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The offspring of the diabetic mother – Short- and long-term implications

https://doi.org/10.1016/j.bpobgyn.2014.08.004Get rights and content

In the 1980s, David Barker and Colleagues proposed that the major causes of cardiovascular and metabolic diseases have their roots in early development. There is now robust evidence that an hyperglycemic intrauterine environment is responsible not only for significant short-term morbidity in the fetus and the neonate but also for an increased risk of developing diabetes as well as other chronic, noncommunicable diseases at adulthood. The risk is higher in pregestational diabetes, but unrecognized and/or poorly managed gestational diabetes (GDM) may have similar consequences. Although a relatively clear picture of the pathogenesis of the fetal and neonatal complications of maternal diabetes and of their interrelationship is available today, the intimate molecular mechanisms involved in the long term are far from being understood. While the rate of GDM is sharply increasing in association with the pandemic of obesity and of type 2 diabetes over the world, we review here the current understanding of short- and long-term outcomes of fetuses exposed to a diabetic environment.

Introduction

The incidence of gestational diabetes (GDM) is dramatically increasing in the context of the pandemic in obesity and type 2 diabetes (T2D) observed in high-income as well as in emerging and developing countries [1], ∗[2]. The real incidence of GDM in low-income countries is underestimated because of the poor involvement of public health policies in the screening for this disease during pregnancy and even in nonpregnant populations. Much of the currently available knowledge on the consequences of maternal diabetes on the neonate has been provided by studies on pregestational diabetes, while GDM is much more frequent. GDM exposes the fetus and the neonate to short-term complications that need to be clarified in order to improve and to adapt neonatal management ∗[3], ∗[4], especially in developing countries where maternal screening and treatment are deficient. Indeed, recent meta-analyses showed that the treatment of GDM improves neonatal outcomes [5], [6]. Moreover, converging clinical and experimental data suggest that the offspring of diabetic mothers is further exposed to an increased risk of developing diabetes as well as other chronic, noncommunicable diseases at adulthood, with potential trans-generational effects involved in the pandemic [7]. The mechanisms by which exposure to altered intrauterine milieu or unsuitable early neonatal care induce such consequences are not fully understood. Subtle phenomena may act during perinatal life and impair long-term outcome. In the 1980s, David Barker and his colleagues proposed that the major causes of cardiovascular mortality in adulthood in industrialized countries have their roots in early development [8].

Obstetricans and pediatricans are faced in the first line today with this crucial epidemiologic context. This article evaluates the currently available knowledge on the short-term and long-term effects of diabetes in pregnancy on the offspring.

Section snippets

Fetal overnutrition: macrosomia

The consequence of fetal overnutrition is macrosomia. The main conditions during pregnancy that expose the fetus to excess of nutrients are maternal diabetes and obesity but also excess of gestational weight gain (GWG). Maternal obesity is tightly linked to GDM or preexisting T2D. The risk of GDM is 2.14-fold higher in overweight pregnant women, 3.56-fold higher in obese pregnant women, and 8.56-fold higher in severely obese pregnant women compared to pregnant women with normal weight [9]. The

Congenital malformations

Maternal diabetes, mainly pregestational diabetes, has huge consequences on the incidence of congenital anomalies. Eight million infants (185,000 in the United States) are born each year worldwide with major congenital anomalies [30]. Babies from pregestational diabetic mothers are more likely to suffer cardiac malformations (transposition of great arteries, ventricular or atrial septal defects, and coarctation of the aorta), caudal regression syndrome, central nervous system defects (neural

Obesity and T2D

The consequences of exposure to diabetes in utero on childhood overweight and obesity and the risk of T2D have been illustrated by studies in Pima Indians. Pima Indians have an exceptionally high prevalence of obesity and T2D due to genetic reasons. The prevalence of T2D in offspring of Pima women increases up to sixfold in those with diabetic or prediabetic mothers, and diabetes during childhood and adolescence occurred almost exclusively among the offspring of diabetic and prediabetic mothers

Disparities in the world: the burden in low-income countries

The prevalence of risk factors for diabetes during pregnancy is increasing all around the world. Indeed, a huge increase in the incidence of T2D and obesity in developing countries is observed, especially in the westernized ones. T2D is an occult disease that can remain undiagnosed especially in young women of reproductive age. In many low-income countries, no screening program for diabetes during pregnancy is available, nor are programs of maternal care, especially in rural areas, because of

Summary

While the incidence of T2D and of GDM is increasing worldwide, both short-term and long-term consequences in the offspring need special attention today. Macrosomia is a common complication in all types of diabetes during pregnancy and also in maternal obesity. It is the main factor related to most of the neonatal adverse outcomes. Furthermore, it is a strong predictor of long-term adverse outcomes. The mechanisms involved in the short- and long-term outcomes in offspring from GDM mothers are

Conflict of interest statement

The authors declare no conflicts of interest.

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