Interventions with pregnant women, new mothers and other primary caregivers for preventing early childhood caries.

BACKGROUND: Dental caries, a common chronic disease of childhood, is associated with adverse health and economic consequences for infants and their families. Socioeconomically disadvantaged children have a higher risk of early childhood caries (ECC). This review updates one published in 2019. OBJECTIVES: To assess the effects of interventions undertaken with pregnant women, new mothers or other primary caregivers of infants in the first year of life, for preventing ECC (from birth to six years). SEARCH METHODS: We searched Cochrane Oral Health's Trials Register, Cochrane Pregnancy and Childbirth's Trials Register, CENTRAL, MEDLINE (Ovid), Embase (Ovid), CINAHL EBSCO, the US National Institutes of Health Ongoing Trials Register (clinicaltrials.gov) and WHO International Clinical Trials Registry Platform (apps.who.int/trialsearch). The latest searches were run on 3 January, 2023. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing interventions with pregnant women, or new mothers and other primary caregivers of infants in the first year of life, against standard care, placebo or another intervention, reporting on a primary outcome: caries presence in primary teeth, dmfs (decayed, missing, filled primary surfaces index), or dmft (decayed, missing, filled teeth index), in children up to six years of age. Intervention types include clinical, oral health promotion/education (hygiene education, breastfeeding and other dietary advice) and policy or service. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data, assessed risk of bias, and assessed certainty of evidence (GRADE). MAIN RESULTS: We included 23 RCTs (5 cluster-randomised), involving 25,953 caregivers (mainly mothers) and their children. Fifteen trials assessed oral health education/promotion interventions against standard care. Six trials assessed a clinical intervention for mother dentition, against placebo, or a different type of clinical intervention. Two trials assessed oral health/education promotion plus clinical intervention (for mother's dentition) against standard care. At most, five trials (maximum of 1326 children and 130 mothers) contributed data to any comparison. Enamel-only caries were included in the diagnosis of caries in some studies. For many trials, the risk of bias was unclear due to lack of methodological details reported. In thirteen trials, participants were socioeconomically disadvantaged. No trial indicated receiving funding that was likely to have influenced their results. Oral health education/promotion interventions Child diet and feeding practice advice versus standard care: We observed a probable 15 per cent reduced risk of caries presence in primary teeth with the intervention (RR 0.85, 95% CI 0.75 to 0.97; 3 trials; 782 participants; moderate-certainty evidence), and there may be a slightly lower mean dmfs (MD -0.29, 95% CI -0.58 to 0; 2 trials; 757 participants; low-certainty evidence); however, the evidence is very uncertain regarding the difference between groups in mean dmft (MD -0.90, 95% CI -1.85 to 0.05; 1 trial; 340 participants; very low-certainty evidence). Breastfeeding promotion and support versus standard care: We observed little or no difference between groups in the risk of caries presence in primary teeth (RR 0.96, 95% CI 0.89 to 1.03; 2 trials; 1148 participants; low-certainty evidence) and in mean dmft (MD -0.12, 95% CI -0.59 to 0.36; 2 trials; 652 participants; low-certainty evidence). dmfs was not reported. Child diet advice compared with standard care: We are very uncertain about the effect on the risk of caries presence in primary teeth (RR 1.08, 95% CI 0.34 to 3.37; 1 trial; 148 participants; very low-certainty evidence). dmfs and dmft were not reported. Oral hygiene, child diet and feeding practice advice versus standard care: The evidence is very uncertain about the effect on the risk of caries presence in primary teeth (RR 0.73, 95% CI 0.50 to 1.07; 5 trials; 1326 participants; very low-certainty evidence) and there maybe little to no difference in mean dmfs (MD -0.87, 95% CI -2.18 to 0.43; 2 trials; 657 participants; low-certainty