ]. Haemoglobin A1C (HbA1C) is a single, non-fasting reliable marker for measurement of chronic hyperglycaemia and has been used widely for diagnosis and monitoring of treatment response in diabetes mellitus. It reflects average glycaemic control over the past three months [ 9 ]. The Royal College of Obstetricians and Gynaecologists and the American College of Obstetricians and Gynecologists recommend HbA1C as an investigation in cases of stillbirth to exclude gestational or pre-existing diabetes [ 10 , 11 ]. While HbA1C can be used to predict adverse outcomes in diabetes in pregnancy, it is unclear whether an early HbA1C level can similarly predict adverse outcomes in GDM [ 12 ]. Intervention for GDM may attenuate the association between baseline HbA1c and pregnancy outcomes. In pregnancy, HbA1C levels are lower due to iron deficiency and reduced red blood cell lifespan [ 13 ]. Prior studies suggest elevated HbA1C correlates with adverse events [ 12 , 14 ]. However, different HbA1C cut-offs have been recommended or proposed. The American Diabetes Association (ADA) recommends a preconception HbA1C below 6.5% for women with pre-existing diabetes and a target of less than 6% during pregnancy if achievable without significant hypoglycaemia [ 15 ]. The World Health Organization (WHO) also uses a threshold of ≥ 6.5% to diagnose diabetes [ 16 ]. The International Association of Diabetes and Pregnancy Study Groups, in line with WHO, recommends an HbA1C threshold of ≥ 6.5% to diagnose pre-existing diabetes in pregnancy, which may be first presented during pregnancy [ 8 ]. This may help identify those with possible pre-existing diabetes in pregnancy in women with early onset GDM (before 24 weeks’ of gestation), allowing early interventions such as insulin and aspirin for pre-eclampsia prophylaxis [ 17 ]. A local study in Hong Kong, China by Cheung et al. 2024 suggested that an early pregnancy HbA1C ≥ 5.7% identifies women at risk of pregnancy and neonatal complications [ 18 ] while a study in Zhejiang, China, suggested a cut-off of 5.5% [ 19 ]. This study aimed to evaluate the association between HbA1C levels and adverse maternal and neonatal outcomes in early and late onset GDM. Methods Subjects This retrospective cohort study was conducted at Queen Elizabeth Hospital, a tertiary public hospital in Hong Kong serving the Kowloon Central cluster. All pregnant women with gestational diabetes who delivered between 1 January 2021 and 31 December 2024 were reviewed. The study included women with singleton pregnancies complicated by GDM. Exclusion criteria comprised pre-existing diabetes, multiple pregnancies, incomplete records, presence of haemoglobinopathies invalidating HbA1C analysis, and those without antenatal follow-up or delivery at our unit. Women with HbA1C ≥ 6.5% at GDM diagnosis were excluded to rule out overt diabetes, ensuring that the study cohort represented a true GDM population [ 16 ]. Haemoglobinopathies excluded on this basis included conditions such as β-thalassaemia major or intermedia, sickle cell disease, and other structural haemoglobin variants associated with absent haemoglobin A. All pregnant women attending antenatal care were assessed by midwives in the first trimester unless referred later. Except for those with known pre-existing diabetes, risk factors for GDM were evaluated, including advanced maternal age (≥ 35 years), obesity (pre-pregnancy body mass index [BMI] ≥ 25 kg/m²), metabolic syndrome, polycystic ovarian syndrome, long-term use of diabetogenic medications (e.g., steroids), previous macrosomic baby (≥ 4000 g), prior GDM, previous stillbirth, previous congenital malformation consistent with diabetic embryopathy, family history of diabetes, and family origin with high diabetes prevalence (e.g., India, Pakistan, Nepal, Bangladesh). Women with any risk factor underwent a 75-gram oral glucose tolerance test (OGTT) at 24–28 weeks’ gestation. Those with two or more risk factors were tested at booking and, if normal, again at 24–28 weeks [ 20 , 21 ]. Women without initial risk factors were tested if risk factors emerged during pregnancy (e.g., large-for-gestational-age foetus, polyhydramnios, glycosuria). GDM was diagnosed using the WHO criteria: fasting plasma glucose above 5.1mmol/L and/or 2-hour plasma glucose above 8.5 mmol/L following a 75g OGTT [ 22 ]. Educational talk would be arranged as soon as the diagnosis of GDM was made. Advice would be given on lifestyle modification to achieve an optimal glycaemic control. They would be seen by the dietitian for advice on diet control and by nurses for technique on home blood glucose monitoring. They received regular follow-up by obstetricians to review of glycaemic control. Insulin therapy would be initiated in collaboration with endocrinologists if failed to achieve glycaemic control on lifestyle modification alone [ 21 ]. Once diagnosed with GDM, HbA1C was checked for all women within 1–2 weeks of OGTT. In all women diagnosed with GDM, ultrasound scans were performed between 34 to 36 weeks’ gestation to monitor foetal growth and liquor status. Additional scans would be arranged between 28 to 32 weeks’ gestation if there was a high concern about foetal complications (e.g., GDM on insulin use, suboptimal glycaemic control). These scans were done or supervised by experienced operators (doctors or midwives) accredited by the Hospital Authority in Hong Kong. If abnormality in foetal growth or liquor was detected, additional scans would be arranged for monitoring. Elective birth by induction or caesarean section would be offered in accordance with NICE guideline if presence of foetal complications [ 21 ]. All newborns were assessed by a paediatrician after delivery. A standard workflow was present in our unit for testing and management of neonatal hypoglycaemia, which is a well-documented consequence of maternal hyperglycaemia [ 23 ]. Blood glucose level would be tested for newborn at risk of hypoglycaemia, including but not limited to preterm birth, low birth weight, macrosomia, poorly controlled GDM, intrapartum asphyxia and infection. In addition to those with risk factors, testing would be performed in case of symptoms of hypoglycaemia, such as change in level of consciousness, seizure, vomiting and hypothermia. Neonatal hypoglycaemia was defined as blood glucose below 2.6 mmol/L within 48 hours of life, a threshold associated with poor neurological outcomes [ 24 , 25 ]. Hypoglycaemia would be corrected by dextrose, usually followed by milk feeding or intravenous infusion if oral feeding was not suitable. Data Collection Data were extracted via the Clinical Data Analysis and Reporting System, a Hong Kong Hospital Authority database integrating patient demographics, diagnoses, procedures, and medications. Data were entered by experienced midwives, and generated data were checked against patient records by the investigator. The outcome was the association between baseline HbA1C and adverse pregnancy outcomes in early vs. late onset GDM. Maternal outcomes included hypertensive disorder in pregnancy, caesarean section, instrumental delivery and insulin treatment. Foetal and neonatal outcomes included large-for-gestational-age foetus, polyhydramnios, preterm birth, shoulder dystocia, neonatal hypoglycaemia, respiratory distress, neonatal intensive care unit (NICU) admission, neonatal jaundice requiring phototherapy, low birth weight and macrosomia. Macrosomia was defined as birth weight above or equal to 4000g, regardless of the gestational age [ 26 ]. Large for gestational age (LGA) foetuses was defined as the estimated weight or the abdominal circumference above 90th percentile specific for the gestational age [ 27 ]. Hypertensive disorder in pregnancy was defined as either gestational hypertension or pre-eclampsia. Gestational hypertension was defined as systolic blood pressure ≥ 140mmHg and/ or diastolic blood pressure ≥ 90mmHg in a previously normotensive pregnant woman who is above 20 weeks gestation. Pre-eclampsia was defined as new onset hypertension with either proteinuria, maternal organ dysfunction or uteroplacental dysfunction [ 17 ]. Preterm delivery was defined as delivery before 37 weeks of gestation [ 28 ]. The birth weight of the newborns was plotted on gestational age and gender specific growth charts for the local Hong Kong population [ 29 ]. Low birth weight was defined as a birth weight of less than 2500g regardless of gestational age [ 30 ]. Polyhydramnios was defined as either the deepest vertical pocket greater than 8cm or the amniotic fluid index greater than 24cm. [ 31 ] Statistical Analysis Categorical variables were reported as numbers and percentages. Continuous variables were reported as means ± standard deviation (SD) for normally distributed data, and medians with interquartile ranges (IQR) for skewed data. Data were grouped according to timing of GDM diagnosis < 24 (early onset GDM) or ≥ 24 weeks’ (late onset GDM) gestation. Data were also divided into four HbA1C categories according to the level of HbA1C at GDM diagnosis: <5.0%, 5.0–5.4%, 5.5–5.9%, and ≥ 6.0%, with the latter aligning with ADA recommendations [ 15 ]. The categories aimed to facilitate a progressive evaluation of glycaemic control. Categorical outcomes were compared using Chi-square or Fisher’s exact tests. For continuous variables, they were compared by the one-way ANOVA test or Kruskal-Wallis tests for normally distributed and skewed data respectively. Multivariate logistic regression analyses calculated adjusted odds ratios (aOR) with 95% confidence intervals (CI), adjusting for ethnicity, and pre-pregnancy BMI. Statistical significance was set at a two-sided p-value < 0.05. Results Of 1701 women with diabetes in pregnancy reviewed in the study period, 170 were excluded due to incomplete records (N = 15), multiple pregnancies (N = 35), pre-existing diabetes (N = 91), HbA1C ≥ 6.5% at diagnosis (N = 20), those with haemoglobinopathies invalidating HbA1C analysis (N = 7) and stillbirth (N = 2). Two cases of stillbirth (related to antiphospholipid syndrome and intrahepatic cholestasis in pregnancy respectively) were excluded because the cause of stillbirth was unrelated to GDM. After exclusions, 1531 singleton pregnancy women with GDM were analysed (Fig. 1 ). Characteristics of women with early onset and late onset GDM Among the 1,531 women diagnosed with GDM, 554 were diagnosed with early onset GDM (prior to 24 weeks of gestation), while 977 were classified as late onset GDM (after 24 weeks of gestation). There were significant differences in maternal age, parity, ethnicity, BMI, overweight, fasting blood glucose, and 2-hour values after OGTT between these two groups, but there was no difference in thalassemia status (Table 1 ). Table 1 Maternal demographics and clinical characteristics in mother with early onset GDM (before 24 weeks) and late onset GDM (after 24 weeks), SD: Standard deviation, IQR: Interquartile range, BMI: body mass index, * statistically significant, p < 0.05 Demographics Early onset GDM (N = 554) Late onset GDM (N = 977) P value Maternal age (years, mean ± SD) 35.3 (+/- 4.6) 33.6 (+/- 4.4) < 0.001* Parity < 0.001* Nulliparity 199 (35.9%) 475 (48.6%) Multiparity 355 (64.1%) 502 (51.4%) Ethnicity < 0.001* Chinese 393 (70.9%) 798 (81.7%) Non-Chinese 161 (29.1%) 179 (18.3%) Pre-pregnancy BMI (kg/m², median & (IQR)) 26.2 (22.8–29.5) 22.9 (20.7–26.0) < 0.001* Overweight < 0.001* BMI < 25 kg/m2 (number/ %) 202 (36.5%) 662 (67.8%) BMI ≥ 25 kg/m2 (number/ %) 352 (63.5%) 315 (32.2%) Thalassaemia 0.346 Normal 510 (92.1%) 912 (93.3%) Thalassaemia trait 44 (7.9%) 65 (6.7%) HbA1C (%, median (IQR)) 5.3 (5.1–5.6) 5.2 (5.2–5.4) < 0.001* OGTT 0 min (mmol/L, median (IQR)) 5.1 (4.6–5.3) 4.8 (4.4–5.2) < 0.001* 120 min (mmol/L, median (IQR)) 8.7 (7.1–9.5) 8.8 (8.2–9.5) 0.005* HbA1C in late onset GDM and pregnancy outcomes In late onset GDM group, increasing HbAlC levels at diagnosis of late onset GDM positively correlated with higher mean birth weight, risk of LGA foetuses, birth weight above 97th percentile, neonatal hypoglycaemia, hypertensive disorders and insulin therapy (all p < 0.05) (Tables 2 and 3 ), even after adjustment of ethnicity and pre-pregnancy BMI. The risk of low birth weight followed a U-shaped distribution, with the lowest risk in the HbA1C 5.5–5.9% group (aOR 0.34 [0.15–0.78]) (Table 3 ). No association was observed with the mode of delivery, macrosomia, polyhydramnios, preterm birth, shoulder dystocia, respiratory distress, NICU admission or neonatal jaundice. Table 2 Adverse pregnancy outcomes across HbA1C groups with late onset GDM (N = 977), SD: Standard deviation, *statistically significant, p < 0.05 HbA1C level at diagnosis of GDM (late onset GDM) < 5.0% (N = 239) 5.0–5.4% (N = 502) 5.5–5.9% (N = 207) ≥ 6.0% (N = 29) P value Mode of delivery Caesarean section 79 (33.1%) 194 (38.6%) 86 (41.5%) 14 (48.3%) 0.174 Instrumental delivery 21 (8.8%) 31 (6.2%) 13 (6.3%) 1 (3.4%) 0.506 Birth weight Mean +/- SD 3077.1 ± 467.3 3140.2 ± 437.8 3256.5 ± 394.9 3330.3 ± 612.1 < 0.001* Low birth weight 24 (10%) 34 (6.8%) 8 (3.9%) 3 (10.3%) 0.071 Birth weight 97th percentile 5 (2.1%) 12 (2.4%) 12 (5.8%) 6 (20.7%) < 0.001* Foetal and neonatal outcomes Large for gestational age foetus 57 (23.8%) 112 (22.3%) 76 (36.7%) 15 (51.7%) < 0.001* Polyhydramnios 6 (2.5%) 13 (2.6%) 9 (4.3%) 3 (10.3%) 0.079 Preterm birth 12 (5.0%) 27 (5.4%) 11 (5.3%) 2 (6.9%) 0.995 Shoulder dystocia 0 (0.0%) 3 (0.6%) 1 (0.5%) 1 (3.4%) 0.130 Neonatal hypoglycaemia 54 (22.6%) 149 (29.7%) 80 (38.6%) 19 (65.5%) < 0.001* Respiratory distress 29 (12.1%) 50 (10.0%) 19 (9.2%) 3 (10.3%) 0.757 NICU admission 29 (12.1%) 56 (11.2%) 19 (9.2%) 3 (10.3%) 0.797 Neonatal jaundice requiring phtotherapy 56 (23.4%) 95 (18.9%) 37 (17.9%) 5 (17.2%) 0.419 Maternal outcomes Hypertensive disorder in pregnancy 9 (3.8%) 18 (3.6%) 10 (4.8%) 6 (20.7%) 0.001* Insulin treatment 1 (0.4%) 4 (0.8%) 7 (3.4%) 10 (34.5%) < 0.001* Table 3 Adjusted odds ratio of pregnancy outcomes in late onset GDM Adjust for ethnicity and pre-pregnancy BMI, *statistically significant HbA1C level at diagnosis of GDM (late onset GDM) < 5.0% (N = 239) 5.0–5.4% (N = 502) 5.5–5.9% (N = 207) ≥ 6.0% (N = 29) Foetal and neonatal outcomes Adjusted odds ratio (OR, 95% CI) Large for gestational age foetus Reference 0.889 (0.616–1.284) 1.760 (1.161–2.669)* 2.973 (1.325–6.671)* Polyhydramnios Reference 1.003 (0.374–2.690) 1.670 (0.575–4.851) 3.846 (0.844–17.525) Low birth weight Reference 0.623 (0.358–1.084) 0.338 (0.147–0.780)* 0.895 (0.241–3.322) Birth weight 97th percentile Reference 1.060 (0.366–3.066) 2.455 (0.833–7.233) 8.233 (2.171–31.228) Neonatal hypoglycaemia Reference 1.387 (0.966–1.991) 2.038 (1.342–3.096)* 5.668 (2.441–13.158)* Maternal outcomes Caesarean section Reference 1.170 (0.842–1.626) 1.255 (0.846–1.862) 1.312 (0.587–2.931) Instrumental delivery Reference 0.712 (0.398–1.274) 0.751 (0.363–1.554) 0.478 (0.060–3.790) Hypertensive disorder Reference 0.901 (0.396–2.050) 1.194 (0.468–3.043) 5.457 (1.671–17.818)* Insulin treatment Reference 2.077 (0.230-18.737) 9.458 (1.147–77.983)* 190.266 (21.080-1717.353)* HbA1c in early-onset GDM and pregnancy outcomes In contrast to late onset GDM group, HbA1C level in early onset GDM was associated with neonatal hypoglycaemia and insulin therapy, but not associated with birthweight > 97th percentile or LGA foetuses (Tables 4 and 5 ). Interestingly, the risk of instrumental delivery was smaller in HbA1C group 5.5–5.9% (aOR 0.24 [0.08–0.76]) than group < 5% (Tables 4 and 5 ). The risk of low birth weight followed a U-shaped distribution, but the association was not significant. Similar to late onset GDM group, no association was observed with the caesarean section, macrosomia, polyhydramnios, preterm birth, shoulder dystocia, respiratory distress, NICU admission or neonatal jaundice. Table 4 Adverse pregnancy outcomes across HbA1C groups in early onset GDM (N = 554) , SD: Standard deviation, *statistically significant, p < 0.05 HbA1C level at diagnosis of GDM (early onset GDM) < 5.0% (N = 82) 5.0–5.4% (N = 280) 5.5–5.9% (N = 167) ≥ 6.0% (N = 25) P value Mode of delivery Caesarean section 28 (34.1%) 128 (45.7%) 69 (41.3%) 12 (48.0%) 0.273 Instrumental delivery 9 (11.0%) 20 (7.1%) 5 (3.0%) 0 (0.0%) 0.041* Birth weight Mean +/- SD 3120.7 +/- 473.0 3159.3 +/- 457.3 3214.6 +/- 480.5 3149.4 +/- 584.7 0.464 Low birth weight 8 (9.8%) 20 (7.1%) 9 (5.4%) 3 (12.0%) 0.479 Birth weight 97th percentile 2 (2.4%) 13 (4.6%) 9 (5.4%) 2 (8.0%) 0.537 Foetal and neonatal outcomes Large for gestational foetus 19 (23.2%) 76 (27.1%) 44 (26.3%) 9 (36.0%) 0.647 Polyhydramnios 1 (1.2%) 5 (1.8%) 6 (3.6%) 1 (4.0%) 0.423 Preterm birth 9 (11.0%) 12 (4.3%) 8 (4.8%) 1 (4.0%) 0.139 Shoulder dystocia 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) N/A Neonatal hypoglycaemia 26 (31.7%) 103 (36.8%) 75 (44.9%) 16 (64.0%) 0.010* Respiratory distress 10 (12.2%) 30 (10.7%) 15 (9.0%) 4 (16.0%) 0.696 NICU admission 11 (13.4%) 30 (10.7%) 16 (9.6%) 4 (16.0%) 0.690 Neonatal jaundice requiring phototherapy 21 (25.6%) 64 (22.9%) 44 (26.3%) 5 (20.0%) 0.802 Maternal outcomes Hypertensive disorder 7 (8.5%) 10 (3.6%) 17 (10.2%) 3 (12.0%) 0.026* Insulin treatment 2 (2.4%) 11 (3.9%) 18 (10.8%) 13 (52%) < 0.001* Table 5 Adjusted odds ratio of pregnancy outcomes in early onset GDM Adjust for ethnicity and pre-pregnancy BMI, *statistically significant HbA1C level at diagnosis of GDM (early onset GDM) < 5.0% (N = 82) 5.0–5.4% (N = 280) 5.5–5.9% (N = 167) ≥ 6.0% (N = 25) Foetal and neonatal outcomes Adjusted odds ratio (OR, 95% CI) Large for gestational foetus Reference 1.207 (0.674–2.161) 1.082 (0.579–2.024) 1.536 (0.570–4.138) Polyhydramnios Reference 1.423 (0.163–12.418) 2.672 (0.313–22.793) 2.594 (0.146–46.084) Low birth weight Reference 0.731 (0.308–1.732) 0.564 (0.207–1.533) 1.415 (0.340–5.886) Birth weight 97th percentile Reference 1.903 (0.419–8.646) 2.032 (0.426–9.696 2.603 (0.330-20.556) Hypoglycaemia Reference 1.242 (0.732–2.107) 1.724 (0.982–3.028) 3.838 (1.479–9.960)* Maternal outcomes Caesarean section Reference 1.590 (0.937–2.697) 1.191 (0.674–2.103) 1.421 (0.548–3.684) Instrumental delivery Reference 0.609 (0.263–1.407) 0.243 (0.077–0.761)* / Hypertensive disorder Reference 0.388 (0.142–1.059) 1.124 (0.443–2.854) 1.167 (0.266–5.108) Insulin treatment Reference 1.598 (0.346–7.377) 4.484 (1.010-19.909)* 39.687 (7.839-200.922)* Discussion In contrast to earlier reports that evaluated HbA1C at a single time point in GDM, our study directly compared early onset (< 24 weeks) and late onset (≥ 24 weeks) GDM and demonstrated that the prognostic value of baseline HbA1C differs by the timing of diagnosis. Consistent with other studies [ 18 , 19 , 32 , 33 , 34 ], our study showed that baseline HbA1C ≥ 6.0% in late onset GDM was associated with higher mean birth weight, birth weight > 97th percentile, LGA foetuses, neonatal hypoglycaemia, hypertensive disorder, and insulin therapy. In contrast to late onset GDM, the same HbA1C threshold in early onset GDM identified only neonatal hypoglycaemia and insulin treatment, without significant association with foetal growth outcomes and hypertensive disorder. Adverse pregnancy outcomes were not associated with elevated HbA1C levels in two of six studies in a systemic review in 2020 [ 35 ]. In contrast to prior studies, we did not find increased risk of preeclampsia, perinatal death or caesarean section in women with higher HbA1C level [ 19 , 32 , 33 ]. Early onset GDM allows for earlier interventions, such as dietary counselling, self-monitoring of blood glucose, and insulin therapy, which can mitigate the impact of hyperglycaemia. This may weaken the relationship between baseline HbA1C and foetal growth outcomes, as effective control can normalize glucose levels before the critical phase of rapid foetal growth in third trimester [ 36 ]. A meta-analysis in 2022 showed that trials that screened all participants at their first visit and treated early, most for an HbA1c of 5.7% to 6.4%, had a reduced risk of LGA at birth compared with routine care [ 37 ].However, a recent systematic review showed that detection and treatment of early GDM have not shown indisputable benefits either in treated women or at the population level [ 38 ]. Further studies are required to determine the benefits of early detection and treatment of early onset GDM. We observed a new finding that the risk of LBW was higher in the HbA1C ≥ 6.0% or < 5% compared to 5.5–5.9% group in late onset GDM, following a U-shape distribution. Similar trend, though not significant, was also observed in early-onset GDM. LBW can be due to preterm birth or foetal growth restriction. The association of small for gestational age foetuses with baseline HbA1C < = 4.9% in women with early onset GDM has been reported [ 34 ]. Possible contributing factors include early intervention, excessive carbohydrate restriction, and poor nutrition in the context of only minimally elevated glucose levels in early pregnancy [ 34 ]. It is well known that maternal hypoglycemia is associated with foetal growth restriction [ 39 ]. Further studies are warranted to determine the exact cause and risk associated with LBW. In late onset GDM, a single HbA1c taken at diagnosis can be used to identify women at risk for specific adverse outcomes including macrosomia, LGA, hypertensive disorders and neonatal hypoglycemia [ 19 , 34 ]. However, a threshold ≥ 6% may not capture all cases of SGA or LBW as a low HbA1C level (< 5%) is also associated with increased risk of LBW as shown in our present study. In clinical management of GDM, HbA1C should be combined with other markers such as as OGTT values, readings of self-monitoring of blood glucose and serial growth scan to enhance risk prediction. Advice on carbohydrate restriction should be cautious because inadvertent adverse effects of excessive carbohydrate restriction with or without caloric restriction including impaired fetal growth and maternal ketonemia can be severe [ 40 , 41 ]. When a low HbA1C or SGA is found, it is important to look for the possible causes including excessive carbohydrate restriction or poor nutrition. A prolonged carbohydrate-restricted diet in pregnant women with GDM may lead to maternal ketonemia, to which fetal exposure remains a safety concern in pregnancy [ 40 , 41 ]. In contrast to HbA1C level ≥ 6.0% at late onset GDM, that at early onset GDM did not identify LGA and hypertensive disorders. Thus, its role as a triage tool in early-onset GDM is limited, as shown in the present and other studies [ 34 ]. Strengths and limitations A key strength of our study is that we examined maternal, foetal and neonatal outcomes in the same cohort, including neonatal hypoglycaemia and birth weight. The birth weight of newborns was plotted against gestational age and gender specific growth charts derived from a cross-sectional survey of over 20,000 participants in Hong Kong [ 29 ]. These local reference data, based on the Hong Kong 2020 Growth References, enable precise estimation of birth weight percentiles, particularly at higher centiles. This allowed adjustment for confounders to isolate the effect