Vitamin D supplementation for women during pregnancy
Cochrane Systematic Review - Intervention Version published: 26 July 2019,
https://doi.org/10.1002/14651858.CD008873.pub4
Cristina PalaciosLia K KostiukJuan Pablo Peña‐Rosas
The benefits reported must have been mighty strong to be noticed by this review which
Ignored dose level - which ranged from 200 IU to 4,000 IU daily
Ignored the vitamin D level before supplementation
Ignored cofactors - such as Magnesium and Omega-3
Ignored when the vitamin D was started (best if start BEFORE becoming pregnant)
Ignored long-term benefits (after age 1)
Also
Did not consider the 2017 - Maternal 25(OH)D concentrations ≥40 ng/mL associated with 60% lower preterm birth risk among general obstetrical patients at an urban medical center. as it did not have a placebo arm with 0 IU of vitamin D (instead used 400 IU)
Pregnancy helped by Vitamin D - 32nd meta-analysis Sept 2019
- The current Cochrane review is not included, as it appears to not be a meta-analysis
Items in both categories Pregnancy and Meta-analysis are listed here:
- Pregnancy and offspring health - umbrella of 250,000 pregnancies - meta-analysis May 2024
- Vitamin D reduces: pre-eclampia 1.6 X, postpartum dep. 3.6 X, autism 1.5X etc. - meta-analysis March 2024
- Vitamin D supplementation decreased the risk of preeclampsia by 39% – meta-analysis Feb 2024
- Yet another reason to take Vitamin D while pregnant – fight COVID - meta-analysis May 2023
- Vitamin D during pregnancy increased child’s bone mineral density – meta-analysis April 2023
- Preeclampsia reduced by 33 percent if high vitamin D – meta-analysis Feb 2023
- Maternal pregnancy problems if Vitamin D is less than 40 ng – meta-analysis Oct 2022
- Worse COVID during 3Q pregnancy if 2.5 ng lower Vitamin D – meta-analysis Sept 2022
- Miscarriage 1.6 X more likely if low vitamin D – meta-analysis May 2022
- Recurrent Miscarriage 4X more likely if low vitamin D – meta-analysis June 2022
- Pregnancy problems (LBW, PTB, SGA) associated with low vitamin D, 42nd meta-analysis – March 2022
- Low Vitamin D associated with preeclampsia - meta-analysis Feb 2022
- Low Vitamin D associated with pre-eclampsia -40th meta-analysis – Feb 2022
- Small vitamin D doses while pregnant do not decrease infant allergies – meta-analysis Feb 2022
- Anemia 1.6 X more likely during pregnancy if low Vitamin D – meta-analysis Dec 2021
- Vitamin D reduces preeclampsia, gestational diabetes and hypertension - 38th meta-analysis Dec 2021
- Need at least 6,000 IU daily while breastfeeding to eliminate Vitamin D deficiency – meta-analysis Oct 2021
- Gestational diabetes risk reduced 1.5X by Vitamin D – meta-analysis March 2021
- Gestational Diabetes – increased risk if poor Vitamin D Receptor – 2 Meta-Analyses 2021
- Small vitamin D doses given during pregnancy do not reduce childhood asthma – meta-analysis Dec 2020
- Multiple Sclerosis 40 percent more likely if mother had low vitamin D – meta-analysis Jan 2020
- Pregnancies helped by Vitamin D (insulin and birth weight in this case) – meta-analysis Oct 2019
- Preeclampsia 2.7 X less likely if 50,000 IU of Vitamin D every 2 weeks – meta-analysis Sept 2019
- Autism risk increased 30 percent by Cesareans (both low vitamin D) – meta-analysis Sept 2019
- Vitamin D treats Gestational Diabetes, decreases hospitalization and newborn complications – meta-analysis March 2019
- Birth size and weight increased by Vitamin D – meta-analysis Feb 2019
- Pregnancies helped by Vitamin D in many ways – 27th meta-analysis Jan 2019
- Vitamin D supplementation reduced SGA, fetal mortality, infant mortality – JAMA Meta – May 2018
