Neonatal Outcomes According to Different Glucose Threshold Values in Gestational Diabetes: A Register-based Study

Neonatal Outcomes According to Different Glucose Threshold Values in Gestational Diabetes: A Register-based Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Neonatal Outcomes According to Different Glucose Threshold Values in Gestational Diabetes: A Register-based Study Kaisa Kariniemi, Marja Vääräsmäki, Tuija Männistö, Sanna Mustaniemi, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3790958/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 12 Apr, 2024 Read the published version in BMC Pregnancy and Childbirth → Version 1 posted 10 You are reading this latest preprint version Abstract Background Mild hyperglycaemia is associated with increased birth weight but association with other neonatal outcomes is controversial. We aimed to study neonatal outcomes in untreated mild hyperglycaemia using different oral glucose tolerance test (OGTT) thresholds. Methods This register-based study included all ( n = 4,939) singleton pregnant women participating a 75 g 2-hour OGTT in six delivery hospitals in Finland in 2009. Finnish diagnostic cut-offs for GDM were fasting ≥ 5.3, 1-hour ≥ 10.0 or 2-hour glucose ≥ 8.6 mmol/L. Women who did not meet these criteria but met the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria (fasting 5.1–5.2 mmol/L and/or 2-hour glucose 8.5 mmol/L, n = 509) or the National Institute for Health and Clinical Excellence (NICE) criteria (2-hour glucose 7.8–8.5 mmol/L, n = 166) were considered as mild untreated hyperglycaemia. Women who met both the Finnish criteria and the IADPSG or the NICE criteria were considered as treated GDM groups ( n = 1292 and n = 612, respectively). Untreated mild hyperglycemia groups and treated GDM groups were compared to controls, who were normoglycemic according to all criteria (fasting < 5.1 mmol/L, 1-hour glucose < 10.0 mmol/L and 2-hour glucose < 8.5 mmol/L, n = 3031). The primary outcome - a composite of adverse neonatal outcomes, including neonatal hypoglycaemia, hyperbilirubinaemia, birth trauma or perinatal mortality – was analysed using multivariate logistic regression. Results Compared to controls, the risk for the adverse neonatal outcome was not increased in mild hyperglycemia according to the IADPSG criteria (adjusted odds ratio [aOR]: 1.01, 95% confidence interval [CI]: 0.71–1.44) or the NICE criteria (aOR: 1.05, 95% CI: 0.60–1.85). Discussion The risk of adverse neonatal outcomes was not increased in mild untreated hyperglycaemia. The OGTT cut-offs of 5.3 mmol/L at fasting and 8.6 mmol/L at 2 hours seem to sufficiently identify clinically relevant GDM, without excluding neonates with a risk of adverse outcomes. Gestational diabetes mellitus Neonatal outcome Neonatal hypoglycaemia Oral glucose tolerance test OGTT IADPSG NICE Figures Figure 1 Figure 2 1 Background Gestational diabetes mellitus (GDM), defined as any degree of glucose intolerance with onset or first recognition during pregnancy [ 1 ], is associated with adverse neonatal outcomes, such as a higher risk of caesarean section [ 2 – 4 ], higher birth weight and risk of neonatal hypoglycaemia[ 4 , 5 ] and hyperbilirubinemia [ 6 – 8 ]. Regardless of these well-documented adverse outcomes, a consensus on the diagnostic criteria for GDM has yet to be reached. The International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommended new diagnostic criteria for GDM in 2010[ 9 ] after the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study[ 6 ] showed a linear association between maternal hyperglycaemia and unfavourable perinatal outcomes. The National Institute for Health and Clinical Excellence (NICE) did not adopt the guidelines introduced by the IADPSG because of insufficient evidence regarding the ability of the guidelines to improve pregnancy outcomes and yield cost savings [ 10 ]. The diagnostic cut-offs for GDM in Finland are based on the diagnostic criteria of the American Diabetes Association in 2003[ 1 ] and differ slightly from both the IADPSG and NICE criteria. Thus, it is possible to study the effects of different threshold glucose values on neonatal outcomes. The aim of this study was to study neonatal outcomes in pregnancies complicated by GDM defined by the criteria of the Finnish national guidelines that were either treated or remained untreated according to the criteria of the IADPSG or NICE. We hypothesised that compared to normoglycemic controls, the risk of adverse neonatal outcomes would be increased in women with treated GDM but not in those with mild untreated hyperglycaemia. 2 Material and Methods 2.1 Study Design This register-based cohort study is part of the Finnish Gestational Diabetes study (FinnGeDi), which was initiated in 2009 after the former risk-based screening program for GDM was replaced with comprehensive screening [ 11 , 12 ]. The registry data for this study were obtained from the Finnish Medical Birth Register (MBR), which contains information on all pregnancies resulting in a live birth or stillbirth at ≥ 22 gestational weeks or birthweight of ≥ 500 g. Data on pregnancy, delivery and neonatal outcomes were recorded, along with International Classification of Diseases (ICD) codes for diagnoses for the mother and child. The registry data were combined with numerical oral glucose tolerance test (OGTT) data obtained from laboratory databases in two tertiary-level (North Ostrobothnia and Tampere) and four secondary-level (Satakunta, South Ostrobothnia, Kainuu and Southern Karelia) hospitals, each serving a specific geographical area, during 2009. Deliveries in these hospitals accounted for 26.3% of all deliveries countrywide. 2.2 Screening and Diagnosis of GDM All women, except those at very low risk for GDM (i.e. aged < 25 years, nullipara, body mass index [BMI] of 18.5–24.9 kg/m 2 and no family history of type 2 diabetes or aged < 40 years, multipara without prior GDM or macrosomia and a BMI of < 25 kg/m 2 ) were screened using the 75-g 2-hour OGTT after an overnight fast at 24–28 weeks of gestation (13). For high-risk women, defined as having a history of GDM, a BMI ≥ 35.0 kg/m², glucosuria during pregnancy, use of glucocorticoids or polycystic ovary syndrome, an OGTT was performed at 12–16 weeks of gestation and repeated at 24–28 weeks of gestation if the test results were initially normal. If pre-pregnancy diabetes were suspected, an OGTT was performed immediately. Venous samples were drawn into fluoride citrate tubes and analysed within 24 hours in a local laboratory using commercial enzymatic assays. GDM was diagnosed using national current care guidelines in Finland if any of the following cut-off values in the OGTT were met: ≥ 5.3 mmol/L, ≥ 10.0 mmol/L or ≥ 8.6 mmol/L for fasting, 1-hour and 2-hour plasma glucose values, respectively [ 13 ]. All women diagnosed with GDM were recommended to receive dietary and lifestyle counselling and instructions to self-monitor their glucose concentrations in public maternity clinics according to Finnish guidelines. Insulin therapy was recommended to initiate if self-monitored capillary glucose concentrations repeatedly exceeded 5.5 mmol/L fasting or 7.8 mmol/L 1 hour postprandial, despite diet treatment. Women requiring medical treatment were recommend to be admitted to the outpatient maternity clinics of the hospitals serving their geographical area. 2.3 Study Population and GDM Groups This study included singleton pregnant women with an OGTT performed at 4–40 weeks of gestation during 2009. Women with pre-pregnancy type 1 or type 2 diabetes (ICD-10 codes E10–E11, E13, E14.9 or O24.0–O24.3) according to the MBR were excluded. Women who fulfilled the diagnostic criteria of the IADPSG or NICE without meeting the Finnish criteria were untreated (Table 1 ). The treated groups met both the Finnish criteria for GDM and those of the IADPSG or NICE. Controls were normoglycemic according to all criteria. Table 1 Diagnostic cut-off values in the 75-g 2-hour OGTT using different criteria. IADPSG NICE Finnish current care guidelines Fasting plasma glucose, mmol/L 5.1 5.6 5.3 1-hour plasma glucose, mmol/L 10.0 - 10.0 2-hour plasma glucose, mmol/L 8.5 7.8 8.6 OGTT, oral glucose tolerance test IADPSG, The International Association of Diabetes and Pregnancy Study Groups NICE, The National Institute for Health and Care Excellence 2.4 Outcomes The primary outcome was a composite of adverse neonatal outcomes comprising hypoglycaemia (ICD-10: P70.0-70.9), hyperbilirubinaemia (ICD-10: P59.0-59.9), birth trauma (Erb’s palsy [ICD-10: P14.0] or clavicle fracture [ICD-10: P13.4]) or perinatal mortality, which was defined as stillbirth or early neonatal death during the 7-day period after delivery. Secondary outcomes were the outcomes in the composite analysed independently. In all newborns exposed to GDM, glucose concentration was advised to be measured six times during the first 48 hours [ 13 ]. Hypoglycaemia was treated with intravenous glucose if a single plasma glucose measurement was ≤ 1.4 mmol/L or where the initial glucose concentration was 1.5–2.5 mmol/L and remained ≤ 2.5 mmol/L after supplementary feeding. Apart from GDM, other possible indications for neonatal glucose screening in asymptomatic newborns included preterm birth, birth weight of 4.5 kg or maternal use of β-blockers. A diagnosis of hypoglycaemia was recorded in the MBR if the newborn required intravenous glucose, although there are no unified diagnostic criteria for neonatal hypoglycaemia in Finland. 2.5 Covariates Maternal age at delivery was determined. BMI (kg/m 2 ) was calculated from self-reported pre-pregnancy height and weight. Parity was categorised according to the number of deliveries: primiparity, one (P1), two (P2), three (P3) and four or more previous deliveries (P4). Smoking status was categorized as non-smokers and smokers during pregnancy. Socioeconomic status was divided into upper-white collar, lower-white collar, blue-collar workers and others, including entrepreneurs, pensioners, stay-at-home-mothers and students. Insulin therapy during pregnancy was recorded. Maternal hypertension included chronic (ICD-10: O10.0-O12.1) and pregnancy-induced hypertension (ICD-10: O13) or pre-eclampsia (ICD-10: O14). Pregnancy-induced hypertension was defined as repeated blood pressure readings ≥ 140/90 mmHg after 20 weeks of gestation and pre-eclampsia as repeated blood pressure readings ≥ 140/90 mmHg after 20 weeks of gestation and proteinuria (> 300 mg of protein in a 24-hour urine collection or protein ≥ 2 + in a urine dipstick test). Data on the use of β-blockers were not available. Instead, maternal hypertension was used as a proxy variable. Labetalol, which is an unselective α- and β-blocker, is the preferred antihypertensive medication during pregnancy in Finland. Birth weight (g); birth weight of 4.5 kg; gestational age (weeks) at delivery; preterm birth, defined as delivery < 37 + 0 weeks of gestation; neonatal respiratory distress syndrome (ICD-10: P22.0); newborn discharge status (home or hospitalized) at the age of 7 days and duration of hospitalisation (days); caesarean section rate; and large for gestational age (LGA), which was determined as a birth weight standard deviation ( SD ) score over the 90th percentile, were reported. The birth weight SD score was calculated from gestational age-adjusted birth weight according to standard growth curves in the Finnish population [ 14 ]. 2.6 Statistical Analysis Values are reported as mean ( SD ) for continuous variables and number and frequency (%) for categorical variables. To compare differences between the study groups, Pearson’s χ 2 test was used for categorical variables, and the independent sample t -test was used for continuous variables. Logistic regression analyses were used to evaluate odds ratios (ORs), along with their 95% confidence intervals (CIs). To assess causality between GDM and adverse neonatal outcomes, a direct acyclic graph (DAG) was used (Fig. 1). Based on the DAG, two models were formulated to adjust the results for potential bias. Model I included potential confounders (maternal age, pre-pregnancy BMI, parity, socioeconomic status and smoking status), and Model II included potential mediators (preterm birth, birth weight 4.5 kg and maternal hypertension), in addition to the confounders in Model I. The level of statistical significance was set at < 0.05 using a two-sided p -value. IBM SPSS Statistics, version 27 (Armonk, NY, USA) was used for analyses. Figure 1. DAG to assess causality between GDM and adverse neonatal outcomes. 