Department of Dietetics and Nutrition, Florida International University, Miami, Florida, USA.
Clinical Safety, Daiichi Sankyo, Basking Ridge, New Jersey, USA.
Cochrane Database Syst Rev. 2024 Jul 30;7(7):CD008873. doi: 10.1002/14651858.CD008873.pub5.
Vitamin D supplementation during pregnancy may help improve maternal and neonatal health outcomes (such as fewer preterm birth and low birthweight babies) and reduce the risk of adverse pregnancy outcomes (such as severe postpartum haemorrhage).
To examine whether vitamin D supplementation alone or in combination with calcium or other vitamins and minerals given to women during pregnancy can safely improve certain maternal and neonatal outcomes.
We searched the Cochrane Pregnancy and Childbirth Trials Register (which includes results of comprehensive searches of CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, and relevant conference proceedings) (3 December 2022). We also searched the reference lists of retrieved studies.
Randomised and quasi-randomised trials evaluating the effect of supplementation with vitamin D alone or in combination with other micronutrients for women during pregnancy in comparison to placebo or no intervention.
Two review authors independently i) assessed the eligibility of studies against the inclusion criteria, ii) assessed trustworthiness based on pre-defined criteria of scientific integrity, iii) extracted data from included studies, and iv) assessed the risk of bias of the included studies. We assessed the certainty of the evidence using the GRADE approach.
The previous version of this review included 30 studies; in this update, we have removed 20 of these studies to 'awaiting classification' following assessments of trustworthiness, one study has been excluded, and one new study included. This current review has a total of 10 included studies, 117 excluded studies, 34 studies in awaiting assessment, and seven ongoing studies. We used the GRADE approach to assess the certainty of the evidence. This removal of the studies resulted in evidence that was downgraded to low-certainty or very low-certainty due to study design limitations, inconsistency between studies, and imprecision. Supplementation with vitamin D compared to no intervention or a placebo A total of eight studies involving 2313 pregnant women were included in this comparison. We assessed four studies as having a low risk of bias for most domains and four studies as having high risk or unclear risk of bias for most domains. The evidence is very uncertain about the effect of supplementation with vitamin D during pregnancy compared to placebo or no intervention on pre-eclampsia (risk ratio (RR) 0.53, 95% confidence interval (CI) 0.21 to 1.33; 1 study, 165 women), gestational diabetes (RR 0.53, 95% CI 0.03 to 8.28; 1 study, 165 women), preterm birth (< 37 weeks) (RR 0.76, 95% CI 0.25 to 2.33; 3 studies, 1368 women), nephritic syndrome (RR 0.17, 95% CI 0.01 to 4.06; 1 study, 135 women), or hypercalcaemia (1 study; no cases reported). Supplementation with vitamin D during pregnancy may reduce the risk of severe postpartum haemorrhage; however, only one study reported this outcome (RR 0.68, 95% CI 0.51 to 0.91; 1 study, 1134 women; low-certainty evidence) and may reduce the risk of low birthweight; however, the upper CI suggests that an increase in risk cannot be ruled out (RR 0.69, 95% CI 0.44 to 1.08; 3 studies, 371 infants; low-certainty evidence). Supplementation with vitamin D + calcium compared to no intervention or a placebo One study involving 84 pregnant women was included in this comparison. Overall, this study was at moderate to high risk of bias. Pre-eclampsia, gestational diabetes, and maternal adverse events were not reported. The evidence is very uncertain about the effect of supplementation with vitamin D and calcium on preterm birth (RR not estimable; very low-certainty evidence) or for low birthweight (RR 1.45, 95% CI 0.14 to 14.94; very low-certainty evidence) compared to women who received placebo or no intervention. Supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D) One study involving 1298 pregnant women was included in this comparison. We assessed this study as having a low risk of bias in all domains. Pre-eclampsia was not reported. The evidence is very uncertain about the effect of supplementation with vitamin D, calcium, and other vitamins and minerals during pregnancy compared to no vitamin D on gestational diabetes (RR 0.42, 95% CI 0.10 to 1.73; very low-certainty evidence), maternal adverse events (hypercalcaemia no events and hypercalciuria RR 0.25, 95% CI 0.02 to 3.97; very low-certainty evidence), preterm birth (RR 1.04, 95% CI 0.68 to 1.59; low-certainty evidence), or low birthweight (RR 1.12, 95% CI 0.82 to 1.51; low-certainty evidence).
AUTHORS' CONCLUSIONS: This updated review using the trustworthy assessment tool removed 21 studies from the previous update and added one new study for a total of 10 included studies. In this setting, supplementation with vitamin D alone compared to no intervention or a placebo resulted in very uncertain evidence on pre-eclampsia, gestational diabetes, preterm birth, or nephritic syndrome. It may reduce the risk of severe postpartum haemorrhage; however, only one study reported this outcome. It may also reduce the risk of low birthweight; however, the upper CI suggests that an increase in risk cannot be ruled out. Supplementation with vitamin D and calcium versus placebo or no intervention resulted in very uncertain evidence on preterm birth and low birthweight. Pre-eclampsia, gestational diabetes, and maternal adverse events were not reported in the only study included in this comparison. Supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D) resulted in very uncertain evidence on gestational diabetes and maternal adverse events (hypercalciuria) and uncertain evidence on preterm birth and low birthweight. Pre-eclampsia was not reported in the only study included in this comparison. All findings warrant further research. Additional rigorous, high-quality, and larger randomised trials are required to evaluate the effects of vitamin D supplementation in pregnancy, particularly in relation to the risk of maternal adverse events.
