Infants born to mothers with HNF1A-maturity-onset diabetes of the young face a significantly higher risk of being large for gestational age than babies born to affected fathers, according to a study published October 12, 2026, in Diabetes, Obesity and Metabolism.
Inheritance Patterns and Birth Weight Disparities in Dublin Research
Researchers at Mater Misericordiae University Hospital in Dublin examined pregnancy outcomes spanning from 1965 to 2023 to understand how parent-of-origin affects infants with HNF1A-MODY, a genetic form of diabetes. The retrospective review evaluated 183 singleton offspring born to 73 parents with confirmed mutations. Among these participants, 142 offspring inherited the condition maternally, while 41 inherited it paternally.
The data revealed a sharp contrast in birth sizes based on which parent passed down the mutation. Overall, 56 maternally inherited offspring were large for gestational age, compared to just six offspring in the paternally inherited group. This translated to 39.4% versus 15.0%, a statistically significant difference reported by the study team led by M.T. Crowley.
Maternal Dysglycaemia Drives Higher Odds of Large-for-Gestational-Age Births
High maternal glucose levels during pregnancy remained directly tied to larger birth weight, regardless of whether the newborn actually carried the genetic mutation. In a subset analysis of 57 offspring with confirmed genotypes, in utero exposure to maternal dysglycaemia drove the odds of a large-for- gestational-age birth up to an adjusted odds ratio of 4.00, even after researchers adjusted for the infant’s own genetic status.
Management strategies during pregnancy altered these outcomes. Pregnancies managed with insulin recorded a lower proportion of large-for-gestational-age births than dysglycaemic pregnancies managed without insulin, showing rates of 35.1% versus 64.3%. However, among the insulin-treated pregnancies that still resulted in large babies, late-pregnancy glucose measures and insulin doses ran higher.
Neonatal Hypoglycaemia Concentration in Maternally Inherited Cases
Low blood sugar in newborns occurred almost exclusively among offspring with maternal inheritance. Most of these affected infants experienced in utero exposure to maternal dysglycaemia, and many were born to mothers receiving insulin therapy. These complications included persistent cases and episodes requiring admissions to neonatal intensive care units.
Study authors pointed out that while these perinatal issues appear less frequent and less severe when the disease comes from an affected father, clinical teams still need targeted awareness. “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,” the authors wrote.
The investigation faced limitations due to its small sample size, which left the research underpowered to confirm certain effects. Only about a third of the offspring—62 out of 183—underwent genetic testing, and those tested showed a higher likelihood of displaying signs of the condition, introducing potential selection bias. Furthermore, maternal glucose data and gestational weight gain records remained incomplete, particularly for pregnancies not treated with insulin. Funding for the work 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 disclosing a research grant from Novo Nordisk.
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