evidence) and mean dmft (MD -0.30, 95% CI -0.96 to 0.36; 1 trial; 187 participants; low-certainty evidence). High-dose versus low-dose vitamin D supplementation during pregnancy: We are very uncertain about the effect on risk of caries presence in primary teeth (RR 0.99, 95% CI 0.70 to 1.41; 1 trial; 496 participants; very low-certainty evidence). dmfs and dmft were not reported. Clinical interventions (for mother dentition) Chlorhexidine (CHX, a commonly prescribed antiseptic agent) or iodine-NaF application and prophylaxis versus placebo: We are very uncertain regarding the difference in risk of caries presence in primary teeth between antimicrobial and placebo treatment for mother dentition (RR 0.97, 95% CI 0.80 to 1.19; 3 trials; 479 participants; very low-certainty evidence). No trial reported dmfs or dmft. Xylitol compared with CHX antimicrobial treatment: We are very uncertain about the effect on caries presence in primary teeth (RR 0.62, 95% CI 0.27 to 1.39; 1 trial, 96 participants; very low-certainty evidence), but we observed there may be a lower mean dmft with xylitol (MD -2.39; 95% CI -4.10 to -0.68; 1 trial, 113 participants; low-certainty evidence). No trial reported dmfs. Oral health education/promotion plus clinical interventions (for mother dentition) Diet and feeding practice advice for infants and young children plus basic dental care for mothers compared with standard care: We are very uncertain about the effect on risk of caries presence in primary teeth (RR 0.44, 95% CI 0.05 to 3.95; 2 trials, 324 participants; very low-certainty evidence) or on mean dmft (1 study, not estimable). No trial reported dmfs. No trials evaluated policy or health service interventions. AUTHORS' CONCLUSIONS: There is moderate-certainty evidence that providing advice on diet and feeding to pregnant women, mothers or other caregivers with children up to the age of one year probably leads to a slightly reduced risk of early childhood caries (ECC). The remaining evidence is low to very-low certainty and is insufficient for determining which, if any, other intervention types and features may be effective for preventing ECC, and in which settings. Large, high-quality RCTs of oral health education/promotion, clinical, and policy and service access interventions, are warranted to determine the effects and relative effects of different interventions and inform practice. We have identified 13 ongoing studies. Future studies should consider if and how effects are modified by intervention features and participant characteristics (including socioeconomic status).

Venous thromboembolism prophylaxis for women at risk during pregnancy and the early postnatal period.

BACKGROUND: Venous thromboembolism (VTE), although rare, is a major cause of maternal mortality and morbidity. Some women are at increased risk of VTE during pregnancy and the early postnatal period (e.g. caesarean section, family history of VTE, or thrombophilia), and so prophylaxis may be considered. As some methods of prophylaxis carry risks of adverse effects, and risk of VTE is often low, benefits of thromboprophylaxis may be outweighed by harms. OBJECTIVES: To assess the effects of thromboprophylaxis during pregnancy and the early postnatal period on the risk of venous thromboembolic disease and adverse effects in women at increased risk of VTE. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (18 October 2019). In addition, we searched ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) for unpublished, planned and ongoing trial reports (18 October 2019). SELECTION CRITERIA: Randomised trials comparing one method of thromboprophylaxis with placebo or no treatment, or two (or more) methods of thromboprophylaxis. DATA COLLECTION AND ANALYSIS: At least two review authors assessed trial eligibility, extracted data, assessed risk of bias, and judged certainty of evidence for selected critical outcomes (using GRADE). We conducted fixed-effect meta-analysis and reported data (all dichotomous) as summary risk ratios (RRs) with 95% confidence intervals (CIs). MAIN RESULTS: Twenty-nine trials (involving 3839 women), overall at moderate to high risk of bias were included. Trials were conducted across the antenatal, peripartum and postnatal periods, with most in high-income countries. Interventions included types and regimens of heparin (low molecular weight heparin (LMWH) and unfractionated heparin (UFH)), hydroxyethyl starch (HES), and compression stockings or devices. Data were limited due to a small number of trials in comparisons and/or few or no events reported. All critical outcomes (assessed for comparisons of heparin versus no treatment/placebo, and LMWH versus UFH) were considered to have very low-certainty evidence, downgraded mainly for study limitations and imprecise effect estimates.  