Pregnancy and neonatal outcomes in women with GCK-MODY: an observational study based on standardised insulin modalities

The management of GCK-MODY during pregnancy remains challenging. We evaluated the impact on pregnancy and neonatal outcomes of two standardised insulin strategies. In this prospective observational study, participants chose (in agreement with their physician) to be treated with insulin either when maternal capillary blood glucose (CBG) ≥ thresholds for gestational diabetes (5.3 mmol/l before or 6.7 mmol/l 2 h after meals) (MG group) or when fetal abdominal circumference ≥75th percentile (FG group). In the FG group, insulin was also initiated if CBG ≥ safety levels (6.7 mmol/l before meals or 11.1 mmol/l 2 h after meals). Data on glycaemic management, modalities and timing of insulin therapy and maternal and neonatal outcomes were recorded. In the MG group (n=25), insulin was initiated more frequently (100% vs 75%, p=0.01) and earlier (p=0.001), with lower CBG and more frequent hypoglycaemic episodes compared with the FG group (n=21). However, there were no differences in pregnancy and neonatal outcomes. In the total cohort, the rate of large for gestational age (LGA) neonates, preterm deliveries and Caesarean sections was 22.2%, 2.2% and 40%, respectively. The rate of LGA was 0% among the neonates with the GCK variant vs 36% in those without (p=0.005). There were no associations between LGA and pregnancy characteristics, insulin therapy strategy or glycaemic management. In our study, the rate of LGA primarily depended on the fetal GCK genotype rather than the treatment strategy or glycaemic management. Our results suggest that a standardised strategy based on ultrasound monitoring of fetal growth and glycaemic safety thresholds, leading to delayed insulin initiation, offers a good fetal prognosis and minimises the risk of maternal hypoglycaemia. ClinTrials.gov NCT02556840.