Diabetes, obesity & metabolism · 2026
Glycaemic Management and Pregnancy Outcomes in HNF1A-MODY.
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Crowley M T, McCluskey P, Ng N, Sanchez-Lechuga B, Fleming A, Hatunic M, Kinsley B, Bacon S, Colclough K, Kennelly M, Byrne M M
Аннотация
INTRODUCTION: Birthweight of HNF1A-affected offspring is largely similar to the background population with rarely reported cases of large for gestational age (LGA) and neonatal hypoglycaemia (NH). Conventional clinical management of pre-gestational diabetes appears to be sufficient in managing HNF1A-affected women in pregnancy. This study aims to evaluate pregnancy outcomes and review glucose management in a cohort with HNF1A-MODY.
METHODOLOGY: This is a retrospective review of 183 offspring (142 maternal and 41 paternal) of 73 parents with confirmed HNF1A-MODY. Data were obtained from maternal/paternal recall and/or review of maternity charts. Variables included glycaemic treatment, HbA1c, fructosamine, gestational weight gain, neonatal birthweight, gestation, incidence of NH, and offspring genotype status.
RESULTS: Maternal offspring had a higher incidence of LGA (39.4% vs. 15%, p = 0.012). LGA was associated with maternal dysglycaemia independent of neonatal mutation status. Rate of LGA was lower with insulin treatment compared to diet (35.1% vs. 64.3%, p = 0.004). Subgroup analysis of insulin treated pregnancies showed LGA was associated with higher mean capillary glucose (p = 0.005) (n = 34), third trimester insulin doses (p = 0.04) (n = 33), HbA1c (p = 0.04) (n = 34) and maternal gestational weight gain (p = 0.011) (n = 31). Weight adjusted total daily dose of insulin was 0.61 unit/kg/day (0.49-0.62) in Trimester 3 (n = 26). Persistent NH was more prevalent in maternally inherited cases with dysglycaemia (8 vs. 0 offspring, p = 0.067).
CONCLUSION: Large birthweight and NH occur in offspring of parents with HNF1A mutations. These sequelae are more frequent and clinically significant in maternally inherited cases. It is prudent to counsel relevant obstetric and neonatal teams around specific perinatal concerns to reduce potential morbidity.
METHODOLOGY: This is a retrospective review of 183 offspring (142 maternal and 41 paternal) of 73 parents with confirmed HNF1A-MODY. Data were obtained from maternal/paternal recall and/or review of maternity charts. Variables included glycaemic treatment, HbA1c, fructosamine, gestational weight gain, neonatal birthweight, gestation, incidence of NH, and offspring genotype status.
RESULTS: Maternal offspring had a higher incidence of LGA (39.4% vs. 15%, p = 0.012). LGA was associated with maternal dysglycaemia independent of neonatal mutation status. Rate of LGA was lower with insulin treatment compared to diet (35.1% vs. 64.3%, p = 0.004). Subgroup analysis of insulin treated pregnancies showed LGA was associated with higher mean capillary glucose (p = 0.005) (n = 34), third trimester insulin doses (p = 0.04) (n = 33), HbA1c (p = 0.04) (n = 34) and maternal gestational weight gain (p = 0.011) (n = 31). Weight adjusted total daily dose of insulin was 0.61 unit/kg/day (0.49-0.62) in Trimester 3 (n = 26). Persistent NH was more prevalent in maternally inherited cases with dysglycaemia (8 vs. 0 offspring, p = 0.067).
CONCLUSION: Large birthweight and NH occur in offspring of parents with HNF1A mutations. These sequelae are more frequent and clinically significant in maternally inherited cases. It is prudent to counsel relevant obstetric and neonatal teams around specific perinatal concerns to reduce potential morbidity.