Maternal death was not reported in most studies. Antenatal (± postnatal) prophylaxis For the primary outcomes symptomatic thromboembolic events pulmonary embolism (PE) and/or deep vein thrombosis (DVT), and the critical outcome of adverse effects sufficient to stop treatment, the evidence was very uncertain.  Symptomatic thromboembolic events: - heparin versus no treatment/placebo (RR 0.39; 95% CI 0.08 to 1.98; 4 trials, 476 women; very low-certainty evidence); - LMWH versus UFH (RR 0.47; 95% CI 0.09 to 2.49; 4 trials, 404 women; very low-certainty evidence); Symptomatic PE: - heparin versus no treatment/placebo (RR 0.33; 95% CI 0.02 to 7.14; 3 trials, 187 women; very low-certainty evidence); - LMWH versus UFH (no events; 3 trials, 287 women); Symptomatic DVT: - heparin versus no treatment/placebo (RR 0.33; 95% CI 0.04 to 3.10; 4 trials, 227 women; very low-certainty evidence); - LMWH versus UFH (no events; 3 trials, 287 women); Adverse effects sufficient to stop treatment: - heparin versus no treatment/placebo (RR 0.49; 95% CI 0.05 to 5.31; 1 trial, 139 women; very low-certainty evidence); - LMWH versus UFH (RR 0.07; 95% CI 0.01 to 0.54; 2 trials, 226 women; very low-certainty evidence). Peripartum/postnatal prophylaxis Vaginal or caesarean birth When UFH and no treatment were compared, the effects on symptomatic thromboembolic events (RR 0.16; 95% CI 0.02 to 1.36; 1 trial, 210 women; very low-certainty evidence), symptomatic PE (RR 0.16; 95% CI 0.01 to 3.34; 1 trial, 210 women; very low-certainty evidence), and symptomatic DVT  (RR 0.27; 95% CI 0.03 to 2.55; 1 trial, 210 women; very low-certainty evidence) were very uncertain.  Maternal death and adverse effects sufficient to stop treatment were not reported. Caesarean birth Symptomatic thromboembolic events: - heparin versus no treatment/placebo (RR 1.30; 95% CI 0.39 to 4.27; 4 trials, 840 women; very low-certainty evidence); - LMWH versus UFH (RR 0.33; 95% CI 0.01 to 7.99; 3 trials, 217 women; very low-certainty evidence); Symptomatic PE: - heparin versus no treatment/placebo (RR 1.10; 95% CI 0.25 to 4.87; 4 trials, 840 women; very low-certainty evidence); - LMWH versus UFH (no events; 3 trials, 217 women);  Symptomatic DVT: - heparin versus no treatment/placebo (RR 1.30; 95% CI 0.24 to 6.94; 5 trials, 1140 women; very low-certainty evidence); LMWH versus UFH (RR 0.33; 95% CI 0.01 to 7.99; 3 trials, 217 women; very low-certainty evidence); Maternal death: - heparin versus placebo (no events, 1 trial, 300 women); Adverse effects sufficient to stop treatment: - heparin versus placebo (no events;  1 trial, 140 women). Postnatal prophylaxis No events were reported for LMWH versus no treatment/placebo for: symptomatic thromboembolic events, symptomatic PE and symptomatic DVT (all 2 trials, 58 women), or maternal death (1 trial, 24 women). Adverse effects sufficient to stop treatment were not reported. We were unable to conduct subgroup analyses due to lack of data. Sensitivity analysis including the nine studies at low risk of bias did not impact overall findings. AUTHORS' CONCLUSIONS: The evidence is very uncertain about benefits and harms of VTE thromboprophylaxis in women during pregnancy and the early postnatal period at increased risk of VTE. Further high-quality very large-scale randomised trials are needed to determine effects of currently used treatments in women with different VTE risk factors. As sufficiently large definitive trials are unlikely to be funded, secondary data analyses based on high-quality registry data are important.

Induction of labour at or beyond 37 weeks' gestation.