- Gestational Diabetes 39 percent more likely if insufficient Vitamin D – Meta-analysis March 2018
- Preeclampsia reduced 2X by Vitamin D, by 5X if also add Calcium – meta-analysis Oct 2017
- Preeclampsia risk reduced 60 percent if supplement with Vitamin D (they ignored dose size) – meta-analysis Sept 2017
- Small for gestational age is 1.6 X more likely if mother was vitamin D deficient – meta-analysis Aug 2017
- Miscarriage 2 times more likely if low vitamin D – meta-analysis May 2017
- Fewer than half of pregnancies will get even 20 ng of vitamin D with 800 IU daily dose – meta-analysis May 2017
- Low Vitamin D results in adverse pregnancy and birth outcomes – Wagner meta-analysis March 2017
- Bacterial vaginosis in pregnancy increased prematurity risk by 60 percent - meta-analysis 1999
- Preterm birth rate reduced by 43 percent with adequate Vitamin D supplementation – meta-analysis Feb 2017
- Vitamin D during pregnancy reduces risk of childhood asthma by 13 percent – meta-analysis Dec 2016
- Vitamin D helps during pregnancy – meta-analysis Feb 2016
- Preterm birth 30 percent more likely if low vitamin D – meta-analysis May 2016
- Preterm birth extended by 2 weeks with Omega-3 – Meta-analysis Nov 2015
- Gestational Diabetes Mellitus 1.5X more likely if low vitamin D – meta-analysis Oct 2015
- Infant wheezing 40 percent less likely if mother supplemented with vitamin D, vitamin E, or Zinc – meta-analysis Aug 2015
- Birth weight and length increased with high levels of vitamin D – meta-analysis March 2015
- Pregnancy and Vitamin D – meta-analysis April 2015
- More vitamin D needed during pregnancy – meta-analysis Oct 2014
- Preeclampsia rate cut in half by high level of vitamin D – meta-analysis March 2014
- Preeclampsia 2.7X more frequent if low vitamin D – meta-analysis Sept 2013
- 2X more preeclampsia when vitamin D less than 30 ng, etc. - meta-analysis March 2013
- 2X more likely to have preeclampsia if less than 20 ng of vitamin D – Meta-analysis Jan 2013
Healthy pregnancies need lots of vitamin D has the following summary
Most were taking 2,000 to 7,000 IU daily for >50% of pregnancy
Click on hyperlinks for details
Problem | Vit. D Reduces | Evidence |
| 0. Chance of not conceiving | 3.4 times | Observe |
| 1. Miscarriage | 2.5 times | Observe |
| 2. Pre-eclampsia | 3.6 times | RCT |
| 3. Gestational Diabetes | 3 times | RCT |
| 4. Good 2nd trimester sleep quality | 3.5 times | Observe |
| 5. Premature birth | 2 times | RCT |
| 6. C-section - unplanned | 1.6 times | Observe |
| Stillbirth - OMEGA-3 | 4 times | RCT - Omega-3 |
| 7. Depression AFTER pregnancy | 1.4 times | RCT |
| 8. Small for Gestational Age | 1.6 times | meta-analysis |
| 9. Infant height, weight, head size within normal limits | RCT | |
| 10. Childhood Wheezing | 1.3 times | RCT |
| 11. Additional child is Autistic | 4 times | Intervention |
| 12.Young adult Multiple Sclerosis | 1.9 times | Observe |
| 13. Preeclampsia in young adult | 3.5 times | RCT |
| 14. Good motor skills @ age 3 | 1.4 times | Observe |
| 15. Childhood Mite allergy | 5 times | RCT |
| 16. Childhood Respiratory Tract visits | 2.5 times | RCT |
RCT = Randomized Controlled Trial
50,000 IU of Vitamin D every 2 weeks provides great health - best if start before conception
Ensure a healthy pregnancy and baby - take Vitamin D before conception has the following
Note: VitaminDWiki was unable to get a free PDF from Sci-Hub, so purchased a copy of the PDF from the publisher
Background
Vitamin D supplementation during pregnancy may be needed to protect against adverse pregnancy outcomes. This is an update of a review that was first published in 2012 and then in 2016.
