HNF1A-MODY Maternal Diabetes Drives Large Birth Size
- Infants born to mothers with HNF1A-maturity-onset diabetes of the young showed a significantly higher likelihood of being large for gestational age compared to those born to affected fathers,...
- Crowley at Mater Misericordiae University Hospital in Dublin, Ireland, investigators evaluated 183 singleton offspring from 73 parents with a genetically confirmed HNF1A mutation.
- Overall, 56 offspring with maternal inheritance were large for gestational age, compared with just six offspring with paternal inheritance, representing 39.4% versus 15.0%.
Infants born to mothers with HNF1A-maturity-onset diabetes of the young showed a significantly higher likelihood of being large for gestational age compared to those born to affected fathers, according to research published online on October 12, 2026, in Diabetes, Obesity and Metabolism. The retrospective review of pregnancies spanning from 1965 to 2023 in Ireland found that high maternal glucose levels during pregnancy remained tied to increased birth size even after researchers accounted for whether the infant carried the genetic mutation.
Irish Retrospective Review Tracks 183 Offspring
Led by M.T. Crowley at Mater Misericordiae University Hospital in Dublin, Ireland, investigators evaluated 183 singleton offspring from 73 parents with a genetically confirmed HNF1A mutation. The study cohort included 142 offspring with maternal inheritance and 41 with paternal inheritance. Data were gathered from maternity records and parental recall, with genetic testing ultimately available for 62 of the 183 offspring, representing 34% of the group.
Overall, 56 offspring with maternal inheritance were large for gestational age, compared with just six offspring with paternal inheritance, representing 39.4% versus 15.0%. In subset analyses of 57 genotyped offspring, in utero exposure to maternal dysglycaemia was linked to higher odds of a large-for-gestational-age birth with an adjusted odds ratio of 4.00, after adjusting for the offspring’s genotype.
Insulin Treatment Outcomes and Neonatal Complications
Pregnancies managed with insulin recorded a lower proportion of large-for-gestational-age births than dysglycaemic pregnancies managed without insulin, at 35.1% versus 64.3%. Among the insulin-treated pregnancies that still resulted in large-for-gestational-age births, late-pregnancy glucose measures and insulin doses ran higher.
Neonatal hypoglycaemia, including persistent cases lasting beyond 72 hours and episodes requiring neonatal intensive care unit admission, occurred almost exclusively among offspring with maternal inheritance. Most of those affected infants experienced in utero exposure to maternal dysglycaemia, and many were born to mothers receiving insulin therapy.
Although these sequelae appear to be less frequent and less severe with paternally inherited disease, it is reasonable to counsel relevant obstetric and neonatal teams around these perinatal concerns to reduce potential morbidity,
M.T. Crowley et al.
Study Limitations and Grant Support
The study faced notable constraints, including a small sample size that lacked the statistical power to confirm certain effects. Only about a third of the offspring underwent genetic testing, and those tested were more likely to show signs of the condition, which could introduce bias into the results. Additionally, maternal glucose data and gestational weight gain figures were incomplete, particularly for pregnancies not treated with insulin.
Financial backing for the research came from grants provided by the Health Research Board/Medical Research Charities Group, the Irish Endocrine Society, and Novo Nordisk A/S, with one author reporting a research grant from Novo Nordisk.