Table of contents
- The impact of COVID-19 on pregnancy outcomes: a systematic review and meta-analysis
- Virus and Pregnancy in Vitamin D Life
- Virus and Mortality in Vitamin D Life
- Virus and Magnesium (also important to pregnancy)
- Virus and Omega-3 (also important to pregnancy)
- Virus and Vitamin D Receptor (also important to pregnancy)
The impact of COVID-19 on pregnancy outcomes: a systematic review and meta-analysis
CMAJ. 2021 Apr 19; 193(16): E540–E548. doi: 10.1503/cmaj.202604
Shu Qin Wei, MD PhD, Marianne Bilodeau-Bertrand, MSc, Shiliang Liu, MB PhD, and Nathalie Auger,
Background:
The impact of coronavirus disease 2019 (COVID-19) on maternal and newborn health is unclear. We aimed to evaluate the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy and adverse pregnancy outcomes.
METHODS:
We conducted a systematic review and meta-analysis of observational studies with comparison data on SARS-CoV-2 infection and severity of COVID-19 during pregnancy. We searched for eligible studies in MEDLINE, Embase, ClinicalTrials.gov, medRxiv and Cochrane databases up to Jan. 29, 2021, using Medical Subject Headings terms and keywords for “severe acute respiratory syndrome coronavirus 2 OR SARS-CoV-2 OR coronavirus disease 2019 OR COVID-19” AND “pregnancy.” We evaluated the methodologic quality of all included studies using the Newcastle–Ottawa Scale. Our primary outcomes were preeclampsia and preterm birth. Secondary outcomes included stillbirth, gestational diabetes and other pregnancy outcomes. We calculated summary odds ratios (ORs) or weighted mean differences with 95% confidence intervals (CI) using random-effects meta-analysis.
RESULTS:
We included 42 studies involving 438 548 people who were pregnant.
Compared with no SARS-CoV-2 infection in pregnancy, COVID-19 was associated with
- preeclampsia (OR 1.33, 95% CI 1.03 to 1.73),
- preterm birth (OR 1.82, 95% CI 1.38 to 2.39) and
- stillbirth (OR 2.11, 95% CI 1.14 to 3.90).
Compared with mild COVID-19, severe COVID-19 was strongly associated with
- preeclampsia (OR 4.16, 95% CI 1.55 to 11.15),
- preterm birth (OR 4.29, 95% CI 2.41 to 7.63),
- gestational diabetes (OR 1.99, 95% CI 1.09 to 3.64) and
- low birth weight (OR 1.89, 95% CI 1.14 to 3.12).
INTERPRETATION:
COVID-19 may be associated with increased risks of preeclampsia, preterm birth and other adverse pregnancy outcomes.
Letter to Editor
RE: The impact of COVID-19 on pregnancy outcomes: a systematic review and meta-analysis
William B. Grant, Health research, Sunligth, Nutrition and Health Research Center
22 March 2021
The recent systematic review and meta-analysis by Wei and colleagues found that having COVID-19 during pregnancy was significantly associated with increased risk for preeclampsia, preterm birth, and stillbirth 1. The underlying reason for these findings was not provided.
A likely reason for these findings was an impaired immune system due to low vitamin D status. There is mounting evidence that serum 25-hydroxyvitamin D [25(OH)D] concentration is inversely correlated with both COVID-19 risk and severity 2 and adverse pregnancy outcomes. The mechanisms whereby vitamin D reduces risk of COVID-19 include induction of cathelicidin and defensins to reduce replication of the SARS-CoV-2 virus and reducing risk of developing the cytokine storm, which damages the linings of many organs 2.
A recent meta-analysis using data pooled from 27 RCTs which included overall 4777 participants, of whom 2487 were in the vitamin D-treated arm and 2290 in the control arm. Vitamin D administration in pregnancy was associated with a reduced risk of preeclampsia (odds ratio = 0.37, 95% confidence interval [CI]: 0.26, 0.52). 3.
An open-label study was conducted in South Carolina involving 1064 pregnant women given free vitamin D3 capsules (5000 IU) and counseled on how to achieve 25(OH)D >40 ng/mL (100 nmol/L) 4. The LOESS curve showed gestational age rising with increasing 25(OH)D. Women who achieved 25(OH)D ≥40 ng/mL had a 62% lower risk of preterm birth compared to those with <20 ng/mL (odds ratio = 0.38, 95% CI = 0.23–0.63, p<0.0001). For more information on vitamin D during
pregnancy, see Wagner and Hollis 5
Thus, women who are pregnant or are planning to become pregnant should supplement with vitamin D and measure serum 25(OH)D concentrations to verify that they achieve optimal concentrations in order to reduce risk of both COVID-19 and adverse pregnancy and birth outcomes.
