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Risk of Adverse Pregnancy Outcomes at Advanced Maternal Age

Frederiksen, Line, Elmerdahl, MSc; Ernst, Andreas, MD; Brix, Nis, MD; Braskhøj Lauridsen, Lea, Lykke, BSc; Roos, Laura, MD; Ramlau-Hansen, Cecilia, Høst, MSc, PhD; Ekelund, Charlotte, Kvist, MD, PhD

doi: 10.1097/AOG.0000000000002504
Contents: Original Research

OBJECTIVE: To study the possible associations between advanced maternal age and risk of selected adverse pregnancy outcomes.

METHODS: The study used a nationwide cohort of 369,516 singleton pregnancies in Denmark followed from 11–14 weeks of gestation to delivery or termination of pregnancy. Pregnant women aged 35 years or older were divided into two advanced maternal age groups, 35–39 years and 40 years or older, and compared with pregnant women aged 20–34 years. Adverse pregnancy outcomes were chromosomal abnormalities, congenital malformations, miscarriage, stillbirth, and birth before 34 weeks of gestation. Multivariable logistic regression analyses were performed to investigate associations between advanced maternal age and adverse pregnancy outcomes. Furthermore, a risk prediction model for a composite adverse pregnancy outcome was made with prespecified predicting factors.

RESULTS: Among the pregnant women aged 40 years or older, 10.82% experienced one or more of the selected adverse pregnancy outcomes compared with 5.46% of pregnant women aged 20–34 years (odds ratio [OR] 2.02, 99.8% CI 1.78–2.29). When pregnant women 40 years or older were compared with women aged 20–34 years, they had a higher risk of chromosomal abnormalities (3.83% vs 0.56%, OR 7.44 [CI 5.93–9.34]), miscarriage (1.68% vs 0.42%, OR 3.10 [CI 2.19–4.38]), and birth before 34 weeks of gestation (2.01% vs 1.21%, OR 1.66 [CI 1.23–2.24]), but no increased risk of congenital malformations and stillbirth. The risk prediction chart showed that advanced maternal age, use of assisted reproductive technology, nulliparous pregnancy, smoking during pregnancy, and obesity increased the absolute predictive risk of an adverse pregnancy outcome.

CONCLUSION: Women older than 40 years have a higher risk of chromosomal abnormalities, miscarriage, and birth before 34 weeks of gestation than younger women and should be monitored accordingly. No increased risk was observed for stillbirth and other congenital malformations. Several factors increase the risk of adverse pregnancy outcomes, but advanced maternal age drives a high proportion of the total risk score.

Advanced maternal age is associated with higher risk of chromosomal abnormalities, miscarriage, and birth before 34 weeks of gestation, but not with congenital malformations and stillbirth.

Department of Public Health and the Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark; and the Department of Clinical Genetics, Juliane Marie Centre, and the Department of Obstetrics, Center of Fetal Medicine, Rigshospitalet, Copenhagen, Denmark.

Corresponding author: Line Elmerdahl Frederiksen, MSc, Strandboulevarden 49, DK-2100, Copenhagen, Denmark; email:

Financial Disclosure The authors did not report any potential conflicts of interest.

Each author has indicated that he or she has met the journal's requirements for authorship.

© 2018 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.