3 Results 3.1 Clinical Characteristics After exclusion of women with multiple pregnancies ( n = 191), women in the control group treated with insulin ( n = 8) and women with a diagnosis of GDM without an OGTT ( n = 38), the total number of participants was 4,939. In the entire study population, 1,801 (36.5%) and 778 (15.8%) had GDM according to the IADPSG and NICE criteria, respectively, and 1,292 (26.2%) had GDM according to the current care guidelines in Finland. In the IADPSG and NICE groups, 1,292 (71.7%) and 612 (78.7%) women, respectively, received treatment. 3,031 (61.4%) women were normoglycemic controls according to all criteria. (Table 1 – 2 ) Maternal characteristics are reported in Table 2 and neonatal characteristics are reported in Table 3 . Table 2 Maternal baseline characteristics. Controls IADPSG NICE Untreated Treated Untreated Treated pª pª pᵇ pª pª pᵇ N (%) 3031 (61.4) 509 (10.3) 1292 (26.2) 166 (3.4) 612 (12.4) Maternal age, years, mean ( SD ) 29.4 (5.29) 30.1 (5.49) 0.009 30.5 (5.56) < 0.001 0.157 30.0 (5.35) 0.127 30.8 (5.74) < 0.001 0.110 Pre-pregnancy BMI, kg/m 2 , mean ( SD ) 25.6 (4.47) 27.3 (5.21) < 0.001 28.4 (5.93) < 0.001 < 0.001 25.9 (5.06) 0.456 28.8 (6.03) < 0.001 < 0.001 Parity, n (%) Primiparity 1461 (48.2) 213 (41.8) 0.008 483 (37.4) < 0.001 0.086 83 (50.0) 0.690 242 (39.5) < 0.001 0.017 P1 932 (30.7) 162 (31.8) 0.641 434 (33.6) 0.068 0.505 39 (23.5) 0.056 198 (32.4) 0.444 0.029 P2 382 (12.6) 74 (14.5) 0.252 205 (15.9) 0.004 0.515 28 (16.9) 0.120 88 (14.4) 0.234 0.461 P3 121 (4.0) 35 (6.9) 0.004 86 (6.7) < 0.001 0.917 10 (6.0) 0.222 42 (6.9) 0.002 0.732 P4 or more 135 (4.5) 25 (4.9) 0.730 84 (6.5) 0.005 0.228 6 (3.6) 0.703 42 (6.9) 0.014 0.146 Smoking during pregnancy, n (%) 366 (12.1) 65 (12.8) 0.770 214 (16.6) < 0.001 0.042 16 (9.6) 0.333 106 (17.3) < 0.001 0.015 Socioeconomic status, n (%) 0.885 0.013 0.267 0.033 0.093 0.328 Upper-white collar worker 536 (17.7) 85 (16.7) 0.615 195 (15.1) 0.041 0.427 17 (10.2) 0.015 93 (15.2) 0.143 0.131 Lower-white collar worker 1017 (33.6) 167 (32.8) 0.761 439 (34.0) 0.806 0.658 56 (33.7) 1.000 210 (34.3) 0.743 0.927 Blue-collar worker 399 (13.2) 68 (13.4) 0.944 211 (16.3) 0.007 0.129 31 (18.7) 0.047 99 (16.2) 0.053 0.482 Other 519 (17.1) 93 (18.3) 0.527 207 (16.0) 0.398 0.261 30 (18.1) 0.833 93 (15.2) 0.260 0.401 IADPSG, The International Association of Diabetes and Pregnancy Study Groups NICE, The National Institute for Health and Care Excellence SD, standard deviation BMI, body mass index pª, p -value between the GDM group and controls pᵇ, p -value between the treated and non-treated GDM groups Parity was categorised according to the number of deliveries: primiparity, one (P1), two (P2), three (P3) and four or more previous deliveries (P4). Upper-white collar workers included administrative, managerial, professional and related occupations; lower-white collar workers included administrative and clerical occupations; blue-collar workers included manual labourers, and other included individuals who did not fit any of the above categories, including students, pensioners and self-employed. Table 3 Neonatal outcomes in the untreated and treated GDM groups using the IADPSG and NICE criteria. Controls IADPSG NICE Untreated Treated Untreated Treated pª pª pᵇ pª pª pᵇ N (%) 3031 (61.4) 509 (10.3) 1292 (26.2) 166 (3.4) 612 (12.4) Composite adverse neonatal outcome, n (%) 279 (9.2) 51 (10.0) 0.564 287 (22.2) < 0.001 < 0.001 20 (12.0) 0.272 164 (26.8) < 0.001 < 0.001 Hypoglycaemia, n (%) 74 (2.4) 17 (3.3) 0.288 187 (14.5) < 0.001 < 0.001 6 (3.6) 0.439 106 (17.3) < 0.001 < 0.001 Hyperbilirubinaemia, n (%) 172 (5.7) 32 (6.3) 0.607 108 (8.4) 0.001 0.144 9 (5.4) 1.000 62 (10.1) < 0.001 0.068 Birth trauma, n (%) 39 (1.3) 4 (0.8) 0.393 21 (1.6) 0.395 0.189 3 (1.8) 0.723 13 (2.1) 0.132 1.000 Perinatal mortality, n (%) 6 (0.2) 1 (0.2) 1.000 5 (0.4) 0.322 0.682 2 (1.2) 0.061 4 (0.7) 0.071 0.613 Birth weight, g, mean ( SD ) 3572.7 (525.7) 3632.9 (543.5) 0.017 3561.5 (562.3) 0.543 0.014 3499.9 (603.2) 0.130 3539.9 (623.5) 0.224 0.461 Birth weight 4.5 kg, n (%) 94 (3.1) 21 (4.1) 0.279 36 (2.8) 0.627 0.177 6 (3.6) 0.818 21 (3.4) 0.703 1.000 Birth weight SD score, mean ( SD ) -0.047 (1.01) 0.12 (1.05) < 0.001 0.072 (1.08) < 0.001 0.434 0.011 (1.05) 0.476 0.12 (1.19) 0.001 0.293 LGA, n (%) 267 (8.8) 65 (12.8) 0.005 147 (11.4) 0.009 0.417 22 (13.3) 0.069 82 (13.4) < 0.001 1.000 Gestational age at delivery in weeks, mean ( SD ) 39.9 (1.57) 39.8 (1.60) 0.154 39.5 (1.81) < 0.001 < 0.001 39.5 (1.93) 0.002 39.2 (2.01) < 0.001 0.185 Preterm birth < 37 weeks, n (%) 114 (3.8) 21 (4.1) 0.707 78 (6.0) 0.001 0.135 12 (7.2) 0.037 49 (8.0) < 0.001 0.751 Neonatal respiratory distress syndrome, n (%) 15 (0.5) 3 (0.6) 1.000 9 (0.7) 0.502 1.000 1 (0.6) 1.000 5 (0.8) 0.001 0.293 Newborn discharge status aged 7 days, n (%) Home 2895 (95.5) 482 (94.7) 0.423 1195 (92.5) < 0.001 0.099 152 (91.6) 0.025 547 (89.4) < 0.001 0.470 Hospitalised 130 (4.3) 25 (4.9) 0.558 91 (7.0) < 0.001 0.110 11 (6.6) 0.170 61 (10.0) < 0.001 0.227 Hospitalisation in days, mean ( SD ) 3.1 (2.61) 3.2 (1.37) 0.514 3.3 (2.09) 0.004 0.157 3.3 (1.45) 0.425 3.5 (2.71) 0.002 0.315 Caesarean section, n (%) 453 (14.9) 98 (19.3) 0.015 271 (21.0) < 0.001 0.437 32 (19.3) 0.148 136 (22.2) < 0.001 0.457 Insulin treatment, n (%) - - - 135 (10.4) < 0.001 < 0.001 3 (1.8) < 0.001 86 (14.1) < 0.001 Maternal hypertension, n (%) 225 (7.4) 49 (9.6) 0.089 151 (11.7) < 0.001 0.213 16 (9.6) 0.364 82 (13.4) < 0.001 GDM, gestational diabetes mellitus IADPSG, The International Association of Diabetes and Pregnancy Study Groups NICE, The National Institute for Health and Care Excellence pª, p -value between the GDM group and controls pᵇ, p -value between the treated and untreated GDM groups SD , standard deviation The composite adverse neonatal outcome included hypoglycaemia, hyperbilirubinaemia, birth trauma or perinatal mortality Birth trauma included Erb’s palsy or clavicle fracture LGA, large for gestational age. LGA was defined as having a birth weight SD score > 90th percentile A diagnosis of maternal hypertension included ICD-10 codes O10-O12.1 and O13-O14 3.2 Outcomes The rate of the composite adverse neonatal outcome was 22.2% in the treated IADPSG group and 26.8% in the treated NICE group, and it was higher compared to that of either the controls (9.2%) or the corresponding untreated group (10.0% in the untreated IADPSG group and 12.0% in the untreated NICE group). Compared to controls, the aORs were 2.75 (95% CI: 2.24–3.37) in the treated IADPSG group and 3.33 (95% CI: 2.59–4.28) in the treated NICE group (Tables 3 – 4 , Fig. 2 a). No differences were found in the frequency of the composite outcome between the untreated groups and the control group. Hypoglycaemia was more frequent in the treated groups than in the control group (treated IADPSG: 14.5% vs. 2.4% in the control group, aOR 6.65, 95% CI: 4.93–8.99; treated NICE: 17.3% vs. 2.4%, aOR 7.45, 95% CI: 5.27–10.5) or the untreated groups (3.3% in the untreated IADPSG group and 3.6% in the untreated NICE group) (Tables 3 – 4 , Fig. 2 b). There were no differences in the frequency of hyperbilirubinaemia between the groups after adjusting for confounders. No between-group differences were observed in the rate of perinatal mortality or birth trauma. Table 4 Multivariate logistic regression analyses of neonatal outcomes compared to the control group. Untreated IADPSG Treated IADPSG Untreated NICE Treated NICE Composite adverse neonatal outcome Unadjusted OR 1.10 (0.80–1.50) 2.82 (2.35–3.37) 1.35 (0.83–2.19) 3.61 (2.91–4.49) Model I 1.07 (0.77–1.48) 2.70 (2.22–3.27) 1.26 (0.75–2.09) 3.39 (2.68–4.29) Model II 1.01 (0.71–1.44) 2.75 (2.24–3.37) 1.05 (0.60–1.85) 3.33 (2.59–4.28) Hypoglycaemia Unadjusted OR 1.38 (0.81–2.36) 6.76 (5.12–8.93) 1.50 (0.64–3.50) 8.37 (6.13–11.4) Model I 1.32 (0.76–2.31) 6.50 (4.84–8.74) 1.59 (0.68–3.76) 7.48 (5.34–10.5) Model II 1.24 (0.70–2.20) 6.65 (4.93–8.99) 1.34 (0.55–3.28) 7.45 (5.27–10.5) Hyperbilirubinaemia Unadjusted OR 1.12 (0.76–1.65) 1.52 (1.18–1.95) 0.95 (0.48–1.90) 1.87 (1.38–2.54) Model I 1.11 (0.75–1.67) 1.47 (1.12–1.92) 0.87 (0.42–1.81) 1.84 (1.32–2.56) Model II 1.04 (0.67–1.63) 1.29 (0.96–1.73) 0.61 (0.26–1.40) 1.45 (1.00-2.10) Perinatal mortality Unadjusted OR 1.0 (0.12–8.26) 1.96 (0.60–6.43) 6.15 (1.23–30.7) 3.32 (0.93–11.8) Model I - 0.85 (0.19–3.76) 4.02 (0.44–36.4) 2.02 (0.45–9.03) Model II - 1.08 (0.21–5.52) 3.69 (0.24–57.9) 2.03 (0.37-11.0) Birth trauma Unadjusted OR 0.61 (0.22–1.71) 1.27 (0.74–2.16) 1.41 (0.43–4.62) 1.67 (0.88–3.14) Model I 0.58 (0.20–1.65) 1.33 (0.76–2.34) 1.46 (0.44–4.83) 1.74 (0.89–3.41) Model II 0.57 (0.20–1.63) 1.35 (0.77–2.38) 1.51 (0.46–5.02) 1.73 (0.88–3.40) IADPSG, The International Association of Diabetes and Pregnancy Study Groups NICE, The National Institute for Health and Care Excellence OR, odds ratio The composite adverse neonatal outcome included neonatal hypoglycaemia, hyperbilirubinaemia, birth trauma or perinatal mortality. Birth trauma included clavicle fracture or Erb’s palsy. Model I: adjusted for maternal age, pre-pregnancy BMI, parity, smoking and socioeconomic status; Model II: adjusted for the variables in Model I; preterm birth: 4.5 kg, very low birth weight: < 2.5 kg birth weight, and maternal hypertension (pre-pregnancy or pregnancy-induced). 4 Discussion 4.1 Main Findings As hypothesised, the risk of adverse neonatal outcomes in the untreated groups representing untreated mild hyperglycaemia was similar to normoglycemic controls. The the risk of neonatal morbidity in the diagnosed and treated GDM groups was higher compared to the normoglycemic control group. We found a 2.8-fold and 3.3-fold increased risk of the adverse neonatal outcome in the treated IADPSG and treated NICE groups, respectively. The risk was also increased compared to the untreated groups. These findings confirm the current understanding that higher maternal blood glucose levels are associated with adverse neonatal outcomes, which was demonstrated first in the HAPO study[ 6 ] and later corroborated in other studies [ 8 , 15 – 19 ]. Therefore, according to our findings, the current diagnostic criteria for GDM in Finland with slightly higher fasting (0.2 mmol/L) and 2-hour (0.1 mmol/L) OGTT cut-offs are sufficient to identify women at risk of adverse outcomes. GDM leads to a hyperglycaemic intrauterine environment, which in turn results in a transient amplified insulin response in the newborn, causing hypoglycaemia. This combined with the neonatal glucose screening used for GDM-exposed newborns explains the high frequency of neonatal hypoglycaemia among the treated GDM groups in our study. We adjusted for other possible risk factors for neonatal hypoglycaemia, which did not significantly attenuate the risk associated with GDM and therefore are unlikely to mediate the association between GDM and neonatal hypoglycaemia in this study. The risk of neonatal hypoglycaemia seems to be greater at higher concentrations of maternal blood glucose [ 15 , 20 – 22 ] and explains why the rate of neonatal hypoglycaemia was similar in the untreated GDM groups and controls in our study. The potential of diagnosing and treating even milder hyperglycaemia as applied in the IADPSG criteria to prevent adverse neonatal outcomes has been discussed in the literature [ 21 – 26 ]. Because of variable diagnostic criteria used for GDM and thresholds for treating GDM, the studies have produced inconsistent results. Most studies have found that treatment of mild hyperglycaemia reduced adverse neonatal outcomes [ 20 – 22 , 25 , 26 ], while others have not [ 23 , 24 ]. In the studies where a favourable treatment effect was found, the participants would have fulfilled the diagnostic criteria of GDM used in Finland and therefore received treatment. In only one study [ 24 ] the OGTT criteria for GDM matched the ones used in the untreated IADPSG group of our study and they found no differences in neonatal outcomes when comparing untreated and treated counterparts. Our group and others have found that mild hyperglycaemia is associated with slightly higher birth weights and caesarean section rates [ 4 , 6 , 15 , 21 , 27 ]. Treatment of GDM could potentially reduce the risk of these outcomes [ 20 – 22 ], but based on our findings, adopting the IADPSG criteria in Finland would not result in clinically significant improvements in adverse neonatal outcomes such as hypoglycaemia. Simultaneously, there would be 39% more GDM diagnoses, as the incidence of GDM in the screened population was 26.2% when using the Finnish cut-offs and 36.5% when using the IAPDSG cut-offs. 4.2 Strengths and Limitations The strengths of this study include the use of well-defined and comprehensive population-base data, as the MBR includes information on all births in Finland. The validity of the data in the MBR has been demonstrated to be high [ 28 ]. The public maternity clinic system in Finland is free of cost, statutorily organized and comprehensive since 99.7% of women attend these clinics during pregnancy [ 29 ]. By collecting numerical data from the OGTTs we were able to divide the participants into GDM groups according to IADPSG and NICE criteria and evaluate neonatal outcomes in the untreated groups. We were able to adjust for important confounding factors and potential mediators. As Finnish national guidelines do not suggest screening very low-risk women for GDM with an OGTT, these women were excluded in our study. An OGTT was performed for 42.6% versus 71.0% of pregnant women in Finland in 2009 and 2021, respectively [ 30 ]. Since this is a register-based study, we were unable to verify whether GDM was managed according to the recommended guidelines. The untreated NICE group was small ( n = 166) and thus, the power to detect small differences in the frequencies of adverse neonatal outcomes in the NICE group versus the control group was limited. Finally, detection bias in the treated GDM groups could have potentially increased the prevalence of particular outcomes in these groups. 