Competing Interests: I receive funding from Bio-Tech Pharmacal, Inc. (Fayetteville, AR, USA).
References
- Shu Qin Wei, Marianne Bilodeau-Bertrand, Shiliang Liu, et al. The impact of COVID-19 on pregnancy outcomes: a systematic review and meta-analysis. CMAJ 2021;10.1503/cmaj.202604.
- Mercola J, Grant WB, Wagner CL. Evidence Regarding Vitamin D and Risk of COVID-19 and Its Severity. Nutrients. 2020;12:3361.
- Fogacci S, Fogacci F, Banach M, et al. Vitamin D supplementation and incident preeclampsia: A systematic review and meta-analysis of randomized clinical trials. Clin Nutr. 2020;39:1742-52.
- McDonnell SL, Baggerly KA, Baggerly CA, et al. Maternal 25(OH)D concentrations >/=40 ng/mL associated with 60% lower preterm birth risk among general obstetrical patients at an urban medical center. PLoS One. 2017;12:e0180483.
- Wagner CL, Hollis BW. The Implications of Vitamin D Status During Pregnancy on Mother and her Developing Child. Front Endocrinol (Lausanne). 2018;9:500.
Virus and Pregnancy in Vitamin D Life
- Yet another reason to take Vitamin D while pregnant – fight COVID - meta-analysis May 2023
- COVID lockdowns reduced Vitamin D levels - should supplement - April 2023
- Pfizer COVID vaccination during pregnancy clinical trial is still not published - Feb 2023
- Worse COVID during 3Q pregnancy if 2.5 ng lower Vitamin D – meta-analysis Sept 2022
- Temporary conception problems after vaccinations, etc. - July 2022
- 2.3 X more poor Neurodevelopment in infant if COVID late in pregnancy – June 2022
- Severe COVID while pregnant - none had taken any vitamin D – Oct 2021
- COVID while pregnant: 2.6 X more likely to be Vitamin D deficient (need to supplement) - March 2022
- COVID breakthru 2X more likely if pregnant (should take Vitamin D) - April 2022
- COVID 2.6 X more likely if low Vitamin D (during pregnancy in this case) – March 2022
- 3 years after congenital virus infection there was a 12X increase in infant deaths (Zika, Brazil) - Feb 2022
- COVID-19 more severe if low Vitamin D (1.8X for pregnancy) – Nov 2021
- Far less vitamin D in breast milk if COVID-19 (no surprise) – Aug 2021
- COVID-21 (COVID-19 with mutations) causing increased pregnancy problems in Brazil and India – May 2021
- COVID-19, dark skin, pregnancy - Dr. Grimes, etc. - May 2021
- Increased pregnancy problems with COVID-19 – meta-analysis and letter to editor – April 2021
- COVID-19 while pregnant increased many infant health problems by 1.5X – April 29, 2021
- COVID-19 while pregnant is not good (increased risk of dying by 22X) – April 2021
- Vaccine trials excluded pregnancies, but it is OK to be vaccinated while pregnant
- Vitamin D plus Inositol might help pregnancies during COVID-19 – April 2021
- 3.7X decrease in Very Low Weight Births (following huge increase in Vitamin D sales) - June 2020
- Flu vaccinations during pregnancy should NOT be the standard of care until tests show it is OK – Nov 2019
- Researchers found flu vaccine increased miscarriage risk by 7X -Sept 2017
Virus and Mortality in Vitamin D Life
- Moderna report: their COVID vax caused "only" 17,751 deaths - April 2024
- COVID infection (without hospitalization) – 1.7X more likely to die in 6 months if low Vitamin D – March 2024
- Vaccines increased your risk of dying of COVID in NZ - official data - Feb 2024
- 3X increase in unspecified causes of Death (Canada 2019-2022) - Dec 2023
- Deaths after vaccination - also reported in Japan - Dec 2023
- Excess deaths after COVID vaccination - 17 countries - Sept 2023
- Excess Deaths in Australia jumped up in 2022– preprint Feb 2023
- Prevent a COVID death: 9 dollars of Vitamin D or 900,000 dollars of vaccine - Aug 2023
- Number needed to vaccinate to prevent 1 Omicron death: 30,000 for age 60-70 - Sept 2022
- COVID survival in Europe in 2020 best predicted by population-level Vitamin D (of 13 variables) – July 2022
- Elderly who had been in COVID ICU were 4X more likely to die if low vitamin D – Nov 2022
- More COVID mortality if less than 20 ng of Vitamin D (Mexico) – May 2022
- 15,000,000 excess deaths in 2 years - May 2022