BACKGROUND: Risks of stillbirth or neonatal death increase as gestation continues beyond term (around 40 weeks' gestation). It is unclear whether a policy of labour induction can reduce these risks. This Cochrane Review is an update of a review that was originally published in 2006 and subsequently updated in 2012 and 2018. OBJECTIVES: To assess the effects of a policy of labour induction at or beyond 37 weeks' gestation compared with a policy of awaiting spontaneous labour indefinitely (or until a later gestational age, or until a maternal or fetal indication for induction of labour arises) on pregnancy outcomes for the infant and the mother. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (17 July 2019), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) conducted in pregnant women at or beyond 37 weeks, comparing a policy of labour induction with a policy of awaiting spontaneous onset of labour (expectant management). We also included trials published in abstract form only. Cluster-RCTs, quasi-RCTs and trials using a cross-over design were not eligible for inclusion in this review. We included pregnant women at or beyond 37 weeks' gestation. Since risk factors at this stage of pregnancy would normally require intervention, only trials including women at low risk for complications, as defined by trialists, were eligible. The trials of induction of labour in women with prelabour rupture of membranes at or beyond term were not considered in this review but are considered in a separate Cochrane Review. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, assessed risk of bias and extracted data. Data were checked for accuracy. We assessed the certainty of evidence using the GRADE approach. MAIN RESULTS: In this updated review, we included 34 RCTs (reporting on over 21,000 women and infants) mostly conducted in high-income settings. The trials compared a policy to induce labour usually after 41 completed weeks of gestation (> 287 days) with waiting for labour to start and/or waiting for a period before inducing labour. The trials were generally at low to moderate risk of bias. Compared with a policy of expectant management, a policy of labour induction was associated with fewer (all-cause) perinatal deaths (risk ratio (RR) 0.31, 95% confidence interval (CI) 0.15 to 0.64; 22 trials, 18,795 infants; high-certainty evidence). There were four perinatal deaths in the labour induction policy group compared with 25 perinatal deaths in the expectant management group. The number needed to treat for an additional beneficial outcome (NNTB) with induction of labour, in order to prevent one perinatal death, was 544 (95% CI 441 to 1042). There were also fewer stillbirths in the induction group (RR 0.30, 95% CI 0.12 to 0.75; 22 trials, 18,795 infants; high-certainty evidence); two in the induction policy group and 16 in the expectant management group. For women in the policy of induction arms of trials, there were probably fewer caesarean sections compared with expectant management (RR 0.90, 95% CI 0.85 to 0.95; 31 trials, 21,030 women; moderate-certainty evidence); and probably little or no difference in operative vaginal births with induction (RR 1.03, 95% CI 0.96 to 1.10; 22 trials, 18,584 women; moderate-certainty evidence). Induction may make little or difference to perineal trauma (severe perineal tear: RR 1.04, 95% CI 0.85 to 1.26; 5 trials; 11,589 women; low-certainty evidence). Induction probably makes little or no difference to postpartum haemorrhage (RR 1.02, 95% CI 0.91 to 1.15, 9 trials; 12,609 women; moderate-certainty evidence), or breastfeeding at discharge (RR 1.00, 95% CI 0.96 to 1.04; 2 trials, 7487 women; moderate-certainty evidence). Very low certainty evidence means that we are uncertain about the effect of induction or expectant management on the length of maternal hospital stay (average mean difference (MD) -0.19 days, 95% CI -0.56 to 0.18; 7 trials; 4120 women; Tau² = 0.20; I² = 94%). Rates of neonatal intensive care unit (NICU) admission were lower (RR 0.88, 95% CI 0.80 to 0.96; 17 trials, 17,826 infants; high-certainty evidence), and probably fewer babies had Apgar scores less than seven at five minutes in the induction groups compared with expectant management (RR 0.73, 95% CI 0.56 to 0.96; 20 trials, 18,345 infants; moderate-certainty evidence). Induction or expectant management may make little or no difference for neonatal encephalopathy (RR 0.69, 95% CI 0.37 to 1.31; 2 trials, 8851 infants; low-certainty evidence, and probably makes little or no difference for neonatal trauma (RR 0.97, 95% CI 0.63 to 1.49; 5 trials, 13,106 infants; moderate-certainty evidence) for induction compared with expectant management. Neurodevelopment at childhood follow-up and postnatal depression were not reported by any trials. In subgroup analyses, no differences were seen for timing of induction (< 40 versus 40-41 versus > 41 weeks' gestation), by parity (primiparous versus multiparous) or state of cervix for any of the main outcomes (perinatal death, stillbirth, NICU admission, caesarean section, operative vaginal birth, or perineal trauma). AUTHORS' CONCLUSIONS: There is a clear reduction in perinatal death with a policy of labour induction at or beyond 37 weeks compared with expectant management, though absolute rates are small (0.4 versus 3 deaths per 1000). There were also lower caesarean rates without increasing rates of operative vaginal births and there were fewer NICU admissions with a policy of induction. Most of the important outcomes assessed using GRADE had high- or moderate-certainty ratings. While existing trials have not yet reported on childhood neurodevelopment, this is an important area for future research. The optimal timing of offering induction of labour to women at or beyond 37 weeks' gestation needs further investigation, as does further exploration of risk profiles of women and their values and preferences. Offering women tailored counselling may help them make an informed choice between induction of labour for pregnancies, particularly those continuing beyond 41 weeks - or waiting for labour to start and/or waiting before inducing labour.