4.3 Conclusions Untreated mild hyperglycaemia was not associated with worse neonatal outcomes. The diagnostic criteria used in Finland seem to sufficiently identify clinically relevant GDM, without excluding neonates with a risk of adverse outcomes. Declarations 5.1 Ethics approval and consent to participate According to the Finnish Act on Secondary Use of Health and Social Data 552/2019, the study participants did not need to provide an information consent form when only anonymous register data were used. The Finnish Institute for Health and Welfare gave their permission for the use of the MBR data (Number: THL132/5.05.00/2011). Hospital administration gave permission to use and combine OGTT laboratory test results with the register data. The FinnGeDi study was approved by the regional ethics committee in Northern Ostrobothnia Hospital District (Number: 2008/43, date of approval: 2008-6-19). 5.2 Consent for publication Not applicable. 5.3 Availability of data and materials The data are not open access according to the Finnish legislation. The use of registry data requires permission from national registry authorities. Metadata of the current study are available from the corresponding author on reasonable request. 5.4 Competing interests The authors declare that they have no competing interests. 5.5 Funding Academy of Finland, Signe and Ane Gyllenberg Foundation, Diabetes Research Foundation, Novo Nordisk Foundation, Juho Vainio Foundation, Sigrid Jusélius Foundation, Foundation for Pediatric Research, Foundation for Cardiovascular Research, University of Oulu Graduate School, Terttu Foundation, Research Funds of Oulu University Hospital and the Finnish Medical Foundation. 5.6 Authors’ contributions KK conducted the data analysis and drafted the manuscript. MV and EK provided clinical interpretation of the data. SE contributed to the data collection and handling. All authors contributed to the design of the study, commented the manuscript during the writing process and approved the final manuscript. 5.7 Acknowledgements Matti Viljakainen MD helped with handling of the data. 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Independent and concomitant associations of gestational diabetes and maternal obesity to perinatal outcome: A register-based study. PLoS ONE. 2019;14(8):e0221549. 10.1371/journal.pone.0221549 . HAPO Study Cooperative Research Group, Metzger BE, Lowe LP, Dyer AR, Chaovarindr U, Hospital R, et al. Hyperglycemia and Adverse Pregnancy Outcomes. N Engl J Med. 2008;358(19):1991–2002. 10.1056/NEJMoa0707943 . Djelmis J, Pavić M, Mulliqi Kotori V, Pavlić Renar I, Ivanisevic M, Oreskovic S. Prevalence of gestational diabetes mellitus according to IADPSG and NICE criteria. Int J Gynaecol Obstet. 2016;135(3):250–4. 10.1016/j.ijgo.2016.07.005 . Black MH, Sacks DA, Xiang AH, Lawrence JM. Clinical outcomes of pregnancies complicated by mild gestational diabetes mellitus differ by combinations of abnormal oral glucose tolerance test values. Diabetes Care. 2010;33(12):2524–30. 10.2337/dc10-1445 . International Association of Diabetes and Pregnancy Study Groups Consensus Panel, Metzger BE, Gabbe SG, Persson B, Buchanan TA, Catalano PA, et al. International Association of Diabetes and Pregnancy Study Groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010;33(3):676–82. 10.2337/dc09-1848 . National Collaborating Centre for Women’s and Children’s Health (UK). Diabetes in Pregnancy: Management of Diabetes and Its Complications from Preconception to the Postnatal Period. London: National Institute for Health and Care Excellence (UK); 2015 Feb. p. 25950069. Keikkala E, Mustaniemi S, Koivunen S, Kinnunen J, Viljakainen M, Männisto T, et al. Cohort profile: The Finnish gestational diabetes (FinnGeDi) study. Int J Epidemiol. 2020;49(3):762–763g. 10.1093/ije/dyaa039 . Koivunen S, Kajantie E, Torkki A, Bloigu A, Gissler M, Pouta A, et al. The changing face of gestational diabetes: The effect of the shift from risk factor-based to comprehensive screening. Eur J Endocrinol. 2015;173(5):623–32. 10.1530/EJE-15-0294 . Gestational diabetes. Current care guidelines. Working group set up by the Finnish Medical Society Duodecim, the Finnish Diabetes Association and the Finnish Society of Obstetrics and Gynaecology. Helsinki: The Finnish Medical Society Duodecim; 2013. (Cited 13.10.2023). Sankilampi U, Hannila ML, Saari A, Gissler M, Dunkel L. New population-based references for birth weight, length, and head circumference in singletons and twins from 23 to 43 gestation weeks. Ann Med. 2013;45(5–6):446–54. 10.3109/07853890.2013.803739 . Sacks DA, Black MH, Li X, Montoro MN, Lawrence JM. Adverse Pregnancy Outcomes Using The International Association of the Diabetes and Pregnancy Study Groups Criteria: Glycemic Thresholds and Associated Risks. Obstet Gynecol. 2015;126(1):67–73. 10.1097/AOG.0000000000000865 . Kim MH, Kwak SH, Kim SH, Hong JS, Chung HR, Choi SH, et al. Pregnancy outcomes of women additionally diagnosed as gestational diabetes by the International Association of the Diabetes and Pregnancy Study groups criteria. Diabetes Metab J. 2019;43(6):766–75. 10.4093/dmj.2018.0192 . Landon MB, Mele L, Spong CY, Carpenter MW, Ramin SM, Casey B, et al. The Relationship Between Maternal Glycemia and Perinatal Outcome. Obstet Gynecol. 2011;117(2 Pt 1):218–24. 10.1097/AOG.0b013e318203ebe0 . Feng H, Zhu WW, Yang HX, Wei YM, Wang C, Su RN, et al. Relationship between oral glucose tolerance test characteristics and adverse pregnancy outcomes among women with gestational diabetes mellitus. Chin Med J (Engl). 2017;130(9):1012–8. 10.4103/0366-6999.204928 . Farrar D, Simmonds M, Bryant M, Sheldon TA, Tuffnell D, Golder S, et al. Hyperglycaemia and risk of adverse perinatal outcomes: Systematic review and meta-analysis. BMJ. 2016;354:i4694. 10.1136/bmj.i4694 . Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS. Effect of Treatment of Gestational Diabetes Mellitus on Pregnancy Outcomes. N Engl J Med. 2005;352(24):2477–86. 10.1056/NEJMoa042973 . Landon MB, Spong CY, Thom E, Carpenter MW, Ramin SM, Casey B, et al. A Multicenter, Randomized Trial of Treatment for Mild Gestational Diabetes. N Engl J Med. 2009;361(14):1339–48. 10.1056/NEJMoa0902430 . Behboudi-Gandevani S, Bidhendi-Yarandi R, Panahi MH, Vaismoradi M. The Effect of Mild Gestational Diabetes Mellitus Treatment on Adverse Pregnancy Outcomes: A Systemic Review and Meta-Analysis. Front Endocrinol (Lausanne). 2021;12:640004. 10.3389/fendo.2021.640004 . Sugiyama T, Metoki H, Hamada H, Nishigori H, Saito M, Yaegashi N, et al. A retrospective multi-institutional study of treatment for mild gestational diabetes in Japan. Diabetes Res Clin Pract. 2014;103(3):412–8. 10.1016/j.diabres.2013.12.017 . Martínez-Cruz N, Rapisarda AMC, Soriano-Ortega KP, Arce-Sánchez L, Cianci A, Ortega-Gonzalez C, et al. Perinatal Outcomes in Mexican Women with Untreated Mild Gestational Diabetes Mellitus Diagnosed by the International Association of Diabetes and Pregnancy Study Groups Criteria. Diabetes Metab Syndr Obes. 2019;12:2667–74. 10.2147/DMSO.S229671 . Goyette F, Wo BL, Iglesias MH, Rey E, Godbout A. Treatment of women with mild gestational diabetes mellitus decreases the risk of adverse perinatal outcomes. Diabetes Metab. 2023;49(4):101458. 10.1016/j.diabet.2023.101458 . Meek CL, Lewis HB, Patient C, Murphy HR, Simmons D. Diagnosis of gestational diabetes mellitus: falling through the net. Diabetologia. 2015;58(9):2003–12. 10.1007/s00125-015-3647-z . Koivunen S, Viljakainen M, Männistö T, Gissler M, Pouta A, Kaaja R, et al. Pregnancy outcomes according to the definition of gestational diabetes. PLoS ONE. 2020;15(3):e0229496. 10.1371/journal.pone.0229496 . Gissler M, Shelley J. Quality of data on subsequent events in a routine Medical Birth Register. Med Inf Internet Med. 2002;27(1):33–8. 10.1080/14639230110119234 . Maternity clinic [Internet]. Finland: Finnish institute for health and welfare. 2023 [Updated 2023; Cited 2023 Oct 10]. Available from: https://thl.fi/fi/web/lapset-nuoret-ja-perheet/sote-palvelut/aitiys-ja-lastenneuvola/aitiysneuvola . Official Statistics of Finland. Perinatal statistics – parturients, deliveries and newborns. Finnish institute for health and welfare. Available from: https://urn.fi/URN:NBN:fi-fe2022112867358 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 12 Apr, 2024 Read the published version in BMC Pregnancy and Childbirth → Version 1 posted Editorial decision: Revision requested 09 Feb, 2024 Reviews received at journal 05 Feb, 2024 Reviewers agreed at journal 16 Jan, 2024 Reviews received at journal 12 Jan, 2024 Reviewers agreed at journal 09 Jan, 2024 Reviewers invited by journal 08 Jan, 2024 Editor assigned by journal 03 Jan, 2024 Editor invited by journal 03 Jan, 2024 Submission checks completed at journal 03 Jan, 2024 First submitted to journal 22 Dec, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3790958","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":265121184,"identity":"de113e6f-e076-416e-82e2-c663aeb9799c","order_by":0,"name":"Kaisa Kariniemi","email":"","orcid":"","institution":"Oulu University Hospital and University of Oulu","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kaisa","middleName":"","lastName":"Kariniemi","suffix":""},{"id":265121185,"identity":"17872d92-08b7-443d-94a5-5690d7838bd4","order_by":1,"name":"Marja Vääräsmäki","email":"","orcid":"","institution":"Oulu University Hospital and University of Oulu","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Marja","middleName":"","lastName":"Vääräsmäki","suffix":""},{"id":265121186,"identity":"90910754-f1db-4656-9371-df4b013bbca5","order_by":2,"name":"Tuija Männistö","email":"","orcid":"","institution":"NordLab","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Tuija","middleName":"","lastName":"Männistö","suffix":""},{"id":265121187,"identity":"f1eff51b-7894-4905-b6ca-5ac7494515e4","order_by":3,"name":"Sanna Mustaniemi","email":"","orcid":"","institution":"Oulu University Hospital and University of Oulu","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sanna","middleName":"","lastName":"Mustaniemi","suffix":""},{"id":265121188,"identity":"20e7569e-4569-499c-93d0-3d542771a74d","order_by":4,"name":"Eero Kajantie","email":"","orcid":"","institution":"Oulu University Hospital and University of Oulu","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Eero","middleName":"","lastName":"Kajantie","suffix":""},{"id":265121189,"identity":"50f221d2-041e-4396-9ea9-23dddcd912ba","order_by":5,"name":"Sanna Eteläinen","email":"","orcid":"","institution":"Oulu University Hospital and University of Oulu","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sanna","middleName":"","lastName":"Eteläinen","suffix":""},{"id":265121190,"identity":"c1bdd40b-e472-4b62-a4e7-4c28855ff6a7","order_by":6,"name":"Elina Keikkala","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9klEQVRIie3OsWrDMBCA4TMCZVHsVSbFeQUZLx1K+yoSAU0eMnoIJGCQl5Bnad9AIHCX0q6FLJ46ZfAUMpiSI8lQClHWDPoHwR186ABCoXtsFK3wlUAZBejgCTc4V8JDyF8iQeMG5w8vOb0S4EzchXhEQojpDqCzmLWql4uvTDgmwM6vk7SOmnwNZUHHxnHZbosz8RwmXGQ4g0qZZLTikm7VKxLSe8gLknSAaomkPsjfzxPx/0IiM2FQSjys5crY24TjL5MHoXPDWv2oNrMidXRufSRpmp90V82m07Uuvvv9cxa/12+dHa6Ty3n/ZnsLhEKhUMjfEXAhSx+9R4HRAAAAAElFTkSuQmCC","orcid":"","institution":"Oulu University Hospital and University of Oulu","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Elina","middleName":"","lastName":"Keikkala","suffix":""}],"badges":[],"createdAt":"2023-12-22 08:59:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3790958/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3790958/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12884-024-06473-4","type":"published","date":"2024-04-12T15:00:47+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":49246040,"identity":"4787e492-976f-4b0c-b752-897af4f866e7","added_by":"auto","created_at":"2024-01-05 20:43:54","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":91012,"visible":true,"origin":"","legend":"\u003cp\u003eDAG to assess causality between GDM and adverse neonatal outcomes.