First-trimester maternal renin–angiotensin–aldosterone system activation and fetal growth and birthweight: the Rotterdam Periconceptional Cohort

Abstract

Research question: Does first-trimester maternal renin–angiotensin–aldosterone system (RAAS) activity determine early and late fetal growth and birthweight? Design: A total of 201 ongoing pregnancies, of which 104 were conceived naturally, seven following single intrauterine insemination (IUI), eight after IUI with ovulation induction and 82 after IVF or intracytoplasmic sperm injection treatment were selected from the Rotterdam Periconceptional Cohort. Renin, prorenin and aldosterone concentrations were determined in blood plasma at 9 and 11 weeks of gestational age. Serial crown–rump length and embryonic volume at 7, 9 and 11 weeks of gestational age were measured using virtual reality software to assess early fetal growth. Estimated fetal weight at 22 and 32 weeks of gestational age and birthweight were measured to assess late fetal growth trajectories. Pregnancy outcomes, small for gestational age (SGA) ( < 0.001) and birthweight (betaz-scores –0.28, 95% CI –0.55 to –0.01, P=0.03), and an increased risk of SGA ( 1 corpus luteum versus pregnancies with 1 corpus luteum (betaz-scores –0.17, 95% CI –0.32 to –0.01, P=0.04). Conclusion: This study shows that excessive first-trimester prorenin release, resulting in angiotensin up-regulation, can explain why pregnancies with >1 corpus luteum are at risk for offspring with decreased birthweight and SGA. Simultaneously, high concentrations of aldosterone, independent of renin, seem to have a beneficial influence.