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

Rosalieke E Wiegel; Damiat Aoulad Fares; Sten P Willemsen; Eric A P Steegers; A H Jan Danser; Régine P M Steegers-Theunissen

doi:10.1016/j.rbmo.2021.12.020

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

Reprod Biomed Online. 2022 Jun;44(6):1110-1122. doi: 10.1016/j.rbmo.2021.12.020. Epub 2022 Jan 19.

Authors

Rosalieke E Wiegel¹, Damiat Aoulad Fares¹, Sten P Willemsen², Eric A P Steegers¹, A H Jan Danser³, Régine P M Steegers-Theunissen⁴

Affiliations

¹ Department of Obstetrics and Gynecology, Erasmus University Medical Center, Rotterdam, the Netherlands.
² Department of Obstetrics and Gynecology, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Biostatistics, Erasmus University Medical Center, Rotterdam, the Netherlands.
³ Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
⁴ Department of Obstetrics and Gynecology, Erasmus University Medical Center, Rotterdam, the Netherlands. Electronic address: r.steegers@erasmusmc.nl.

PMID: 35379566
DOI: 10.1016/j.rbmo.2021.12.020

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) (<p10) and birthweight were retrieved from medical records.

Results: Prorenin concentrations at 11 weeks of gestation showed significant negative associations with late fetal growth (beta -0.07, 95% CI -0.11 to -0.03, P < 0.001) and birthweight (beta_z_-scores -0.28, 95% CI -0.55 to -0.01, P=0.03), and an increased risk of SGA (<p10) (OR 10.47, 95% CI 2.49 to 53.21, P=0.002). The aldosterone/renin ratio associated negatively with the risk of SGA (OR 0.38, 95% CI 0.15 to 0.91, P=0.03). In addition, adjusted linear regression models using the total Rotterdam Periconceptional Cohort (n=1401) confirmed decreased birthweight percentiles in pregnancies with >1 corpus luteum versus pregnancies with 1 corpus luteum (beta_z_-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.

Keywords: Corpus luteum; Fetal growth; Pregnancy; Prorenin; Renin–angiotensin–aldosterone system; Small for gestational age.

MeSH terms

Aldosterone
Birth Weight
Female
Fetal Development
Humans
Pregnancy
Pregnancy Trimester, First
Prospective Studies
Renin*
Renin-Angiotensin System* / physiology
Ultrasonography, Prenatal

Substances

Aldosterone
Renin