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

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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 (betaz-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 (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.

Original languageEnglish
Pages (from-to)1110-1122
Number of pages13
JournalReproductive BioMedicine Online
Volume44
Issue number6
Early online date19 Jan 2022
DOIs
Publication statusPublished - 1 Jun 2022

Bibliographical note

Funding Information:
The Rotterdam Periconceptional Cohort (Predict Study) is conducted by the Department of Obstetrics and Gynecology at the Erasmus University Medical Center, Rotterdam, the Netherlands. We gratefully acknowledge the Rotterdam Periconceptional Cohort team for data acquisition and the participating couples, gynaecologists and midwifery practices in Rotterdam for their contributions. The authors thank Anton Koning for technical support. This research was funded by the Department of Obstetrics and Gynecology of the Erasmus University Medical Center.

Funding Information:
The Rotterdam Periconceptional Cohort (Predict Study) is conducted by the Department of Obstetrics and Gynecology at the Erasmus University Medical Center, Rotterdam, the Netherlands. We gratefully acknowledge the Rotterdam Periconceptional Cohort team for data acquisition and the participating couples, gynaecologists and midwifery practices in Rotterdam for their contributions. The authors thank Anton Koning for technical support. This research was funded by the Department of Obstetrics and Gynecology of the Erasmus University Medical Center.

Publisher Copyright:
© 2022 The Author(s)

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