Perinatal and maternal outcomes of extremely early‐onset fetal growth restriction (≤ 26 weeks): systematic review and meta‐analysis

ABSTRACT Objective To report the perinatal and maternal outcomes of singleton pregnancies complicated by extremely early‐onset fetal growth restriction (FGR), defined as FGR diagnosed ≤ 26 weeks of gestation. Methods MEDLINE, EMBASE and Cochrane databases were searched for studies reporting the outcome of singleton pregnancies complicated by FGR diagnosed ≤ 26 weeks of gestation. The primary outcome was perinatal death (PND), defined as the sum of intrauterine death (IUD) and neonatal death (NND). Secondary outcomes included genetic anomaly, structural anomaly, infection, pre‐eclampsia (PE), IUD, NND, termination of pregnancy, preterm birth (PTB) ≤ 32 and ≤ 28 weeks of gestation, Cesarean delivery, vaginal delivery, admission to the neonatal intensive care unit, abnormal brain imaging, respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, neonatal sepsis, neurological morbidity, composite adverse perinatal outcome (CAPO) and intact survival. All outcomes were explored in the overall population of pregnancies complicated by extremely early‐onset FGR. A subset of outcomes was explored in a subgroup analysis of FGR etiology: apparently isolated FGR, FGR defined according to the Delphi criteria, or FGR due to genetic or structural anomaly. Among those with apparently isolated FGR, subgroup analyses were conducted according to the gestational‐age cut‐off used to define extremely early onset, gestational age at diagnosis, gestational age at birth and presence of abnormal Doppler findings. Random‐effects meta‐analysis of proportions was used to combine the data. Results Fourteen studies (2818 pregnancies) were included in the systematic review, of which 13 (2573 pregnancies) were included in the meta‐analysis. Among all fetuses with extremely early‐onset FGR, PND, IUD and NND occurred in 16.0% (95% CI, 8.1–26.0%), 8.8% (95% CI, 4.0–15.2%) and 6.2% (95% CI, 3.0–10.4%) of cases, respectively. PTB ≤ 32 and ≤ 28 weeks of gestation complicated 54.6% (95% CI, 23.1–84.2%) and 23.3% (95% CI, 4.7–50.3%) of pregnancies, respectively, while 45.6% (95% CI, 32.6–58.9%) underwent Cesarean delivery. CAPO affected 30.5% (95% CI, 19.4–42.8%) of infants, while neurological morbidity was reported in 38.3% (95% CI, 9.8–72.1%). Among pregnancies complicated by apparently isolated extremely early‐onset FGR, PND occurred in 14.3% (95% CI, 6.2–25.0%) of cases. PTB ≤ 32 and ≤ 28 weeks of gestation occurred in 54.8% (95% CI, 49.8–59.7%) and 23.6% (95% CI, 4.9–50.6%) of cases, respectively. CAPO occurred in 28.8% (95% CI, 20.4–38.0%) of infants, while neurological morbidity was present in 38.3% (95% CI, 9.8–72.1%). In pregnancies complicated by extremely early‐onset FGR due to a genetic or structural anomaly, PND occurred in 17.6% (95% CI, 6.2–33.3%) and CAPO in 19.3% (95% CI, 7.6–34.9%). Conclusion Pregnancies with extremely early‐onset FGR are at high risk of genetic and structural anomalies, as well as adverse maternal and perinatal outcomes. © 2025 International Society of Ultrasound in Obstetrics and Gynecology.