A Finnish Medical Birth Register study 11 included all 24 577 women with a singleton pregnancy who underwent an oral glucose tolerance test (OGTT). Women were divided into groups according to the result of GDM/no GDM and pre-pregnancy BMI: normal weight (≤24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obese (≥30.0 kg/m2). Compared to reference group (normal BMI, no GDM), overweight or obese women without GDM had an increased risk of macrosomia: adjusted odds ratio (aOR, for age, parity, smoking and socio-economic status) 1.18 (95% CI 1.09 to 1.28) and 1.50 (95% CI 1.19 to 1.88), and caesarean delivery aORs 1.17 (95% CI 1.07 to 1.28) and 1.52 (95% CI 1.37 to 1.69), respectively. In normal weight GDM women the risk of macrosomia aOR 1.17 (95% CI 0.85 to 1 .62) and caesarean delivery aOR 1.10 (95% CI 0.96 to 1.27) was not significantly increased as compared to normal weight women without GDM. Maternal obesity increased the risk of treatment at neonatal ward. Interaction p values between BMI and GDM on these outcomes were <0.001.
A population-based cohort study 12 in Sweden included 1 294 006 women, with a GDM prevalence of 1% (n = 14,833). The rate of overweight/obesity was 67.7% in the GDM-group and 36.1% in the non-GDM-group. Offspring of women with GDM had significantly increased risk of malformations, aOR 1.16 (95% CI 1.06 to 1.26), prematurity, aOR 1.86 (1.76 to 1. 98), low Apgar score, aOR 1.36 (1.10 to 1.70), fetal distress, aOR 1.09 (1.02 to 1.16) and Erb's palsy aOR 2.26 (1.79 to 2.86). No risk for stillbirth or perinatal mortality was seen. Offspring of overweight, obese, and severely obese women (BMI ≥ 35.0 kg/m2 ) had significantly increased risks of all outcomes including stillbirth 1.51 (1.40 to1.62) to 2.85 (2.52 to 3.22) and perinatal mortality 1.49 (1.40 to 1.59) to 2.83 (2.54 to 3.15).
An umbrella review and meta-analyses 9 studied associations between adiposity and risk of any type of obstetric or gynaecological conditions. Of the 144 meta-analyses that included cohort studies, only 11 (8%) had strong evidence for 8 outcomes: adiposity was associated with a higher risk of endometrial cancer, ovarian cancer, antenatal depression, total and emergency caesarean section, pre-eclampsia, fetal macrosomia, and low Apgar score. Pre-eclampsia was more common in women with BMI over 35 vs under 25 (RR 4.14, 95% CI 3.61 to 4.75; 5 studies with 12 614 cases/901 409 cohort). Apgar score under 7 at 1 minute was more common with BMI 30-40 vs under 25 (RR 1.29, 95% CI 1.23 to 1.36; 4 studies, 16 187cases/230 884). Macrosomia over 4000g was more common with BMI 25 to 30 vs BMI under 25 (RR 1.54, 95% CI 1.45 to 1.64; 19 studies, 93 168 cases/1 049 501) and with BMI over 30 vs under 25 (RR 2.08, 95% CI 1.94 to 2.23; 20 studies, 89 849 cases/977 613); as well as macrosomia over 4500g with BMI over 30 vs under 25 (RR 3.59, 95% CI 2.53 to 5.09; 7 studies 2405/154 197). With BMI over 30 vs under 25, gestational diabetes (RR 3.78, 95% CI 3.31 to 4.32; 30 studies, 7941/3 613 404) was more common.
Swedish Medical Birth Register gave data for population based cohort studies. One trial 5 investigated associations between change in maternal body-mass index (BMI) during early pregnancy from first to second pregnancies and adverse pregnancy outcomes (456 711 participants, years 1992 to 2012). Compared with women with a stable BMI (change under 2 BMI units), the adjusted RRs for women who gained at least 4 BMI units between pregnancies were 1.55 (95% CI 1.23 to 1.96) for stillbirth and 1.29 (1.00 to 1.67) for infant mortality. Stillbirth risks increased linearly with increased BMI gain. Another trial 6 investigated infant mortality outcomes (1 857 822 live single births 1992-2010), which increased from 2.4/1000 among normal weight women (BMI 18.5 to 24.9) to 5.8/1000 among women with obesity grade 3 (BMI ≥ 40.0). Compared with normal weight, overweight (BMI 25 to 29.9) and obesity grade 1 (BMI 30 to 34.9) were associated with modestly increased risks of infant mortality (aOR 1.25 (95% CI 1.16 to 1.35) and 1.37 (1.22 to 1.53), respectively), and obesity grade 2 (BMI 35 to 39.9) and grade 3 were associated with more than doubled risks (aOR 2.11 (1.79 to 2.49) and 2.44 (1.88 to 3.17)). In the third study 7 (1 599 551 deliveries), risks of extremely, very, and moderately preterm deliveries increased with BMI and the risks were highest for extremely preterm delivery. Among normal-weight women, the rate of extremely preterm delivery was 0.17%. As compared with normal-weight women, rates (%) and adjusted odds ratios (ORs [95% CIs]) of extremely preterm delivery were as follows: BMI 25 to 29.9 (0.21%; OR, 1.26; 95% CI, 1.15-1.37), BMI 30 to 34.9 (0.27%; OR, 1.58; 95% CI, 1.39-1.79), BMI 35 to 39.9 (0.35%; OR, 2.01; 95% CI, 1.66-2.45), and BMI of 40 or greater (0.52%; OR, 2.99; 95% CI, 2.28-3.92).