of HbA1C on the outcomes. Our data system facilitated comprehensive and reliable data collection, thereby minimizing selection bias. All HbA1C measurements were performed within the same laboratory to ensure consistency and reliability. We screened for hemoglobinopathy or iron deficiency, which would have impacted the accuracy of HbA1C assessment. Finally, the presence of a well-defined workflow for neonatal hypoglycaemia facilitated screening and management of neonatal hypoglycaemia and its clinical applicability. Several limitations should be acknowledged. First, our research is a retrospective study. Our GDM screening relied on risk factors rather than universal screening. Certain risk factors, including a family history of diabetes, personal history of polycystic ovarian syndrome, or a previous macrosomic baby, were self-reported, which may introduce reporting bias and potentially lead to underdiagnosis of GDM. Second, HbA1C testing was performed within 1–2 weeks after diagnosis of GDM confirmed instead of at the same time as the OGTT. There could be a potential delay in reflecting the actual glycaemic control at GDM diagnosis. Third, the diagnosis of large for gestational age foetus was based on local growth data specific to the Chinese population [ 27 ]. However, our study included mothers of non-Chinese ethnicity, which may potentially impact the accuracy of the study outcomes by overestimating LGA [ 42 ]. There was no data on small for gestational age foetuses. Finally, potential confounders, such as gestational weight gain, nutritional status, physical activity, were not fully accounted for in our multivariate analysis. Conclusion The significance of baseline HbA1C is different between early and late-onset GDM. Baseline HbA1C levels ≥ 6.0% at late onset GDM identified the risk of LGA, neonatal hypoglycaemia, hypertensive disorder and insulin treatment, whereas that at early GDM did not identify LGA and hypertensive disorders. Besides, high HbA1C levels as well as low HbA1C level (< 5%) at late-onset GDM are associated with increased risk of LBW. Abbreviations GDM Gestational diabetes mellitus HbA1C Haemoglobin A1C ADA American Diabetes Association WHO World Health Organization OGTT Oral glucose tolerance NICU Neonatal intensive care unit LGA Large for gestational age SD Standard deviation IQR Interquartile range aOR Adjusted odds ratio CI Confidence intervals BMI Body mass index PPV Positive predictive value NPV Negative predictive value Declarations Consent for publication Not applicable. Competing interests All authors have disclosed no conflicts of interest. Ethics approval and consent to participate: This research was approved by the Central Institutional Review Board of Hospital Authority, Hong Kong (reference: CIRB-2024-412-1). A waiver of patient consent was granted by the Ethics Committee (Central Institutional Review Board of Hospital Authority, Hong Kong) due to the retrospective nature of the research. Funding Not applicable. Author Contribution LC and KYL designed the study. LC performed data acquisition and responsible for the integrity of the data. LC and KYL contributed to analysis and interpretation of data, literature review, drafting of manuscript and revising the manuscript. All authors read and approved the final manuscript. Acknowledgement The authors thank the pregnant women in this study, as well as doctors and midwives at Queen Elizabeth Hospital for performing foetal ultrasound scans and assisting with data entry. Data Availability The datasets generated and/or analysed during the current study are available upon request. References Wang H, Li N, Chivese T, Werfalli M, Sun H, Yuen L, et al. IDF Diabetes Atlas: estimation of Global and Regional Gestational Diabetes Mellitus Prevalence for 2021 by International Association of Diabetes in Pregnancy Study Group’s Criteria. Diabetes Res Clin Pract. 2022;183:109050. Diagnostic criteria and classification of hyperglycaemia first. detected in pregnancy: A World Health Organization Guideline. 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International Association of Diabetes and Pregnancy Study Groups Consensus Panel, Metzger BE, Gabbe SG, Persson B, Buchanan TA, Catalano PA, Damm P, et al. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010;33:676–82. Radin MS. Pitfalls in hemoglobin A1c measurement: when results may be misleading. J Gen Intern Med. 2014;29(2):388–94. Burden C, Merriel A, Bakhbakhi D, Heazell A, Siassakos D. Royal College of Obstetricians and Gynaecologists. Care of late intrauterine fetal death and stillbirth. Green-top Guideline 55 BJOG. 2025;132(1):e1–41. Metz TD, Berry RS, Fretts RC, Reddy UM, et al. Obstetric Care Consensus #10: Management of Stillbirth. Am J Obstet Gynecol. 2020;222(3):B2–20. Hong JGS, Fadzleeyanna MYN, Omar SZ, Tan PC. HbA1c at term delivery and adverse pregnancy outcome. BMC Pregnancy Childbirth. 2022;22(1):679. 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NICE Guideline NG133. Available from: https://www.nice.org.uk/guidance/ng133 Cheung KW, Au TS, Lee CH, Ng VWY, Wong FC, Chow WS, et al. Hemoglobin A1c in early pregnancy to identify preexisting diabetes mellitus and women at risk of hyperglycemic pregnancy complications. AJOG Glob Rep. 2024;4:100315. Muhuza MPU, Zhang L, Wu Q, Qi L, Chen D, Liang Z. The association between maternal HbA1c and adverse outcomes in gestational diabetes. Front Endocrinol. 2023;14:1105899. Hong Kong College of Obstetricians and Gynaecologists. Guidelines for the Management of Gestational Diabetes Mellitus. Hong Kong: HKCOG. 2016. Available from: https://www.hkcog.org.hk/hkcog/Download/Guidelines_on_GDM_updated.pdf National Institute for Health and Care Excellence. Diabetes in pregnancy: management from preconception to the postnatal period. London: NICE. 2020. NICE Guideline NG3. Available from: https://www.nice.org.uk/guidance/ng3 World Health Organization. Diagnostic criteria and classification of hyperglycaemia first detected in pregnancy: A World Health Organization Guideline. Diabetes Res Clin Pract. 2014;103:341–63. Flores-le Roux JA, Sagarra E, Benaiges D, et al. A prospective evaluation of neonatal hypoglycaemia in infants of women with gestational diabetes mellitus. Diabetes Res Clin Pract. 2012;97:217–22. Harding JE, Alsweiler JM, Edwards TE. McKinlay C.J. Neonatal hypoglycaemia. BMJ Med. 2024;3(1). Lucas A, Morley R, Cole TJ. Adverse neurodevelopmental outcome of moderate neonatal hypoglycaemia. BMJ. 1988;297(6659):1304–8. American College of Obstetricians and Gynecologists, Macrosomia. ACOG Practice Bulletin, Number 216. Obstet Gynecol. 2020;135(1):e18–35. Liu F, Lu J, Kwan AH, et al. Consolidated and updated ultrasonographic fetal biometry and estimated fetal weight references for the Hong Kong Chinese population. Hong Kong Med J. 2024;30(6):444. National Institute for Health and Care Excellence. Preterm labour and birth. NICE guideline NG25. London: NICE. 2022. Available from: https://www.nice.org.uk/guidance/ng25 Department of Health, The Chinese University of Hong Kong. The University of Hong Kong. Hong Kong 2020 Growth References (HK2020). Hong Kong: Department of Health; 2024. Available from: https://www.dh.gov.hk/english/useful/useful_HP_Growth_Chart/files/growth_charts.pdf World Health Organization. Low birth weight: country, regional and global estimates. Geneva: World Health Organization. 2004. Available from: https://iris.who.int/handle/10665/43184 Dashe JS, Pressman EK, Hibbard JU. Society for maternal-fetal medicine (SMFM. SMFM Consult Series# 46: evaluation and management of polyhydramnios. Am J Obstet Gynecol. 2018;219(4):B2–8. 10.1016/j.ajog.2018.07.016 – . Hughes RCE, Moore MP, Gullam JE, Mohamed K, Rowan J. An early pregnancy HbA1c ≥ 5.9% (41 mmol/mol) is optimal for detecting diabetes and identifies women at increased risk of adverse pregnancy outcomes. Diabetes Care. 2014;37:2953–9. 10.2337/dc14-1312 . Mañé L, Navarro H, Pedro-Botet J, et al. Early HbA1c Levels as a Predictor of Adverse Obstetric Outcomes: A Systematic Review and Meta-Analysis. J Clin Med. 2024;13:1732. 10.3390/jcm13061732 . Sweeting AN, Ross GP, Hyett J, et al. Baseline HbA1c to identify high-risk gestational diabetes: utility in early vs standard gestational diabetes. J Clin Endocrinol Metab. 2017;102(1):150–6. 10.1210/jc.2016-2951 . Kattini R, Hummelen R, Kelly L. Early Gestational Diabetes Mellitus Screening with Glycated Hemoglobin: A Systematic Review. J Obstet Gynaecol Can. 2020;42:1379–84. Cunningham FG, Leveno KJ, Bloom SL, et al. Williams Obstetrics. 26th ed. New York, NY: McGraw-Hill Education; 2022. McLaren RA, Ruymann KR, Ramos GA, et al. Early screening for gestational diabetes mellitus: a meta-analysis of randomized controlled trials. Am J Obstet Gynecol MFM. 2022;4:100737. García-Patterson A, Balsells M, Solà I, Corcoy R. Detection and treatment of early gestational diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. Am J Obstet Gynecol. 2025;233(5):380–95. Long PA, Abell DA, Beischer NA. Importance of abnormal glucose tolerance (hypoglycaemia and hyperglycaemia) in the aetiology of pre-eclampsia. Lancet. 1977;1(8018):923–5. Sweeting A, Mijatovic J, Brinkworth GD, Markovic TP, Ross GP, Brand-Miller J. Hernandez T.L. The carbohydrate threshold in pregnancy and gestational diabetes: How low can we go? Nutrients. 2021;13:2599. Tanner HL, Dekker Nitert M, Callaway LK, Barrett HL. Ketones in pregnancy: why is it considered necessary to avoid them and what is the evidence behind their perceived risk? Diabetes Care. 2021;44(1):280–9. Hanley GE, Janssen PA. Ethnicity-specific birthweight distributions improve identification of term newborns at risk for short-term morbidity. Am J Obstet Gynecol. 2013;209(428):e421–426. 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09:12:13","extension":"html","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":140978,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8510465/v1/8e503d11b57bb2ea1834fbe4.html"},{"id":100595522,"identity":"292696cd-b5d8-4630-9ef6-4387380b438b","added_by":"auto","created_at":"2026-01-19 13:48:40","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":44114,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eInclusion and exclusion criteria for the study population\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8510465/v1/2adeca424eb74b73c8e9b6c7.png"},{"id":104719364,"identity":"0bf885e3-90a8-4809-b128-b77f558ba4c9","added_by":"auto","created_at":"2026-03-16 11:58:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1572220,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8510465/v1/00ac7ab5-3260-47c1-8106-62fad35745f2.