- COVID death 5.2X more likely if Vitamin D deficient – May 2022
- 29 X more likely to die of COVID if less than 20 ng of Vitamin D - March 2022
- Giving Vitamin D reduced COVID Mortality– Review of 11 studies – March 2022
- 18 million excess global deaths in past 2 years: COVID plus collateral damage - Lancet March 2022
- COVID severity and death more likely if low vitamin D (Egypt this time) - March 2022
- US nursing homes are epicenters for COVID deaths (200,000) - Feb 2022
- Ivermectin taken before COVID decreased death rate by 68 percent (3,000 with Ivermectin vs 3,000 without) - Dec 24, 2021
- Increase in non-COVID deaths (ages 18-64) in Indiana, India, etc. - Jan 5, 2022
- Only 35,000 died in US of COVID who previously had been healthy
- COVID-19 mortality extrapolates to zero at 50 ng of vitamin D – 18th Meta-analysis Sept 2021
- COVID-19 patients getting 300,000 IU of Vitamin D were 5X less likely to die – Sept 2021
- Predict 2X more likely to die of COVID-19 if vitamin D Deficient (Iran 2020) – Sept 2021
- COVID-19 mortality not associated with Vitamin D (everyone had very low levels) -Sept 2021
- COVID-19 mortality for Blacks is 5X that for whites in 2 LA Hospitals - July 2021
- COVID-19 mortality was associated with vitamin D deficiency of 47 countries – July 2021
- Similar death rate for Vaccination and COVID-19 study and video – June 24, 2021
- COVID-19 death in hospital 5X more likely if low vs high vitamin D – preprint June 2021
- COVID-19 deaths 1.7X more likely if low vitamin D (even after “adjusting” for low D health problems) – May 2021
- COVID-19 deaths 1.5X less likely if more than 40 ng of vitamin D – US VA – April 2021
- Vitamin D supplementation and high levels reduce COVID-19 deaths in elderly – Review April 17, 2021
- Less COVID-19 infection, mortality in countries with higher Vitamin D (Asia in this case) – May 2021
- COVID-19 was the third-leading cause of death in the US, especially in those with dark skins - April 1, 2021
- Risk of COVID-19 death was 4.9 X higher if very low vitamin D – March 31, 2021
- COVID-19 mortality 2X higher if low Vitamin D (Mexican hospital, preprint) - March 2021
- All COVID-19 patients had low vitamin D, the lowest were more likely to die – Feb 18, 2021
- 2.7 fewer COVID-19 hospital deaths in those having more than 30 ng of vitamin D – Mayo Jan 9, 2021
- Worse COVID-19 patients got 400,000 IU of vitamin D, deaths cut in half – Jan 14, 2021
- Iranians with COVID-19 were 2.3 X more likely to die if low vitamin D – Jan 2021
- Poor COVID-19 prognosis was 6 X more likely if low vitamin D – Jan 21, 2021
- Less than 10 dollars of Vitamin D per COVID-19 life saved in Myanmar - Jan 2021
- 2.8 X fewer COVID-19 nursing home deaths if add 10,000 IU Vitamin D daily for a week (small observation)- Jan 2021
- Italian nursing home COVID-19 – 4X less likely to die if taking Vitamin D– Dec 22, 2020
- Shift workers 2X more likely to get COVID-19 (low Vitamin D) - Dec 2020
- Those getting high dose vitamin D were 7 X less likely to die of COVID-19 - Dec 11, 2020
- COVID-19 male mortality increased 3.9 X if low vitamin D – observation Nov 25, 2020
- Hospital COVID-19 observation: 7X more likely to live if more than 20 ng of vitamin D– Nov 19, 2020
- COVID-19 lung death 4X more likely in Iran if less than 25 ng of vitamin D – Oct 30, 2020
Virus and Magnesium (also important to pregnancy)
- Long-COVID 3.1 X more likely if insufficient amounts of Magnesium and Vitamin D – March 2024
- COVID appears to be treated by many antioxidants (Vitamins D, C, E, K, and Quercetin, Curcumin, etc) – Jan 2023
- Fatigue and other long-haul problems appear to be associated with low Magnesium - Chambers Oct 2022
- Low Magnesium associated with severe COVID – many studies
- COVID and Magnesium - hypothesis, clinical trials, Long-Haul - Oct 2021
- COVID treatment patent applied for - using Rutin, Vitamin D, Vitamin C, Magnesium, etc. – April 2022
- COVID death 6.9X less likely if high Magnesium to Calcium ratio – April 2022
- Hypothesis: 2 long-haul COVIDs: had mild symptoms and had needed ICU - April 2022
