Abstract

BackgroundDiabetes in pregnancy has been associated with a paradoxically reduced risk of neonatal death in twin pregnancies. Risk “shift” may be a concern in that the reduction in neonatal deaths may be due to an increase in fetal deaths (stillbirths). This study aimed to clarify the impact of diabetes on the risk of perinatal death (neonatal death plus stillbirth) in twin pregnancies.MethodsThis was a retrospective cohort study of twin births using the largest available dataset on twin births (the U.S. matched multiple birth data 1995-2000; 19,676 neonates from diabetic pregnancies, 541,481 from non-diabetic pregnancies). Cox proportional hazard models were applied to estimate the adjusted hazard ratios (aHR) of perinatal death accounting for twin cluster-level dependence.ResultsComparing diabetic versus non-diabetic twin pregnancies, overall perinatal mortality rate was counterintuitively lower [2.1% versus 3.3%, aHR 0.70 (95% confidence intervals 0.63-0.78)]. Individually, both stillbirth and neonatal mortality rates were lower in diabetic pregnancies, but we identified significant differences by gestational age and birth weight. Diabetes was associated with a survival benefit in pregnancies completed before 32 weeks [aHR 0.55 (0.48-0.63)] or with birth weight <1500 g [aHR 0.61 (0.53-0.69)]. In contrast, diabetes was associated with an elevated risk of perinatal death in pregnancies delivered between 32 and 36 weeks [aHR 1.38 (1.10-1.72)] or with birth weight >=2500 g [aHR 2.20 (1.55-3.13)].ConclusionsDiabetes in pregnancy appears to be “protective” against perinatal death in twin pregnancies ending in very preterm or very low birth weight births. Prospective studies are required to clarify whether these patterns of risk are real, or they are artifacts of unmeasured confounders. Additional data correlating these outcomes with the types of diabetes in pregnancy are also needed to distinguish the effects of pre-gestational vs. gestational diabetes.

Highlights

  • Diabetes mellitus affects 2 to 10% of pregnancies, and most of diabetes in pregnancy are gestational diabetes [1,2,3]

  • Diabetes in pregnancy has been associated with a number of adverse outcomes including congenital anomalies, preterm birth, macrosomia, neonatal hypoglycemia, and neonatal death [8,9,10,11,12,13,14]

  • A logical concern in data interpretation is that the reduction in neonatal deaths in twin diabetic pregnancies may be due to an increase in fetal deaths

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Summary

Introduction

Diabetes mellitus affects 2 to 10% of pregnancies, and most (about 90%) of diabetes in pregnancy are gestational diabetes [1,2,3]. A recent study suggests a potential differential impact of diabetes on perinatal outcomes in multiple versus singleton pregnancies; there appears to be a “protective” effect of diabetes against neonatal death in twin (but not singleton) pregnancies [15]. Results: Comparing diabetic versus non-diabetic twin pregnancies, overall perinatal mortality rate was counterintuitively lower [2.1% versus 3.3%, aHR 0.70 (95% confidence intervals 0.63-0.78)] Both stillbirth and neonatal mortality rates were lower in diabetic pregnancies, but we identified significant differences by gestational age and birth weight. Prospective studies are required to clarify whether these patterns of risk are real, or they are artifacts of unmeasured confounders Additional data correlating these outcomes with the types of diabetes in pregnancy are needed to distinguish the effects of pre-gestational vs gestational diabetes

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