Risks of stillbirth and neonatal death with advancing gestation at term: A systematic review and meta-analysis of cohort studies of 15 million pregnancies

Javaid Muglu, Henna Rather, David Arroyo-Manzano, Sohinee Bhattacharya, Imelda Balchin, Asma Khalil, Basky Thilaganathan, Khalid S. Khan, Javier Zamora, Shakila Thangaratinam (Corresponding Author)

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background
Despite advances in healthcare, stillbirth rates remain relatively unchanged. We conducted a systematic review to quantify the risks of stillbirth and neonatal death at term (from 37 weeks gestation) according to gestational age.

Methods and findings
We searched the major electronic databases Medline, Embase, and Google Scholar (January 1990–October 2018) without language restrictions. We included cohort studies on term pregnancies that provided estimates of stillbirths or neonatal deaths by gestation week. We estimated the additional weekly risk of stillbirth in term pregnancies that continued versus delivered at various gestational ages. We compared week-specific neonatal mortality rates by gestational age at delivery. We used mixed-effects logistic regression models with random intercepts, and computed risk ratios (RRs), odds ratios (ORs), and 95% confidence intervals (CIs). Thirteen studies (15 million pregnancies, 17,830 stillbirths) were included. All studies were from high-income countries. Four studies provided the risks of stillbirth in mothers of White and Black race, 2 in mothers of White and Asian race, 5 in mothers of White race only, and 2 in mothers of Black race only. The prospective risk of stillbirth increased with gestational age from 0.11 per 1,000 pregnancies at 37 weeks (95% CI 0.07 to 0.15) to 3.18 per 1,000 at 42 weeks (95% CI 1.84 to 4.35). Neonatal mortality increased when pregnancies continued beyond 41 weeks; the risk increased significantly for deliveries at 42 versus 41 weeks gestation (RR 1.87, 95% CI 1.07 to 2.86, p = 0.012). One additional stillbirth occurred for every 1,449 (95% CI 1,237 to 1,747) pregnancies that advanced from 40 to 41 weeks. Limitations include variations in the definition of low-risk pregnancy, the wide time span of the studies, the use of registry-based data, and potential confounders affecting the outcome.

Conclusions
Our findings suggest there is a significant additional risk of stillbirth, with no corresponding reduction in neonatal mortality, when term pregnancies continue to 41 weeks compared to delivery at 40 weeks.

Systematic review registration
PROSPERO CRD42015013785
Original languageEnglish
Article numbere1002838
Number of pages16
JournalPLoS Medicine
Volume16
Issue number7
DOIs
Publication statusPublished - 2 Jul 2019

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Stillbirth
Meta-Analysis
Cohort Studies
Pregnancy
Gestational Age
Confidence Intervals
Infant Mortality
Mothers
Odds Ratio
Perinatal Death
Logistic Models
Registries
Language
Databases
Delivery of Health Care

Keywords

  • LABOR INDUCTION
  • FETAL-DEATH
  • UNEXPLAINED STILLBIRTH
  • BIRTH-WEIGHT
  • AGE
  • POPULATION
  • MORTALITY

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Risks of stillbirth and neonatal death with advancing gestation at term : A systematic review and meta-analysis of cohort studies of 15 million pregnancies. / Muglu, Javaid; Rather, Henna; Arroyo-Manzano, David; Bhattacharya, Sohinee; Balchin, Imelda; Khalil, Asma; Thilaganathan, Basky; Khan, Khalid S.; Zamora, Javier; Thangaratinam, Shakila (Corresponding Author).

In: PLoS Medicine, Vol. 16, No. 7, e1002838, 02.07.2019.

Research output: Contribution to journalArticle

Muglu, J, Rather, H, Arroyo-Manzano, D, Bhattacharya, S, Balchin, I, Khalil, A, Thilaganathan, B, Khan, KS, Zamora, J & Thangaratinam, S 2019, 'Risks of stillbirth and neonatal death with advancing gestation at term: A systematic review and meta-analysis of cohort studies of 15 million pregnancies' PLoS Medicine, vol. 16, no. 7, e1002838. https://doi.org/10.1371/journal.pmed.1002838
Muglu, Javaid ; Rather, Henna ; Arroyo-Manzano, David ; Bhattacharya, Sohinee ; Balchin, Imelda ; Khalil, Asma ; Thilaganathan, Basky ; Khan, Khalid S. ; Zamora, Javier ; Thangaratinam, Shakila. / Risks of stillbirth and neonatal death with advancing gestation at term : A systematic review and meta-analysis of cohort studies of 15 million pregnancies. In: PLoS Medicine. 2019 ; Vol. 16, No. 7.
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abstract = "BackgroundDespite advances in healthcare, stillbirth rates remain relatively unchanged. We conducted a systematic review to quantify the risks of stillbirth and neonatal death at term (from 37 weeks gestation) according to gestational age.Methods and findingsWe searched the major electronic databases Medline, Embase, and Google Scholar (January 1990–October 2018) without language restrictions. We included cohort studies on term pregnancies that provided estimates of stillbirths or neonatal deaths by gestation week. We estimated the additional weekly risk of stillbirth in term pregnancies that continued versus delivered at various gestational ages. We compared week-specific neonatal mortality rates by gestational age at delivery. We used mixed-effects logistic regression models with random intercepts, and computed risk ratios (RRs), odds ratios (ORs), and 95{\%} confidence intervals (CIs). Thirteen studies (15 million pregnancies, 17,830 stillbirths) were included. All studies were from high-income countries. Four studies provided the risks of stillbirth in mothers of White and Black race, 2 in mothers of White and Asian race, 5 in mothers of White race only, and 2 in mothers of Black race only. The prospective risk of stillbirth increased with gestational age from 0.11 per 1,000 pregnancies at 37 weeks (95{\%} CI 0.07 to 0.15) to 3.18 per 1,000 at 42 weeks (95{\%} CI 1.84 to 4.35). Neonatal mortality increased when pregnancies continued beyond 41 weeks; the risk increased significantly for deliveries at 42 versus 41 weeks gestation (RR 1.87, 95{\%} CI 1.07 to 2.86, p = 0.012). One additional stillbirth occurred for every 1,449 (95{\%} CI 1,237 to 1,747) pregnancies that advanced from 40 to 41 weeks. Limitations include variations in the definition of low-risk pregnancy, the wide time span of the studies, the use of registry-based data, and potential confounders affecting the outcome.ConclusionsOur findings suggest there is a significant additional risk of stillbirth, with no corresponding reduction in neonatal mortality, when term pregnancies continue to 41 weeks compared to delivery at 40 weeks.Systematic review registrationPROSPERO CRD42015013785",
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T2 - A systematic review and meta-analysis of cohort studies of 15 million pregnancies

