Biomarkers predicting adverse pregnancy outcomes in women living with obesity: a systematic review and meta-analysis

Objective

To systematically review the literature on associations between antenatal biomarkers and adverse pregnancy outcomes in women with BMI ≥30 kg/m². Data sources: Systematic literature searches used predefined search terms in PubMed, Ovid Embase, Ovid MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials. Databases were searched from inception to August 2024.

Study eligibility criteria

Interventional and observational studies comparing pregnancy outcomes amongst women with a pre- or early-pregnancy (<20 weeks’ gestation) BMI ≥30 kg/m² according to presence or amount of any antenatally measured biomarker were included.

Study appraisal and synthesis methods

Two reviewers independently assessed studies for inclusion against predefined inclusion and exclusion criteria. Risk of bias assessment was performed on included studies using the Newcastle-Ottawa Risk of Bias Tool. A narrative synthesis of eligible studies was constructed and data were meta-analysed, where possible, using random effects models. Certainty of evidence was assessed by GRADE rating.

Results

Total 49 studies were included in the review, representing >500 different biomarkers in 7479 pregnancies across 16 countries. Adiponectin was the only biomarker with sufficient data to meta-analyse with respect to the composite outcome. Lower adiponectin was associated with increased risk of the composite outcome (SMD −0.52, 95% CI −0.63, −0.41; P<.001, I² 0%). Lower adiponectin was also associated with increased risk of gestational diabetes (SMD −0.57, 95% CI −0.70, −0.43; P<.001, I² 0%) and pre-eclampsia (OR 0.65, 95% CI 0.44, 0.99; P=.047, I² 61.5%). Increased insulin concentrations were associated with gestational diabetes (SMD 0.35, 95% CI 0.22, −0.47; P<.001, I² 0%). Certainty of evidence regarding all associations was low or very low.

Conclusions

Decreased adiponectin and increased insulin are associated with increased risk of adverse pregnancy outcomes in women with BMI ≥30 kg/m². However, the low number of studies available for inclusion and low certainty of evidence mean that biomarker-based risk-stratification within pregnant women with BMI ≥30 kg/m² is not currently feasible. Further research is required to find ways of reliably targeting investigations during maternity care towards the subset of women living with obesity who are at highest risk of adverse outcomes.