The effect of gestational diabetes mellitus on maternal and child health

Introduction: Gestational diabetes mellitus (GDM) affects 1 in 7 pregnancies globally. Development of GDM can be influenced by antenatal factors, such as maternal BMI, metabolic syndrome and poor mental health. Furthermore, previous research suggests that GDM increases the risk of diabetes and coronary heart disease to the mother and child and is associated with impaired neurodevelopment in the child. Therefore, greater understanding of the lifestyle factors which influence GDM development, the trajectory of cardiovascular risk factor appearance in women and children and assessing neurodevelopment in the child will aid intervention strategies that can significantly reduce the risk of chronic disease later in life. Methods: This thesis includes a comprehensive series of systematic reviews and meta-analyses to identify the cardiovascular risk factors seen in women with a history of GDM and their offspring exposed to GDM in utero. To complement the review series, an observational followup study of the Screening Tests to Predict Poor Outcomes of Pregnancy (STOP) cohort was undertaken with women and children being recruited at 3 years postpartum. The original STOP study recruited 1,363 nulliparous women from 2015 to 2018 primarily from the Lyell McEwin Hospital in South Australia. This hospital services patients from the Northern Adelaide region which statistically has some of the worst chronic health outcomes in metropolitan Australia due to significant socioeconomic disadvantage in the community. The follow-up study consisted of hemodynamic and metabolic assessments that were undertaken to determine the prevalence of cardiometabolic risk factors three years postpartum in women with a history of GDM 3 years later, and to determine whether the children also exhibited any cardiovascular risk factors or measures of poor neurodevelopment at 3 years of age. Results: The systematic review and meta-analysis series identified that women who have a history of GDM have an increase in blood pressure, BMI lipids, serum glucose, and serum insulin and are at a higher risk of metabolic syndrome than those without a history of GDM. Children exposed to GDM in utero exhibited higher blood pressure, BMI z-score, blood glucose and risk of metabolic syndrome than those who were not exposed to GDM in utero. Women with a history of GDM who breastfed had reduced serum glucose and reduced risk of type II diabetes mellitus than those who did not. In the original STOP study, there was no difference in history of depression in women who developed GDM compared to those who did not. The latter comprised women with uncomplicated pregnancies, and one or more of the following complications: gestational hypertension, preeclampsia, and delivery of a preterm infant and/or a small for gestational age infant. A total of 281 women-children dyads attended a 3 year follow-up appointment. There were no significant differences in cardiometabolic variables between women with a history of GDM and those without a history of GDM at 3 years postpartum, nor in their offspring exposed to GDM in utero compared to unexposed offspring, when adjusted for BMI and socioeconomic index (SEI). Breastfeeding for at least 6 months postpartum provided some protection against cardiovascular risk factors in all women in the cohort at 3 years postpartum but this was attenuated by maternal BMI in first trimester and socioeconomic index. Anthropometric and hemodynamic outcomes were not different between children who were breastfed for at least 6 months compared to those who were not. Within the group of women with at least one pregnancy complication in their index pregnancy and their in utero exposed children, breastfeeding or being breastfed until at least 6 months old, was some protection against cardiovascular risk factors. Children who were exposed to GDM in utero had significantly reduced communication, gross motor and problem-solving skills than those who were not exposed to GDM in utero, even after adjustment for maternal history of depression during pregnancy. Three year old females who were exposed to GDM in utero appeared to be less able at problem solving than exposed males. Conclusion: Based on the systematic review and meta-analyses conducted, women with a history of GDM are likely to exhibit an increase in conventional cardiovascular risk factors later in life. However, in our smaller cohort, this was not completely evident in women with a history of GDM at 3 years postpartum. Much of this association is largely mediated by covariates including SEI in this socioeconomically disadvantaged community. Breastfeeding may confer some protection to women with GDM but further studies are warranted to assess this association. Exposure to GDM in utero promotes an increase in some cardiovascular risk factors in the literature but this was not evident in our cohort. However, children who were exposed to GDM in utero appear to have impaired neurodevelopment. Interventions in preconception and in early pregnancy that target obesity may significantly reduce the risk of GDM and associated cardiovascular risk factors in the early years after delivery for both women and their children.Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 202