Interventions with pregnant women, new mothers and other primary caregivers for preventing early childhood caries.

BACKGROUND: Dental caries is one of the most common chronic diseases of childhood and is associated with adverse health and economic consequences for infants and their families. Socioeconomically disadvantaged children have a higher risk of early childhood caries (ECC). OBJECTIVES: To assess the effects of interventions with pregnant women, new mothers or other primary caregivers of infants in the first year of life, for preventing ECC (from birth to six years of age). SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 14 January 2019), Cochrane Pregnancy and Childbirth Group's Trials Register (to 22 January 2019), Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Register of Studies, to 14 January 2019), MEDLINE Ovid (1946 to 14 January 2019), Embase Ovid (1980 to 14 January 2019) and CINAHL EBSCO (1937 to 14 January 2019). The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on language or publication status. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing one or more interventions with pregnant women, mothers, or other caregivers of infants in the first year of life (intervention types included clinical, oral health education/promotion such as hygiene education, breastfeeding and other dietary advice, and policy or health service), versus standard care or placebo or another intervention. For inclusion, trials had to report at least one caries outcome. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility, extracted data, assessed risk of bias, and assessed certainty of evidence using the GRADE approach. MAIN RESULTS: We included 17 RCTs (4 cluster-randomised), involving 23,732 caregivers (mainly mothers) and their children. Eleven RCTs assessed four oral health education/promotion interventions against standard care: child diet advice, child diet and feeding practice advice, breastfeeding promotion and support, and oral hygiene with child diet and feeding practice advice. Six trials assessed clinical interventions in mother's dentition, four trials chlorhexidine (CHX, a commonly prescribed antiseptic agent) or iodine-NaF application and prophylaxis versus placebo, and two trials xylitol against CHX or CHX + xylitol. At most, three trials (maximum of 1148 children and 130 mothers) contributed data to any comparison. For many trials, risk of bias was judged unclear due to lack of methodological details reported, and there was high risk of attrition bias in some trials. None of the included trials indicated receiving funding that is likely to have influenced their results. The trials were performed in high-, middle- and low-income countries. In nine trials, participants were socioeconomically disadvantaged. For child diet and feeding practice advice versus standard care, we observed a probable 15 per cent reduced risk of caries presence in primary teeth with the intervention (RR 0.85, 95% CI 0.75 to 0.97; 3 trials; 782 participants; moderate-certainty evidence), and there may be a lower mean dmfs (decayed, missing, filled primary surfaces) score (MD -0.29, 95% CI -0.58 to 0; 2 trials; 757 participants; low-certainty evidence); however, we are uncertain regarding the difference between the groups in mean dmft (decayed, missing, filled teeth) score (MD -0.90, 95% CI -1.85 to 0.05; 1 trial; 340 participants; very low-certainty evidence). For breastfeeding promotion and support versus standard care, we observed that there may be little or no a difference between groups in the risk of caries presence in primary teeth (RR 0.96, 95% CI 0.89 to 1.03; 2 trials; 1148 participants; low-certainty evidence), or mean dmft score (MD -0.12, 95% CI -0.59 to 0.36; 2 trials; 652 participants; low-certainty evidence). Dmfs was not reported for this comparison. We are uncertain whether child diet advice only compared with standard care reduces risk of caries presence in primary teeth (RR 1.08, 95% CI 0.34 to 3.37; 1 trial; 148 participants; very low-certainty evidence). Dmfs and dmft were not reported for this comparison. For oral hygiene, child diet and feeding practice advice versus standard care, we observed little or no reduced risk