Hypoxia-ischaemia and the insulin-like growth factor (IGF) family at birth
PJ Pringle1, MG Geary2, CH Rodeck2, JCP Kingdom3 & PC Hindmarsh1
Animal studies suggest that circulating IGF-1 concentrations are influenced by hypoxia. To test whether a similar situation pertains in humans we related cord IGF-1 concentrations to cord pH in the babies of 1650 Caucasian mothers delivering at term. All pregnancies were singleton and antenatal growth and uterine blood flow was assessed at 20 and 32 weeks gestation. Hypoxia was chronic if associated with preeclampsia in non-smokers and acute based on cord pH. Effects of cigarette smoking was evaluated seperately. At birth mean cord pH was 7.29 (range 6.90-7.49) and was related to neonatal APGAR score at 1 minute (r=0.29; p<0.01) but not at 5 minutes indicating that cord pH reflected acute hypoxia. Mean birth weight expressed as a standard deviation score (SDS) was +0.15 (SD 0.96) and cord IGF-1 and IGF-2 concentrations 69.9 nmol/L (SD 26.4) and 517 nmol/L (SD 120) respectively. Cord IGF-1 concentrations were weakly related to cord pH (r=0.20; p<0.001). Cord IGF-2 and IGFBP3 were not. There was no relationship between cord pH and markers of palcenta function, placental weight and infarction grading. Preeclapsia had no effect on the IGF family. There was a clear effect of cigarette smoking on cord IGF-1 concentrations (70.2ng/ml non-smokers versus 60.7ng/ml in 20 per day smokers) and birth size (150g reduction). Neither cord IGF-2 concentrations nor cord pH were influenced by cigarette smoking. Cord IGFBP3 concentrations paralleled those of IGF-1. Placental weight was unaffected by smoking but the proportion of infarcted placentae increased (p<0.001) resulting in reduced uterine artery blood flow. In multiple regression analysis cord IGF-1 and cigarette smoking were the dominant factors in determining birth weight (R2=0.45; p<0.001).
These data suggest that smoking reduces uterine artery blood flow leading to placental infarction and compensatory changes in the placental vasculature in an attempt to maintain nutrient delivery. This effect is dose dependent leading to a reduction in IGF-1 and body size.