孕期补充维生素 D 可能有助于改善母婴健康结局（如减少早产和低出生体重儿的发生），并降低不良妊娠结局的风险（如严重产后出血）。
评估孕期单独或联合补充维生素 D 与钙或其他维生素和矿物质是否能安全地改善某些母婴结局。
我们检索了 Cochrane 妊娠和分娩试验注册库（其中包括对 CENTRAL、MEDLINE、Embase、CINAHL、ClinicalTrials.gov、世界卫生组织国际临床试验注册平台和相关会议论文集的全面检索结果）（2022 年 12 月 3 日）。我们还检索了纳入研究的参考文献列表。
评估孕期单独或联合补充维生素 D 与钙或其他维生素和矿物质与安慰剂或不干预相比对妇女的影响的随机和准随机试验。
评估孕期单独或联合补充维生素 D 与钙或其他维生素和矿物质与安慰剂或不干预相比对母亲和新生儿结局的影响的随机和准随机试验。
两名综述作者独立地评估了研究是否符合纳入标准、评估了基于科学完整性预定义标准的可信度、从纳入研究中提取数据、评估了纳入研究的偏倚风险。我们使用 GRADE 方法评估证据的确定性。
先前的版本包含 30 项研究；在本次更新中，我们根据可信度评估将其中 20 项研究归类为“待分类”，一项研究被排除，一项新研究被纳入。本次更新共纳入 10 项研究，117 项研究被排除，34 项研究正在评估中，7 项研究正在进行中。我们使用 GRADE 方法评估证据的确定性。由于研究设计的局限性、研究之间的不一致性以及精度不足，对这些研究的排除导致证据降级为低确定性或非常低确定性。
与安慰剂或不干预相比，孕期补充维生素 D：共纳入了八项涉及 2313 名孕妇的研究。我们评估了四项研究的大多数领域存在低偏倚风险，四项研究的大多数领域存在高偏倚或不确定风险。与安慰剂或不干预相比，孕期补充维生素 D 对先兆子痫（风险比（RR）0.53，95%置信区间（CI）0.21 至 1.33；1 项研究，165 名妇女）、妊娠期糖尿病（RR 0.53，95%CI 0.03 至 8.28；1 项研究，165 名妇女）、早产（<37 周）（RR 0.76，95%CI 0.25 至 2.33；3 项研究，1368 名妇女）、肾病综合征（RR 0.17，95%CI 0.01 至 4.06；1 项研究，135 名妇女）或高钙血症（1 项研究；无病例报告）的影响的证据非常不确定。与安慰剂或不干预相比，孕期补充维生素 D 可能降低严重产后出血的风险；然而，只有一项研究报告了这一结局（RR 0.68，95%CI 0.51 至 0.91；1 项研究，1134 名妇女；低确定性证据），并且可能降低低出生体重的风险；然而，上限 CI 表明不能排除风险增加的可能性（RR 0.69，95%CI 0.44 至 1.08；3 项研究，371 名婴儿；低确定性证据）。
与安慰剂或不干预相比，孕期补充维生素 D +钙：纳入了一项涉及 84 名孕妇的研究。总体而言，这项研究的偏倚风险为中至高。未报告子痫前期、妊娠期糖尿病和母亲不良事件。与安慰剂或不干预相比，孕期补充维生素 D 和钙对早产（RR 无法估计；极低确定性证据）或低出生体重（RR 1.45，95%CI 0.14 至 14.94；极低确定性证据）的影响的证据非常不确定。
与安慰剂或不干预相比，孕期补充维生素 D +钙+其他维生素和矿物质与钙+其他维生素和矿物质（但无维生素 D）：纳入了一项涉及 1298 名孕妇的研究。我们评估了这项研究在所有领域的低偏倚风险。未报告子痫前期。与安慰剂或不干预相比，孕期补充维生素 D、钙和其他维生素和矿物质与不补充维生素 D 对妊娠期糖尿病（RR 0.42，95%CI 0.10 至 1.73；极低确定性证据）、母亲不良事件（高钙血症无事件和高钙尿症 RR 0.25，95%CI 0.02 至 3.97；极低确定性证据）、早产（RR 1.04，95%CI 0.68 至 1.59；低确定性证据）或低出生体重（RR 1.12，95%CI 0.82 至 1.51；低确定性证据）的影响的证据非常不确定。
本研究使用可信性评估工具更新后，将先前更新中的 21 项研究排除在外，并新增了一项研究，共纳入 10 项研究。在此背景下，与安慰剂或不干预相比，单独补充维生素 D 对先兆子痫、妊娠期糖尿病、早产或肾病综合征的证据非常不确定。它可能降低严重产后出血的风险；然而，只有一项研究报告了这一结局。它也可能降低低出生体重的风险；然而，上限 CI 表明不能排除风险增加的可能性。与安慰剂或不干预相比，孕期补充维生素 D 和钙的证据非常不确定早产和低出生体重。仅在这项比较中报告了子痫前期、妊娠期糖尿病和母亲不良事件。与安慰剂或不干预相比，孕期补充维生素 D +钙+其他维生素和矿物质与钙+其他维生素和矿物质（但无维生素 D）的证据非常不确定妊娠糖尿病和母亲不良事件（高钙尿症）和早产和低出生体重的证据不确定。仅在这项比较中报告了子痫前期。所有的发现都需要进一步的研究。需要更多严格、高质量和更大规模的随机试验来评估维生素 D 补充剂在妊娠中的作用，特别是与母婴不良事件的风险有关。
