Title: Stillbirth and long-term maternal morbidity and mortality; a systematic review and meta-analysis
Authors: Florentia Vlachou, Despoina Iakovou, Jahnavi Daru, Stamatina Iliodromiti
Introduction
·Stillbirth is a type of fetal loss in the mid-late 2nd trimester (1-3)
·Reported in >2,500,000 women annually, mostly in low and middle-income households (4)
·Evidence suggests correlation between stillbirth and future maternal disease (cardiovascular, metabolic, malignant) and increase risk of mortality. (5-7)
·Results are controversial with differences in size and population groups.
Objective:
·To quantify the correlation between stillbirth and long-term maternal morbidity and mortality
Methodology
·Design: Systematic review (SR) and meta-analysis (MA)
·Databases: MEDLINE, EMBASE, AMED, BNI, CINAHL, Cochrane Library and grey literature search
·Study selection: 2 independent reviewers
·Data Extraction: study design, participant and comparator demographic characteristics, definition of fetal loss, incidence of morbidity and mortality outcomes
·Risk of Bias: Newcastle Ottawa Scale (NOS) by 2 independent reviewers
·Statistical analysis:
oOutcomes: Ischaemic Heart Disease (IHD), Cerebrovascular Disease (CVD), All circulatory disease, Renal disease, Malignant disease, Type 2 Diabetes Mellitus (T2DM), Depression
oDichotomous outcomes using random effects model, presented as pooled risk ratios (RR) with 95% confidence intervals (CI)
oHeterogenicity: I2 statistics
Results
General characteristics
·29 studies included in SR and 22 in MA (PRISMA chart in figure 1)
·Total Exposed: 168,557 vs Total Controls: 8,547,276
·Mean follow-up 16.4 years
·Risk of bias: 18/29 studies low risk (NOS 7-9/9) and 1 high risk (NOS 5-9)
Outcomes
·IHD: RR 1.74 (95% CI [1.39-2.19, p<0.001)
·Cerebrovascular Disease: RR 1.71 (95% CI [1.44-2.04; p<0.001)
·Circulatory Disease: RR 1.86 (95% CI (1.01-3.45]; p=0.05)
·Renal disease: RR 1.97 (95% CI [1.51-2.57], p<0.001)
·T2DM: RR 1.34 (95% CI [0.95-1.89);p =0.09)
·Malignant disease:
Breast cancer: RR 0.83 (95% CI [0.69-0.99]; p=0.04)
Endometrial & ovarian cancer: no meta-analysis; no association
All cancer mortality: RR 1.17 (95% CI [0.95-1.45]; p=0.15, I2: 0%)
·Depression: RR 1.90 (95% CI [0.96-3.88]; p=0.08)
Conclusion and future work
·Women exposed to stillbirth have an increased risk of IHD, cerebrovascular and renal disease compared to those without previous history.
·We suggest follow up of women with stillbirth with focus on early lifestyle modifications aiming to prevent or diagnose such conditions early.
·However, the small number of studies in some analysis and the potential contributing confounders such as diet, exercise, and socioeconomic background require further research.
