Exposure to treated GDM or untreated GDM detected by lower but not higher criteria, was not associated with increased infant risk factors for obesity or adverse cognitive outcomes.
Gestational diabetes mellitus (GDM) or hyperglycemia first diagnosed in pregnancy is a major public health concern, affecting an estimated 14% of pregnant women globally [1]. GDM is associated with an increased risk of type 2 diabetes for women and obesity and metabolic syndrome in offspring [1]. It may also contribute to neurocognitive impairment and emotional and behavioral difficulties in childhood [2]. Randomized trials have shown that treating GDM with dietary and lifestyle approaches and pharmacological therapy, as appropriate, reduces the risk of large-for-gestational-age infants (LGA >90th centile) by 40-50% [3, 4], but it is unclear whether detection and treatment of GDM reduces the risk of obesity, metabolic disease and adverse neurodevelopment in the next generation.
The Gestational Diabetes Mellitus Trial of Detection Thresholds (GEMS) [5] investigated whether the detection and treatment of GDM in a general obstetric population using the lower diagnostic thresholds set by the International Association of Diabetes in Pregnancy Study Groups (IADPSG) [6], compared to higher criteria in use for over 20 years [7], would decrease the risk of LGA. The use of the IADPSG criteria did not alter the rate of LGA (8.8% vs. 8.9%) but increased the number of inductions (34% vs. 30%) and infants treated for hypoglycemia (11% vs. 8%) [5]. Groups had similar rates of the composite serious outcome (stillbirth, neonatal death, birth trauma, or shoulder dystocia: 2.5% vs. 2.2%), pre-eclampsia (3.7% vs. 3.7%) and neonatal unit admission (4.6% vs. 3.6%), despite more women being diagnosed with GDM (15% vs. 6%). However, in secondary analysis of GEMS participants who met the lower but not higher criteria, the risk of LGA was lower among those who received treatment for GDM compared to those who did not (6.2% vs. 18%) [5].
Late gestation and infancy are a critical period for the establishment of long-term homeostatic set-points and trajectories. For example, increased infant weight gain [8], adipose accrual [8], energy and protein intake [9, 10], and reduced lean mass [11] and duration of breastfeeding [12] have been associated with increased risk of obesity and cardiometabolic disorders later in life. Similarly, late gestation and early infancy are a critical period for the development of brain networks and microstructure [13, 14]. Thus, if the reported associations between GDM and offspring obesity, metabolic disease and adverse neurodevelopment are causal, an association between different severities of GDM and its treatment and infant risk factors for obesity and early developmental progress would be expected. However, there is a paucity of data on the effect of GDM on infant health, especially from clinical trials [15, 16]. We report the results of the BabyGEMS Study at 9 and 12-18 months' corrected age, a nested cohort study within GEMS, designed to prospectively evaluate the effect of different severities of GDM, both treated and untreated, on infant risk factors for later obesity. We hypothesized that compared to randomly selected control infants without exposure to GDM by lower criteria, infants exposed to GDM detected by higher criteria and infants exposed to GDM by lower (IAPDSG) but not higher criteria that was untreated, but not those exposed to GDM detected by lower (IAPDGS) but not higher criteria that was treated, would have increased overweight or rapid weight gain from birth, higher food approach appetitive trait scores, higher energy intake, and lower cognitive developmental scores.