\u003c/p\u003e\n\u003cp\u003eDAG, direct acyclic graph\u003cbr\u003e\nGDM, gestational diabetes mellitus\u003cbr\u003e\nBMI, body mass index\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-3790958/v1/0df0186c5cfe0691ab5dbf32.png"},{"id":49246039,"identity":"27766e63-297e-4209-8fd5-bb46a02834b9","added_by":"auto","created_at":"2024-01-05 20:43:54","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":20465,"visible":true,"origin":"","legend":"\u003cp\u003eAssociation between adverse neonatal outcomes and treated and untreated GDM groups versus the control group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 2a. \u003c/strong\u003eORs and 95% CIs for the composite adverse neonatal outcome in the treated and untreated IADPSG and NICE groups versus the control group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 2b. \u003c/strong\u003eORs and 95% CIs for hypoglycaemia in the treated and untreated IADPSG and NICE groups versus the control group.\u003c/p\u003e\n\u003cp\u003eORs, odds ratios\u003cbr\u003e\n CIs, confidence intervals\u003cbr\u003e\n GDM, gestational diabetes mellitus\u003c/p\u003e\n\u003cp\u003eIADPSG, The International Association of Diabetes and Pregnancy Study Groups\u003cbr\u003e\n NICE, The National Institute for Health and Care Excellence\u003cbr\u003e\n The composite adverse neonatal outcome included neonatal hypoglycaemia, hyperbilirubinaemia, birth trauma or perinatal mortality. \u003cbr\u003e\nBirth trauma included clavicle fracture or Erb’s palsy.\u003cbr\u003e\n Model II: adjusted for maternal age, pre-pregnancy body mass index (BMI), parity, smoking status, socioeconomic status, preterm birth \u0026lt; 37 weeks of gestation, birth weight \u0026gt; 4. 5 kg or \u0026lt; 2.5 kg and maternal hypertension (pre-pregnancy or pregnancy-induced).\u003c/p\u003e","description":"","filename":"F2.png","url":"https://assets-eu.researchsquare.com/files/rs-3790958/v1/60e0dbb3385fc8e38a613e8d.png"},{"id":54712593,"identity":"c6aa2793-ed7d-4665-9edc-5752f4c68116","added_by":"auto","created_at":"2024-04-15 15:11:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":477725,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3790958/v1/cfa75637-0279-420b-a184-4163ca29463f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Neonatal Outcomes According to Different Glucose Threshold Values in Gestational Diabetes: A Register-based Study","fulltext":[{"header":"1 Background","content":"\u003cp\u003eGestational diabetes mellitus (GDM), defined as any degree of glucose intolerance with onset or first recognition during pregnancy [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], is associated with adverse neonatal outcomes, such as a higher risk of caesarean section [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], higher birth weight and risk of neonatal hypoglycaemia[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] and hyperbilirubinemia [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRegardless of these well-documented adverse outcomes, a consensus on the diagnostic criteria for GDM has yet to be reached. The International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommended new diagnostic criteria for GDM in 2010[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] after the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] showed a linear association between maternal hyperglycaemia and unfavourable perinatal outcomes. The National Institute for Health and Clinical Excellence (NICE) did not adopt the guidelines introduced by the IADPSG because of insufficient evidence regarding the ability of the guidelines to improve pregnancy outcomes and yield cost savings [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The diagnostic cut-offs for GDM in Finland are based on the diagnostic criteria of the American Diabetes Association in 2003[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] and differ slightly from both the IADPSG and NICE criteria. Thus, it is possible to study the effects of different threshold glucose values on neonatal outcomes.\u003c/p\u003e \u003cp\u003e The aim of this study was to study neonatal outcomes in pregnancies complicated by GDM defined by the criteria of the Finnish national guidelines that were either treated or remained untreated according to the criteria of the IADPSG or NICE. We hypothesised that compared to normoglycemic controls, the risk of adverse neonatal outcomes would be increased in women with treated GDM but not in those with mild untreated hyperglycaemia.\u003c/p\u003e"},{"header":"2 Material and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study Design\u003c/h2\u003e \u003cp\u003eThis register-based cohort study is part of the Finnish Gestational Diabetes study (FinnGeDi), which was initiated in 2009 after the former risk-based screening program for GDM was replaced with comprehensive screening [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The registry data for this study were obtained from the Finnish Medical Birth Register (MBR), which contains information on all pregnancies resulting in a live birth or stillbirth at \u0026ge;\u0026thinsp;22 gestational weeks or birthweight of \u0026ge;\u0026thinsp;500 g. Data on pregnancy, delivery and neonatal outcomes were recorded, along with International Classification of Diseases (ICD) codes for diagnoses for the mother and child.\u003c/p\u003e \u003cp\u003eThe registry data were combined with numerical oral glucose tolerance test (OGTT) data obtained from laboratory databases in two tertiary-level (North Ostrobothnia and Tampere) and four secondary-level (Satakunta, South Ostrobothnia, Kainuu and Southern Karelia) hospitals, each serving a specific geographical area, during 2009. Deliveries in these hospitals accounted for 26.3% of all deliveries countrywide.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Screening and Diagnosis of GDM\u003c/h2\u003e \u003cp\u003eAll women, except those at very low risk for GDM (i.e. aged\u0026thinsp;\u0026lt;\u0026thinsp;25 years, nullipara, body mass index [BMI] of 18.5\u0026ndash;24.9 kg/m\u003csup\u003e2\u003c/sup\u003e and no family history of type 2 diabetes or aged\u0026thinsp;\u0026lt;\u0026thinsp;40 years, multipara without prior GDM or macrosomia and a BMI of \u0026lt;\u0026thinsp;25 kg/m\u003csup\u003e2\u003c/sup\u003e) were screened using the 75-g 2-hour OGTT after an overnight fast at 24\u0026ndash;28 weeks of gestation (13). For high-risk women, defined as having a history of GDM, a BMI\u0026thinsp;\u0026ge;\u0026thinsp;35.0 kg/m\u0026sup2;, glucosuria during pregnancy, use of glucocorticoids or polycystic ovary syndrome, an OGTT was performed at 12\u0026ndash;16 weeks of gestation and repeated at 24\u0026ndash;28 weeks of gestation if the test results were initially normal. If pre-pregnancy diabetes were suspected, an OGTT was performed immediately. Venous samples were drawn into fluoride citrate tubes and analysed within 24 hours in a local laboratory using commercial enzymatic assays.\u003c/p\u003e \u003cp\u003eGDM was diagnosed using national current care guidelines in Finland if any of the following cut-off values in the OGTT were met: \u0026ge; 5.3 mmol/L, \u0026ge; 10.0 mmol/L or \u0026ge;\u0026thinsp;8.6 mmol/L for fasting, 1-hour and 2-hour plasma glucose values, respectively [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. All women diagnosed with GDM were recommended to receive dietary and lifestyle counselling and instructions to self-monitor their glucose concentrations in public maternity clinics according to Finnish guidelines. Insulin therapy was recommended to initiate if self-monitored capillary glucose concentrations repeatedly exceeded 5.5 mmol/L fasting or 7.8 mmol/L 1 hour postprandial, despite diet treatment. Women requiring medical treatment were recommend to be admitted to the outpatient maternity clinics of the hospitals serving their geographical area.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Study Population and GDM Groups\u003c/h2\u003e \u003cp\u003eThis study included singleton pregnant women with an OGTT performed at 4\u0026ndash;40 weeks of gestation during 2009. Women with pre-pregnancy type 1 or type 2 diabetes (ICD-10 codes E10\u0026ndash;E11, E13, E14.9 or O24.0\u0026ndash;O24.3) according to the MBR were excluded.\u003c/p\u003e \u003cp\u003eWomen who fulfilled the diagnostic criteria of the IADPSG or NICE without meeting the Finnish criteria were untreated (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The treated groups met both the Finnish criteria for GDM and those of the IADPSG or NICE. Controls were normoglycemic according to all criteria.\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\u003eDiagnostic cut-off values in the 75-g 2-hour OGTT using different criteria.\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=\"char\" char=\".\" 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\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIADPSG\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNICE\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eFinnish current care guidelines\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFasting plasma glucose, mmol/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1-hour plasma glucose, mmol/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e10.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e10.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2-hour plasma glucose, mmol/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e8.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e8.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eOGTT, oral glucose tolerance test\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eIADPSG, The International Association of Diabetes and Pregnancy Study Groups\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e NICE, The National Institute for Health and Care Excellence\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Outcomes\u003c/h2\u003e \u003cp\u003eThe primary outcome was a composite of adverse neonatal outcomes comprising hypoglycaemia (ICD-10: P70.0-70.9), hyperbilirubinaemia (ICD-10: P59.0-59.9), birth trauma (Erb\u0026rsquo;s palsy [ICD-10: P14.0] or clavicle fracture [ICD-10: P13.4]) or perinatal mortality, which was defined as stillbirth or early neonatal death during the 7-day period after delivery. Secondary outcomes were the outcomes in the composite analysed independently.\u003c/p\u003e \u003cp\u003eIn all newborns exposed to GDM, glucose concentration was advised to be measured six times during the first 48 hours [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Hypoglycaemia was treated with intravenous glucose if a single plasma glucose measurement was \u0026le;\u0026thinsp;1.4 mmol/L or where the initial glucose concentration was 1.5\u0026ndash;2.5 mmol/L and remained\u0026thinsp;\u0026le;\u0026thinsp;2.5 mmol/L after supplementary feeding. Apart from GDM, other possible indications for neonatal glucose screening in asymptomatic newborns included preterm birth, birth weight of \u0026lt;\u0026thinsp;2.5 kg or \u0026gt;\u0026thinsp;4.5 kg or maternal use of β-blockers. A diagnosis of hypoglycaemia was recorded in the MBR if the newborn required intravenous glucose, although there are no unified diagnostic criteria for neonatal hypoglycaemia in Finland.