背景:建议在妊娠期补充铁和叶酸以预防贫血,并可能改善其他产妇,怀孕,和婴儿结局。
目的:研究孕期每日口服补铁的效果,单独或与叶酸或其他维生素和矿物质联合使用,作为产前保健的干预措施。
方法:我们于2024年1月18日检索了Cochrane妊娠和分娩试验登记处(包括CENTRAL,MEDLINE,Embase,CINAHL,ClinicalTrials.gov,世卫组织国际临床试验注册平台,会议记录),并搜索了检索到的研究的参考列表。
方法:评估口服补铁效果的随机或准随机试验,铁+叶酸,或铁+怀孕期间的其他维生素和矿物质。
方法:综述作者独立评估试验资格,根据预定义的标准确定可信度,评估的偏见风险,提取的数据,并进行了准确性检查。我们使用GRADE方法来评估主要结局证据的确定性。我们预计试验之间的异质性很高;我们使用随机效应模型(平均治疗效果)汇总了试验结果。
结果:我们纳入了57项试验,涉及48,971名女性。共有40项试验比较了每日口服补铁与安慰剂或不含铁的效果;8项试验评估了铁+叶酸与安慰剂或不含铁+叶酸的效果。与安慰剂或无铁相比,补充铁母体结局:怀孕期间补充铁可以减少母体贫血(4.0%对7.4%;风险比(RR)0.30,95%置信区间(CI)0.20至0.47;14项试验,13,543名女性;低确定性证据)和足月铁缺乏症(44.0%对66.0%;RR0.51,95%CI0.38至0.68;8项试验,2873名妇女;低确定性证据),并可能减少产妇足月缺铁性贫血(5.0%对18.4%;RR0.41,95%CI0.26至0.63;7项试验,2704名妇女;中度确定性证据),与安慰剂或不补充铁相比。产妇死亡可能几乎没有差异(2和4个事件,RR0.57,95%CI0.12至2.69;3项试验,14060名妇女;中度确定性证据)。不良反应的证据非常不确定(21.6%对18.0%;RR1.29,95%CI0.83至2.02;12项试验,2423名女性;非常低的确定性证据)和严重贫血(Hb<70g/L)在孕中期/晚期(<1%对3.6%;RR0.22,95%CI0.01至3.20;8项试验,1398名妇女;非常低的确定性证据)。没有临床试验报告临床疟疾或怀孕期间感染。婴儿结局:服用铁补充剂的女性可能不太可能有低出生体重的婴儿(5.2%对6.1%;RR0.84,95%CI0.72至0.99;12项试验,18,290名婴儿;中度确定性证据),与安慰剂或不补充铁相比。然而,婴儿出生体重的证据非常不确定(MD24.9克,95%CI-125.81至175.60;16项试验,18,554名婴儿;非常低的确定性证据)。早产可能几乎没有差异(7.6%对8.2%;RR0.93,95%CI0.84至1.02;11项试验,18,827名婴儿;中度确定性证据),新生儿死亡可能几乎没有差异(1.4%对1.5%,RR0.98,95%CI0.77至1.24;4项试验,17,243名婴儿;低确定性证据)或先天性异常,包括神经管缺陷(41对48例事件;RR0.88,95%CI0.58至1.33;4项试验,14,377名婴儿;低确定性证据)。与安慰剂或无铁+叶酸相比,铁+叶酸补充剂产妇结局:每日口服铁+叶酸补充剂可能减少足月产妇贫血(12.1%对25.5%;RR0.44,95%CI0.30至0.64;4项试验,1962年妇女;中度确定性证据),并且可以减少孕妇足月铁缺乏(3.6%对15%;RR0.24,95%CI0.06至0.99;1项试验,131名妇女;低确定性证据),与安慰剂或不含铁+叶酸相比。关于铁+叶酸对产妇缺铁性贫血的影响的证据非常不确定(10.8%对25%;RR0.43,95%CI0.17至1.09;1项试验,131名女性;非常低的确定性证据),或孕产妇死亡(无事件;1项试验;非常低的确定性证据)。不良反应的证据不确定(21.0%对0.0%;RR44.32,95%CI2.77至709.09;1项试验,456名妇女;低确定性证据),妊娠中期或晚期严重贫血的证据非常不确定(<1%对5.6%;RR0.12,95%CI0.02至0.63;4项试验,506名女性;非常低的确定性证据),与安慰剂或不含铁+叶酸相比。婴儿结局:婴儿低出生体重可能几乎没有差异(33.4%对40.2%;RR1.07,95%CI0.31至3.74;2项试验,1311名婴儿;低确定性证据),比较补充铁+叶酸与安慰剂或不补充铁+叶酸。怀孕期间接受铁+叶酸的女性所生的婴儿出生体重可能较高(MD57.73g,95%CI7.66至107.79;2项试验,1365名婴儿;中度确定性证据),与安慰剂或不含铁+叶酸相比。其他婴儿结局可能几乎没有差异,包括早产(19.4%对19.2%;RR1.55,95%CI0.40至6.00;3项试验,1497名婴儿;低确定性证据),新生儿死亡(3.4%对4.2%;RR0.81,95%CI0.51至1.30;1项试验,1793名婴儿;低确定性证据),或先天性异常(1.7%对2.4;RR0.70,95%CI0.35至1.40;1项试验,1652名婴儿;低确定性证据),比较补充铁+叶酸与安慰剂或不补充铁+叶酸。在疟疾流行国家共进行了19项试验,或者在有疟疾风险的环境中。没有研究报告母体临床疟疾;一项研究报告了胎盘疟疾的数据。
结论:孕期每日口服补铁可以减少孕妇足月贫血和铁缺乏。对于其他母婴结局,组间几乎没有差异,或者证据不确定.未来的研究需要检查铁补充剂对其他母婴健康结果的影响,包括婴儿铁状态,增长,和发展。
BACKGROUND: Iron and folic acid supplementation have been recommended in pregnancy for anaemia prevention, and may improve other maternal, pregnancy, and infant outcomes.
OBJECTIVE: To examine the effects of daily oral iron supplementation during pregnancy, either alone or in combination with folic acid or with other vitamins and minerals, as an intervention in antenatal care.
METHODS: We searched the Cochrane Pregnancy and Childbirth Trials Registry on 18 January 2024 (including CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, WHO\'s International Clinical Trials Registry Platform, conference proceedings), and searched reference lists of retrieved studies.