A population-based cohort study 8 using Perinatal Database in Canada compared obstetric outcomes in women with extreme obesity BMI (pre-pregnancy BMI ≥ 50.0 kg/m2; n=71) and those with a normal BMI (pre-pregnancy BMI 18.5 to 24.9; n=5717) between years 2002 and 2011. Extremely obese women were more likely to have caesarean section (60% vs. 25%) (adjusted OR 1.46; 95% CI 1.29 to 1.65), gestational hypertension (aOR 1.56, 95% CI 1.33 to 1.82), gestational diabetes (aOR 2.04; 95% CI 1.74 to 2.38), shoulder dystocia (aOR 1.51; 95% CI 1.05 to 2.19), length of hospital stay more than 5 days (excluding caesarean section) (aOR 1.42; 95% CI 1.07 to 1.89), birth weight≥ 4000 g (aOR 1.58; 95% CI 1.38 to 1.80), birth weight ≥ 4500 g (aOR 1.87; 95% CI 1.57 to 2.23), neonatal metabolic abnormality (aOR 1.50; 95% CI 1.20 to 1.86), stillbirth (aOR 1.68; 95% CI 1.00 to 2.82) and composite adverse outcome (aOR 1.57; 95% CI 1.35 to 1.83).
A Cochrane review [Abstract] 10 including 3 studies with a total of 1099 women with a body mass index (BMI) of 30 kg/m2 (1 study) and 35 kg/m2 (2 studies) assessed the role of metformin compared with placebo for pregnancy outcomes. Metformin (500 mg twice daily to 3.0 g per day) was started early in the second trimester. Metformin did not decrease the risk of large for gestational age (RR 0.95, 95% CI 0.70 to 1.30; 2 studies, n=831; high-quality evidence). Women who received metformin had a slightly but insignifanctly lower gestational weight gain (mean difference (MD) -2.60 kg, 95% CI -5.29 to 0.10; 3 studies, n=899 women). There were no difference in the risk gestational hypertension (average RR 1.02, 95% CI 0.54 to 1.94; 3 studies, n=1040), pre-eclampsia (RR 0.74, 95% CI 0.09 to 6.28; 2 studies, n=840), or gestational diabetes (RR 0.85, 95% CI 0.61 to 1.19; 3 studies, n=892).
In a prospective population-based cohort study in Sweden 1, 3, 480 women with morbid obesity (body mass index, BMI > 40), and 12 698 women with a BMI between 35.1 and 40 were compared with normal-weight women (BMI 19.8-26). In the group of morbidly obese mothers as compared with the normal-weight mothers, there was an increased risk of the following outcomes (adjusted odds ratio; 95% confidence interval): preeclampsia (4.82; 4.04, 5.74), antepartum stillbirth (2.79; 1.94, 4.02), caesarean delivery (2.69; 2.49, 2.90), instrumental delivery (1.34; 1.16, 1.56), shoulder dystocia (3.14; 1.86, 5.31), meconium aspiration (2.85; 1.60, 5.07), fetal distress (2.52; 2.12, 2.99), early neonatal death (3.41; 2.07, 5.63), and large-for-gestational age (3.82; 3.50, 4.16). The associations were similar for women with BMIs between 35.1 and 40 but to a lesser degree.
A population-based cohort study 13 included 212 889 women. Compared with women who stayed at a normal weight in their second pregnancies, those becoming overweight had 1.4 (95% CI 0.6 to 2.1) excess stillbirths per 1000 pregnancies. Those becoming obese had 3.6 (95% CI 1.3 to 5.9) excess stillbirths per 1000 pregnancies and 2.4 (95% CI 0.4 to 4.4) excess neonatal deaths per 1000 live births. There was a dose-response relationship between prepregnancy BMI increases of more than 2 units and increased risk of stillbirth and infant mortality.
In a retrospective analysis 3 of a total of 287 213 completed singleton pregnancies in London, England, 176 923 (61.6%) normal weight (BMI 20-24.9), 79 014 (27.5%) moderately obese (BMI 25-29.9) and 31 276 (10.9%) very obese (BMI ≥ 30) women were included. Compared to women with normal BMI, the following outcomes were significantly more common in obese pregnant women (odds ratio [99% confidence interval] for BMI 25-30 and BMI ≥ 30 respectively): gestational diabetes mellitus (1.68 [1.53-1.84], 3.6 [3.25-3.98]); proteinuric pre-eclampsia (1.44 [1.28-1.62], 2.14 [1.85-2.47]); induction of labour (2.14 [1.85-2.47], 1.70 [1.64-1.76]); delivery by emergency caesarean section (1.30 [1.25-1.34], 1.83 [1.74-1.93]); postpartum haemorrhage (1.16 [1.12-1.21], 1.39 [1.32-1.46]); birthweight above the 90th centile (1.57 [1.50-1.64], 2.36 [2.23-2.50]), and intrauterine death (1.10 [0.94-1.28], 1.40 [1.14-1.71]). Also infections in the genital or urinary tract and wound infections were more common. Delivery before 32 weeks' gestation and breastfeeding at discharge were significantly less likely in the overweight groups.
A study based on a large prospective multicenter database in the United States 4 included 16 102 patients: 3 752 control, 1 473 obese (BMI 30 to 34.9), and 877 morbidly obese (BMI 35 or greater). Obesity and morbid obesity had a statistically significant association with gestational hypertension (odds ratios [ORs] 2.5 and 3.2), preeclampsia (ORs 1.6 and 3.3), gestational diabetes (ORs 2.6 and 4.0), and fetal birth weight greater than 4000 g (ORs 1.7 and 1.9) and greater than 4500 g (ORs 2.0 and 2.4). For nulliparous patients, the cesarean delivery rate was 20.7% for the control group, 33.8% for obese, and 47.4% for morbidly obese patients.
Comment: The quality of evidence is upgraded by strong association and clear dose-response gradient.
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