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Maternal Haemoglobin A1C Level as a Predictor of Adverse Pregnancy Outcomes in Women with early versus late Gestational Diabetes Mellitus","fulltext":[{"header":"Background","content":"\u003cp\u003eGestational diabetes mellitus (GDM) affects 14% of pregnancies worldwide, with the highest prevalence of 27% in Southeast Asia [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It is defined as glucose intolerance first developed or diagnosed during pregnancy [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGDM increases the risk of adverse maternal and neonatal outcomes including pre-eclampsia, caesarean section, preterm birth, macrosomia, shoulder dystocia, respiratory distress, neonatal hypoglycaemia, neonatal jaundice, and rarely perinatal death [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Offspring born to mothers with GDM face increased risks of childhood and adulthood obesity and cardiometabolic disorders [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Long-term maternal complications include an increased risk of type 2 diabetes mellitus, cardiovascular disease, and metabolic syndrome later in life [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The prevalence of GDM has risen due to increasing maternal obesity, advanced maternal age, sedentary lifestyles [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], as well as the revised diagnostic criteria of GDM by the International Association for Diabetes in Pregnancy Study Group [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHaemoglobin A1C (HbA1C) is a single, non-fasting reliable marker for measurement of chronic hyperglycaemia and has been used widely for diagnosis and monitoring of treatment response in diabetes mellitus. It reflects average glycaemic control over the past three months [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The Royal College of Obstetricians and Gynaecologists and the American College of Obstetricians and Gynecologists recommend HbA1C as an investigation in cases of stillbirth to exclude gestational or pre-existing diabetes [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. While HbA1C can be used to predict adverse outcomes in diabetes in pregnancy, it is unclear whether an early HbA1C level can similarly predict adverse outcomes in GDM [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Intervention for GDM may attenuate the association between baseline HbA1c and pregnancy outcomes.\u003c/p\u003e \u003cp\u003eIn pregnancy, HbA1C levels are lower due to iron deficiency and reduced red blood cell lifespan [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Prior studies suggest elevated HbA1C correlates with adverse events [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. However, different HbA1C cut-offs have been recommended or proposed. The American Diabetes Association (ADA) recommends a preconception HbA1C below 6.5% for women with pre-existing diabetes and a target of less than 6% during pregnancy if achievable without significant hypoglycaemia [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The World Health Organization (WHO) also uses a threshold of \u0026ge;\u0026thinsp;6.5% to diagnose diabetes [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The International Association of Diabetes and Pregnancy Study Groups, in line with WHO, recommends an HbA1C threshold of \u0026ge;\u0026thinsp;6.5% to diagnose pre-existing diabetes in pregnancy, which may be first presented during pregnancy [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. This may help identify those with possible pre-existing diabetes in pregnancy in women with early onset GDM (before 24 weeks\u0026rsquo; of gestation), allowing early interventions such as insulin and aspirin for pre-eclampsia prophylaxis [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. A local study in Hong Kong, China by Cheung et al. 2024 suggested that an early pregnancy HbA1C\u0026thinsp;\u0026ge;\u0026thinsp;5.7% identifies women at risk of pregnancy and neonatal complications [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] while a study in Zhejiang, China, suggested a cut-off of 5.5% [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study aimed to evaluate the association between HbA1C levels and adverse maternal and neonatal outcomes in early and late onset GDM.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSubjects\u003c/h2\u003e \u003cp\u003eThis retrospective cohort study was conducted at Queen Elizabeth Hospital, a tertiary public hospital in Hong Kong serving the Kowloon Central cluster. All pregnant women with gestational diabetes who delivered between 1 January 2021 and 31 December 2024 were reviewed. The study included women with singleton pregnancies complicated by GDM. Exclusion criteria comprised pre-existing diabetes, multiple pregnancies, incomplete records, presence of haemoglobinopathies invalidating HbA1C analysis, and those without antenatal follow-up or delivery at our unit. Women with HbA1C\u0026thinsp;\u0026ge;\u0026thinsp;6.5% at GDM diagnosis were excluded to rule out overt diabetes, ensuring that the study cohort represented a true GDM population [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Haemoglobinopathies excluded on this basis included conditions such as β-thalassaemia major or intermedia, sickle cell disease, and other structural haemoglobin variants associated with absent haemoglobin A.\u003c/p\u003e \u003cp\u003eAll pregnant women attending antenatal care were assessed by midwives in the first trimester unless referred later. Except for those with known pre-existing diabetes, risk factors for GDM were evaluated, including advanced maternal age (\u0026ge;\u0026thinsp;35 years), obesity (pre-pregnancy body mass index [BMI]\u0026thinsp;\u0026ge;\u0026thinsp;25 kg/m\u0026sup2;), metabolic syndrome, polycystic ovarian syndrome, long-term use of diabetogenic medications (e.g., steroids), previous macrosomic baby (\u0026ge;\u0026thinsp;4000 g), prior GDM, previous stillbirth, previous congenital malformation consistent with diabetic embryopathy, family history of diabetes, and family origin with high diabetes prevalence (e.g., India, Pakistan, Nepal, Bangladesh). Women with any risk factor underwent a 75-gram oral glucose tolerance test (OGTT) at 24\u0026ndash;28 weeks\u0026rsquo; gestation. Those with two or more risk factors were tested at booking and, if normal, again at 24\u0026ndash;28 weeks [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Women without initial risk factors were tested if risk factors emerged during pregnancy (e.g., large-for-gestational-age foetus, polyhydramnios, glycosuria).\u003c/p\u003e \u003cp\u003eGDM was diagnosed using the WHO criteria: fasting plasma glucose above 5.1mmol/L and/or 2-hour plasma glucose above 8.5 mmol/L following a 75g OGTT [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Educational talk would be arranged as soon as the diagnosis of GDM was made. Advice would be given on lifestyle modification to achieve an optimal glycaemic control. They would be seen by the dietitian for advice on diet control and by nurses for technique on home blood glucose monitoring. They received regular follow-up by obstetricians to review of glycaemic control. Insulin therapy would be initiated in collaboration with endocrinologists if failed to achieve glycaemic control on lifestyle modification alone [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Once diagnosed with GDM, HbA1C was checked for all women within 1\u0026ndash;2 weeks of OGTT. In all women diagnosed with GDM, ultrasound scans were performed between 34 to 36 weeks\u0026rsquo; gestation to monitor foetal growth and liquor status. Additional scans would be arranged between 28 to 32 weeks\u0026rsquo; gestation if there was a high concern about foetal complications (e.g., GDM on insulin use, suboptimal glycaemic control). These scans were done or supervised by experienced operators (doctors or midwives) accredited by the Hospital Authority in Hong Kong. If abnormality in foetal growth or liquor was detected, additional scans would be arranged for monitoring. Elective birth by induction or caesarean section would be offered in accordance with NICE guideline if presence of foetal complications [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAll newborns were assessed by a paediatrician after delivery. A standard workflow was present in our unit for testing and management of neonatal hypoglycaemia, which is a well-documented consequence of maternal hyperglycaemia [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Blood glucose level would be tested for newborn at risk of hypoglycaemia, including but not limited to preterm birth, low birth weight, macrosomia, poorly controlled GDM, intrapartum asphyxia and infection. In addition to those with risk factors, testing would be performed in case of symptoms of hypoglycaemia, such as change in level of consciousness, seizure, vomiting and hypothermia. Neonatal hypoglycaemia was defined as blood glucose below 2.6 mmol/L within 48 hours of life, a threshold associated with poor neurological outcomes [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Hypoglycaemia would be corrected by dextrose, usually followed by milk feeding or intravenous infusion if oral feeding was not suitable.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData Collection\u003c/h3\u003e\n\u003cp\u003eData were extracted via the Clinical Data Analysis and Reporting System, a Hong Kong Hospital Authority database integrating patient demographics, diagnoses, procedures, and medications. Data were entered by experienced midwives, and generated data were checked against patient records by the investigator.\u003c/p\u003e \u003cp\u003eThe outcome was the association between baseline HbA1C and adverse pregnancy outcomes in early vs. late onset GDM. Maternal outcomes included hypertensive disorder in pregnancy, caesarean section, instrumental delivery and insulin treatment. Foetal and neonatal outcomes included large-for-gestational-age foetus, polyhydramnios, preterm birth, shoulder dystocia, neonatal hypoglycaemia, respiratory distress, neonatal intensive care unit (NICU) admission, neonatal jaundice requiring phototherapy, low birth weight and macrosomia. Macrosomia was defined as birth weight above or equal to 4000g, regardless of the gestational age [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Large for gestational age (LGA) foetuses was defined as the estimated weight or the abdominal circumference above 90th percentile specific for the gestational age [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Hypertensive disorder in pregnancy was defined as either gestational hypertension or pre-eclampsia. Gestational hypertension was defined as systolic blood pressure\u0026thinsp;\u0026ge;\u0026thinsp;140mmHg and/ or diastolic blood pressure\u0026thinsp;\u0026ge;\u0026thinsp;90mmHg in a previously normotensive pregnant woman who is above 20 weeks gestation. Pre-eclampsia was defined as new onset hypertension with either proteinuria, maternal organ dysfunction or uteroplacental dysfunction [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Preterm delivery was defined as delivery before 37 weeks of gestation [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe birth weight of the newborns was plotted on gestational age and gender specific growth charts for the local Hong Kong population [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Low birth weight was defined as a birth weight of less than 2500g regardless of gestational age [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Polyhydramnios was defined as either the deepest vertical pocket greater than 8cm or the amniotic fluid index greater than 24cm. [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eCategorical variables were reported as numbers and percentages. Continuous variables were reported as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) for normally distributed data, and medians with interquartile ranges (IQR) for skewed data. Data were grouped according to timing of GDM diagnosis\u0026thinsp;\u0026lt;\u0026thinsp;24 (early onset GDM) or \u0026ge;\u0026thinsp;24 weeks\u0026rsquo; (late onset GDM) gestation. Data were also divided into four HbA1C categories according to the level of HbA1C at GDM diagnosis: \u0026lt;5.0%, 5.0\u0026ndash;5.4%, 5.5\u0026ndash;5.9%, and \u0026ge;\u0026thinsp;6.0%, with