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BACKGROUND: Patent ductus arteriosus (PDA) is associated with significant morbidity and mortality in preterm infants. Cyclooxygenase inhibitors (COX‐I) may prevent PDA‐related complications. Controversy exists on which COX‐I drug is the most effective and has the best safety profile in preterm infants. OBJECTIVES: To compare the effectiveness and safety of prophylactic COX‐I drugs and 'no COXI prophylaxis' in preterm infants using a Bayesian network meta‐analysis (NMA). SEARCH METHODS: Searches of Cochrane CENTRAL via Wiley, OVID MEDLINE and Embase via Elsevier were conducted on 9 December 2021. We conducted independent searches of clinical trial registries and conference abstracts; and scanned the reference lists of included trials and related systematic reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that enrolled preterm or low birth weight infants within the first 72 hours of birth without a prior clinical or echocardiographic diagnosis of PDA and compared prophylactic administration of indomethacin or ibuprofen or acetaminophen versus each other, placebo or no treatment. DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane Neonatal. We used the GRADE NMA approach to assess the certainty of evidence derived from the NMA for the following outcomes: severe intraventricular haemorrhage (IVH), mortality, surgical or interventional PDA closure, necrotizing enterocolitis (NEC), gastrointestinal perforation, chronic lung disease (CLD) and cerebral palsy (CP). MAIN RESULTS: We included 28 RCTs (3999 preterm infants). Nineteen RCTs (n = 2877) compared prophylactic indomethacin versus placebo/no treatment, 7 RCTs (n = 914) compared prophylactic ibuprofen versus placebo/no treatment and 2 RCTs (n = 208) compared prophylactic acetaminophen versus placebo/no treatment. Nine RCTs were judged to have high risk of bias in one or more domains.We identified two ongoing trials on prophylactic acetaminophen. Bayesian random‐effects NMA demonstrated that prophylactic indomethacin probably led to a small reduction in severe IVH (network RR 0.66, 95% Credible Intervals [CrI] 0.49 to 0.87; absolute risk difference [ARD] 43 fewer [95% CrI, 65 fewer to 16 fewer] per 1000; median rank 2, 95% CrI 1‐3; moderate‐certainty), a moderate reduction in mortality (network RR 0.85, 95% CrI 0.64 to 1.1; ARD 24 fewer [95% CrI, 58 fewer to 16 more] per 1000; median rank 2, 95% CrI 1‐4; moderate‐certainty) and surgical PDA closure (network RR 0.40, 95% CrI 0.14 to 0.66; ARD 52 fewer [95% CrI, 75 fewer to 30 fewer] per 1000; median rank 2, 95% CrI 1‐2; moderate‐certainty) compared to placebo. Prophylactic indomethacin resulted in trivial difference in NEC (network RR 0.76, 95% CrI 0.35 to 1.2; ARD 16 fewer [95% CrI, 42 fewer to 13 more] per 1000; median rank 2, 95% CrI 1‐3; high‐certainty), gastrointestinal perforation (network RR 0.92, 95% CrI 0.11 to 3.9; ARD 4 fewer [95% CrI, 42 fewer to 137 more] per 1000; median rank 1, 95% CrI 1‐3; moderate‐certainty) or CP (network RR 0.97, 95% CrI 0.44 to 2.1; ARD 3 fewer [95% CrI, 62 fewer to 121 more] per 1000; median rank 2, 95% CrI 1‐3; low‐certainty) and may result in a small increase in CLD (network RR 1.10, 95% CrI 0.93 to 1.3; ARD 36 more [95% CrI, 25 fewer to 108 more] per 1000; median rank 3, 95% CrI 1‐3; low‐certainty). Prophylactic ibuprofen probably led to a small reduction in severe IVH (network RR 0.69, 95% CrI 0.41 to 1.14; ARD 39 fewer [95% CrI, 75 fewer to 18 more] per 1000; median rank 2, 95% CrI 1‐4; moderate‐certainty) and moderate reduction in surgical PDA closure (network RR 0.24, 95% CrI 0.06 to 0.64; ARD 66 fewer [95% CrI, from 82 fewer to 31 fewer] per 1000; median rank 1, 95% CrI 1‐2; moderate‐certainty) compared to placebo. Prophylactic ibuprofen may result in moderate reduction in mortality (network RR 0.83, 95% CrI 0.57 to 1.2; ARD 27 fewer [95% CrI, from 69 fewer to 32 more] per 1000; median rank 2, 95% CrI 1‐4; low‐certainty) and leads to trivial difference in NEC (network RR 0.73, 95% CrI 0.31 to 1.4; ARD 18 fewer [95% CrI, from 45 fewer to 26 more] per 1000; median rank 1, 95% CrI 1‐3; high‐certainty), or CLD (network RR 1.00, 95% CrI 0.83 to 1.3; ARD 0 fewer [95% CrI, from 61 fewer to 108 more] per 1000; median rank 2, 95% CrI 1‐3; low‐certainty). The evidence is very uncertain on effect of ibuprofen on gastrointestinal perforation (network RR 2.6, 95% CrI 0.42 to 20.0; ARD 76 more [95% CrI, from 27 fewer to 897 more] per 1000; median rank 3, 95% CrI 1‐3; very low‐certainty). The evidence is very uncertain on the effect of prophylactic acetaminophen on severe IVH (network RR 1.17, 95% CrI 0.04 to 55.2; ARD 22 more [95% CrI, from 122 fewer to 1000 more] per 1000; median rank 4, 95% CrI 1‐4; very low‐certainty), mortality (network RR 0.49, 95% CrI 0.16 to 1.4; ARD 82 fewer [95% CrI, from 135 fewer to 64 more] per 1000; median rank 1, 95% CrI 1‐4; very low‐certainty), or CP (network RR 0.36, 95% CrI 0.01 to 6.3; ARD 70 fewer [95% CrI, from 109 fewer to 583 more] per 1000; median rank 1, 95% CrI 1‐3; very low‐certainty). In summary, based on ranking