4,000 IU of daily Vitamin D during pregnancy is good (Mongolia this time) – RCT Oct 2023

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Maternal vitamin D intakes during pregnancy and child health outcome

J. of Steroid Biochemistry and Molecular Biology October 2023, https://doi.org/10.1016/j.jsbmb.2023.106411
Erdenebileg Nasantogtokh a b, Davaasambuu Ganma a c d, Shirchinjav Altantuya a b, Bayarsaikhan Amgalan b, Davaasambuu Enkhmaa а

We conducted a follow up of the children in Mongolia whose mothers received one of the three doses of vitamin D (600, 2000, or 4000 IU daily) during pregnancy as part of the randomized, double-blind, clinical trial of vitamin D supplementation to determine their impact on child health to two years.

In the parental trial, 119 pregnant women were assigned to 600 IU/day, 121 were assigned 2000 IU/day, and 120 were assigned 4000 IU/day starting at 12-16 weeks’ gestation and continuing throughout pregnancy.

At baseline, maternal serum 25(OH)D concentrations were similar across arms; 91% were < 50 nmol/l. As expected, there was a dose-response association between the amount of vitamin D consumed (600, 2000, or 4000 IU daily) and maternal 25(OH)D levels at the end of the intervention.

Total 311 children of 311 mothers were followed for 2 years to evaluate health outcomes. We determined the child's health outcomes (rickets, respiratory disease [pneumonia, asthma], and diarrhea/vomiting) using a questionnaire and physical examination (3, 6, and 24 months of age). Low levels of mothers’ serum 25(OH)D during pregnancy increased the risk of developing rickets, respiratory illness, and other diseases in children during the early childhood period. Rickets was diagnosed in 15.6% of children of women who received 600 IU of vitamin D during pregnancy, which was higher than in other vitamin D groups. Children in the group whose mothers received low doses of vitamin D (600 IU/day) had a greater probability of developing respiratory diseases compared to the other groups: pneumonia was diagnosed in n=36 (35.0%) which was significantly higher than the group receiving vitamin D 4000 IU/day (n=34 (31.5%) p=0.048).

In the group whose pregnant mother consumed 600 IU/day of vitamin D, the risk of child pneumonia was ~ 2 times higher than in the group who consumed 4000 IU/day (OR=1.99, 95% CI: 1.01-3.90). The incidence of diarrhea and vomiting in children was 12.1% lower in the 2000 IU/day group and 13.1% lower in the 4000 IU/day group compared with the 600 IU/day group (p=0.051). The offspring of pregnant women who regularly used vitamin D at doses above 600 IU/day had lower respiratory disease, rickets, and diarrheal risks at 2 years.

Introduction
Vitamin D is consumed in the diet either as ergocalciferol (vitamin D2) from plants and fungi or as cholecalciferol (vitamin D3) from animal sources [1], [2]. When exposed to sunlight, 7-dehydrocholesterol in the epidermis absorbs UVB rays and is converted to pre-vitamin D3. Moreover, 7-dehydrocholesterol can also produce vitamin D internally in the skin when exposed to ultraviolet B (UVB) light [3].

Vitamin D has a significant effect on regulating calcium and phosphate balance. As stated in literature, the vitamin D receptor identification (VDR; essential to the steroid hormone activity of 1,25(OH)2D) is a critical mediator for the biological plausibility of extraskeletal functions beside the point of calcium and bone homeostasis [4], [5], [6]. Data from observational studies indicate that the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D), may have a functional role in the immunological, cardiovascular, and neurological systems, as well as in glucose regulation. In addition, vitamin D may have an impact on the development of the placenta and fetus through several biologically plausible processes during pregnancy. Developing a healthy maternal immune response to the placenta is related to vitamin D because vitamin D has a significant immune modulating effect [7], [8], [9], [10]. When vitamin D is scarce, several numbers of above-mentioned physiological activity is impaired. Therefore, vitamin D deficiency impacts metabolic disorders, infections, cancers, and skeletal diseases [4].

Researchers indicated that breast milk is a poor source of vitamin D when maternal vitamin D status is measured low. Therefore, the mother’s vitamin D status during pregnancy and lactation is a significant predictor of the baby’s vitamin D status [11], [13]. Moreover, the vitamin D supplementation during breastfeeding is an effective approach for preventing vitamin D deficiency in children. One study demonstrated that the breastfeeding woman needs high doses of vitamin D (100 mg or 4000 IU/day) to achieve adult-normal vitamin D level [11]. As Hollis et al. reported in their randomized clinical trial (RCT), breastfeeding mothers who take 6400 IU of vitamin D per day provide enough vitamin D in their breast milk to meet the needs of their children [12]. There is increasing scientific evidence that maternal vitamin D levels may have an important effect on the offspring's development and low vitamin D levels have been studied to affect immune disorders, and impaired glucose metabolism in the offspring. According to the clinical data on evaluating the association between vitamin D deficiency in pregnancy and other health-related outcomes and overall mortality, maternal vitamin D deficiency affects offspring health outcomes [13], [14], [15], [16], [17], [18], [19]. Thus, we aimed to investigate the effect of different doses of vitamin D supplementation during pregnancy on child health at two years.