of caries presence in primary teeth (RR 0.91, 95% CI 0.75 to 1.10; 2 trials; 365 participants; low-certainty evidence), and are uncertain regarding difference between the groups in mean dmfs score (MD -0.99, 95% CI -2.45 to 0.47; 1 trial; 187 participants; very low-certainty evidence) and dmft score (MD -0.30, 95% CI -0.96 to 0.36; 1 trial; 187 participants; very low-certainty evidence). We observed there may be little or no difference in risk of caries presence in primary teeth between antimicrobial and placebo treatment in mother's dentition (RR 0.97, 95% CI 0.80 to 1.19; 3 trials; 479 participants; very low-certainty evidence). No trials assessing this comparison reported dmfs or dmft. For xylitol compared with CHX antimicrobial treatment, we observed there may be a lower mean dmft score with xylitol (MD -2.39; 95% CI -4.10 to -0.68; 1 trial, 113 participants; low-certainty evidence); however, we are uncertain regarding the difference between groups in caries presence in primary teeth (RR 0.62, 95% CI 0.27 to 1.39; 1 trial, 96 participants; very low-certainty evidence). Neither trial evaluating this comparison reported dmfs. No trials assessed a health policy or service intervention. AUTHORS' CONCLUSIONS: Moderate-certainty evidence suggests that providing advice on diet and feeding to pregnant women, mothers or other caregivers with children up to the age of one year probably leads to a slightly reduced risk of early childhood caries (ECC). The remaining evidence is low to very low certainty and is insufficient for determining which, if any, other interventions types and features may be effective for preventing ECC. Large, high-quality RCTs of oral health education/promotion, clinical, and policy and service access interventions, are warranted to determine effects and relative effects of different interventions and inform practice. We have identified 12 studies currently in progress. Those designing future studies should describe the intervention components, setting and participants, consider if and how effects are modified by intervention features and participant characteristics, and adopt a consistent approach to measuring and reporting ECC.

Omega-3 fatty acid addition during pregnancy.

BACKGROUND: Higher intakes of foods containing omega-3 long-chain polyunsaturated fatty acids (LCPUFA), such as fish, during pregnancy have been associated with longer gestations and improved perinatal outcomes. This is an update of a review that was first published in 2006. OBJECTIVES: To assess the effects of omega-3 LCPUFA, as supplements or as dietary additions, during pregnancy on maternal, perinatal, and neonatal outcomes and longer-term outcomes for mother and child. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (16 August 2018), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing omega-3 fatty acids (as supplements or as foods, stand-alone interventions, or with a co-intervention) during pregnancy with placebo or no omega-3, and studies or study arms directly comparing omega-3 LCPUFA doses or types. Trials published in abstract form were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data, assessed risk of bias in trials and assessed quality of evidence for prespecified birth/infant, maternal, child/adult and health service outcomes using the GRADE approach. MAIN RESULTS: In this update, we included 70 RCTs (involving 19,927 women at low, mixed or high risk of poor pregnancy outcomes) which compared omega-3 LCPUFA interventions (supplements and food) compared with placebo or no omega-3. Overall study-level risk of bias was mixed, with selection and performance bias mostly at low risk, but there was high risk of attrition bias in some trials. Most trials were conducted in upper-middle or high-income countries; and nearly half the trials included women at increased/high risk for factors which might increase the risk of adverse maternal and birth outcomes.Preterm birth < 37 weeks (13.4% versus 11.9%; risk ratio (RR) 0.89, 95% confidence interval (CI) 0.81 to 0.97; 26 RCTs, 10,304 participants; high-quality evidence) and early preterm birth < 34 weeks (4.6% versus 2.7%; RR 0.58, 95% CI 0.44 to 0.77; 9 RCTs, 5204 participants; high-quality