Best Practice & Research Clinical Obstetrics & Gynaecology
11The offspring of the diabetic mother – Short- and long-term implications
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.
References (100)
- et al.
Offspring of diabetic pregnancy: long-term outcomes
Semin Fetal Neonatal Med
(2009) Foetal and neonatal complications in gestational diabetes: perinatal mortality, congenital malformations, macrosomia, shoulder dystocia, birth injuries, neonatal complications
Diabetes Metab
(2010)Management of infants born to mothers with gestational diabetes. Paediatric environment
Diabetes Metab
(2010)- et al.
Effectiveness of gestational diabetes treatment: a systematic review with quality of evidence assessment
Diabetes Res Clin Pract
(2012) - et al.
Infants born to mothers with gestational diabetes mellitus: mild neonatal effects, a long-term threat to global health
J Pediatr
(2014) Intrauterine programming of adult disease
Mol Med Today
(1995)- et al.
Is it time to revisit the Pedersen hypothesis in the face of the obesity epidemic?
Am J Obstet Gynecol
(2011) - et al.
Increased neonatal fat mass, not lean body mass, is associated with maternal obesity
Am J Obstet Gynecol
(2006) - et al.
Is birth weight modified during pregnancy? Using sibling differences to understand the impact of blood glucose, obesity, and maternal weight gain in gestational diabetes
Am J Obstet Gynecol
(2006) - et al.
Pregnancy complicated by type 2 diabetes: an emerging problem
Diabetes Res Clin Pract
(2008)
Diabetic-associated stillbirth: incidence, pathophysiology, and prevention
Obstet Gynecol Clin North Am
Stillbirth in diabetic pregnancies
Best Pract Res Clin Obstet Gynaecol
Fetal myocardial morphological and functional changes associated with well-controlled gestational diabetes
Eur J Obstet Gynecol Reprod Biol
The impacts of maternal gestational diabetes mellitus (GDM) on fetal hearts
Biomed Environ Sci
Gestational diabetes mellitus and lesser degrees of pregnancy hyperglycemia: association with increased risk of spontaneous preterm birth
Obstet Gynecol
A comparison of amniotic fluid fetal pulmonary phospholipids in normal and diabetic pregnancy
Am J Obstet Gynecol
Amlodipine treatment prevents angiotensin II-induced human umbilical vein endothelial cell apoptosis
Arch Med Res
Reactive oxygen species as mediators of signal transduction in cardiovascular disease
Trends Cardiovasc Med
A switch toward angiostatic gene expression impairs the angiogenic properties of endothelial progenitor cells in low birth weight preterm infants
Blood
Breastmilk feeding and lipoprotein profile in adolescents born preterm: follow-up of a prospective randomised study
Lancet
Contribute data to the 6th edition of the IDF Diabetes Atlas
Diabetes Res Clin Pract
Pregnancy and diabetes scenario around the world: India
Int J Gynaecol Obstet
Macrosomia in 23 developing countries: an analysis of a multicountry, facility-based, cross-sectional survey
Lancet
Sociodemographic correlates of the increasing trend in prevalence of gestational diabetes mellitus in a large population of women between 1995 and 2005
Diabetes Care
Effects of treatment in women with gestational diabetes mellitus: systematic review and meta-analysis
Bmj
Maternal obesity and risk of gestational diabetes mellitus
Diabetes Care
Trends in prevalence and outcomes of pregnancy in women with pre-existing type I and type II diabetes
Bjog
The macrosomic fetus: a challenge in current obstetrics
Acta Obstet Gynecol Scand
Weight and length at birth of infants of diabetic mothers
Acta Endocrinol (Copenh)
Hyperglycemia and adverse pregnancy outcomes
N Engl J Med
Differential regulation of genes for fetoplacental lipid pathways in pregnancy with gestational and type 1 diabetes mellitus
Am J Obstet Gynecol
Gestational diabetes induces placental genes for chronic stress and inflammatory pathways
Diabetes
Fetal epigenetic programming of adipokines
Adipocyte
Pre-pregnancy body mass index in relation to infant birth weight and offspring overweight/obesity: a systematic review and meta-analysis
PLoS One
The role of gestational diabetes, pre-pregnancy body mass index and gestational weight gain on the risk of newborn macrosomia: results from a prospective multicentre study
BMC Pregnancy Childbirth
Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: associations with neonatal anthropometrics
Diabetes
Macrosomia despite good glycaemic control in Type I diabetic pregnancy; results of a nationwide study in The Netherlands
Diabetologia
Maternal and fetal outcome in women with type 2 versus type 1 diabetes mellitus: a systematic review and metaanalysis
J Clin Endocrinol Metab
How big is too big? the perinatal consequences of fetal macrosomia
Am J Obstet Gynecol
Maternal and neonatal outcomes of large for gestational age pregnancies
Acta Obstet Gynecol Scand
Congenital brachial palsy: incidence, causes, and outcome in the United Kingdom and Republic of Ireland
Arch Dis Child Fetal Neonatal Ed
Offspring of diabetic pregnancy: short term outcomes
Semin Fetal Neonatal Med
Diabetes-induced birth defects: what do we know? what can we do?
Curr Diab Rep
Prevention and detection of diabetic embryopathy
Community Genet
Perinatal mortality and congenital anomalies in babies of women with type 1 or type 2 diabetes in England, Wales, and Northern Ireland: population based study
BMJ
Major congenital malformations in women with gestational diabetes mellitus: a systematic review and meta-analysis
Diabetes Metab Res Rev
Patent ductus arteriosus
Circulation
Oxidant regulation of gene expression and neural tube development: insights gained from diabetic pregnancy on molecular causes of neural tube defects
Diabetologia
Caspase-8: a key role in the pathogenesis of diabetic embryopathy
Birth Defects Res B Dev Reprod Toxicol
Perinatal mortality in Type 2 diabetes mellitus
Diabet Med
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