Abstract: Our search strategy identified six reports for potential inclusion. Of those, we included one trial (four reports) involving 158 women, which was at low risk of bias. The one included trial examined the effect of prenatal repair versus postnatal repair. For the primary infant outcome of neonatal mortality, there was no clear evidence of a difference identified for prenatal versus postnatal repair (one study, 158 infants, risk ratio (RR) 0.51, 95% confidence interval (CI) 0.05 to 5.54), however event rates were uncommon and so the analysis is likely to be underpowered to detect differences. Prenatal repair was associated with an earlier gestational age at birth (one study, 158 infants, mean difference (MD) -3.20 weeks, 95% CI -3.93 to -2.47) and a corresponding increase in both the risk of preterm birth before 37 weeks (one study, 158 infants, RR 5.30, 95% CI 3.11 to 9.04) and preterm birth before 34 weeks (one study, 158 infants, RR 9.23, 95% CI 3.45 to 24.71). Prenatal repair was associated with a reduction in shunt dependent hydrocephalus and moderate to severe hindbrain herniation. For women, prenatal repair was associated with increased preterm ruptured membranes (one study, 158 women, RR 6.15, 95% CI 2.75 to 13.78), although there was no clear evidence of difference in the risk of chorioamnionitis or blood transfusion, although again, event rates were uncommon. A number of this review's secondary infant and maternal outcomes were not reported. For the infant: days of hospital admission; survival to discharge; stillbirth; need for further surgery (e.g. skin grafting); neurogenic bladder dysfunction; childhood/infant quality of life. For the mother: admission to intensive care; women's emotional wellbeing and satisfaction with care. This review is based one small well-conducted study. There is insufficient evidence to recommend drawing firm conclusions on the benefits or harms of prenatal repair as an intervention for fetuses with spina bifida. Current evidence is limited by the small number of pregnancies that have been included in the single conducted randomised trial to date.

Plain-language summary: This review aimed to compare the effects of in utero repair versus repair as a newborn. We included one randomised controlled trial involving 158 women who were from 19 to 27 weeks pregnant with a baby with severe spina bifida and evidence of hindbrain herniation. For neonatal mortality, there was no clear difference identified for prenatal versus postnatal repair. However, the numbers of neonates who died were low and so the review was likely underpowered to detect any difference. Prenatal repair was associated with reduced need for shunt placement and a reduction in the risk of moderate to severe hindbrain herniation after birth. No direct complications of the repair procedure were evident, including orthopaedic deformities. Prenatal repair was associated with an increased risk of the women experiencing preterm ruptured membranes and subsequent preterm birth (both before 34 and 37 weeks). Severe maternal illness (infection and need for blood transfusion) were not clearly different; although the review was underpowered to detect any difference in these important, less common outcomes. The included trial was of high quality (low risk of bias) but included a small number of pregnancies. There is currently insufficient evidence to recommend in utero repair for unborn babies with spina bifida.