Pregnancy with multiple high-risk factors: a systematic review and meta-analysis.

Background: A wide spectrum of high-risk factors in pregnancy can lead to adverse pregnancy outcomes or short- or long-term health effects. Despite this, there has been no synthesis of findings on the measurement, potential causes, and health outcomes of multiple high-risk factors in pregnancy (MHFP). We aimed to address this gap by summarising the existing research on this topic. Methods: We retrieved studies published up to 3 June 2024 through systematic database searches and used a narrative synthesis approach to summarise the measurement, patterns, causes, and outcomes of MHFP. We also estimated the pooled MHFP prevalence through meta-analysis with a random effects model and performed subgroup analyses and meta-regression to examine potential sources of between-study heterogeneity. Results: We included 83 observational studies published between 2010 and 2024, of which 72% were from high-income countries. These studied factors can be grouped into four categories: physical conditions, mental conditions, sociobehavioural problems, and pregnancy history. We identified 16 MHFP patterns, among which co-existing multiple physical conditions were the most common pattern. The overall pooled prevalence of MHFP was 12% (95% confidence interval (CI) = 12-13), with an increasing trend and relatively higher levels in low- and middle-income countries (LMICs). We observed heterogeneity in the measurement of MHFP across the studies, possibly due to the number of risk factors in the definition of MHFP. About 78% of included studies investigated MHFP-associated health outcomes for women and offspring, with only two studies examining long-term maternal or offspring outcomes later in life. Conclusions: Research into MHFP has been emerging over the past decade, but is far from complete. The burden of MHFP is increasing worldwide, particularly LMICs. Maternal healthcare systems must shift to a multidisciplinary and integrated framework so as to better design and implement prevention and intervention programmes and sustain the healthy development of the next generation. Registration: PROSPERO: CRD42022358889.