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Covariates\u003c/h2\u003e \u003cp\u003eMaternal age at delivery was determined. BMI (kg/m\u003csup\u003e2\u003c/sup\u003e) was calculated from self-reported pre-pregnancy height and weight. Parity was categorised according to the number of deliveries: primiparity, one (P1), two (P2), three (P3) and four or more previous deliveries (P4). Smoking status was categorized as non-smokers and smokers during pregnancy. Socioeconomic status was divided into upper-white collar, lower-white collar, blue-collar workers and others, including entrepreneurs, pensioners, stay-at-home-mothers and students. Insulin therapy during pregnancy was recorded. Maternal hypertension included chronic (ICD-10: O10.0-O12.1) and pregnancy-induced hypertension (ICD-10: O13) or pre-eclampsia (ICD-10: O14). Pregnancy-induced hypertension was defined as repeated blood pressure readings\u0026thinsp;\u0026ge;\u0026thinsp;140/90 mmHg after 20 weeks of gestation and pre-eclampsia as repeated blood pressure readings\u0026thinsp;\u0026ge;\u0026thinsp;140/90 mmHg after 20 weeks of gestation and proteinuria (\u0026gt;\u0026thinsp;300 mg of protein in a 24-hour urine collection or protein\u0026thinsp;\u0026ge;\u0026thinsp;2\u0026thinsp;+\u0026thinsp;in a urine dipstick test). Data on the use of β-blockers were not available. Instead, maternal hypertension was used as a proxy variable. Labetalol, which is an unselective α- and β-blocker, is the preferred antihypertensive medication during pregnancy in Finland.\u003c/p\u003e \u003cp\u003eBirth weight (g); birth weight of \u0026lt;\u0026thinsp;2.5 kg or \u0026gt;\u0026thinsp;4.5 kg; gestational age (weeks) at delivery; preterm birth, defined as delivery\u0026thinsp;\u0026lt;\u0026thinsp;37\u0026thinsp;+\u0026thinsp;0 weeks of gestation; neonatal respiratory distress syndrome (ICD-10: P22.0); newborn discharge status (home or hospitalized) at the age of 7 days and duration of hospitalisation (days); caesarean section rate; and large for gestational age (LGA), which was determined as a birth weight standard deviation (\u003cem\u003eSD\u003c/em\u003e) score over the 90th percentile, were reported. The birth weight \u003cem\u003eSD\u003c/em\u003e score was calculated from gestational age-adjusted birth weight according to standard growth curves in the Finnish population [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.6 Statistical Analysis\u003c/h2\u003e \u003cp\u003eValues are reported as mean (\u003cem\u003eSD\u003c/em\u003e) for continuous variables and number and frequency (%) for categorical variables. To compare differences between the study groups, Pearson\u0026rsquo;s χ\u003csup\u003e2\u003c/sup\u003e test was used for categorical variables, and the independent sample \u003cem\u003et\u003c/em\u003e-test was used for continuous variables. Logistic regression analyses were used to evaluate odds ratios (ORs), along with their 95% confidence intervals (CIs). To assess causality between GDM and adverse neonatal outcomes, a direct acyclic graph (DAG) was used (Fig.\u0026nbsp;1). Based on the DAG, two models were formulated to adjust the results for potential bias. Model I included potential confounders (maternal age, pre-pregnancy BMI, parity, socioeconomic status and smoking status), and Model II included potential mediators (preterm birth, birth weight\u0026thinsp;\u0026lt;\u0026thinsp;2.5 kg or \u0026gt;\u0026thinsp;4.5 kg and maternal hypertension), in addition to the confounders in Model I. The level of statistical significance was set at \u0026lt;\u0026thinsp;0.05 using a two-sided \u003cem\u003ep\u003c/em\u003e-value. IBM SPSS Statistics, version 27 (Armonk, NY, USA) was used for analyses.\u003c/p\u003e \u003cp\u003e \u003cb\u003eFigure 1.\u003c/b\u003e DAG to assess causality between GDM and adverse neonatal outcomes.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"3 Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Clinical Characteristics\u003c/h2\u003e \u003cp\u003eAfter exclusion of women with multiple pregnancies (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;191), women in the control group treated with insulin (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8) and women with a diagnosis of GDM without an OGTT (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;38), the total number of participants was 4,939. In the entire study population, 1,801 (36.5%) and 778 (15.8%) had GDM according to the IADPSG and NICE criteria, respectively, and 1,292 (26.2%) had GDM according to the current care guidelines in Finland. In the IADPSG and NICE groups, 1,292 (71.7%) and 612 (78.7%) women, respectively, received treatment. 3,031 (61.4%) women were normoglycemic controls according to all criteria. (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) Maternal characteristics are reported in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and neonatal characteristics are reported in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMaternal baseline characteristics.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"12\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControls\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIADPSG\u003c/p\u003e \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 \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNICE\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUntreated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTreated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eUntreated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eTreated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u0026ordf;\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003ep\u0026ordf;\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003epᵇ\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cem\u003ep\u0026ordf;\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cem\u003ep\u0026ordf;\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cem\u003epᵇ\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eN\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3031 (61.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e509 (10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1292 (26.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e166 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e612 (12.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal age, years, mean (\u003cem\u003eSD\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e29.4 (5.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.1 (5.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30.5 (5.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.157\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e30.0 (5.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.127\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e30.8 (5.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.110\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-pregnancy BMI, kg/m\u003csup\u003e2\u003c/sup\u003e, mean (\u003cem\u003eSD\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e25.6 (4.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.3 (5.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28.4 (5.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e25.9 (5.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.456\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e28.8 (6.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParity, \u003cem\u003en\u003c/em\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 \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimiparity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1461 (48.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e213 (41.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e483 (37.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.086\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e83 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.690\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e242 (39.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.017\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e932 (30.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e162 (31.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.641\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e434 (33.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.068\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.505\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e39 (23.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.056\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e198 (32.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.444\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e382 (12.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74 (14.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.252\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e205 (15.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.515\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e28 (16.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.120\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e88 (14.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.234\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.461\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e121 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (6.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e86 (6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.917\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10 (6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.222\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e42 (6.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.732\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP4 or more\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e135 (4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (4.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.730\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e84 (6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.228\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.703\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e42 (6.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.146\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking during pregnancy, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e366 (12.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65 (12.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.770\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e214 (16.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.042\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e16 (9.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.333\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e106 (17.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSocioeconomic status, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.885\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.267\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.033\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.093\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.328\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUpper-white collar worker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e536 (17.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e85 (16.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.615\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e195 (15.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.041\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.427\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e17 (10.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e93 (15.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.143\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.131\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLower-white collar worker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1017 (33.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e167 (32.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.761\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e439 (34.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.806\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.658\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e56 (33.