The ADELIN analysis: the presence of ADenomyosis and its effects on matErnal, neonataL, and obstetrIc outcomes: a systematic review and meta-aNalysis

OBJECTIVE: To systematically review and quantify the impact of adenomyosis on maternal, neonatal, and obstetric outcomes. DATA SOURCES: A comprehensive, unrestricted search was conducted in MEDLINE, Scopus, Embase, Literatura Latino-Americana e do Caribe em Ciências da Saúde, Scientific Electronic Library Online, Cochrane, ClinicalTrials.gov, Cumulative Index to Nursing and Allied Health Literature, Psychological Information Database, Allied and Complementary Medicine Database, and gray literature up to the present date. STUDY ELIGIBILITY CRITERIA: Studies were selected if they compared maternal, neonatal, and/or obstetric outcomes in women with adenomyosis compared to those without adenomyosis. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to carry out meta-analyses using random-effects models reporting relative risks and 95% confidence intervals. The Risk Of Bias In Nonrandomized Studies-of Exposure tool and the Grading of Recommendations, Assessment, Development, and Evaluations methodology were used to rate the risk of bias and evidence certainty. Subgroup analysis was carried out by dividing studies according to the mode of conception. RESULTS: Thirty-nine studies (5,521,417 patients; 25,564 with adenomyosis) showed that adenomyosis was associated with increased risks of preeclampsia (relative risk, 2.24; 95% confidence interval, 1.34-3.75; I2=72.6%, low certainty), postpartum hemorrhage (relative risk, 1.73; 95% confidence interval, 1.2-2.49; I2=63.9%, low certainty), small for gestational age (relative risk, 1.79; 95% confidence interval, 1.34-2.39; I2=74.7%, low certainty), fetal malpresentation (relative risk, 1.95; 95% confidence interval, 1.29-2.93; I2=77.7%, low certainty), miscarriage (relative risk, 1.61; 95% confidence interval, 1.31-1.99; I2=82.99%, low certainty), preterm premature rupture of membranes (relative risk, 2.87; 95% confidence interval, 1.37-6.0; I2=35.2%, low certainty), placental malposition (relative risk, 3.26; 95% confidence interval, 2.76-3.86; I2=0%, low certainty), extreme preterm birth (relative risk, 3.71; 95% confidence interval, 1.75-7.88; I2=88.5%, low certainty), low birthweight (relative risk, 2.29; 95% confidence interval, 1.24-4.24; I2=91.5%, low certainty), and threatened preterm labor (relative risk, 1.54; 95% confidence interval, 1.37-1.73; very low certainty), although certainty of evidence was low to very low. No significant differences were observed for gestational diabetes, HELLP syndrome, uterine rupture, fetal growth restriction, fetal distress, intrauterine death, ectopic pregnancy, multiple pregnancy, premature rupture of membranes, Apgar <7, umbilical artery pH <7, or neonatal intensive care admission. CONCLUSION: Adenomyosis may be associated with increased risks of adverse maternal, obstetric, and neonatal outcomes; however, certainty of evidence was low to very low. While high-quality studies are needed to corroborate available findings, clinicians should be aware of these plausible increased risks to implement targeted prenatal surveillance, tailor pregnancy management, and optimize preconception counselling for women with adenomyosis.