The optimum treatment for HNF1A/HNF4A maturity-onset diabetes of the young and ATP-sensitive potassium (KATP) channel neonatal diabetes, outside pregnancy, is sulfonylureas, but there is little evidence regarding the most appropriate treatment during pregnancy. Glibenclamide has been widely used in the treatment of gestational diabetes, but recent data have established that glibenclamide crosses the placenta and stimulates fetal insulin secretion, increasing the risk of macrosomia and neonatal hypoglycaemia.
This raises questions about its use in pregnancy.
Optimum management of HNF1A/HNF4A maturity onset diabetes of the young (MODY) in pregnancy requires excellent glycaemic control in the first trimester to minimize the risk of fetal malformations, whilst avoiding the negative impact of glibenclamide on fetal weight gain in the third trimester. Due to the risk of stimulating increased insulin secretion in utero, we recommend that in women with HNF1A/HNF4A maturity-onset diabetes of the young, those with good glycaemic control who are on a sulfonylurea per conception either transfer to insulin before conception (at the risk of a short-term deterioration of glycaemic control) or continue with sulfonylurea (glibenclamide) treatment in the first trimester and transfer to insulin in the second trimester.
Early delivery is needed if the fetus inherits an HNF4A mutation from either parent because increased insulin secretion results in ~800g weight gain in utero, and prolonged severe neonatal hypoglycaemia can occur post-delivery.
In mothers with ATP-sensitive potassium channel (KATP) neonatal diabetes, glibenclamide treatment in pregnancy can be beneficial depending on whether the fetus has inherited the KATP gene mutation. If the fetus inherits a KATP neonatal diabetes mutation from their mother they have greatly reduced insulin secretion in utero that reduces fetal growth by ~900g. Treating the mother with glibenclamide in the third trimester also treats the affected fetus in utero, normalising fetal growth. But it is not desirable if the fetus has not inherited the mutation and is unaffected, especially given the high doses used in this condition. Prospective studies of pregnancy in monogenic diabetes are needed.
When a parent has KATP neonatal diabetes or HNF4A MODY, genotype of the fetus is unknown, serial antenatal ultrasound assessment of fetal growth may be used as a proxy to aid management decisions. The Exeter Genomics Laboratory are currently developing a non-invasive fetal genotyping test using cell-free fetal DNA isolated from a maternal blood sample. This will enable rapid fetal genotyping to help provide the appropriate clinical management needed for