TOPLINE

Infants born to mothers with HNF1A-maturity‑onset diabetes of the young (HNF1A-MODY), a genetic form of diabetes, were more likely to be large for gestational age than those born to affected fathers. High maternal glucose levels in pregnancy remained associated with larger birth size even after researchers accounted for whether the infant carried the mutation.

METHODOLOGY

• Investigators performed a retrospective review of pregnancies spanning 1965-2023 in Ireland to compare pregnancy and neonatal outcomes by parent of inheritance and assess the roles of maternal dysglycaemia and infant mutation status in these outcomes in pregnancies involving HNF1A-MODY.
• They included 183 singleton offspring (142 with maternal inheritance and 41 with paternal inheritance) from 73 parents with a genetically confirmed HNF1A mutation.
• Data came from maternity records and parental recall; genetic testing was available for 62 of 183 offspring (34%).
• Outcomes included birth weight, large‑for‑gestational‑age status (birth weight above the 90th percentile), small‑for‑gestational‑age status (birth weight below the 10th percentile), and neonatal hypoglycaemia (blood glucose level < 2.6 mmol/L; persistent if lasting beyond 72 hours).

TAKEAWAY

• Overall, 56 offspring with maternal inheritance and six with paternal inheritance were large for gestational age (39.4% vs 15.0%; P = .004).
• In analyses using the subset with a confirmed genotype (n = 57 offspring), in utero exposure to maternal dysglycaemia was associated with higher odds of a large‑for‑gestational‑age birth (adjusted odds ratio, 4.00; P = .009) after adjustment for offspring genotype.
• Pregnancies treated with insulin had a lower proportion of large-for-gestational-age births than dysglycaemic pregnancies managed without insulin (35.1% vs 64.3%; P = .004). Among insulin‑treated pregnancies that still resulted in large-for-gestational-age births, late‑pregnancy glucose measures and insulin doses were higher.
• Neonatal hypoglycaemia, including persistent cases and episodes requiring admissions to neonatal intensive care, occurred almost exclusively among offspring with maternal inheritance; most affected infants had in utero exposure to maternal dysglycaemia, and many were born to mothers receiving insulin.

IN PRACTICE

"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. 

SOURCE

The study was led by M.T. Crowley, Mater Misericordiae University Hospital, Dublin, Ireland. It was published online on October 12, 2026, in Diabetes, Obesity and Metabolism.

LIMITATIONS

The study was small and lacked the power to confirm some effects. Only about a third of offspring underwent genetic testing, and those tested were more likely to show signs of the condition, which could have biased the results. Maternal glucose data and gestational weight gain data were incomplete, especially for pregnancies not treated with insulin.

DISCLOSURES

The study was supported by grants from the Health Research Board/Medical Research Charities Group, the Irish Endocrine Society, and Novo Nordisk A/S. One author reported receiving a research grant from Novo Nordisk. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.