Introduction & Objective: HNF4A-MODY is associated with macrosomia and neonatal hypoglycemia. Glycemic control is achieved during pregnancy with insulin or sulphonylurea therapy. We aim to determine pregnancy outcomes in women with HNF4A-MODY and HNF1A-MODY.
Methods: We performed a multi-center retrospective review of pregnancy outcomes (n=39) in 14 women with HNF4A-MODY and (n=145) in 46 women with HNF1A-MODY. Offspring genotype was known in 13 HNF4A-MODY and 36 HNF1A-MODY. Outcomes included offspring birth centile, gestational age, mode of delivery and incidence of neonatal hypoglycemia (NH).
Results: Miscarriage rates were 15% for HNF4A-MODY and 23% for HNF1A-MODY respectively (p=0.24). Overall median birthweight was 3.7±0.5 vs. 3.6±0.5kg (p = 0.11) and birthweight centiles were 85±17 vs. 70±29 (p=0.22). Incidence of LGA was 50% vs 32% (p=0.41). Cesarean section rate was 17% vs 26% respectively (p=0.3). NH was significantly greater in HNF4A-MODY (36% vs 14%, p value = 0.014). HNF4A-MODY genotype positive offspring (n=12) had a median birthweight of 4.78±1.2kg (83% LGA).
Diabetes was confirmed in 137 pregnancies (HNF4A:HNF1A = 26:111). Third trimester median insulin doses were 0.33unit/kg/day vs. 0.61±0.13unit/kg/day for HNF4A vs. HNF1A (p=0.85). HbA1c was similar(trimester one: 42±11 vs. 40±6 mmol/mol, p = 0.86, trimester 3: 37±7 vs. 34±4mmol/mol, p = 0.88). HNF4A-MODY offspring of diabetic mothers were significantly heavier than offspring of nondiabetic mothers (3.82±0.6 vs. 3.3±0.5kg, p=0.048) however HNF1A-MODY offspring were not (3.64±0.43 vs. 3.32±0.5kg, p=0.2).
Conclusion: Increased birthweight and neonatal hypoglycemia was observed in HNF4A-MODY positive offspring. Glycemic control was achieved with relatively low doses of insulin.
M. Crowley: None. S. Bacon: None. B.T. Kinsley: None. M. Hatunic: None. M. Kennelly: None. M.M. Byrne: Speaker's Bureau; Novo Nordisk A/S. Advisory Panel; Novo Nordisk A/S. Research Support; Novo Nordisk A/S.
Irish Endocrine Society Clinical Science Award 2022
