Pregnancy Conditions Associated with Delayed Villous Maturation in Placenta: A Systematic Review and Meta-Analysis

Background: Delayed villous maturation (DVM) also called DVI (distal villous immaturity) is a placental maturation disorder that mainly affects maternal-to-fetal oxygen transfer. Objective: We conducted a systematic review and meta-analysis of conditions associated with histopathological findings of DVM based on pathologist assessment after delivery. Search strategy Medline, EMBASE, Web of Science, and MIDIRS databases were searched from inception to December 2023. Selection criteria Peer-reviewed, observational studies including cohort, case-control, and cross-sectional studies reported the histopathological findings of DVM after placenta delivery. Data collection and analysis Two reviewers performed the systematic article screening, bias assessment, and data extraction. Senior authors resolved disagreement between reviewers. The risk of bias scoring was assessed using the Newcastle-Ottawa scale for cohort and case-control studies. The random-effect model was used for meta-analysis since there was clinical and statistical heterogeneity ( I 2 ) across studies. For comparisons with an I 2 value < 50% (low heterogeneity), the fixed-effect model was used. Main result There were 52 included studies considered eligible that reported DVM and linked pregnancy conditions. The conditions associated with DVM in term placentas were gestational diabetes (GDM) [OR(95%CI)=3.75(1.93, 7.29)], pregestational diabetes (PGDM) [OR(95%CI)=2.64(1.65, 4.22)], obesity [OR(95%CI)=1.91 (1.23, 2.98)], stillbirth [OR(95%CI)=5.46 (2.26, 13.20)], preterm birth [OR(95%CI)= 3.48 (1.11, 10.97)], and congenital anomalies [OR(95%CI)= 7.57 (3.91, 14.65)]. Conclusion: DVM is a placental abnormality associated with dysmetabolism, particularly pregnancy diabetes, and obesity; and with adverse outcomes including stillbirth and congenital anomalies. In studies with variable DVM definition, it was also associated with preterm birth. Optimising metabolism could avoid preventable harm to the baby.