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e210 (34.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.743\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.927\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlue-collar worker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e399 (13.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68 (13.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.944\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e211 (16.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.129\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e31 (18.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.047\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e99 (16.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.053\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.482\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e519 (17.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e93 (18.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.527\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e207 (16.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.398\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.261\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e30 (18.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.833\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e93 (15.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.260\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.401\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"12\"\u003eIADPSG, The International Association of Diabetes and Pregnancy Study Groups\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"12\"\u003eNICE, The National Institute for Health and Care Excellence\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"12\"\u003eSD, standard deviation\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"12\"\u003eBMI, body mass index\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"12\"\u003e\u003cem\u003ep\u0026ordf;, p\u003c/em\u003e-value between the GDM group and controls\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"12\"\u003e\u003cem\u003epᵇ, p\u003c/em\u003e-value between the treated and non-treated GDM groups\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"12\"\u003eParity was categorised according to the number of deliveries: primiparity, one (P1), two (P2), three (P3) and four or more previous deliveries (P4).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"12\"\u003eUpper-white collar workers included administrative, managerial, professional and related occupations; lower-white collar workers included administrative and clerical occupations; blue-collar workers included manual labourers, and other included individuals who did not fit any of the above categories, including students, pensioners and self-employed.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\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\u003eNeonatal outcomes in the untreated and treated GDM groups using the IADPSG and NICE criteria.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"12\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControls\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIADPSG\u003c/p\u003e \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 \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNICE\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUntreated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTreated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eUntreated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eTreated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u0026ordf;\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003ep\u0026ordf;\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003epᵇ\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cem\u003ep\u0026ordf;\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cem\u003ep\u0026ordf;\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cem\u003epᵇ\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eN\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3031 (61.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e509 (10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1292 (26.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e166 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e612 (12.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComposite adverse neonatal outcome, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e279 (9.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.564\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e287 (22.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e20 (12.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.272\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e164 (26.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypoglycaemia, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.288\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e187 (14.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.439\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e106 (17.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyperbilirubinaemia, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e172 (5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.607\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e108 (8.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.144\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e9 (5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e62 (10.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.068\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth trauma, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (1.3)\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\u003e0.393\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.395\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.189\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.723\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e13 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.132\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePerinatal mortality, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.322\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.682\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.061\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e4 (0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.071\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.613\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight, g, mean (\u003cem\u003eSD\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3572.7 (525.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3632.9 (543.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3561.5 (562.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.543\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3499.9 (603.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.130\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3539.9 (623.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.224\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.461\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight\u0026thinsp;\u0026lt;\u0026thinsp;2.5 kg, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.483\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e49 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.156\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.890\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e9 (5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.098\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e34 (5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight\u0026thinsp;\u0026gt;\u0026thinsp;4.5 kg, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e94 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (4.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36 (2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.627\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.177\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.818\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e21 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.703\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight \u003cem\u003eSD\u003c/em\u003e score, mean (\u003cem\u003eSD\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.047 (1.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.12 (1.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.072 (1.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.434\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.011 (1.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.476\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.12 (1.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.293\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLGA, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e267 (8.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65 (12.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e147 (11.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.417\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e22 (13.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.069\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e82 (13.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational age at delivery in weeks, mean (\u003cem\u003eSD\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39.9 (1.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39.8 (1.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.154\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e39.5 (1.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e39.5 (1.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e39.2 (2.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.185\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm birth\u0026thinsp;\u0026lt;\u0026thinsp;37 weeks, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e114 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (4.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.707\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e78 (6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.135\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e12 (7.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.037\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e49 (8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.751\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal respiratory distress syndrome, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (0.5)\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\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9 (0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.502\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e5 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.293\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNewborn discharge status aged 7 days, \u003cem\u003en\u003c/em\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 \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2895 (95.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e482 (94.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.423\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1195 (92.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.099\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e152 (91.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e547 (89.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.470\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospitalised\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e130 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (4.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.558\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e91 (7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e11 (6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.170\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e61 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.227\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospitalisation in days, mean (\u003cem\u003eSD\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.1 (2.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.2 (1.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.514\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.3 (2.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.157\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.3 (1.