AU - Muglu, Javaid

AU - Rather, Henna

AU - Arroyo-Manzano, David

AU - Bhattacharya, Sohinee

AU - Balchin, Imelda

AU - Khalil, Asma

AU - Thilaganathan, Basky

AU - Khan, Khalid S.

AU - Zamora, Javier

AU - Thangaratinam, Shakila

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Y1 - 2019/7/2

N2 - BackgroundDespite advances in healthcare, stillbirth rates remain relatively unchanged. We conducted a systematic review to quantify the risks of stillbirth and neonatal death at term (from 37 weeks gestation) according to gestational age.Methods and findingsWe searched the major electronic databases Medline, Embase, and Google Scholar (January 1990–October 2018) without language restrictions. We included cohort studies on term pregnancies that provided estimates of stillbirths or neonatal deaths by gestation week. We estimated the additional weekly risk of stillbirth in term pregnancies that continued versus delivered at various gestational ages. We compared week-specific neonatal mortality rates by gestational age at delivery. We used mixed-effects logistic regression models with random intercepts, and computed risk ratios (RRs), odds ratios (ORs), and 95% confidence intervals (CIs). Thirteen studies (15 million pregnancies, 17,830 stillbirths) were included. All studies were from high-income countries. Four studies provided the risks of stillbirth in mothers of White and Black race, 2 in mothers of White and Asian race, 5 in mothers of White race only, and 2 in mothers of Black race only. The prospective risk of stillbirth increased with gestational age from 0.11 per 1,000 pregnancies at 37 weeks (95% CI 0.07 to 0.15) to 3.18 per 1,000 at 42 weeks (95% CI 1.84 to 4.35). Neonatal mortality increased when pregnancies continued beyond 41 weeks; the risk increased significantly for deliveries at 42 versus 41 weeks gestation (RR 1.87, 95% CI 1.07 to 2.86, p = 0.012). One additional stillbirth occurred for every 1,449 (95% CI 1,237 to 1,747) pregnancies that advanced from 40 to 41 weeks. Limitations include variations in the definition of low-risk pregnancy, the wide time span of the studies, the use of registry-based data, and potential confounders affecting the outcome.ConclusionsOur findings suggest there is a significant additional risk of stillbirth, with no corresponding reduction in neonatal mortality, when term pregnancies continue to 41 weeks compared to delivery at 40 weeks.Systematic review registrationPROSPERO CRD42015013785

AB - BackgroundDespite advances in healthcare, stillbirth rates remain relatively unchanged. We conducted a systematic review to quantify the risks of stillbirth and neonatal death at term (from 37 weeks gestation) according to gestational age.Methods and findingsWe searched the major electronic databases Medline, Embase, and Google Scholar (January 1990–October 2018) without language restrictions. We included cohort studies on term pregnancies that provided estimates of stillbirths or neonatal deaths by gestation week. We estimated the additional weekly risk of stillbirth in term pregnancies that continued versus delivered at various gestational ages. We compared week-specific neonatal mortality rates by gestational age at delivery. We used mixed-effects logistic regression models with random intercepts, and computed risk ratios (RRs), odds ratios (ORs), and 95% confidence intervals (CIs). Thirteen studies (15 million pregnancies, 17,830 stillbirths) were included. All studies were from high-income countries. Four studies provided the risks of stillbirth in mothers of White and Black race, 2 in mothers of White and Asian race, 5 in mothers of White race only, and 2 in mothers of Black race only. The prospective risk of stillbirth increased with gestational age from 0.11 per 1,000 pregnancies at 37 weeks (95% CI 0.07 to 0.15) to 3.18 per 1,000 at 42 weeks (95% CI 1.84 to 4.35). Neonatal mortality increased when pregnancies continued beyond 41 weeks; the risk increased significantly for deliveries at 42 versus 41 weeks gestation (RR 1.87, 95% CI 1.07 to 2.86, p = 0.012). One additional stillbirth occurred for every 1,449 (95% CI 1,237 to 1,747) pregnancies that advanced from 40 to 41 weeks. Limitations include variations in the definition of low-risk pregnancy, the wide time span of the studies, the use of registry-based data, and potential confounders affecting the outcome.ConclusionsOur findings suggest there is a significant additional risk of stillbirth, with no corresponding reduction in neonatal mortality, when term pregnancies continue to 41 weeks compared to delivery at 40 weeks.Systematic review registrationPROSPERO CRD42015013785

KW - LABOR INDUCTION

KW - FETAL-DEATH

KW - UNEXPLAINED STILLBIRTH

KW - BIRTH-WEIGHT

KW - AGE

KW - POPULATION

KW - MORTALITY

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