the latter aligning with ADA recommendations [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The categories aimed to facilitate a progressive evaluation of glycaemic control. Categorical outcomes were compared using Chi-square or Fisher\u0026rsquo;s exact tests. For continuous variables, they were compared by the one-way ANOVA test or Kruskal-Wallis tests for normally distributed and skewed data respectively. Multivariate logistic regression analyses calculated adjusted odds ratios (aOR) with 95% confidence intervals (CI), adjusting for ethnicity, and pre-pregnancy BMI. Statistical significance was set at a two-sided p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eOf 1701 women with diabetes in pregnancy reviewed in the study period, 170 were excluded due to incomplete records (N\u0026thinsp;=\u0026thinsp;15), multiple pregnancies (N\u0026thinsp;=\u0026thinsp;35), pre-existing diabetes (N\u0026thinsp;=\u0026thinsp;91), HbA1C\u0026thinsp;\u0026ge;\u0026thinsp;6.5% at diagnosis (N\u0026thinsp;=\u0026thinsp;20), those with haemoglobinopathies invalidating HbA1C analysis (N\u0026thinsp;=\u0026thinsp;7) and stillbirth (N\u0026thinsp;=\u0026thinsp;2). Two cases of stillbirth (related to antiphospholipid syndrome and intrahepatic cholestasis in pregnancy respectively) were excluded because the cause of stillbirth was unrelated to GDM. After exclusions, 1531 singleton pregnancy women with GDM were analysed (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"1\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\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 \u003c/p\u003e\n\u003ch3\u003eCharacteristics of women with early onset and late onset GDM\u003c/h3\u003e\n\u003cp\u003eAmong the 1,531 women diagnosed with GDM, 554 were diagnosed with early onset GDM (prior to 24 weeks of gestation), while 977 were classified as late onset GDM (after 24 weeks of gestation). There were significant differences in maternal age, parity, ethnicity, BMI, overweight, fasting blood glucose, and 2-hour values after OGTT between these two groups, but there was no difference in thalassemia status (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMaternal demographics and clinical characteristics in mother with early onset GDM (before 24 weeks) and late onset GDM (after 24 weeks), \u003cem\u003eSD: Standard deviation, IQR: Interquartile range, BMI: body mass index, * statistically significant, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/em\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDemographics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEarly onset GDM\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;554)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLate onset GDM\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;977)\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\u003eMaternal age (years, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35.3 (+/- 4.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.6 (+/- 4.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\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\u003e\u003cb\u003eParity\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\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\u003eNulliparity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e199 (35.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e475 (48.6%)\u003c/p\u003e \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\u003eMultiparity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e355 (64.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e502 (51.4%)\u003c/p\u003e \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\u003e\u003cb\u003eEthnicity\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\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\u003eChinese\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e393 (70.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e798 (81.7%)\u003c/p\u003e \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\u003eNon-Chinese\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e161 (29.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e179 (18.3%)\u003c/p\u003e \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\u003e\u003cb\u003ePre-pregnancy BMI (kg/m\u0026sup2;, median \u0026amp; (IQR))\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.2 (22.8\u0026ndash;29.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.9 (20.7\u0026ndash;26.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\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\u003e\u003cb\u003eOverweight\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\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\u003eBMI\u0026thinsp;\u0026lt;\u0026thinsp;25 kg/m2 (number/ %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e202 (36.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e662 (67.8%)\u003c/p\u003e \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\u003eBMI\u0026thinsp;\u0026ge;\u0026thinsp;25 kg/m2 (number/ %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e352 (63.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e315 (32.2%)\u003c/p\u003e \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\u003e\u003cb\u003eThalassaemia\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\u003e0.346\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e510 (92.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e912 (93.3%)\u003c/p\u003e \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\u003eThalassaemia trait\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44 (7.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65 (6.7%)\u003c/p\u003e \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\u003eHbA1C (%, median (IQR))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.3 (5.1\u0026ndash;5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.2 (5.2\u0026ndash;5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\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\u003e\u003cb\u003eOGTT\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0 min (mmol/L, median (IQR))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.1 (4.6\u0026ndash;5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.8 (4.4\u0026ndash;5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\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\u003e120 min (mmol/L, median (IQR))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.7 (7.1\u0026ndash;9.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.8 (8.2\u0026ndash;9.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.005*\u003c/b\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 \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eHbA1C in late onset GDM and pregnancy outcomes\u003c/h2\u003e \u003cp\u003eIn late onset GDM group, increasing HbAlC levels at diagnosis of late onset GDM positively correlated with higher mean birth weight, risk of LGA foetuses, birth weight above 97th percentile, neonatal hypoglycaemia, hypertensive disorders and insulin therapy (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Tables\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), even after adjustment of ethnicity and pre-pregnancy BMI. The risk of low birth weight followed a U-shaped distribution, with the lowest risk in the HbA1C 5.5\u0026ndash;5.9% group (aOR 0.34 [0.15\u0026ndash;0.78]) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). No association was observed with the mode of delivery, macrosomia, polyhydramnios, preterm birth, shoulder dystocia, respiratory distress, NICU admission or neonatal jaundice.\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\u003eAdverse pregnancy outcomes across HbA1C groups with late onset GDM (N\u0026thinsp;=\u0026thinsp;977), \u003cem\u003eSD: Standard deviation, *statistically significant, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/em\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\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=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eHbA1C level at diagnosis of GDM (late onset GDM)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;5.0%\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;239)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.0\u0026ndash;5.4%\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;502)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.5\u0026ndash;5.9%\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;207)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;6.0%\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;29)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMode of delivery\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\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCaesarean section\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e79 (33.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e194 (38.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e86 (41.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14 (48.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.174\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInstrumental delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (8.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (6.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (6.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.506\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBirth weight\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 \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean +/- SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3077.1\u0026thinsp;\u0026plusmn;\u0026thinsp;467.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3140.2\u0026thinsp;\u0026plusmn;\u0026thinsp;437.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3256.5\u0026thinsp;\u0026plusmn;\u0026thinsp;394.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3330.3\u0026thinsp;\u0026plusmn;\u0026thinsp;612.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\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\u003eLow birth weight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (10%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (6.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (3.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (10.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.071\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight\u0026thinsp;\u0026lt;\u0026thinsp;3rd percentile\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (1.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (1.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.626\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMacrosomia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (1.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (1.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (10.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.062\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight\u0026thinsp;\u0026gt;\u0026thinsp;97th percentile\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (2.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (5.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (20.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\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\u003e\u003cb\u003eFoetal and neonatal outcomes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLarge for gestational age foetus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57 (23.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e112 (22.