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      Advanced maternal age and adverse pregnancy outcomes: A systematic review and meta-analysis

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          Abstract

          Background

          Advanced maternal age (AMA; ≥35 years) is an increasing trend and is reported to be associated with various pregnancy complications.

          Objective

          To determine the risk of stillbirth and other adverse pregnancy outcomes in women of AMA.

          Search strategy

          Embase, Medline (Ovid), Cochrane Database of Systematic Reviews, ClinicalTrials.gov, LILACS and conference proceedings were searched from ≥2000.

          Selection criteria

          Cohort and case-control studies reporting data on one or more co-primary outcomes (stillbirth or fetal growth restriction (FGR)) and/or secondary outcomes in mothers ≥35 years and <35 years.

          Data collection and analysis

          The effect of age on pregnancy outcome was investigated by random effects meta-analysis and meta-regression. Stillbirth rates were correlated to rates of maternal diabetes, obesity, hypertension and use of assisted reproductive therapies (ART).

          Main results

          Out of 1940 identified titles; 63 cohort studies and 12 case-control studies were included in the meta-analysis. AMA increased the risk of stillbirth (OR 1.75, 95%CI 1.62 to 1.89) with a population attributable risk of 4.7%. Similar trends were seen for risks of FGR, neonatal death, NICU unit admission restriction and GDM. The relationship between AMA and stillbirth was not related to maternal morbidity or ART.

          Conclusions

          Stillbirth risk increases with increasing maternal age. This is not wholly explained by maternal co-morbidities and use of ART. We propose that placental dysfunction may mediate adverse pregnancy outcome in AMA. Further prospective studies are needed to directly test this hypothesis.

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          Most cited references29

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          Impact of maternal age on obstetric outcome.

          To estimate the effect of maternal age on obstetric outcomes. A prospective database from a multicenter investigation of singletons, the FASTER trial, was studied. Subjects were divided into 3 age groups: 1) less than 35 years, 2) 35-39 years, and 3) 40 years and older. Multivariable logistic regression analysis was used to assess the effect of age on outcomes after adjusting for race, parity, body mass index, education, marital status, smoking, medical history, use of assisted conception, and patient's study site. A total of 36,056 women with complete data were available: 28,398 (79%) less than 35 years of age; 6,294 (17%) 35-39 years; and 1,364 (4%) 40 years and older. Increasing age was significantly associated with miscarriage (adjusted odds ratio [adjOR]2.0 and 2.4 for ages 35-39 years and age 40 years and older, respectively), chromosomal abnormalities (adjOR 4.0 and 9.9), congenital anomalies (adjOR 1.4 and 1.7), gestational diabetes (adjOR 1.8 and 2.4), placenta previa (adjOR 1.8 and 2.8), and cesarean delivery (adjOR 1.6 and 2.0). Patients aged 35-39 years were at increased risk for macrosomia (adjOR 1.4). Increased risk for abruption (adjOR 2.3), preterm delivery (adjOR 1.4), low birth weight (adjOR 1.6), and perinatal mortality (adjOR 2.2) was noted in women aged 40 years and older. Increasing maternal age is independently associated with specific adverse pregnancy outcomes. Increasing age is a continuum rather than a threshold effect.
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            Maternal age and adverse pregnancy outcome: a cohort study.

            To examine the association between maternal age and a wide range of adverse pregnancy outcomes after adjustment for confounding factors in obstetric history and maternal characteristics.
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              Advanced maternal age and the risk of cesarean birth: a systematic review.

              The increasing pregnancy rate at advanced maternal age is contemporaneous with the increasing rate of cesarean birth. Several studies have found that advanced maternal age is a risk factor for cesarean birth. The objective of this systematic review was to assess the relationship between advanced maternal age and cesarean birth among nulliparous and multiparous women. To identify relevant studies, we searched the literature for articles published from January 1, 1995 to March 1, 2008, using Medline, EMBASE, PsychINFO, and CINAHL. We also hand-searched the bibliographies of retrieved articles to identify additional related studies. We included all cohort studies and all case-control studies that examined this association in developed countries. The Cochrane Collaboration's Review Manager software (5.0) was used to summarize the data. Twenty-one studies met the inclusion criteria and were included in the review. All studies demonstrated an increased risk of cesarean birth among women at advanced maternal age compared with younger women, for both nulliparas and multiparas (relative risk varied from 1.39 to 2.76). Because we found extreme heterogeneity (both statistical and clinical) among the included studies, we did not provide a pooled estimate of the risk of cesarean birth. All included studies illustrated an increased risk of cesarean birth among older women. Fifteen studies adjusted this association for potential confounders, which suggests that a valid and independent association is likely to exist between advanced maternal age and cesarean birth. However, the associated factors for this increased risk are not totally understood in the literature.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draft
                Role: Data curationRole: MethodologyRole: Validation
                Role: ConceptualizationRole: Funding acquisitionRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                17 October 2017
                2017
                : 12
                : 10
                : e0186287
                Affiliations
                [1 ] Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
                [2 ] St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom
                The Hospital for Sick Children, CANADA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist

                Author information
                http://orcid.org/0000-0001-6434-0782
                Article
                PONE-D-17-24584
                10.1371/journal.pone.0186287
                5645107
                29040334
                e5c506e5-775d-4591-afcf-d0a38e11c9b0
                © 2017 Lean et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 29 June 2017
                : 28 September 2017
                Page count
                Figures: 4, Tables: 2, Pages: 15
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100000306, Tommy's Baby Charity;
                Award Recipient :
                Tommy's the Baby Charity paid the salary of the primary investigator during the period of these studies. However, the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript and the author(s) received no specific funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Women's Health
                Obstetrics and Gynecology
                Stillbirths
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Meta-Analysis
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Methods
                Meta-Analysis
                Medicine and Health Sciences
                Women's Health
                Maternal Health
                Pregnancy
                Medicine and Health Sciences
                Women's Health
                Obstetrics and Gynecology
                Pregnancy
                Research and Analysis Methods
                Research Assessment
                Systematic Reviews
                Biology and Life Sciences
                Developmental Biology
                Embryology
                Placenta
                Biology and Life Sciences
                Anatomy
                Reproductive System
                Placenta
                Medicine and Health Sciences
                Anatomy
                Reproductive System
                Placenta
                Medicine and Health Sciences
                Vascular Medicine
                Blood Pressure
                Hypertension
                Hypertensive Disorders in Pregnancy
                Medicine and Health Sciences
                Women's Health
                Maternal Health
                Pregnancy
                Hypertensive Disorders in Pregnancy
                Medicine and Health Sciences
                Women's Health
                Obstetrics and Gynecology
                Pregnancy
                Hypertensive Disorders in Pregnancy
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Metabolic Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Women's Health
                Obstetrics and Gynecology
                Assisted Reproductive Technology
                Custom metadata
                All data included in this systematic review and meta-analysis are published and therefore accessible to the public. All publications used in our systematic review are referenced and a full table of included studies is available in the supplementary material.

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                Uncategorized

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