Pregnancy outcome in patients with raised blood glucose due to a heterozygous glucokinase gene mutation

Abstract

Aim: To assess determinants of fetal growth in the offspring of pregnant women with hyperglycaemia due to a heterozygous glucokinase (GCK) gene mutation.

Methods: Details of gestational age at delivery, fetal birth weight and maternal antenatal treatment were collected from patients and retrospective case note review of 82 offspring born to 42 women with GCK gene mutations and 31 offspring born to 13 unaffected normoglycaemic women with an affected partner. Fetal genotype was determined using direct sequencing from either a mouth swab or a blood sample.

Results: In mothers with GCK mutations, non-mutation-carrying offspring were heavier than mutation-carrying offspring (corrected birth weight 3.9 +/- 0.6 vs. 3.2 +/- 0.8 kg; P < 0.001) and more likely to be macrosomic (> 4.0 kg; 39% vs. 7%, P = 0.001). There was no difference in corrected birth weight between offspring of insulin- and diet-treated women (3.7 +/- 0.7 vs. 3.8 +/- 0.6 kg; P = 0.1), although insulin-treated mothers delivered earlier (37.5 +/- 1.7 vs. 38.9 +/- 2.3 weeks; P < 0.001) due to increased obstetric intervention.

Conclusions: Offspring of women with GCK mutations are at increased risk of macrosomia and its obstetric consequences. Fetal birth weight is predominantly altered by fetal genotype and not treatment of maternal hyperglycaemia with insulin. This probably reflects the large effect of a fetal GCK mutation on fetal insulin secretion and the difficulty in reducing the regulated maternal glycaemia caused by a glucose sensing defect in people with GCK mutations.