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e76 (36.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15 (51.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\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\u003ePolyhydramnios\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (2.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (10.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.079\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm birth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (5.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (5.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (5.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (6.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.995\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShoulder dystocia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (0.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.130\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal hypoglycaemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54 (22.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e149 (29.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e80 (38.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19 (65.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\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\u003eRespiratory distress\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (12.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50 (10.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (9.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (10.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.757\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNICU admission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (12.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56 (11.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (9.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (10.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.797\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal jaundice requiring phtotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56 (23.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95 (18.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37 (17.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 (17.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.419\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMaternal outcomes\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 \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertensive disorder in pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (3.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (3.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (4.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (20.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInsulin treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (0.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (34.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001*\u003c/b\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 \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\u003e\u003cb\u003eAdjusted odds ratio of pregnancy outcomes in late onset GDM\u003c/b\u003e \u003cem\u003eAdjust for ethnicity and pre-pregnancy BMI, *statistically significant\u003c/em\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eHbA1C level at diagnosis of GDM (late onset GDM)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;5.0%\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;239)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.0\u0026ndash;5.4%\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;502)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.5\u0026ndash;5.9%\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;207)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;6.0%\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;29)\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\u003eFoetal and neonatal outcomes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eAdjusted odds ratio (OR, 95% CI)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLarge for gestational age foetus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.889 (0.616\u0026ndash;1.284)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e1.760 (1.161\u0026ndash;2.669)*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e2.973 (1.325\u0026ndash;6.671)*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePolyhydramnios\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.003 (0.374\u0026ndash;2.690)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.670 (0.575\u0026ndash;4.851)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.846 (0.844\u0026ndash;17.525)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow birth weight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.623 (0.358\u0026ndash;1.084)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.338 (0.147\u0026ndash;0.780)*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.895 (0.241\u0026ndash;3.322)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight\u0026thinsp;\u0026lt;\u0026thinsp;3rd percentile\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.229 (0.385\u0026ndash;3.919)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.712 (0.153\u0026ndash;3.304)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.437 (0.144\u0026ndash;14.321)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMacrosomia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.966 (0.291\u0026ndash;3.208\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.153 (0.295\u0026ndash;4.506\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.899 (0.738\u0026ndash;20.584)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight\u0026thinsp;\u0026gt;\u0026thinsp;97th percentile\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.060 (0.366\u0026ndash;3.066)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.455 (0.833\u0026ndash;7.233)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e8.233 (2.171\u0026ndash;31.228)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal hypoglycaemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.387 (0.966\u0026ndash;1.991)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e2.038 (1.342\u0026ndash;3.096)*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e5.668 (2.441\u0026ndash;13.158)*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMaternal outcomes\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\u003eCaesarean section\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.170 (0.842\u0026ndash;1.626)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.255 (0.846\u0026ndash;1.862)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.312 (0.587\u0026ndash;2.931)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInstrumental delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.712 (0.398\u0026ndash;1.274)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.751 (0.363\u0026ndash;1.554)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.478 (0.060\u0026ndash;3.790)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertensive disorder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.901 (0.396\u0026ndash;2.050)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.194 (0.468\u0026ndash;3.043)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e5.457 (1.671\u0026ndash;17.818)*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInsulin treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.077 (0.230-18.737)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e9.458 (1.147\u0026ndash;77.983)*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e190.266 (21.080-1717.353)*\u003c/b\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 \u003c/div\u003e\n\u003ch3\u003eHbA1c in early-onset GDM and pregnancy outcomes\u003c/h3\u003e\n\u003cp\u003eIn contrast to late onset GDM group, HbA1C level in early onset GDM was associated with neonatal hypoglycaemia and insulin therapy, but not associated with birthweight\u0026thinsp;\u0026gt;\u0026thinsp;97th percentile or LGA foetuses (Tables\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Interestingly, the risk of instrumental delivery was smaller in HbA1C group 5.5\u0026ndash;5.9% (aOR 0.24 [0.08\u0026ndash;0.76]) than group\u0026thinsp;\u0026lt;\u0026thinsp;5% (Tables\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). The risk of low birth weight followed a U-shaped distribution, but the association was not significant. Similar to late onset GDM group, no association was observed with the caesarean section, macrosomia, polyhydramnios, preterm birth, shoulder dystocia, respiratory distress, NICU admission or neonatal jaundice.\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\u003e\u003cb\u003eAdverse pregnancy outcomes across HbA1C groups in early onset GDM (N\u0026thinsp;=\u0026thinsp;554)\u003c/b\u003e, \u003cem\u003eSD: Standard deviation, *statistically significant, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/em\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eHbA1C level at diagnosis of GDM (early onset GDM)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;5.0%\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;82)\u003c/p\u003e\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.0\u0026ndash;5.4% (N\u0026thinsp;=\u0026thinsp;280)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.5\u0026ndash;5.9% (N\u0026thinsp;=\u0026thinsp;167)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;6.0%\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;25)\u003c/p\u003e\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMode of delivery\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\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCaesarean section\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (34.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e128 (45.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e69 (41.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12 (48.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.273\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInstrumental delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (11.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (3.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.041*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBirth weight\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 \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean +/- SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3120.7 +/- 473.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3159.3 +/- 457.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3214.6 +/- 480.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3149.4 +/- 584.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.464\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow birth weight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (9.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (5.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (12.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.479\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight\u0026thinsp;\u0026lt;\u0026thinsp;3rd percentile\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (1.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (1.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (4.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.652\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMacrosomia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (3.