Department of Obstetrics and Gynaecology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Department of Epidemiology and Biostatistics, Faculty of Public Health, Khon Kaen University, Khon Kaen, Thailand.
Cochrane Database Syst Rev. 2024 Nov 19;11(11):CD007079. doi: 10.1002/14651858.CD007079.pub4.
Maternal nutrition during pregnancy is known to have an effect on fetal growth and development. It is recommended that women increase their calcium intake during pregnancy and lactation, although the recommended dosage varies among professionals. Currently, there is no consensus on the role of routine calcium supplementation for pregnant women other than for preventing or treating hypertension.
To determine the effect of calcium supplementation on maternal, fetal and neonatal outcomes, excluding women with multiple gestation (other than for preventing or treating hypertension), including the occurrence of adverse effects.
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (which includes results of comprehensive searches of CENTRAL, MEDLINE, Embase, CINAHL, two trials registers and relevant conference proceedings) on 3 December 2022. We also searched the reference lists of retrieved studies.
We considered all published, unpublished and ongoing randomised controlled trials (RCTs) comparing maternal, fetal and neonatal outcomes in pregnant women who received calcium supplementation versus placebo or no treatment. Cluster-RCTs were eligible for inclusion but none were identified. Quasi-RCTs and cross-over studies were not eligible for inclusion.
Two review authors independently assessed trials for inclusion. At least one review author assessed trials meeting the inclusion criteria for trustworthiness, consulting another review author in cases that were not immediately clear. Two review authors independently assessed the studies for risk of bias, extracted data, and checked trials for accuracy. We assessed the certainty of the evidence using GRADE.
Twenty-one studies met the inclusion criteria, but only 19 studies contributed data to the review. These 19 trials recruited 17,370 women, with 16,625 women included in the final analyses. The trials were generally at low risk of bias for randomisation and allocation concealment. We chose three outcomes for GRADE assessment: preterm birth less than 37 weeks, preterm birth less than 34 weeks and low birthweight (less than 2500 g). All trials compared calcium supplementation with placebo or no treatment with 17 trials comparing high-dose calcium (greater than 1000 mg/day). Calcium supplementation probably slightly reduces the risk of preterm birth less than 37 weeks (average risk ratio (RR) 0.80, 95% confidence interval (CI) 0.65 to 0.99; 11 trials, 15,379 women; moderate-certainty evidence), but probably has little effect on the risk of preterm birth less than 34 weeks (average RR 1.03, 95% CI 0.79 to 1.35; 3 trials, 5569 women; moderate-certainty evidence), and may have little or no effect on low birthweight (less than 2500 g) (average RR 0.93, 95% CI 0.81 to 1.07; 6 trials, 14,162 women; low-certainty evidence; 1 study reported low birthweight (less than 2500 g) but recorded 0 events in both groups. Thus, the RR and CIs were calculated from 5 studies rather than 6). We downgraded the evidence for imprecision (wide CIs crossing the line of no effect) and inconsistency (high levels of heterogeneity between the studies). There was no evidence that calcium supplementation had any effect on maternal weight gain during pregnancy; increasing bone mineral density in pregnant women; rate of intrauterine growth restriction; perinatal mortality; stillbirth or fetal death rate; increase birth length or fetal head circumference; and adverse effects such as postpartum haemorrhage, gall stones, gastrointestinal symptoms, headache, urinary stones, urinary tract infection or impaired renal function.
AUTHORS' CONCLUSIONS: This review indicates that calcium supplementation probably reduces preterm birth before 37 weeks. There are no clear additional benefits to calcium supplementation in preterm birth before 34 weeks or prevention of low birthweight. Large multicentre trials to detect the effect of calcium supplementation on fetal birthweight and preterm birth before 34 weeks as the primary outcomes are needed. Further research into the short- and long-term effects of calcium supplementation would also be beneficial.
已知孕妇营养状况会对胎儿的生长和发育产生影响。建议孕妇在妊娠和哺乳期增加钙的摄入量，尽管不同专业人士推荐的剂量有所不同。目前，对于除了预防或治疗高血压以外的孕妇，常规补钙的作用尚未达成共识。
确定钙补充对母婴和新生儿结局的影响，不包括多胎妊娠（除了预防或治疗高血压）的女性，包括不良事件的发生。
我们于 2022 年 12 月 3 日在 Cochrane 妊娠与分娩组试验注册库（其中包括对 CENTRAL、MEDLINE、Embase、CINAHL、两个试验注册库和相关会议记录的全面检索结果）中进行了检索。我们还检索了已检索研究的参考文献列表。
我们考虑了所有已发表、未发表和正在进行的随机对照试验（RCT），比较了接受钙补充剂与安慰剂或不治疗的孕妇的母婴和新生儿结局。集群 RCT 有资格纳入，但未发现集群 RCT。准 RCT 和交叉研究没有资格纳入。
两位综述作者独立评估试验的纳入情况。至少有一位综述作者评估了符合纳入标准的试验的可信度，并在情况不明确时咨询了另一位综述作者。两位综述作者独立评估了研究的偏倚风险，提取数据，并检查了试验的准确性。我们使用 GRADE 评估证据的确定性。
21 项研究符合纳入标准，但只有 19 项研究提供了数据。这 19 项试验共招募了 17370 名女性，其中 16625 名女性纳入最终分析。这些试验在随机化和分配隐藏方面通常具有较低的偏倚风险。我们选择了三个结局进行 GRADE 评估：早产少于 37 周、早产少于 34 周和低出生体重（少于 2500 克）。所有试验均将钙补充与安慰剂或不治疗进行比较，其中 17 项试验比较了高剂量钙（大于 1000 毫克/天）。钙补充可能略微降低早产少于 37 周的风险（平均风险比（RR）0.80，95%置信区间（CI）0.65 至 0.99；11 项试验，15379 名女性；中等确定性证据），但可能对早产少于 34 周的风险影响不大（平均 RR 1.03，95% CI 0.79 至 1.35；3 项试验，5569 名女性；中等确定性证据），并且可能对低出生体重（少于 2500 克）的影响不大或没有影响（平均 RR 0.93，95% CI 0.81 至 1.07；6 项试验，14162 名女性；低确定性证据；1 项研究报告了低出生体重（少于 2500 克），但两组均记录了 0 个事件。因此，RR 和 CIs 是从 5 项研究而不是 6 项研究中计算出来的）。我们因不精确（置信区间宽，跨越无效应线）和不一致（研究之间存在高水平的异质性）而下调了证据的确定性。没有证据表明钙补充对孕妇怀孕期间的体重增加、增加孕妇的骨密度、宫内生长受限的发生率、围产期死亡率、死胎或胎儿死亡率、增加出生长度或胎儿头围有任何影响，以及产后出血、胆结石、胃肠道症状、头痛、尿路结石、尿路感染或肾功能损害等不良影响。
本综述表明，钙补充可能会降低早产少于 37 周的风险。钙补充对早产少于 34 周或预防低出生体重没有明显的额外益处。需要进行大型多中心试验，以检测钙补充对胎儿出生体重和早产少于 34 周的影响作为主要结局。进一步研究钙补充的短期和长期影响也将是有益的。
