Reference ranges of anti‐Müllerian hormone and interaction with placental biomarkers in early pregnancy: the Generation R Study, a population-based prospective cohort study

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Abstract

Objective

The primary objective of this study is to establish maternal reference values of anti‐Müllerian hormone (AMH) in a fertile multi-ethnic urban pregnant population and to evaluate the effect of gestational age. The secondary objective of this study is to explore the association between AMH and placental biomarkers.

Design

This study was embedded in the Generation R Study, an ongoing population-based prospective cohort study from early pregnancy onwards.

Setting

City of Rotterdam, the Netherlands, out of hospital setting.

Patients

In 5806 women, serum AMH levels were determined in early pregnancy (median 13.5 weeks; 95% range 10.5–17.2).

Intervention(s)

None.

Main outcome measures

Maternal AMH levels in early pregnancy and its association with placental biomarkers, including human chorionic gonadotrophin (hCG), soluble fms-like tyrosine kinase-1 (sFLT), and placental growth factor (PLGF).

Results

A nomogram of AMH in early pregnancy was developed. Serum AMH levels showed a decline with advancing gestational age. Higher AMH levels were associated with a higher level of the placental biomarkers hCG and sFLT in early pregnancy. This last association was predominantly mediated by hCG. AMH levels were negatively associated with PLGF levels.

Conclusion

In this large study, we show that AMH levels in early pregnancy decrease with advancing gestational age. The association between AMH and the placental biomarkers hCG, sFLT, and PLGF suggests a better placental development with lower vascular resistance in mothers with higher AMH levels. Hence, AMH might be useful in predicting adverse pregnancy outcomes due to impaired placental development.

Related collections

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Pre-eclampsia remains a leading cause of maternal and perinatal mortality and morbidity. It is a pregnancy-specific disease characterised by de-novo development of concurrent hypertension and proteinuria, sometimes progressing into a multiorgan cluster of varying clinical features. Poor early placentation is especially associated with early onset disease. Predisposing cardiovascular or metabolic risks for endothelial dysfunction, as part of an exaggerated systemic inflammatory response, might dominate in the origins of late onset pre-eclampsia. Because the multifactorial pathogenesis of different pre-eclampsia phenotypes has not been fully elucidated, prevention and prediction are still not possible, and symptomatic clinical management should be mainly directed to prevent maternal morbidity (eg, eclampsia) and mortality. Expectant management of women with early onset disease to improve perinatal outcome should not preclude timely delivery-the only definitive cure. Pre-eclampsia foretells raised rates of cardiovascular and metabolic disease in later life, which could be reason for subsequent lifestyle education and intervention. Copyright 2010 Elsevier Ltd. All rights reserved.

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The Generation R Study: design and cohort update 2017

Marjolein Kooijman, Claudia Kruithof, Cornelia M. van Duijn … (2016)

The Generation R Study is a population-based prospective cohort study from fetal life until adulthood. The study is designed to identify early environmental and genetic causes and causal pathways leading to normal and abnormal growth, development and health from fetal life, childhood and young adulthood. This multidisciplinary study focuses on several health outcomes including behaviour and cognition, body composition, eye development, growth, hearing, heart and vascular development, infectious disease and immunity, oral health and facial growth, respiratory health, allergy and skin disorders of children and their parents. Main exposures of interest include environmental, endocrine, genomic (genetic, epigenetic, microbiome), lifestyle related, nutritional and socio-demographic determinants. In total, 9778 mothers with a delivery date from April 2002 until January 2006 were enrolled in the study. Response at baseline was 61%, and general follow-up rates until the age of 10 years were around 80%. Data collection in children and their parents includes questionnaires, interviews, detailed physical and ultrasound examinations, behavioural observations, lung function, Magnetic Resonance Imaging and biological sampling. Genome and epigenome wide association screens are available. Eventually, results from the Generation R Study contribute to the development of strategies for optimizing health and healthcare for pregnant women and children.

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Author and article information

Journal

Journal ID (nlm-ta): Endocr Connect

Journal ID (iso-abbrev): Endocr Connect

Journal ID (hwp): EC

Title: Endocrine Connections

Publisher: Bioscientifica Ltd (Bristol )

ISSN (Electronic): 2049-3614

Publication date (Electronic): 16 December 2022

Publication date Collection: 01 March 2023

Volume: 12

Issue: 3

Electronic Location Identifier: e220320

Affiliations

[1 ]Division of Reproductive Endocrinology and Infertility , Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

[2 ]Division of Obstetrics and Fetal Medicine , Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

[3 ]Generation R Study Group , Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

[4 ]Department of Clinical Chemistry , Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

[5 ]Department of Internal Medicine , Academic Center for Thyroid Diseases, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

[6 ]Ansh Labs , Webster, Texas, USA

Author notes

Correspondence should be addressed to R H Dykgraaf: r.dykgraaf@ 123456erasmusmc.nl

^†Deceased.

Author information

R H M Dykgraaf http://orcid.org/0000-0003-1519-4285

Article

Publisher ID: EC-22-0320

DOI: 10.1530/EC-22-0320

PMC ID: 9986396

PubMed ID: 36524811

SO-VID: d893c3ba-5fa0-4193-a718-0cee64a5bcec

License:

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

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