Objectives
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 maternal and neonatal outcomes.
Search methods
For this update, we searched Cochrane Pregnancy and Childbirth’s Trials Register (12 July 2018), contacted relevant organisations (15 May 2018), reference lists of retrieved trials and registries at clinicaltrials.gov and WHO International Clinical Trials Registry Platform (12 July 2018). Abstracts were included if they had enough information to extract the data.
Selection criteria
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.
Data collection and analysis
Two review authors independently i) assessed the eligibility of trials against the inclusion criteria, ii) extracted data from included trials, and iii) assessed the risk of bias of the included trials. The certainty of the evidence was assessed using the GRADE approach.
Main results
We included 30 trials (7033 women), excluded 60 trials, identified six as ongoing/unpublished trials and two trials are awaiting assessments.
Supplementation with vitamin D alone versus placebo/no intervention
A total of 22 trials involving 3725 pregnant women were included in this comparison; 19 trials were assessed as having low‐to‐moderate risk of bias for most domains and three trials were assessed as having high risk of bias for most domains. Supplementation with vitamin D alone during pregnancy probably reduces the risk of pre‐eclampsia (risk ratio (RR) 0.48, 95% confidence interval (CI) 0.30 to 0.79; 4 trials, 499 women, moderate‐certainty evidence) and gestational diabetes (RR 0.51, 95% CI 0.27 to 0.97; 4 trials, 446 women, moderate‐certainty evidence); and probably reduces the risk of having a baby with low birthweight (less than 2500 g) (RR 0.55, 95% CI 0.35 to 0.87; 5 trials, 697 women, moderate‐certainty evidence) compared to women who received placebo or no intervention. Vitamin D supplementation may make little or no difference in the risk of having a preterm birth < 37 weeks compared to no intervention or placebo (RR 0.66, 95% CI 0.34 to 1.30; 7 trials, 1640 women, low‐certainty evidence). In terms of maternal adverse events, vitamin D supplementation may reduce the risk of severe postpartum haemorrhage (RR 0.68, 95% CI 0.51 to 0.91; 1 trial, 1134 women, low‐certainty evidence). There were no cases of hypercalcaemia (1 trial, 1134 women, low‐certainty evidence), and we are very uncertain as to whether vitamin D increases or decreases the risk of nephritic syndrome (RR 0.17, 95% CI 0.01 to 4.06; 1 trial, 135 women, very low‐certainty evidence). However, given the scarcity of data in general for maternal adverse events, no firm conclusions can be drawn.
Supplementation with vitamin D and calcium versus placebo/no intervention
Nine trials involving 1916 pregnant women were included in this comparison; three trials were assessed as having low risk of bias for allocation and blinding, four trials were assessed as having high risk of bias and two had some components having a low risk, high risk, or unclear risk. Supplementation with vitamin D and calcium during pregnancy probably reduces the risk of pre‐eclampsia (RR 0.50, 95% CI 0.32 to 0.78; 4 trials, 1174 women, moderate‐certainty evidence). The effect of the intervention is uncertain on gestational diabetes (RR 0.33,% CI 0.01 to 7.84; 1 trial, 54 women, very low‐certainty evidence); and low birthweight (less than 2500 g) (RR 0.68, 95% CI 0.10 to 4.55; 2 trials, 110 women, very low‐certainty evidence) compared to women who received placebo or no intervention. Supplementation with vitamin D and calcium during pregnancy may increase the risk of preterm birth < 37 weeks in comparison to women who received placebo or no intervention (RR 1.52, 95% CI 1.01 to 2.28; 5 trials, 942 women, low‐certainty evidence). No trial in this comparison reported on maternal adverse events.
Supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D)
One trial in 1300 participants was included in this comparison; it was assessed as having low risk of bias. Pre‐eclampsia was not assessed. Supplementation with vitamin D + other nutrients may make little or no difference in the risk of preterm birth < 37 weeks (RR 1.04, 95% CI 0.68 to 1.59; 1 trial, 1298 women, low‐certainty evidence); or low birthweight (less than 2500 g) (RR 1.12, 95% CI 0.82 to 1.51; 1 trial, 1298 women, low‐certainty evidence). It is unclear whether it makes any difference to the risk of gestational diabetes (RR 0.42, 95% CI 0.10 to 1.73) or maternal adverse events (hypercalcaemia no events; hypercalciuria RR 0.25, 95% CI 0.02 to 3.97; 1 trial, 1298 women,) because the certainty of the evidence for both outcomes was found to be very low.
Authors' conclusions
We included 30 trials (7033 women) across three separate comparisons. Our GRADE assessments ranged from moderate to very low, with downgrading decisions based on limitations in study design, imprecision and indirectness.
Supplementing pregnant women with vitamin D alone probably reduces the risk of pre‐eclampsia, gestational diabetes, low birthweight and may reduce the risk of severe postpartum haemorrhage. It may make little or no difference in the risk of having a preterm birth < 37 weeks' gestation. Supplementing pregnant women with vitamin D and calcium probably reduces the risk of pre‐eclampsia but may increase the risk of preterm births < 37 weeks (these findings warrant further research). Supplementing pregnant women with vitamin D and other nutrients may make little or no difference in the risk of preterm birth < 37 weeks' gestation or low birthweight (less than 2500 g). 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.
Plain language summary
Is vitamin D supplementation beneficial or harmful for women during pregnancy?
What is the issue?
It is not clear if vitamin D supplementation, alone or in combination with calcium or other vitamins and minerals, during pregnancy have benefits or harms to the mother or her offspring.
Why is this important?
Vitamin D is essential for human health, particularly bone, muscle contraction, nerve conduction, and general cellular function. Low concentrations of blood vitamin D in pregnant women have been associated with pregnancy complications. It is thought that additional vitamin D through supplementation during pregnancy might be needed to protect against pregnancy complications.
What was studied in the review?
This is an update of a review that was first published in 2012 and subsequently updated in 2016. This review evaluated 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, irrespective of dose, duration or time of commencement of supplementation or type of supplementation (oral or by injection).
What evidence did we find?
We searched for evidence (July 2018) and found 30 trials (involving 7033 women) for inclusion in this update.
Evidence from 22 trials involving 3725 pregnant women suggest that supplementation with vitamin D alone during pregnancy probably reduces the risk of pre‐eclampsia, gestational diabetes, and the risk of having a baby with low birthweight compared to placebo or no intervention and may make little or no difference in the risk of having a preterm birth. It may reduce the risk of maternal adverse events, such as severe postpartum haemorrhage, although it should be noted that this result was unexpected and based on a single trial.
Evidence from nine trials involving 1916 pregnant women suggest that supplementation with vitamin D and calcium probably reduces the risk for pre‐eclampsia but may increase the risk of preterm birth. This slight potential harm warrants consideration in women receiving calcium supplementation as part of antenatal care.
Evidence from one study involving 1300 pregnant women suggest that supplementation with vitamin D plus other nutrients may make little or no difference in the risk of most outcomes evaluated.
Data on maternal adverse events were lacking in most trials.
What does this mean?
Supplementing pregnant women with vitamin D alone probably reduces the risk of pre‐eclampsia, gestational diabetes, low birthweight and the risk of severe postpartum haemorrhage. It may make little or no difference in the risk of having a preterm birth < 37 weeks' gestation. Supplementing pregnant women with vitamin D and calcium probably reduces the risk of pre‐eclampsia but may increase the risk of preterm births < 37 weeks (these findings warrant further research). Supplementing pregnant women with vitamin D and other nutrients may make little or no difference in the risk of preterm birth or low birthweight (less than 2500 g) and the effects for gestational diabetes and maternal adverse events are unclear. 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.