Middleton Philippa, Gomersall Judith C, Gould Jacqueline F, Shepherd Emily, Olsen Sjurdur F, Makrides Maria
Healthy Mothers, Babies and Children, South Australian Health and Medical Research Institute, Women's and Children's Hospital, 72 King William Road, Adelaide, South Australia, Australia, 5006.
Cochrane Database Syst Rev. 2018 Nov 15;11(11):CD003402. doi: 10.1002/14651858.CD003402.pub3.
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.
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.
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.
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.
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.
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.
孕期摄入更多富含ω-3长链多不饱和脂肪酸（LCPUFA）的食物，如鱼类，与更长的孕期及更好的围产期结局相关。这是一篇首次发表于2006年的综述的更新版。
评估孕期补充ω-3 LCPUFA或通过饮食摄入ω-3 LCPUFA对孕产妇、围产期和新生儿结局以及母婴长期结局的影响。
本次更新，我们检索了Cochrane妊娠与分娩试验注册库、ClinicalTrials.gov、世界卫生组织国际临床试验注册平台（ICTRP）（2018年8月16日）以及检索到的研究的参考文献列表。
随机对照试验（RCT），比较孕期补充ω-3脂肪酸（作为补充剂或食物、单独干预或联合干预）与安慰剂或不补充ω-3的情况，以及直接比较ω-3 LCPUFA剂量或类型的研究或研究组。以摘要形式发表的试验符合纳入条件。
两位综述作者独立评估研究的纳入资格、提取数据、评估试验中的偏倚风险，并使用GRADE方法评估预先设定的出生/婴儿、孕产妇、儿童/成人和卫生服务结局的证据质量。
在本次更新中，我们纳入了70项RCT（涉及19927名妊娠结局不良风险低、中或高的女性），这些研究比较了ω-3 LCPUFA干预措施（补充剂和食物）与安慰剂或不补充ω-3的情况。总体研究水平的偏倚风险不一，选择和实施偏倚大多处于低风险，但部分试验存在较高的失访偏倚风险。大多数试验在中高收入国家进行；近一半的试验纳入了因可能增加孕产妇和分娩不良结局风险的因素而处于增加/高风险的女性。孕周<37周的早产（13.4%对11.9%；风险比（RR）0.89，95%置信区间（CI）0.81至0.97；26项RCT，10304名参与者；高质量证据）和孕周<34周的早期早产（4.6%对2.7%；RR 0.58，95%CI 0.44至0.77；9项RCT，5204名参与者；高质量证据）在接受ω-3 LCPUFA的女性中均低于未接受ω-3的女性。与未接受ω-3的女性相比，接受ω-3 LCPUFA的女性孕周>42周的过期妊娠可能从1.6%增加到2.6%（RR 1.61，95%CI 1.11至2.33；5141名参与者；6项RCT；中等质量证据）。对于婴儿，围产期死亡风险可能降低（RR 0.75，95%CI 0.54至 1.03；10项RCT，7416名参与者；中等质量证据：62/3715名婴儿对83/3701名婴儿），新生儿护理入院可能减少（RR 0.92，95%CI 0.83至1.03；9项RCT，6920名参与者；中等质量证据 - 483/3475名婴儿对519/3445名婴儿）。低出生体重（LBW）婴儿的风险降低（15.6%对14%；RR 0.90，95%CI 0.82至0.99；15项试验，8449名参与者；高质量证据）；但与未接受ω-3相比，接受ω-3 LCPUFA的巨大儿（LGA）婴儿可能略有增加（RR 1.15，95%CI 0.97至1.36；6项RCT，3722名参与者；中等质量证据）。小于胎龄儿或宫内生长受限几乎没有差异（RR 1.01，95%CI 0.90至1.13；8项RCT，6907名参与者；中等质量证据）。对于孕产妇结局，没有足够的证据来确定ω-3对过期引产的影响（平均RR 0.82，95%CI 0.22至2.98；3项试验，2900名参与者；低质量证据）、孕产妇严重不良事件（RR 1.04，95%CI 0.40至2.72；2项试验，2690名参与者；低质量证据）、孕产妇入住重症监护病房（RR 0.5 6，95%CI 0.12至2.63；2项试验，2458名参与者；低质量证据）或产后抑郁症（平均RR 0.99，95%CI 0.56至1.77；2项试验，2431名参与者；低质量证据）。接受ω-3 LCPUFA的女性平均孕周更长（平均差异（MD）1.67天 ，95%CI 0.95至2.39；41项试验 ，12517名参与者；中等质量证据），ω-3 LCPUFA可能会降低子痫前期的风险（RR 0.84，95%CI 0.69至1.01；20项试验，8306名参与者；低质量证据）。对于儿童/成人结局，在认知、智商、视力、其他神经发育和生长结局、语言和行为方面，产前补充ω-3 LCPUFA与不补充ω-3之间几乎没有差异（大多为低质量至极低质量证据）。ω-3 LCPUFA对19岁时体重指数的影响（MD 0，95%CI -0.83至0.83；1项试验，243名参与者；极低质量证据）尚不确定。未报告研究参与者子女患糖尿病的情况。
在总体分析中，与未接受ω-3相比，接受ω-3 LCPUFA的女性孕周<37周的早产和孕周<34周的早期早产减少。围产期死亡和新生儿护理入院风险可能降低，LBW婴儿风险降低；接受ω-3 LCPUFA的LGA婴儿风险可能略有增加 。对于我们的GRADE质量评估，我们将大多数重要的围产期结局评估为高质量（如早产）或中等质量证据（如围产期死亡）。对于其他结局领域（孕产妇、儿童/成人和卫生服务结局），GRADE评级从中等到极低不等，超过一半被评为低质量。各领域降级的原因主要是设计局限性和不精确性。孕期补充ω-3 LCPUFA是降低早产发生率的有效策略，尽管它可能会增加过期妊娠的发生率。现阶段不需要更多比较ω-3 LCPUFA和安慰剂（以确定与早产的因果关系）的研究。另外23项正在进行的试验仍有待报告5000多名女性的情况，因此不需要更多比较ω-3 LCPUFA与安慰剂或无干预措施的RCT。然而，需要对已完成的试验进行进一步随访，以评估母婴的长期结局，特别是提高对代谢、生长和神经发育途径的理解，并确定结局是否以及如何因不同类型的ω-3 LCPUFA、时间和剂量或女性特征而异。