METHODS: Randomised or quasi-randomised trials that evaluated the effects of oral supplementation with daily iron, iron + folic acid, or iron + other vitamins and minerals during pregnancy were included.
METHODS: Review authors independently assessed trial eligibility, ascertained trustworthiness based on pre-defined criteria, assessed risk of bias, extracted data, and conducted checks for accuracy. We used the GRADE approach to assess the certainty of the evidence for primary outcomes. We anticipated high heterogeneity amongst trials; we pooled trial results using a random-effects model (average treatment effect).
RESULTS: We included 57 trials involving 48,971 women. A total of 40 trials compared the effects of daily oral supplements with iron to placebo or no iron; eight trials evaluated the effects of iron + folic acid compared to placebo or no iron + folic acid. Iron supplementation compared to placebo or no iron Maternal outcomes: Iron supplementation during pregnancy may reduce maternal anaemia (4.0% versus 7.4%; risk ratio (RR) 0.30, 95% confidence interval (CI) 0.20 to 0.47; 14 trials, 13,543 women; low-certainty evidence) and iron deficiency at term (44.0% versus 66.0%; RR 0.51, 95% CI 0.38 to 0.68; 8 trials, 2873 women; low-certainty evidence), and probably reduces maternal iron-deficiency anaemia at term (5.0% versus 18.4%; RR 0.41, 95% CI 0.26 to 0.63; 7 trials, 2704 women; moderate-certainty evidence), compared to placebo or no iron supplementation. There is probably little to no difference in maternal death (2 versus 4 events, RR 0.57, 95% CI 0.12 to 2.69; 3 trials, 14,060 women; moderate-certainty evidence). The evidence is very uncertain for adverse effects (21.6% versus 18.0%; RR 1.29, 95% CI 0.83 to 2.02; 12 trials, 2423 women; very low-certainty evidence) and severe anaemia (Hb < 70 g/L) in the second/third trimester (< 1% versus 3.6%; RR 0.22, 95% CI 0.01 to 3.20; 8 trials, 1398 women; very low-certainty evidence). No trials reported clinical malaria or infection during pregnancy. Infant outcomes: Women taking iron supplements are probably less likely to have infants with low birthweight (5.2% versus 6.1%; RR 0.84, 95% CI 0.72 to 0.99; 12 trials, 18,290 infants; moderate-certainty evidence), compared to placebo or no iron supplementation. However, the evidence is very uncertain for infant birthweight (MD 24.9 g, 95% CI -125.81 to 175.60; 16 trials, 18,554 infants; very low-certainty evidence). There is probably little to no difference in preterm birth (7.6% versus 8.2%; RR 0.93, 95% CI 0.84 to 1.02; 11 trials, 18,827 infants; moderate-certainty evidence) and there may be little to no difference in neonatal death (1.4% versus 1.5%, RR 0.98, 95% CI 0.77 to 1.24; 4 trials, 17,243 infants; low-certainty evidence) or