PMID- 38335157 OWN - NLM STAT- MEDLINE DCOM- 20240214 LR - 20240214 IS - 1549-1676 (Electronic) IS - 1549-1277 (Print) IS - 1549-1277 (Linking) VI - 21 IP - 2 DP - 2024 Feb TI - Fetal loss and long-term maternal morbidity and mortality: A systematic review and meta-analysis. PG - e1004342 LID - 10.1371/journal.pmed.1004342 [doi] LID - e1004342 AB - BACKGROUND: Evidence suggests common pathways between pregnancy losses and subsequent long-term maternal morbidity, rendering pregnancy complications an early chronic disease marker. There is a plethora of studies exploring associations between miscarriage and stillbirth with long-term adverse maternal health; however, these data are inconclusive. METHODS AND FINDINGS: We systematically searched MEDLINE, EMBASE, AMED, BNI, CINAHL, and the Cochrane Library with relevant keywords and MeSH terms from inception to June 2023 (no language restrictions). We included studies exploring associations between stillbirth or miscarriage and incidence of cardiovascular, malignancy, mental health, other morbidities, and all-cause mortality in women without previous pregnancy loss. Studies reporting short-term morbidity (within a year of loss), case reports, letters, and animal studies were excluded. Study selection and data extraction were performed by 2 independent reviewers. Risk of bias was assessed using the Newcastle Ottawa Scale (NOS) and publication bias with funnel plots. Subgroup analysis explored the effect of recurrent losses on adverse outcomes. Statistical analysis was performed using an inverse variance random effects model and results are reported as risk ratios (RRs) with 95% confidence intervals (CIs) and prediction intervals (PIs) by combining the most adjusted RR, odds ratios (ORs) and hazard ratios (HRs) under the rare outcome assumption. We included 56 observational studies, including 45 in meta-analysis. There were 1,119,815 women who experienced pregnancy loss of whom 951,258 had a miscarriage and 168,557 stillbirth, compared with 11,965,574 women without previous loss. Women with a history of stillbirth had a greater risk of ischaemic heart disease (IHD) RR 1.56, 95% CI [1.30, 1.88]; p < 0.001, 95% PI [0.49 to 5.15]), cerebrovascular (RR 1.71, 95% CI [1.44, 2.03], p < 0.001, 95% PI [1.92, 2.42]), and any circulatory/cardiovascular disease (RR 1.86, 95% CI [1.01, 3.45], p = 0.05, 95% PI [0.74, 4.10]) compared with women without pregnancy loss. There was no evidence of increased risk of cardiovascular disease (IHD: RR 1.11, 95% CI [0.98, 1.27], 95% PI [0.46, 2.76] or cerebrovascular: RR 1.01, 95% CI [0.85, 1.21]) in women experiencing a miscarriage. Only women with a previous stillbirth were more likely to develop type 2 diabetes mellitus (T2DM) (RR: 1.16, 95% CI [1.07 to 2.26]; p < 0.001, 95% PI [1.05, 1.35]). Women with a stillbirth history had an increased risk of developing renal morbidities (RR 1.97, 95% CI [1.51, 2.57], p < 0.001, 95% [1.06, 4.72]) compared with controls. Women with a history of stillbirth had lower risk of breast cancer (RR: 0.80, 95% CI [0.67, 0.96], p-0.02, 95% PI [0.72, 0.93]). There was no evidence of altered risk of other malignancies in women experiencing pregnancy loss compared to controls. There was no evidence of long-term mental illness risk in women with previous pregnancy losses (stillbirth: RR 1.90, 95% CI [0.93, 3.88], 95% PI [0.34, 9.51], miscarriage: RR 1.78, 95% CI [0.88, 3.63], 95% PI [1.13, 4.16]). The main limitations include the potential for confounding due to use of aggregated data with variable degrees of adjustment. CONCLUSIONS: Our results suggest that women with a history of stillbirth have a greater risk of future cardiovascular disease, T2DM, and renal morbidities. Women experiencing miscarriages, single or multiple, do not seem to have an altered risk. CI - Copyright: (c) 2024 Vlachou 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. FAU - Vlachou, Florentia AU - Vlachou F AUID- ORCID: 0000-0001-5044-8039 AD - Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Whitechapel, London, United Kingdom. FAU - Iakovou, Despoina AU - Iakovou D AUID- ORCID: 0000-0003-2416-7764 AD - Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Whitechapel, London, United Kingdom. FAU - Daru, Jahnavi AU - Daru J AUID- ORCID: 0000-0001-5816-2609 AD - Women's Health Research Unit, Institute for Population Health, Queen Mary University of London, London, United Kingdom. FAU - Khan, Rehan AU - Khan R AUID- ORCID: 0000-0003-0428-3039 AD - Royal London Hospital, Department of Obstetrics & Gynaecology, Barts Health NHS Trust, London, United Kingdom. FAU - Pepas, Litha AU - Pepas L AUID- ORCID: 0009-0002-1608-757X AD - Barts Centre of Reproductive Medicine, Barts NHS Trust, London, United Kingdom. FAU - Quenby, Siobhan AU - Quenby S AD - Division of Reproductive Health, Centre for Early Life, Warwick Medical School, University of Warwick, Coventry, United Kingdom. FAU - Iliodromiti, Stamatina AU - Iliodromiti S AD - Women's Health Research Unit, Institute for Population Health, Queen Mary University of London, London, United Kingdom. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20240209 PL - United States TA - PLoS Med JT - PLoS medicine JID - 101231360 SB - IM MH - Pregnancy MH - Female MH - Humans MH - Pregnancy Outcome MH - Stillbirth/epidemiology MH - *Abortion, Spontaneous/epidemiology MH - *Diabetes Mellitus, Type 2 MH - *Cardiovascular Diseases PMC - PMC10857720 COIS- JD has been employed as a consultant to the World Health Organisation in the Department of Nutrition and Food Safety. This has had no impact on this work or the decision to submit this manuscript. The other authors have declared no competing interests. EDAT- 2024/02/09 18:42 MHDA- 2024/02/09 18:43 PMCR- 2024/02/09 CRDT- 2024/02/09 13:23 PHST- 2023/02/17 00:00 [received] PHST- 2024/01/03 00:00 [accepted] PHST- 2024/02/09 18:43 [medline] PHST- 2024/02/09 18:42 [pubmed] PHST- 2024/02/09 13:23 [entrez] PHST- 2024/02/09 00:00 [pmc-release] AID - PMEDICINE-D-23-00438 [pii] AID - 10.1371/journal.pmed.1004342 [doi] PST - epublish SO - PLoS Med. 2024 Feb 9;21(2):e1004342. doi: 10.1371/journal.pmed.1004342. eCollection 2024 Feb.