evidence) were both lower in women who received omega-3 LCPUFA compared with no omega-3. Prolonged gestation > 42 weeks was probably increased from 1.6% to 2.6% in women who received omega-3 LCPUFA compared with no omega-3 (RR 1.61 95% CI 1.11 to 2.33; 5141 participants; 6 RCTs; moderate-quality evidence).For infants, there was a possibly reduced risk of perinatal death (RR 0.75, 95% CI 0.54 to 1.03; 10 RCTs, 7416 participants; moderate-quality evidence: 62/3715 versus 83/3701 infants) and possibly fewer neonatal care admissions (RR 0.92, 95% CI 0.83 to 1.03; 9 RCTs, 6920 participants; moderate-quality evidence - 483/3475 infants versus 519/3445 infants). There was a reduced risk of low birthweight (LBW) babies (15.6% versus 14%; RR 0.90, 95% CI 0.82 to 0.99; 15 trials, 8449 participants; high-quality evidence); but a possible small increase in large-for-gestational age (LGA) babies (RR 1.15, 95% CI 0.97 to 1.36; 6 RCTs, 3722 participants; moderate-quality evidence, for omega-3 LCPUFA compared with no omega-3. Little or no difference in small-for-gestational age or intrauterine growth restriction (RR 1.01, 95% CI 0.90 to 1.13; 8 RCTs, 6907 participants; moderate-quality evidence) was seen.For the maternal outcomes, there is insufficient evidence to determine the effects of omega-3 on induction post-term (average RR 0.82, 95% CI 0.22 to 2.98; 3 trials, 2900 participants; low-quality evidence), maternal serious adverse events (RR 1.04, 95% CI 0.40 to 2.72; 2 trials, 2690 participants; low-quality evidence), maternal admission to intensive care (RR 0.56, 95% CI 0.12 to 2.63; 2 trials, 2458 participants; low-quality evidence), or postnatal depression (average RR 0.99, 95% CI 0.56 to 1.77; 2 trials, 2431 participants; low-quality evidence). Mean gestational length was greater in women who received omega-3 LCPUFA (mean difference (MD) 1.67 days, 95% CI 0.95 to 2.39; 41 trials, 12,517 participants; moderate-quality evidence), and pre-eclampsia may possibly be reduced with omega-3 LCPUFA (RR 0.84, 95% CI 0.69 to 1.01; 20 trials, 8306 participants; low-quality evidence).For the child/adult outcomes, very few differences between antenatal omega-3 LCPUFA supplementation and no omega-3 were observed in cognition, IQ, vision, other neurodevelopment and growth outcomes, language and behaviour (mostly low-quality to very low-quality evidence). The effect of omega-3 LCPUFA on body mass index at 19 years (MD 0, 95% CI -0.83 to 0.83; 1 trial, 243 participants; very low-quality evidence) was uncertain. No data were reported for development of diabetes in the children of study participants. AUTHORS' CONCLUSIONS: In the overall analysis, preterm birth < 37 weeks and early preterm birth < 34 weeks were reduced in women receiving omega-3 LCPUFA compared with no omega-3. There was a possibly reduced risk of perinatal death and of neonatal care admission, a reduced risk of LBW babies; and possibly a small increased risk of LGA babies with omega-3 LCPUFA.For our GRADE quality assessments, we assessed most of the important perinatal outcomes as high-quality (e.g. preterm birth) or moderate-quality evidence (e.g. perinatal death). For the other outcome domains (maternal, child/adult and health service outcomes) GRADE ratings ranged from moderate to very low, with over half rated as low. Reasons for downgrading across the domain were mostly due to design limitations and imprecision.Omega-3 LCPUFA supplementation during pregnancy is an effective strategy for reducing the incidence of preterm birth, although it probably increases the incidence of post-term pregnancies. More studies comparing omega-3 LCPUFA and placebo (to establish causality in relation to preterm birth) are not needed at this stage. A further 23 ongoing trials are still to report on over 5000 women, so no more RCTs are needed that compare omega-3 LCPUFA against placebo or no intervention. However, further follow-up of completed trials is needed to assess longer-term outcomes for mother and child, to improve understanding of metabolic, growth and neurodevelopment pathways in particular, and to establish if, and how, outcomes vary by different types of omega-3 LCPUFA, timing and doses; or by characteristics of women.

