Adverse pregnancy outcomes in women with diabetes-related microvascular disease and risks of disease progression in pregnancy: A systematic review and meta-analysis

BACKGROUND: The rise in the global prevalence of diabetes, particularly among younger people, has led to an increase in the number of pregnant women with preexisting diabetes, many of whom have diabetes-related microvascular complications. We aimed to estimate the magnitude of the risks of adverse pregnancy outcomes or disease progression in this population. METHODS AND FINDINGS: We undertook a systematic review and meta-analysis on maternal and perinatal complications in women with type 1 or 2 diabetic microvascular disease and the risk factors for worsening of microvascular disease in pregnancy using a prospective protocol (PROSPERO CRD42017076647). We searched major databases (January 1990 to July 2021) for relevant cohort studies. Study quality was assessed using the Newcastle-Ottawa Scale. We summarized the findings as odds ratios (ORs) with 95% confidence intervals (CIs) using random effects meta-analysis. We included 56 cohort studies involving 12,819 pregnant women with diabetes; including 40 from Europe and 9 from North America. Pregnant women with diabetic nephropathy were at greater risk of preeclampsia (OR 10.76, CI 6.43 to 17.99, p < 0.001), early (<34 weeks) (OR 6.90, 95% CI 3.38 to 14.06, p < 0.001) and any preterm birth (OR 4.48, CI 3.40 to 5.92, p < 0.001), and cesarean section (OR 3.04, CI 1.24 to 7.47, p = 0.015); their babies were at higher risk of perinatal death (OR 2.26, CI 1.07 to 4.75, p = 0.032), congenital abnormality (OR 2.71, CI 1.58 to 4.66, p < 0.001), small for gestational age (OR 16.89, CI 7.07 to 40.37, p < 0.001), and admission to neonatal unit (OR 2.59, CI 1.72 to 3.90, p < 0.001) compared to those without nephropathy. Diabetic retinopathy was associated with any preterm birth (OR 1.67, CI 1.27 to 2.20, p < 0.001) and preeclampsia (OR 2.20, CI 1.57 to 3.10, p < 0.001) but not other complications. The risks of onset or worsening of retinopathy were increased in women who were nulliparous (OR 1.75, 95% CI 1.28 to 2.40, p < 0.001), smokers (OR 2.31, 95% CI 1.25 to 4.27, p = 0.008), with existing proliferative disease (OR 2.12, 95% CI 1.11 to 4.04, p = 0.022), and longer duration of diabetes (weighted mean difference: 4.51 years, 95% CI 2.26 to 6.76, p < 0.001) compared to those without the risk factors. The main limitations of this analysis are the heterogeneity of definition of retinopathy and nephropathy and the inclusion of women both with type 1 and type 2 diabetes. CONCLUSIONS: In pregnant women with diabetes, presence of nephropathy and/or retinopathy appear to further increase the risks of maternal complications.