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (4.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (4.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.521\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight\u0026thinsp;\u0026gt;\u0026thinsp;97th percentile\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (4.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (5.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (8.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.537\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFoetal and neonatal outcomes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLarge for gestational foetus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (23.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76 (27.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44 (26.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9 (36.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.647\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePolyhydramnios\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (1.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (3.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (4.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.423\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm birth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (11.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (4.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (4.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.139\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShoulder dystocia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal hypoglycaemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (31.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e103 (36.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75 (44.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16 (64.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.010*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory distress\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (12.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (10.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (9.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (16.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.696\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNICU admission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (13.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (10.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (9.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (16.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.690\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal jaundice requiring phototherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (25.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64 (22.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44 (26.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 (20.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.802\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMaternal outcomes\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 \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertensive disorder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (8.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (3.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 (10.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (12.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.026*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInsulin treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (3.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18 (10.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13 (52%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001*\u003c/b\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 \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\u003e\u003cb\u003eAdjusted odds ratio of pregnancy outcomes in early onset GDM\u003c/b\u003e \u003cem\u003eAdjust for ethnicity and pre-pregnancy BMI, *statistically significant\u003c/em\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eHbA1C level at diagnosis of GDM (early onset GDM)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;5.0%\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;82)\u003c/p\u003e\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.0\u0026ndash;5.4% (N\u0026thinsp;=\u0026thinsp;280)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.5\u0026ndash;5.9% (N\u0026thinsp;=\u0026thinsp;167)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;6.0%\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;25)\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\u003eFoetal and neonatal outcomes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eAdjusted odds ratio (OR, 95% CI)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLarge for gestational foetus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.207 (0.674\u0026ndash;2.161)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.082 (0.579\u0026ndash;2.024)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.536 (0.570\u0026ndash;4.138)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePolyhydramnios\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.423 (0.163\u0026ndash;12.418)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.672 (0.313\u0026ndash;22.793)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.594 (0.146\u0026ndash;46.084)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow birth weight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.731 (0.308\u0026ndash;1.732)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.564 (0.207\u0026ndash;1.533)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.415 (0.340\u0026ndash;5.886)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight\u0026thinsp;\u0026lt;\u0026thinsp;3rd percentile\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.618 (0.184\u0026ndash;14.223)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.241 (0.108\u0026ndash;14.250)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.567 (0.267\u0026ndash;78.256)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMacrosomia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.927 (0.368\u0026ndash;23.278)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.663 (0.448\u0026ndash;29.979)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.605 (0.150-45.318)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight\u0026thinsp;\u0026gt;\u0026thinsp;97th percentile\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.903 (0.419\u0026ndash;8.646)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.032 (0.426\u0026ndash;9.696\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.603 (0.330-20.556)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypoglycaemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.242 (0.732\u0026ndash;2.107)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.724 (0.982\u0026ndash;3.028)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e3.838 (1.479\u0026ndash;9.960)*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMaternal outcomes\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\u003eCaesarean section\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.590 (0.937\u0026ndash;2.697)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.191 (0.674\u0026ndash;2.103)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.421 (0.548\u0026ndash;3.684)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInstrumental delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.609 (0.263\u0026ndash;1.407)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.243 (0.077\u0026ndash;0.761)*\u003c/b\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\u003eHypertensive disorder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.388 (0.142\u0026ndash;1.059)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.124 (0.443\u0026ndash;2.854)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.167 (0.266\u0026ndash;5.108)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInsulin treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.598 (0.346\u0026ndash;7.377)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e4.484 (1.010-19.909)*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e39.687 (7.839-200.922)*\u003c/b\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"},{"header":"Discussion","content":"\u003cp\u003eIn contrast to earlier reports that evaluated HbA1C at a single time point in GDM, our study directly compared early onset (\u0026lt;\u0026thinsp;24 weeks) and late onset (\u0026ge;\u0026thinsp;24 weeks) GDM and demonstrated that the prognostic value of baseline HbA1C differs by the timing of diagnosis. Consistent with other studies [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], our study showed that baseline HbA1C\u0026thinsp;\u0026ge;\u0026thinsp;6.0% in late onset GDM was associated with higher mean birth weight, birth weight\u0026thinsp;\u0026gt;\u0026thinsp;97th percentile, LGA foetuses, neonatal hypoglycaemia, hypertensive disorder, and insulin therapy. In contrast to late onset GDM, the same HbA1C threshold in early onset GDM identified only neonatal hypoglycaemia and insulin treatment, without significant association with foetal growth outcomes and hypertensive disorder.\u003c/p\u003e \u003cp\u003eAdverse pregnancy outcomes were not associated with elevated HbA1C levels in two of six studies in a systemic review in 2020 [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. In contrast to prior studies, we did not find increased risk of preeclampsia, perinatal death or caesarean section in women with higher HbA1C level [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Early onset GDM allows for earlier interventions, such as dietary counselling, self-monitoring of blood glucose, and insulin therapy, which can mitigate the impact of hyperglycaemia. This may weaken the relationship between baseline HbA1C and foetal growth outcomes, as effective control can normalize glucose levels before the critical phase of rapid foetal growth in third trimester [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. A meta-analysis in 2022 showed that trials that screened all participants at their first visit and treated early, most for an HbA1c of 5.7% to 6.4%, had a reduced risk of LGA at birth compared with routine care [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e].However, a recent systematic review showed that detection and treatment of early GDM have not shown indisputable benefits either in treated women or at the population level [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Further studies are required to determine the benefits of early detection and treatment of early onset GDM.\u003c/p\u003e \u003cp\u003eWe observed a new finding that the risk of LBW was higher in the HbA1C\u0026thinsp;\u0026ge;\u0026thinsp;6.0% or \u0026lt;\u0026thinsp;5%\u003c/p\u003e \u003cp\u003ecompared to 5.5\u0026ndash;5.9% group in late onset GDM, following a U-shape distribution. Similar trend, though not significant, was also observed in early-onset GDM. LBW can be due to preterm birth or foetal growth restriction. The association of small for gestational age foetuses with baseline HbA1C\u0026thinsp;\u0026lt;\u0026thinsp;=\u0026thinsp;4.9% in women with early onset GDM has been reported [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Possible contributing factors include early intervention, excessive carbohydrate restriction, and poor nutrition in the context of only minimally elevated glucose levels in early pregnancy [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. It is well known that maternal hypoglycemia is associated with foetal growth restriction [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Further studies are warranted to determine the exact cause and risk associated with LBW.