statistics, both indomethacin and ibuprofen were equally effective (median ranks 2 respectively) in reducing severe IVH and mortality. Ibuprofen (median rank 1) was more effective than indomethacin in reducing surgical PDA ligation (median rank 2). However, no statistically‐significant differences were observed between the COX‐I drugs for any of the relevant outcomes. AUTHORS' CONCLUSIONS: Prophylactic indomethacin probably results in a small reduction in severe IVH and moderate reduction in mortality and surgical PDA closure (moderate‐certainty), may result in a small increase in CLD (low‐certainty) and results in trivial differences in NEC (high‐certainty), gastrointestinal perforation (moderate‐certainty) and cerebral palsy (low‐certainty). Prophylactic ibuprofen probably results in a small reduction in severe IVH and moderate reduction in surgical PDA closure (moderate‐certainty), may result in a moderate reduction in mortality (low‐certainty) and trivial differences in CLD (low‐certainty) and NEC (high‐certainty). The evidence is very uncertain about the effect of acetaminophen on any of the clinically‐relevant outcomes.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of family nutrition educational interventions to improve growth and development of term infants, for weaning, compared with conventional management.

Background: Gastroschisis is an uncommon congenital defect of the interior abdominal wall that results in herniation of intestinal loops outside the abdominal cavity. Babies with gastroschisis generally do well, but there remains a mortality rate of 5% to 10% and some require prolonged parenteral nutrition and intensive care. Significant injury to the exposed bowel may occur in-utero, and earlier birth may reduce this, improve long-term outcomes and reduce complications, such as necrotising enterocolitis. However, it may also increase complications related to prematurity. There is a lack of published data in this area. Objectives: To assess the effects of elective preterm birth for fetal gastroschisis in pregnancies complicated by this condition. The mode of birth may be either vaginal or by caesarean section, but this review is studying only timing, not the route, of birth. Search methods: We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (16 January 2013). Selection criteria: Individual patient randomised controlled trials of planned preterm birth in pregnancies complicated by fetal gastroschisis, diagnosed by ultrasound scanning in time for preterm birth to be an option, and without other fetal anomalies. The intervention is planned preterm birth, prior to 37 weeks and 0 days’ gestation, versus planned later birth, at or after 37 weeks and 0 days’ gestation (mode of birth is not part of the intervention). We did not include quasi-randomised controlled trials and cluster trials. Cross-over trials are not appropriate for this condition. Studies that were presented in abstract form only were eligible for inclusion, providing that the population included women with pregnancies affected by fetal gastroschisis, the interventions were defined and the treatment selection was randomised. Data collection and analysis: Two review authors independently assessed for inclusion the one trial identified as a result of the search strategy and assessed trial quality. Two review authors extracted data and checked it for accuracy. Main results: We included one study, involving 40 infants and 42 women. The trial was underpowered to detect clinically important outcome differences between the two policies. There were no significant benefits or adverse effects of elective preterm birth at 36 weeks’ gestation for fetal gastroschisis. The primary outcomes were caesarean section and neonatal survival to discharge. Two babies died after birth but before discharge in the elective (intervention) group versus none in the spontaneous group (risk ratio (RR) 5.00; 95% confidence interval (CI) 0.26 to 98.00; one study, n = 40). Seven women (33%) in the elective group and nine women (43%) in the spontaneous group delivered by caesarean section (RR 0.78; 95% CI 0.36 to 1.70). Similarly, for the secondary outcomes, there were no statistical differences in birthweight, ventilation requirements, necrotising enterocolitis and requirement for repeat surgery between the two groups. None of our prespecified maternal secondary outcomes were reported in the included study. We also examined gestational age at birth as a non-prespecified outcome. There was a difference in gestational age at birth between the two arms of the trial (35.8 weeks (SD 0.7) in the elective group and 36.7 (SD 1.5) in the spontaneous group. Possible reasons for this small mean difference include a trend towards spontaneous preterm birth in pregnancies complicated by fetal gastroschisis. Authors’ conclusions: This review is unable to draw any firm conclusions regarding pretermbirth for infants with gastroschisis. It is not possible to say whether the intervention is beneficial or harmful for these babies or their mothers. Only one small trial is included. Further research is needed in this area.