- Excess Magnesium is bad for health (COVID hospital days in this case) – April 2022
- Vitamin D, Zinc, Magnesium etc. are needed to fight COVID – April 2022
- Long Covid, Short Magnesium - Chambers April 2022
- Lower Magnesium, 6 percent more COVID - Feb 2022
- Nutritional supplementation during COVID hospitalization helped - RCT - Jan 2022
- How Vitamin D, Magnesium, Omega-3 and Zinc prevent and treat COVID-19 and many other health problems – June 2021
- Elderly nutrition and COVID-19 – systematic review July 2021
- Magnesium in Infectious Diseases in Older People - Jan 2021
- COVID-19 Cytokine storms attenuated by Vitamin D, Omega-3, Mg, Resveratrol, etc – April 2021
- 6X less risk of COVID-19 ICU if Vitamin D and Vit B12 and Mg – Jan 2021
- Cytokine storms (COVID-19, etc.) eliminated by Vitamin D (Magnesium helps)
- Magnesium and Vitamin D deficiencies associated with worse COVID-19 – Jan, 2021
- Excessive insulin decreases vitamin D in 4 ways – problems for diabetic COVID-19 – Dec 2020
- Magnesium (which increases vitamin D) may fight COVID-19 - Oct 2020
- COVID-19 1.8 X more likely if proton pump inhibitor (decreases Mg and Vitamin D) – Aug 2020
- COVID-19 might be treated with Mg IV and Potassium – July 2020
- COVID-19 prompts awareness of deficiencies of Vitamin D, C and Magnesium - April 6 2020
- Obesity pandemic since 1975 - is it due to Vitamin D, Magnesium, Iodine, adenovirus, or what
Virus and Omega-3 (also important to pregnancy)
- How vitamins A, B, C, D, E, F (Omega), K fight COVID - Feb 2022
- Nutritional supplementation during COVID hospitalization helped - RCT - Jan 2022
- Omega-3 decreases heart disease and COVID: Harris and Patrick, video and transcript - Dec 2021
- COVID-19 decreased risk if add Vitamin D, A, C, NAC, Se, Zn, or Omega-3 – Dec 2021
- High-dose Omega-3 fought COVID in 2 hospital trials (6x reduction in ICU, reduced time) – Masterjohn Oct 2021
- COVID-19 risk reduced 4X by each of: Vitamin D, Omega-3, Curcumin, Zinc (each increases D in cells)
- Omega-3 reduces risk of COVID-19 - many studies
- How Vitamin D, Magnesium, Omega-3 and Zinc prevent and treat COVID-19 and many other health problems – June 2021
- Many supplements appear to fight COVID-19 – vitamin D cited 52 times – May 2021
- COVID-19 Cytokine storms attenuated by Vitamin D, Omega-3, Mg, Resveratrol, etc – April 2021
- COVID-19 ICU survival rate increased 7X by daily Omega-3 – RCT March 2021
- 4X fewer COVID-19 deaths in those having high Omega-3 index – Jan 6, 2021
Virus and Vitamin D Receptor (also important to pregnancy)
- COVID maximum downregulation of Vitamin D receptor and CYP27B1 resulted in death - Feb 2024
- COVID in hospital stopped by Vitamin D Receptor activators (curcumin, quercetin) – RCT June 2023
- Children with COVID 4X more likely to have poor Vitamin D Receptors (Note: COVID deactivates VDR) – April 2023
- Diabetes 3X more likely if had COVID ICU (VDR was deactivated) - April 2023
- COVID variants protect themselves by deactivating different VDR variants– March 2023
- Dengue Fever decimated by Vitamin D - many studies
- COVID kids were more likely to have a poor VDR (4.3 X), than low Vitamin D (2.6 X) – Sept 2022
- Cancers are associated with low vitamin D, poor vaccination response and perhaps poor VDR – July 2022
- COVID 3X more likely if a poor Receptor (cells get less Vitamin D from the blood) – July 2022
- Long-COVID is now the biggest COVID concern - many studies
- COVID death 12X more likely if poor Vitamin D Receptor (less D gets to cells) - many studies
- COVID severity, ICU, and mortality all associated with poor vitamin D receptor (but not D, everyone had low D) -Dec 2021
- Different Vitamin D Receptor problems cause different COVID problems - Dec 2021
- COVID-19 severity associated with 3 vitamin D genes – Oct 2021
- Poor Vitamin D receptor blocked Vitamin D from fighting avian influenza viruses (in mice) – July 2021
- Epstein-Barr is yet another virus that deactivates the Vitamin D receptor (COVID later suspected as well)– 2010
- COVID-19 symptoms and comorbidities associated with the type of Vitamin D Receptor – Oct 2021
