# Risk Factors and Outcomes Associated With Delayed Villous Maturation in Placenta: A Systematic Review and Meta‐Analysis

## TL;DR

This study finds that delayed villous maturation in the placenta is linked to maternal conditions like diabetes and obesity, and leads to serious pregnancy complications such as stillbirth and preterm birth.

## Contribution

The study provides a comprehensive meta-analysis of risk factors and outcomes for delayed villous maturation using a systematic review approach.

## Key findings

- Gestational diabetes, pregestational diabetes, and maternal obesity are significant risk factors for DVM.
- DVM is strongly associated with stillbirth, preterm birth, and congenital fetal malformations.
- The association between DVM and stillbirth remains significant when using the Amsterdam criteria for DVM.

## Abstract

Delayed villous maturation (DVM) is a placental maturation disorder that mainly affects maternal‐to‐foetal oxygen transfer.

We conducted a systematic review, meta‐analysis, and sensitivity analysis exploring study heterogeneities (I

2
) of risk factors and outcomes associated with histopathological findings of DVM.

Medline, EMBASE, Web of Science, and MIDIRS databases were searched from inception to December 2023.

Peer‐reviewed, observational studies including cohort, case–control, and cross‐sectional studies reported the histopathological findings of DVM after placenta delivery. All eligible studies were included and assessed for their risk of bias using the Newcastle‐Ottawa scale (NOS) for cohort and case–control studies.

Two reviewers independently performed the systematic article screening, bias assessment, and data extraction. Senior authors resolved the disagreement between reviewers. The risk of bias was assessed by two reviewers using NOS criteria. The random‐effects model was used for meta‐analysis due to heterogeneity across studies. Sensitivity analyses were performed according to the NOS risk of bias assessment and the DVM definition per the Amsterdam criteria.

Fifty‐two eligible studies reporting DVM and linked risk factors and outcomes were included. The risk factors associated with DVM were gestational diabetes (GDM) (OR = 4.90; 95% CI = 2.98, 8.06; I
2 = 39%), pregestational diabetes (PGDM) (OR = 2.77; 95% CI = 1.56, 4.92; I
2 = 0%), and maternal obesity (OR = 1.88; 95% CI = 1.20, 2.96; I
2 = 0%). DVM was also associated with congenital foetal malformations (OR = 5.22; 95% CI =2.39, 11.39; I

2
 = 40), stillbirth (OR = 4.89; 95% CI = 3.55, 6.72; I

2
 = 0) and preterm birth (OR = 17.41; 95% CI = 10.14, 29.90; I
2 = 0). The association between DVM and stillbirth (OR = 12.06; 95% CI =3.40, 42.78; I
2 = 50; 2/5 studies) persisted in analyses limited to studies that used Amsterdam criteria exclusively for DVM.

DVM is a placental abnormality associated with congenital foetal malformations and maternal dysmetabolism, including GDM, PGDM, and maternal obesity; and with adverse outcomes including stillbirth and preterm birth. In studies using Amsterdam criteria, placenta with DVM was associated with stillbirth and congenital malformations. Optimising metabolism could prevent harm to the baby.