Combined diet and exercise interventions for preventing gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with a wide range of adverse health consequences for women and their infants in the short and long term. With an increasing prevalence of GDM worldwide, there is an urgent need to assess strategies for GDM prevention, such as combined diet and exercise interventions. This is an update of a Cochrane review that was first published in 2015. OBJECTIVES: To assess the effects of diet interventions in combination with exercise interventions for pregnant women for preventing GDM, and associated adverse health consequences for the mother and her infant/child. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (27 November 2016) and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cluster-RCTs, comparing combined diet and exercise interventions with no intervention (i.e. standard care), that reported on GDM diagnosis as an outcome. Quasi-RCTs were excluded. Cross-over trials were not eligible for inclusion. We planned to include RCTs comparing two or more different diet/exercise interventions, however none were identified. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data, assessed the risk of bias of the included trials and assessed quality of evidence for selected maternal and infant/child outcomes using the GRADE approach. We checked data for accuracy. MAIN RESULTS: In this update, we included 23 RCTs (involving 8918 women and 8709 infants) that compared combined diet and exercise interventions with no intervention (standard care). The studies varied in the diet and exercise programs evaluated and health outcomes reported. None reported receiving funding from a drug manufacturer or agency with interests in the results. Overall risk of bias was judged to be unclear due to the lack of methodological detail reported. Most studies were undertaken in high-income countries.For our primary review outcomes, there was a possible reduced risk of GDM in the diet and exercise intervention group compared with the standard care group (average risk ratio (RR) 0.85, 95% confidence interval (CI) 0.71 to 1.01; 6633 women; 19 RCTs; Tau² = 0.05; I² = 42%; P = 0.07; moderate-quality evidence). There was also a possible reduced risk of caesarean section (RR 0.95, 95% CI 0.88 to 1.02; 6089 women; 14 RCTs; moderate-quality evidence). No clear differences were seen between groups for pre-eclampsia (RR 0.98, 95% CI 0.79 to 1.22; 5366 participants; 8 RCTs; low-quality evidence), pregnancy-induced hypertension and/or hypertension (average RR 0.78, 95% CI 0.47 to 1.27; 3073 participants; 6 RCTs; Tau² = 0.19; I² = 62%; very low-quality evidence), perinatal mortality (RR 0.82, 95% CI 0.42 to 1.63; 3757 participants; 2 RCTs; low-quality evidence) or large-for-gestational age (RR 0.93, 95% CI 0.81 to 1.07; 5353 participants; 11 RCTs; low-quality evidence). No data were reported for infant mortality or morbidity composite.Subgroup analyses (based on trial design, maternal body mass index (BMI) and ethnicity) revealed no clear differential treatment effects. We were unable to assess the impact of maternal age, parity and specific features of the diet and exercise interventions. Findings from sensitivity analyses (based on RCT quality) generally supported those observed in the main analyses. We were not able to perform subgroup analyses based on maternal age, parity or nature of the exercise/dietary interventions due to the paucity of information/data on these characteristics and the inability to meaningfully group intervention characteristics.For most of the secondary review outcomes assessed using GRADE, there were no clear differences between groups, including for perineal trauma (RR 1.27, 95% CI 0.78 to 2.05; 2733 participants; 2 RCTs; moderate-quality evidence), neonatal hypoglycaemia (average RR 1.42, 95% CI 0.67 to 2.98; 3653 participants; 2 RCTs; Tau² = 0.23; I² = 77%; low quality evidence); and childhood adiposity (BMI z score) (MD 0.05, 95% CI -0.29 to 0.40; 794 participants; 2 RCTs; Tau² = 0.04; I² = 59%; low-quality evidence). However, there was evidence of less gestational weight gain in the diet and exercise intervention group compared with the control group (mean difference (MD) -0.89 kg, 95% CI -1.39 to -0.40; 5052 women; 16 RCTs; Tau² = 0.37; I² = 43%;moderate-quality evidence). No data were reported for maternal postnatal depression or type 2 diabetes; childhood/adulthood type 2 diabetes, or neurosensory disability. AUTHORS' CONCLUSIONS: Moderate-quality evidence suggests reduced risks of GDM and caesarean section with combined diet and exercise interventions during pregnancy as well as reductions in gestational weight gain, compared with standard care. There were no clear differences in hypertensive disorders of pregnancy, perinatal mortality, large-for-gestational age, perineal trauma, neonatal hypoglycaemia, and childhood adiposity (moderate- tovery low-quality evidence).Using GRADE methodology, the evidence was assessed as moderate to very low quality. Downgrading decisions were predominantly due to design limitations (risk of bias), and imprecision (uncertain effect estimates, and at times, small sample sizes and low event rates), however two outcomes (pregnancy-induced hypertension/hypertension and neonatal hypoglycaemia), were also downgraded for unexplained inconsistency (statistical heterogeneity).Due to the variability of the diet and exercise components tested in the included studies, the evidence in this review has limited ability to inform practice. Future studies could describe the interventions used in more detail, if and how these influenced behaviour change and ideally be standardised between studies. Studies could also consider using existing core outcome sets to facilitate more standardised reporting.