Vitamin D supplementation to improve pregnancy and perinatal outcomes: an overview of 42 systematic reviews
Liza Bialy1, Tanis Fenton2,3, Jocelyn Shulhan-Kilroy4, David W Johnson5,6, Deborah A McNeil5,7, Lisa Hartling1,4
Appears to Ignore
- Vitamin D levels of trial participants
- If say half of the trial participants had sufficient vitamin D, then that half would not benefit,
- this would greatly reduce the chance that Vitamin D would be statistically significant
- Vitamin D: Giveth to Those Who Needeth – Jan 2020
- Intervention Dose size used
- Many reviews have given equal weighting to dose size of 400 IU as 4,000 IU
- How often the dose was given (daily, weekly, biweekly, etc)
- Which trimester the Vitamin D was started
- The form/type of vitamin D
- gut-friendly form sometimes needed to improve bioavailability
- If any Vitamin D cofactors were also given
- Genes which limit the vitamin D from getting to the tissues (maternal or fetal)
- Health benefits later in life ( > 1 month?)
- Vitamin D levels have been crashing - studies which are >10 years old have very little relevance
- Vitamin D levels are not accurately tested during pregnancy unless a LC-MS/MS test is used
- FDA allows the claim that Vitamin D “supports healthy pregnancies and promotes full-term births” – Oct 2019
- Vitamin D cuts pregnancy risks in half – low birth weight, preeclampsia, gestational diabetes – Cochrane July 2019
- Call to action – more Vitamin D for pregnancies, loading doses are OK – Holick Aug 2019
Ensure a healthy pregnancy and baby - take Vitamin D before conception has the following
Objective To review the evidence to assess effectiveness of vitamin D supplementation during pregnancy and associations of serum vitamin D levels with perinatal outcomes.
Design Overview of systematic reviews (SRs).
Data sources Searches conducted in January 2019: Ovid Medline (1946–), Cochrane Library databases.
Eligibility criteria for selecting studies Two reviewers independently screened titles and abstracts, and full texts using predefined inclusion criteria: SRs evaluating vitamin D supplementation in pregnant women and/or examining the association between serum vitamin D levels reporting at least one predefined perinatal outcome. Only SRs with high AMSTAR scores were analysed.
Data extraction and synthesis Data were extracted independently by one reviewer and checked by a second. Results were assessed for quality independently by two reviewers using GRADE criteria.
Thirteen SRs were included, synthesizing evidence from 204 unique primary studies. SRs of randomised controlled trials (RCTs) with the highest level of evidence showed
no significant benefit from vitamin D in terms of
- preterm birth (RR 1.00 (95% CI 0.77, 1.30); high quality),
- pre-eclampsia (RR 0.91 (0.45, 1.86); low quality),
- gestational diabetes (RR 0.65 (0.39, 1.08); very low quality),
- stillbirth (RR 0.75 (0.50, 1.12); high quality),
- low birth weight (RR 0.74 (0.47, 1.16); low quality),
- caesarean section (RR 1.02 (0.93, 1.12); high quality).
A significant difference was found for
- small for gestational age (RR 0.72 (0.52, 0.99); low quality).
SRs of observational studies showed associations between vitamin D levels and
- preterm birth (RR 1.19 (1.08, 1.31); moderate quality),
- pre-eclampsia (RR 1.57 (1.21, 2.03) for 25-hydroxy vitamin D (25 (OH)D)<50 nmol/L subgroup; low quality),
- gestational diabetes (RR 1.12 (1.02, 1.22) for 25 (OH)D<50 nmol/L and
- RR 1.09 (1.03, 1.15)<75 nmol/L; moderate quality) and
- small for gestational age (RR 1.35 (1.18, 1.54)<50 nmol/L; low quality).
SRs showed mixed results for associations between vitamin D and
- low birth weight (very low quality) and
- caesarean section (very low quality).
Conclusion There is some evidence from SRs of observational studies for associations between vitamin D serum levels and some outcomes; however SRs examining effectiveness from RCTs showed no effect of vitamin D supplementation in pregnancy with the exception of one predefined outcome, which had low quality evidence. Credibility of the evidence in this field is compromised by study limitations (in particular, the possibility of confounding among observational studies), inconsistency, imprecision and potential for reporting and publication biases.