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.425\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3.5 (2.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.315\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCaesarean section, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e453 (14.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98 (19.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e271 (21.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.437\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e32 (19.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.148\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e136 (22.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.457\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInsulin treatment, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e135 (10.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e86 (14.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal hypertension, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e225 (7.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 (9.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.089\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e151 (11.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.213\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e16 (9.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.364\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e82 (13.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"12\"\u003eGDM, gestational diabetes mellitus\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"12\"\u003eIADPSG, The International Association of Diabetes and Pregnancy Study Groups\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"12\"\u003eNICE, The National Institute for Health and Care Excellence\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"12\"\u003e\u003cem\u003ep\u0026ordf;, p\u003c/em\u003e-value between the GDM group and controls\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"12\"\u003e\u003cem\u003epᵇ, p\u003c/em\u003e-value between the treated and untreated GDM groups\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"12\"\u003e\u003cem\u003eSD\u003c/em\u003e, standard deviation\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"12\"\u003eThe composite adverse neonatal outcome included hypoglycaemia, hyperbilirubinaemia, birth trauma or perinatal mortality\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"12\"\u003eBirth trauma included Erb\u0026rsquo;s palsy or clavicle fracture\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"12\"\u003eLGA, large for gestational age. LGA was defined as having a birth weight \u003cem\u003eSD\u003c/em\u003e score\u0026thinsp;\u0026gt;\u0026thinsp;90th percentile\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"12\"\u003eA diagnosis of maternal hypertension included ICD-10 codes O10-O12.1 and O13-O14\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Outcomes\u003c/h2\u003e \u003cp\u003eThe rate of the composite adverse neonatal outcome was 22.2% in the treated IADPSG group and 26.8% in the treated NICE group, and it was higher compared to that of either the controls (9.2%) or the corresponding untreated group (10.0% in the untreated IADPSG group and 12.0% in the untreated NICE group). Compared to controls, the aORs were 2.75 (95% CI: 2.24\u0026ndash;3.37) in the treated IADPSG group and 3.33 (95% CI: 2.59\u0026ndash;4.28) in the treated NICE group (Tables\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea). No differences were found in the frequency of the composite outcome between the untreated groups and the control group. Hypoglycaemia was more frequent in the treated groups than in the control group (treated IADPSG: 14.5% vs. 2.4% in the control group, aOR 6.65, 95% CI: 4.93\u0026ndash;8.99; treated NICE: 17.3% vs. 2.4%, aOR 7.45, 95% CI: 5.27\u0026ndash;10.5) or the untreated groups (3.3% in the untreated IADPSG group and 3.6% in the untreated NICE group) (Tables\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb). There were no differences in the frequency of hyperbilirubinaemia between the groups after adjusting for confounders. No between-group differences were observed in the rate of perinatal mortality or birth trauma.\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\u003eMultivariate logistic regression analyses of neonatal outcomes compared to the control group.\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=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUntreated IADPSG\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTreated IADPSG\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUntreated NICE\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTreated NICE\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComposite adverse neonatal outcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnadjusted OR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.10 (0.80\u0026ndash;1.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.82 (2.35\u0026ndash;3.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.35 (0.83\u0026ndash;2.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.61 (2.91\u0026ndash;4.49)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel I\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.07 (0.77\u0026ndash;1.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.70 (2.22\u0026ndash;3.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.26 (0.75\u0026ndash;2.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.39 (2.68\u0026ndash;4.29)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.01 (0.71\u0026ndash;1.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.75 (2.24\u0026ndash;3.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.05 (0.60\u0026ndash;1.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.33 (2.59\u0026ndash;4.28)\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\u003eUnadjusted OR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.38 (0.81\u0026ndash;2.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6.76 (5.12\u0026ndash;8.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.50 (0.64\u0026ndash;3.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e8.37 (6.13\u0026ndash;11.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel I\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.32 (0.76\u0026ndash;2.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6.50 (4.84\u0026ndash;8.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.59 (0.68\u0026ndash;3.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e7.48 (5.34\u0026ndash;10.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.24 (0.70\u0026ndash;2.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6.65 (4.93\u0026ndash;8.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.34 (0.55\u0026ndash;3.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e7.45 (5.27\u0026ndash;10.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyperbilirubinaemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnadjusted OR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.12 (0.76\u0026ndash;1.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.52 (1.18\u0026ndash;1.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.95 (0.48\u0026ndash;1.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.87 (1.38\u0026ndash;2.54)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel I\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.11 (0.75\u0026ndash;1.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.47 (1.12\u0026ndash;1.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.87 (0.42\u0026ndash;1.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.84 (1.32\u0026ndash;2.56)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.04 (0.67\u0026ndash;1.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.29 (0.96\u0026ndash;1.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.61 (0.26\u0026ndash;1.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.45 (1.00-2.10)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePerinatal mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnadjusted OR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0 (0.12\u0026ndash;8.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.96 (0.60\u0026ndash;6.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.15 (1.23\u0026ndash;30.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.32 (0.93\u0026ndash;11.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel I\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.85 (0.19\u0026ndash;3.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.02 (0.44\u0026ndash;36.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.02 (0.45\u0026ndash;9.03)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.08 (0.21\u0026ndash;5.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.69 (0.24\u0026ndash;57.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.03 (0.37-11.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth trauma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnadjusted OR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.61 (0.22\u0026ndash;1.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.27 (0.74\u0026ndash;2.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.41 (0.43\u0026ndash;4.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.67 (0.88\u0026ndash;3.14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel I\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.58 (0.20\u0026ndash;1.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.33 (0.76\u0026ndash;2.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.46 (0.44\u0026ndash;4.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.74 (0.89\u0026ndash;3.41)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.57 (0.20\u0026ndash;1.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.35 (0.77\u0026ndash;2.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.51 (0.46\u0026ndash;5.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.73 (0.88\u0026ndash;3.40)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eIADPSG, The International Association of Diabetes and Pregnancy Study Groups\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eNICE, The National Institute for Health and Care Excellence\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eOR, odds ratio\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eThe composite adverse neonatal outcome included neonatal hypoglycaemia, hyperbilirubinaemia, birth trauma or perinatal mortality.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eBirth trauma included clavicle fracture or Erb\u0026rsquo;s palsy.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eModel I: adjusted for maternal age, pre-pregnancy BMI, parity, smoking and socioeconomic status; Model II: adjusted for the variables in Model I; preterm birth: \u0026lt; 37 weeks of gestation, very high birth weight: \u0026gt; 4.5 kg, very low birth weight: \u0026lt; 2.5 kg birth weight, and maternal hypertension (pre-pregnancy or pregnancy-induced).\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e4.1 Main Findings\u003c/h2\u003e \u003cp\u003eAs hypothesised, the risk of adverse neonatal outcomes in the untreated groups representing untreated mild hyperglycaemia was similar to normoglycemic controls. The the risk of neonatal morbidity in the diagnosed and treated GDM groups was higher compared to the normoglycemic control group. We found a 2.8-fold and 3.3-fold increased risk of the adverse neonatal outcome in the treated IADPSG and treated NICE groups, respectively. The risk was also increased compared to the untreated groups. These findings confirm the current understanding that higher maternal blood glucose levels are associated with adverse neonatal outcomes, which was demonstrated first in the HAPO study[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] and later corroborated in other studies [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan additionalcitationids=\"CR16 CR17 CR18\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Therefore, according to our findings, the current diagnostic criteria for GDM in Finland with slightly higher fasting (0.2 mmol/L) and 2-hour (0.1 mmol/L) OGTT cut-offs are sufficient to identify women at risk of adverse outcomes.