Abstract
Extremes in birth weight are associated with adverse pregnancy outcomes and long-term risk of cardiometabolic disease. Fetal insulin has long been recognized as an important regulator of fetal growth, but the overall contribution of fetal insulin to birth weight in humans has not been quantified.
Single-gene mutations resulting in absent fetal insulin secretion provide a unique opportunity to study the effects of fetal insulin on birth weight in humans. We sought to quantify the role of fetal insulin in fetal growth by studying birth weights in individuals without fetal insulin, either due to recessive loss-of-function mutations in the INS gene or pancreatic agenesis (Supplemental Note for methods and Supplemental Tables 1 and 2 for clinical details and genetics, respectively).
We also investigated whether reduced insulin-mediated fetal growth impacted on postnatal growth once insulin was replaced. The study was approved by the Wales Research Ethics Committee (17/WA/0327).
P values <0.05 were considered statistically significant and specific statistical tests are detailed in Figure 1.