Regimens of vitamin D supplementation for women during pregnancy
Bibliographic record
Abstract
BACKGROUND: Vitamin D deficiency during pregnancy increases the risk of pre-eclampsia, gestational diabetes, preterm birth, and low birthweight. In a previous Cochrane Review we found that supplementing pregnant women with vitamin D alone compared to no vitamin D supplementation may reduce the risk of pre-eclampsia, gestational diabetes, and low birthweight and may increase the risk of preterm births if it is combined with calcium. However the effects of different vitamin D regimens are not yet clear. OBJECTIVES: To assess the effects and safety of different regimens of vitamin D supplementation alone or in combination with calcium or other vitamins, minerals or nutrients during pregnancy, specifically doses of 601 international units per day (IU/d) or more versus 600 IU/d or less; and 4000 IU/d or more versus 3999 IU/d or less. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (12 July 2018), and the reference lists of retrieved studies. SELECTION CRITERIA: Randomised trials evaluating the effect of different vitamin D regimens (dose, frequency, duration, and time of commencement of supplementation during pregnancy), alone or in combination with other nutrients on pregnancy and neonatal health outcomes. We only included trials that compared 601 IU/d or more versus 600 IU/d or less and 4000 IU/d or more versus 3999 IU/d or less. We did not include in the analysis groups that received no vitamin D, as that comparison is assessed in another Cochrane Review. DATA COLLECTION AND ANALYSIS: Two review authors independently: i) assessed the eligibility of studies against the inclusion criteria; ii) extracted data from included studies, and iii) assessed the risk of bias of the included studies. Our primary maternal outcomes were: pre-eclampsia, gestational diabetes, and any adverse effects; our primary infant outcomes were preterm birth and low birthweight. Data were checked for accuracy. The certainty of the evidence was assessed using the GRADE approach. MAIN RESULTS: In this review, we included data from 30 trials involving 7289 women. We excluded 11 trials, identified 16 ongoing/unpublished trials and two trials are awaiting classification. Overall risk of bias for the trials was mixed.Comparison 1. 601 IU/d or more versus 600 IU/d or less of vitamin D alone or with any other nutrient (19 trials; 5214 participants)Supplementation with 601 IU/d or more of vitamin D during pregnancy may make little or no difference to the risk of pre-eclampsia (risk ratio (RR) 0.96, 95% confidence interval (CI) 0.65 to 1.42); 5 trials; 1553 participants,low-certainty evidence), may reduce the risk of gestational diabetes (RR 0.54, 95% CI 0.34 to 0.86; 5 trials; 1846 participants; moderate-certainty evidence), may make little or no difference to the risk of preterm birth (RR 1.25, 95% CI 0.92 to 1.69; 4 trials; 2294 participants; low-certainty evidence); and may make little or no difference to the risk of low birthweight (RR 0.90, 95% CI 0.66 to 1.24; 4 trials; 1550 participants; very low-certainty evidence) compared to women receiving 600 IU/d or less.Comparison 2. 4000 IU or more versus 3999 IU or less of vitamin D alone (15 trials; 4763 participants)Supplementation with 4000 IU/d or more of vitamin D during pregnancy may make little or no difference to the risk of: pre-eclampsia (RR 0.87, 95% CI 0.62 to 1.22; 4 trials, 1903 participants, low-certainty evidence); gestational diabetes (RR 0.89, 95% CI 0.56 to 1.42; 5 trials, 2276 participants; low-certainty evidence); preterm birth (RR 0.85, 95% CI 0.64 to 1.12; 6 trials, 2948 participants, low-certainty evidence); and low birthweight (RR 0.92, 95% CI 0.49 to 1.70; 2 trials; 1099 participants; low-certainty evidence) compared to women receiving 3999 IU/d or less.Adverse events (such as hypercalcaemia, hypocalcaemia, hypercalciuria, and hypovitaminosis D) were reported differently in most trials; however, in general, there was little to no side effects reported or similar cases between groups. AUTHORS' CONCLUSIONS: Supplementing pregnant women with more than the current vitamin D recommendation may reduce the risk of gestational diabetes; however, it may make little or no difference to the risk of pre-eclampsia, preterm birth and low birthweight. Supplementing pregnant women with more than the current upper limit for vitamin D seems not to increase the risk of the outcomes evaluated. In general, the GRADE was considered low certainty for most of the primary outcomes due to serious risk of bias and imprecision of results. With respect to safety, it appears that vitamin D supplementation is a safe intervention during pregnancy, although the parameters used to determine this were either not reported or not consistent between trials. Future trials should be consistent in their reports of adverse events. There are 16 ongoing trials that when published, will increase the body of knowledge.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.012 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".