congenital anomalies, including neural tube defects (41 versus 48 events; RR 0.88, 95% CI 0.58 to 1.33; 4 trials, 14,377 infants; low-certainty evidence). Iron + folic supplementation compared to placebo or no iron + folic acid Maternal outcomes: Daily oral supplementation with iron + folic acid probably reduces maternal anaemia at term (12.1% versus 25.5%; RR 0.44, 95% CI 0.30 to 0.64; 4 trials, 1962 women; moderate-certainty evidence), and may reduce maternal iron deficiency at term (3.6% versus 15%; RR 0.24, 95% CI 0.06 to 0.99; 1 trial, 131 women; low-certainty evidence), compared to placebo or no iron + folic acid. The evidence is very uncertain about the effects of iron + folic acid on maternal iron-deficiency anaemia (10.8% versus 25%; RR 0.43, 95% CI 0.17 to 1.09; 1 trial, 131 women; very low-certainty evidence), or maternal deaths (no events; 1 trial; very low-certainty evidence). The evidence is uncertain for adverse effects (21.0% versus 0.0%; RR 44.32, 95% CI 2.77 to 709.09; 1 trial, 456 women; low-certainty evidence), and the evidence is very uncertain for severe anaemia in the second or third trimester (< 1% versus 5.6%; RR 0.12, 95% CI 0.02 to 0.63; 4 trials, 506 women; very low-certainty evidence), compared to placebo or no iron + folic acid. Infant outcomes: There may be little to no difference in infant low birthweight (33.4% versus 40.2%; RR 1.07, 95% CI 0.31 to 3.74; 2 trials, 1311 infants; low-certainty evidence), comparing iron + folic acid supplementation to placebo or no iron + folic acid. Infants born to women who received iron + folic acid during pregnancy probably had higher birthweight (MD 57.73 g, 95% CI 7.66 to 107.79; 2 trials, 1365 infants; moderate-certainty evidence), compared to placebo or no iron + folic acid. There may be little to no difference in other infant outcomes, including preterm birth (19.4% versus 19.2%; RR 1.55, 95% CI 0.40 to 6.00; 3 trials, 1497 infants; low-certainty evidence), neonatal death (3.4% versus 4.2%; RR 0.81, 95% CI 0.51 to 1.30; 1 trial, 1793 infants; low-certainty evidence), or congenital anomalies (1.7% versus 2.4; RR 0.70, 95% CI 0.35 to 1.40; 1 trial, 1652 infants; low-certainty evidence), comparing iron + folic acid supplementation to placebo or no iron + folic acid. A total of 19 trials were conducted in malaria-endemic countries, or in settings with some malaria risk. No studies reported maternal clinical malaria; one study reported data on placental malaria.
CONCLUSIONS: Daily oral iron supplementation during pregnancy may reduce maternal anaemia and iron deficiency at term. For other maternal and infant outcomes, there was little to no difference between groups or the evidence was uncertain. Future research is needed to examine the effects of iron supplementation on other maternal and infant health outcomes, including infant iron status, growth, and development.