\u003c/p\u003e \u003cp\u003eIn late onset GDM, a single HbA1c taken at diagnosis can be used to identify women at risk for specific adverse outcomes including macrosomia, LGA, hypertensive disorders and neonatal hypoglycemia [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. However, a threshold\u0026thinsp;\u0026ge;\u0026thinsp;6% may not capture all cases of SGA or LBW as a low HbA1C level (\u0026lt;\u0026thinsp;5%) is also associated with increased risk of LBW as shown in our present study. In clinical management of GDM, HbA1C should be combined with other markers such as as OGTT values, readings of self-monitoring of blood glucose and serial growth scan to enhance risk prediction. Advice on carbohydrate restriction should be cautious because inadvertent adverse effects of excessive carbohydrate restriction with or without caloric restriction including impaired fetal growth and maternal ketonemia can be severe [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. When a low HbA1C or SGA is found, it is important to look for the possible causes including excessive carbohydrate restriction or poor nutrition. A prolonged carbohydrate-restricted diet in pregnant women with GDM may lead to maternal ketonemia, to which fetal exposure remains a safety concern in pregnancy [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn contrast to HbA1C level\u0026thinsp;\u0026ge;\u0026thinsp;6.0% at late onset GDM, that at early onset GDM did not identify LGA and hypertensive disorders. Thus, its role as a triage tool in early-onset GDM is limited, as shown in the present and other studies [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eStrengths and limitations\u003c/h2\u003e \u003cp\u003eA key strength of our study is that we examined maternal, foetal and neonatal outcomes in the same cohort, including neonatal hypoglycaemia and birth weight. The birth weight of newborns was plotted against gestational age and gender specific growth charts derived from a cross-sectional survey of over 20,000 participants in Hong Kong [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. These local reference data, based on the Hong Kong 2020 Growth References, enable precise estimation of birth weight percentiles, particularly at higher centiles. This allowed adjustment for confounders to isolate the effect of HbA1C on the outcomes. Our data system facilitated comprehensive and reliable data collection, thereby minimizing selection bias. All HbA1C measurements were performed within the same laboratory to ensure consistency and reliability. We screened for hemoglobinopathy or iron deficiency, which would have impacted the accuracy of HbA1C assessment. Finally, the presence of a well-defined workflow for neonatal hypoglycaemia facilitated screening and management of neonatal hypoglycaemia and its clinical applicability.\u003c/p\u003e \u003cp\u003eSeveral limitations should be acknowledged. First, our research is a retrospective study. Our GDM screening relied on risk factors rather than universal screening. Certain risk factors, including a family history of diabetes, personal history of polycystic ovarian syndrome, or a previous macrosomic baby, were self-reported, which may introduce reporting bias and potentially lead to underdiagnosis of GDM. Second, HbA1C testing was performed within 1\u0026ndash;2 weeks after diagnosis of GDM confirmed instead of at the same time as the OGTT. There could be a potential delay in reflecting the actual glycaemic control at GDM diagnosis. Third, the diagnosis of large for gestational age foetus was based on local growth data specific to the Chinese population [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. However, our study included mothers of non-Chinese ethnicity, which may potentially impact the accuracy of the study outcomes by overestimating LGA [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. There was no data on small for gestational age foetuses. Finally, potential confounders, such as gestational weight gain, nutritional status, physical activity, were not fully accounted for in our multivariate analysis.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe significance of baseline HbA1C is different between early and late-onset GDM. Baseline HbA1C levels\u0026thinsp;\u0026ge;\u0026thinsp;6.0% at late onset GDM identified the risk of LGA, neonatal hypoglycaemia, hypertensive disorder and insulin treatment, whereas that at early GDM did not identify LGA and hypertensive disorders. Besides, high HbA1C levels as well as low HbA1C level (\u0026lt;\u0026thinsp;5%) at late-onset GDM are associated with increased risk of LBW.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGDM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGestational diabetes mellitus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHbA1C\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHaemoglobin A1C\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eADA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAmerican Diabetes Association\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWHO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWorld Health Organization\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOGTT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOral glucose tolerance\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNICU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNeonatal intensive care unit\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLGA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLarge for gestational age\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eStandard deviation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIQR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInterquartile range\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eaOR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAdjusted odds ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eConfidence intervals\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\"\u003ePPV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePositive predictive value\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNPV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNegative predictive value\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003eConsent for publication\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eAll authors have disclosed no conflicts of interest.\u003c/p\u003e \u003ch2\u003eEthics approval and consent to participate:\u003c/h2\u003e \u003cp\u003e This research was approved by the Central Institutional Review Board of Hospital Authority, Hong Kong (reference: CIRB-2024-412-1). A waiver of patient consent was granted by the Ethics Committee (Central Institutional Review Board of Hospital Authority, Hong Kong) due to the retrospective nature of the research.\u003c/p\u003e \u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eLC and KYL designed the study. LC performed data acquisition and responsible for the integrity of the data. LC and KYL contributed to analysis and interpretation of data, literature review, drafting of manuscript and revising the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe authors thank the pregnant women in this study, as well as doctors and midwives at Queen Elizabeth Hospital for performing foetal ultrasound scans and assisting with data entry.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets generated and/or analysed during the current study are available upon request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWang H, Li N, Chivese T, Werfalli M, Sun H, Yuen L, et al. IDF Diabetes Atlas: estimation of Global and Regional Gestational Diabetes Mellitus Prevalence for 2021 by International Association of Diabetes in Pregnancy Study Group\u0026rsquo;s Criteria. 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Ketones in pregnancy: why is it considered necessary to avoid them and what is the evidence behind their perceived risk? Diabetes Care. 2021;44(1):280\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHanley GE, Janssen PA. Ethnicity-specific birthweight distributions improve identification of term newborns at risk for short-term morbidity. Am J Obstet Gynecol. 2013;209(428):e421\u0026ndash;426.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"[email protected]","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":"gestational diabetes, haemoglobin A1C, adverse pregnancy outcomes","lastPublishedDoi":"10.21203/rs.3.rs-8510465/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8510465/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\u003eThe objective was to evaluate the association between baseline maternal haemoglobin A1C (HbA1C) levels and adverse pregnancy outcomes in early (\u0026lt; 24 weeks) and late (≥ 24 weeks) gestational diabetes mellitus (GDM).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis was a retrospective cohort undertaken at a public hospital in Hong Kong between 2021 and 2024. The associations between baseline HbA1C level (taken within 1–2 weeks after the diagnosis of GDM) and pregnancy outcomes were analysed using multivariate logistic regression.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOf 1,531 women studied, 554 and 977 had early and late onset GDM, respectively. In late onset GDM, baseline HbA1C ≥ 6.0% showed associations with birth weight \u0026gt; 97th percentile (adjusted odds ratio [95% confidence interval = 8.2 [2.2–31.2]), large for gestational age (LGA) foetus (3.0 [1.3–6.7]), neonatal hypoglycaemia (5.7 [2.4–13.2]), hypertensive disorder (5.5 [1.7–17.8]), and insulin treatment (190.3 [21.1–1717.4]). The risk of low birth weight (\u0026lt; 2.5kg) followed a U-shaped distribution, with the lowest risk in the HbA1C 5.5–5.9% group (0.34 [0.15–0.78]). However, in early onset GDM, the associations were limited to neonatal hypoglycaemia (3.8 [1.5–10.0]) and insulin treatment (39.7 [7.8–200.9]).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe significance of baseline HbA1C is different between early and late-onset GDM. In contrast to baseline HbA1C levels ≥ 6.0% at late-onset GDM, that at early-onset GDM did not identify LGA and hypertensive disorders. Besides, high HbA1C levels as well as low HbA1C level (\u0026lt; 5%) at late onset GDM are associated with increased risk of LBW.\u003c/p\u003e","manuscriptTitle":"Maternal Haemoglobin A1C Level as a Predictor of Adverse Pregnancy Outcomes in Women with early versus late Gestational Diabetes Mellitus","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-19 09:12:04","doi":"10.21203/rs.3.rs-8510465/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","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":"70c09729-d3da-4fb2-94b1-5aedae37db01","owner":[],"postedDate":"January 19th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-16T11:57:03+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-19 09:12:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8510465","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8510465","identity":"rs-8510465","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}