- Enveloped virus infection (RSV, coronavirus, HIV, etc.) 1.5X more likely if poor Vitamin D Receptor – meta-analysis Dec 2018
- COVID-19 outpatients getting Quercetin nanoemulsion had excellent outcomes (Q increased Vitamin D in cells) – RCT – June 2021
- A virus that most adults have (Cytomegalovirus) decreases the amount of Vitamin D which gets to the cells – Jan 2017
- COVID virus alters the activation of 100 vitamin D related genes in the lung – April 2021
- Common sense COVID-19 risk reduction - masks, social distancing, vitamin D - Oct 2020
- AI is examining 170,000 potential COVID-19 treatments, Vitamin D is one of only 6 found – Sept 4, 2020
- Vitamin D Receptor activation should reduce ARDS associated with COVID-19 - June 2020
- Dengue viral production decreased 1000X if activate Vitamin D Receptor (in lab) – July 2020
- Vitamin D, Quercetin, and Estradiol all increase vitamin D in cells and increase genes which reduce COVID-19 – May 21, 2020
- Quercetin and Vitamin D - Allies Against COVID-19
- Risk of enveloped virus infection is increased 50 percent if poor Vitamin D Receptor - meta-analysis Dec 2018
- Hand, foot, and Mouth disease is 14X more likely if poor Vitamin D Receptor – Oct 2019
- Treating herpes reduced incidence of senile dementia by 10 X (HSV1 reduces VDR by 8X) – 2018
- Severe hand, foot, and mouth virus is 2.9 X more likely if poor Vitamin D receptor – Oct 2018
- Hepatitis B virus reduced by 5X the Vitamin D getting to liver cells in the lab – Oct 2018
- Some enveloped virus are 1.2 X more likely if have a poor Vitamin D Receptor -Aug 2018
- Severe Pertussis is 1.5 times more likely if poor vitamin D receptor – Feb 2016
- Dengue Fever associated with poor vitamin D receptor – July 2002
- Dengue virus 2X to 4X more likely if vitamin D receptor gene problems
Vitamin D Receptor and Pregnancy
A poor receptor will restrict vitamin D from getting to cells
- Gestational Diabetes and Vitamin D - many studies
- Hypertension during pregnancy: low Vitamin D, poor Vit. D genes – June 2022
- Preeclampsia reduced by Vitamin D - many studies
- After lactation Vitamin D levels are low, increased risk of Breast Cancer, vitamin D should decrease risk – Aug 2021
- Gestational Diabetes – increased risk if poor Vitamin D Receptor – 2 Meta-Analyses 2021
- Higher risk of Recurrent Pregnancy Loss if poor Vitamin D Receptor – Feb 2021
- Spontaneous Miscarriage strongly associated with 2 vitamin D genes – March 2020
- Preterm birth associated with many genes, including the Vitamin D Receptor again – Jan 2020
- Preterm birth 8X more likely if poor Vitamin D Receptor – Dec 2019
- Preterm birth 9 X more likely if fetus had a poor Vitamin D Receptor and previous miscarriage – Aug 2017
- Recurrent miscarriage occurs 2.2 more often if poor Vitamin D Receptor – Aug 2019
- Gestational Diabetes 2.4X more likely if poor Vitamin D Receptor (region in China) – June 2019
- Gestational Diabetes 3 X more likely if poor Vitamin D receptor (Turkey) – May 2019
- Preeclampsia 2X more likely if poor Vitamin D Receptor – April 2019
- Preterm births 12 X more likely if poor Vitamin D Receptor (white infants in Italy) – meta-analysis Aug 2018
- UV at time of conception associated with Vitamin D Receptor activation 65 years later – Sept 2017
- A good Vitamin D Receptor (or perhaps more vitamin D) protects against lead during pregnancy
- Vitamin D Receptor is associated with preeclampsia, gestational diabetes and preterm birth – Nov 2017
- Gestational Diabetes Mellitus associated with 4 Vitamin D genes – Oct 2015
- Frequent miscarriage associated with both lower vitamin D and poor Vitamin D receptor – Sept 2017
- Vitamin D genes and pregnancy – 7th study - Sept 2017
- Preterm births strongly related to Vitamin D, Vitamin D Receptor, Iodine, Omega-3, etc
- Recurrent miscarriage associated with half as much vitamin D getting to fetus – Sept 2016
- Progesterone activates vitamin D receptor - many studies
Healthy pregnancies need lots of vitamin D
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
See Healthy pregnancies need lots of vitamin D for details