\u003c/p\u003e \u003cp\u003eGDM leads to a hyperglycaemic intrauterine environment, which in turn results in a transient amplified insulin response in the newborn, causing hypoglycaemia. This combined with the neonatal glucose screening used for GDM-exposed newborns explains the high frequency of neonatal hypoglycaemia among the treated GDM groups in our study. We adjusted for other possible risk factors for neonatal hypoglycaemia, which did not significantly attenuate the risk associated with GDM and therefore are unlikely to mediate the association between GDM and neonatal hypoglycaemia in this study. The risk of neonatal hypoglycaemia seems to be greater at higher concentrations of maternal blood glucose [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] and explains why the rate of neonatal hypoglycaemia was similar in the untreated GDM groups and controls in our study.\u003c/p\u003e \u003cp\u003eThe potential of diagnosing and treating even milder hyperglycaemia as applied in the IADPSG criteria to prevent adverse neonatal outcomes has been discussed in the literature [\u003cspan additionalcitationids=\"CR22 CR23 CR24 CR25\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Because of variable diagnostic criteria used for GDM and thresholds for treating GDM, the studies have produced inconsistent results. Most studies have found that treatment of mild hyperglycaemia reduced adverse neonatal outcomes [\u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], while others have not [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. In the studies where a favourable treatment effect was found, the participants would have fulfilled the diagnostic criteria of GDM used in Finland and therefore received treatment. In only one study [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] the OGTT criteria for GDM matched the ones used in the untreated IADPSG group of our study and they found no differences in neonatal outcomes when comparing untreated and treated counterparts. Our group and others have found that mild hyperglycaemia is associated with slightly higher birth weights and caesarean section rates [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Treatment of GDM could potentially reduce the risk of these outcomes [\u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], but based on our findings, adopting the IADPSG criteria in Finland would not result in clinically significant improvements in adverse neonatal outcomes such as hypoglycaemia. Simultaneously, there would be 39% more GDM diagnoses, as the incidence of GDM in the screened population was 26.2% when using the Finnish cut-offs and 36.5% when using the IAPDSG cut-offs.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e4.2 Strengths and Limitations\u003c/h2\u003e \u003cp\u003eThe strengths of this study include the use of well-defined and comprehensive population-base data, as the MBR includes information on all births in Finland. The validity of the data in the MBR has been demonstrated to be high [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. The public maternity clinic system in Finland is free of cost, statutorily organized and comprehensive since 99.7% of women attend these clinics during pregnancy [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. By collecting numerical data from the OGTTs we were able to divide the participants into GDM groups according to IADPSG and NICE criteria and evaluate neonatal outcomes in the untreated groups. We were able to adjust for important confounding factors and potential mediators.\u003c/p\u003e \u003cp\u003e As Finnish national guidelines do not suggest screening very low-risk women for GDM with an OGTT, these women were excluded in our study. An OGTT was performed for 42.6% versus 71.0% of pregnant women in Finland in 2009 and 2021, respectively [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Since this is a register-based study, we were unable to verify whether GDM was managed according to the recommended guidelines. The untreated NICE group was small (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;166) and thus, the power to detect small differences in the frequencies of adverse neonatal outcomes in the NICE group versus the control group was limited. Finally, detection bias in the treated GDM groups could have potentially increased the prevalence of particular outcomes in these groups.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e4.3 Conclusions\u003c/h2\u003e \u003cp\u003eUntreated mild hyperglycaemia was not associated with worse neonatal outcomes. The diagnostic criteria used in Finland seem to sufficiently identify clinically relevant GDM, without excluding neonates with a risk of adverse outcomes.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003e5.1\u0026nbsp; \u0026nbsp; \u0026nbsp;Ethics approval and consent to participate\u003c/h2\u003e\n\u003cp\u003eAccording to the Finnish Act on Secondary Use of Health and Social Data 552/2019, the study participants did not need to provide an information consent form when only anonymous register data were used. The Finnish Institute for Health and Welfare gave their permission for the use of the MBR data (Number: THL132/5.05.00/2011). Hospital administration gave permission to use and combine OGTT laboratory test results with the register data. The FinnGeDi study was approved by the regional ethics committee in Northern Ostrobothnia Hospital District (Number: 2008/43, date of approval: 2008-6-19).\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e5.2\u0026nbsp; \u0026nbsp; \u0026nbsp;Consent for publication\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2\u003e5.3\u0026nbsp; \u0026nbsp; \u0026nbsp;Availability of data and materials\u003c/h2\u003e\n\u003cp\u003eThe data are not open access according to the Finnish legislation. The use of registry data requires permission from national registry authorities.\u0026nbsp;Metadata of the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003ch2\u003e5.4\u0026nbsp; \u0026nbsp; \u0026nbsp;Competing interests\u003c/h2\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003ch2\u003e5.5\u0026nbsp; \u0026nbsp; \u0026nbsp;Funding\u003c/h2\u003e\n\u003cp\u003eAcademy of Finland, Signe and Ane Gyllenberg Foundation, Diabetes Research Foundation, Novo Nordisk Foundation, Juho Vainio Foundation, Sigrid Jus\u0026eacute;lius Foundation, Foundation for Pediatric Research, Foundation for Cardiovascular Research, University of Oulu Graduate School, Terttu Foundation, Research Funds of Oulu University Hospital and the Finnish Medical Foundation.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e5.6\u0026nbsp; \u0026nbsp; \u0026nbsp;Authors\u0026rsquo; contributions\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eKK conducted the data analysis and drafted the manuscript. MV and EK provided clinical interpretation of the data. SE contributed to the data collection and handling. All authors contributed to the design of the study, commented the manuscript during the writing process and approved the final manuscript.\u003c/p\u003e\n\u003ch2\u003e5.7\u0026nbsp; \u0026nbsp; \u0026nbsp;Acknowledgements\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eMatti Viljakainen MD helped with handling of the data.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAmerican Diabetes Association. Gestational Diabetes Mellitus. 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Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://urn.fi/URN:NBN:fi-fe2022112867358\u003c/span\u003e\u003cspan address=\"https://urn.fi/URN:NBN:fi-fe2022112867358\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Gestational diabetes mellitus, Neonatal outcome, Neonatal hypoglycaemia, Oral glucose tolerance test, OGTT, IADPSG, NICE","lastPublishedDoi":"10.21203/rs.3.rs-3790958/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3790958/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eMild hyperglycaemia is associated with increased birth weight but association with other neonatal outcomes is controversial. We aimed to study neonatal outcomes in untreated mild hyperglycaemia using different oral glucose tolerance test (OGTT) thresholds.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis register-based study included all (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;4,939) singleton pregnant women participating a 75 g 2-hour OGTT in six delivery hospitals in Finland in 2009. Finnish diagnostic cut-offs for GDM were fasting\u0026thinsp;\u0026ge;\u0026thinsp;5.3, 1-hour\u0026thinsp;\u0026ge;\u0026thinsp;10.0 or 2-hour glucose\u0026thinsp;\u0026ge;\u0026thinsp;8.6 mmol/L. Women who did not meet these criteria but met the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria (fasting 5.1\u0026ndash;5.2 mmol/L and/or 2-hour glucose 8.5 mmol/L, \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;509) or the National Institute for Health and Clinical Excellence (NICE) criteria (2-hour glucose 7.8\u0026ndash;8.5 mmol/L, \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;166) were considered as mild untreated hyperglycaemia. Women who met both the Finnish criteria and the IADPSG or the NICE criteria were considered as treated GDM groups (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1292 and \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;612, respectively). Untreated mild hyperglycemia groups and treated GDM groups were compared to controls, who were normoglycemic according to all criteria (fasting\u0026thinsp;\u0026lt;\u0026thinsp;5.1 mmol/L, 1-hour glucose\u0026thinsp;\u0026lt;\u0026thinsp;10.0 mmol/L and 2-hour glucose\u0026thinsp;\u0026lt;\u0026thinsp;8.5 mmol/L, \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;3031). The primary outcome - a composite of adverse neonatal outcomes, including neonatal hypoglycaemia, hyperbilirubinaemia, birth trauma or perinatal mortality \u0026ndash; was analysed using multivariate logistic regression.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eCompared to controls, the risk for the adverse neonatal outcome was not increased in mild hyperglycemia according to the IADPSG criteria (adjusted odds ratio [aOR]: 1.01, 95% confidence interval [CI]: 0.71\u0026ndash;1.44) or the NICE criteria (aOR: 1.05, 95% CI: 0.60\u0026ndash;1.85).\u003c/p\u003e\u003ch2\u003eDiscussion\u003c/h2\u003e \u003cp\u003eThe risk of adverse neonatal outcomes was not increased in mild untreated hyperglycaemia. The OGTT cut-offs of 5.3 mmol/L at fasting and 8.6 mmol/L at 2 hours seem to sufficiently identify clinically relevant GDM, without excluding neonates with a risk of adverse outcomes.\u003c/p\u003e","manuscriptTitle":"Neonatal Outcomes According to Different Glucose Threshold Values in Gestational Diabetes: A Register-based Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-05 20:43:49","doi":"10.21203/rs.3.rs-3790958/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-02-09T08:55:22+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-02-05T07:36:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"fdaafe98-182a-409d-8191-613f1f6390ef","date":"2024-01-16T08:09:17+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-01-12T21:45:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"3eafe212-2f57-4132-94c3-ec5b80224f7b","date":"2024-01-09T08:04:20+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-01-09T00:00:30+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-01-04T04:27:03+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-01-03T12:18:51+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-01-03T12:17:47+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pregnancy and Childbirth","date":"2023-12-22T08:48:36+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"815724ac-ea18-4749-937b-eb520b65d5e1","owner":[],"postedDate":"January 5th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-04-15T15:03:50+00:00","versionOfRecord":{"articleIdentity":"rs-3790958","link":"https://doi.org/10.1186/s12884-024-06473-4","journal":{"identity":"bmc-pregnancy-and-childbirth","isVorOnly":false,"title":"BMC Pregnancy and Childbirth"},"publishedOn":"2024-04-12 15:00:47","publishedOnDateReadable":"April 12th, 2024"},"versionCreatedAt":"2024-01-05 20:43:49","video":"","vorDoi":"10.1186/s12884-024-06473-4","vorDoiUrl":"https://doi.org/10.1186/s12884-024-06473-4","workflowStages":[]},"version":"v1","identity":"rs-3790958","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3790958","identity":"rs-3790958","version":["v1"]},"buildId":"zQwnuV7TCBrMSSSToR1PI","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}