Section snippets
Study design, setting RCT, and follow-up
This is a follow-up study of the “From Healthy Mother, Healthy Baby” a randomized, controlled, double-blind study among pregnant women. The trial included pregnant women with 12–16 weeks' gestation who were allocated to one of three vitamin D supplementation groups: daily 600, 2000, or 4000 IU/day, respectively. Pregnant women were recruited from February 2015 through December 2016 at Mandal Soum Hospital in Selenge province in northern Mongolia. The groups were balanced by enrollment season . . .

Characteristics of the study population
In this follow-up study, 311 (86.3% of the original cohort) born to 311 pregnant women aged 18-42 who had been randomized to one of three doses of vitamin D were followed (Fig. 1). The mean age of pregnant women was 29±5 years, and the gestation period was 39±1.2 weeks. Table 1 shows the general characteristics of the children and their mothers (Table 1). . . .

Effect of maternal Vitamin D supplement on child rickets
The 15% of all study participants were diagnosed with rickets during the study period. Fig. 2 compares the cumulative percentage of children . . .

Discussions
This is the follow up study of a randomized, double-blinded clinical trial that evaluated the health outcomes of prenatal vitamin D in the offspring of 311 mothers who lived in the region and with available health records from birth to two years of age in Mongolia. The study showed that pregnant women's 25-hydroxyvitamin D levels were markedly increased by supplementing with 4000 IU/day of vitamin D. Significant correlation between vitamin D intake and umbilical cord blood vitamin D levels were . . .

Conclusion
Pregnant women's intake of vitamin D at doses of 2000 IU/day and 4000 IU/day reduced the incidence of rickets and diarrhea/vomiting in children under 2 years of age by more than 600 IU/day. Regular intake of vitamin D during pregnancy can reduce respiratory diseases, vomiting and diarrhea in children under 2 years of age. . . . .

28 References

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C.S. Kovacs
Vitamin D in pregnancy and lactation: maternal, fetal, and neonatal outcomes from human and animal studies
American Journal of Clinical Nutrition (2008)
D. Enkhmaa et al.
Randomized trial of three doses of vitamin D to reduce deficiency in pregnant Mongolian women
EBioMedicine (2019 Jan)
T.O. Scholl et al.
Vitamin D intake during pregnancy: association with maternal characteristics and infant birth weight
Early Hum Dev (2009)
M.K. Javaid et al.
Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: a longitudinal study
Lancet (2006)
Tserendolgor Uush
Prevalence of classic signs and symptoms of rickets and vitamin D deficiency in Mongolian children and women
The Journal of Steroid Biochemistry and Molecular Biology (2013)
C.A. Camargo et al.
Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age
American Journal of Clinical Nutrition (2007)
R.J. Moon et al.
Vitamin D, and Maternal and Child Health
Calcif Tissue Int (2020 Jan)
L.J. Dominguez et al.
Vitamin D Sources, Metabolism, and Deficiency: Available Compounds and Guidelines for Its Treatment
Metabolites (2021 Apr 20)
D. Ganmaa et al.
Vitamin D, respiratory infections, and chronic disease: Review of meta-analyses and randomized clinical trials
J Intern Med (2022 Feb)
C. Aranow
Vitamin D and the immune system
J Investig Med (2011 Aug)
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VitaminDWiki - 61 studies in both categories Pregnancy and Intervention

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VitaminDWiki - Pregnancy category contains

922 items in Pregnancy category

 - see also

• Overview Pregnancy and vitamin D
• Number of articles in both categories of Pregnancy and:Dark Skin 30;   Depression 21;   Diabetes 44;   Obesity 17;  Hypertension 44;   Breathing 35;  Omega-3 44;  Vitamin D Receptor 24 Click here for details
• All items in category Infant/Child 854 items
• Pregnancy needs at least 40 ng of vitamin D, achieved by at least 4,000 IU – Hollis Aug 2017
• 38+ papers with Breastfed etc, in the title
• Call to action – more Vitamin D for pregnancies, loading doses are OK – Holick Aug 2019
• 53+ preeclampsia studies
• 94+ studies with PRETERM in the title
• Fertility problem (PCOS) reduced by vitamin D, etc: many studies 15+
• 94+ Gestational Diabetes
• Caesarean birth much more likely if low Vitamin D - many studies 15+ studies
• Post-partum depression and low Vitamin D - many studies 15+ studies
• Stillbirth reduced by Vitamin D, Zinc, Omega-3 - several studies 5+ studies
• Search VitaminDWiki for "Assisted reproduction" 33 items as of Aug 2022
• Fertility and Sperm category listing has 142 items along with related searches
• (Stunting OR “low birth weight” OR LBW) 1180 items as of June 2020
• Less labor pain if higher level of vitamin D – August 2021
• Healthy pregnancies need lots of vitamin D
• Ensure a healthy pregnancy and baby - take Vitamin D before conception
  

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VitaminDWiki – Healthy pregnancies need lots of vitamin D contains

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

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12+ VitaminDWiki Pregnancy pages have 4,000 IU in the title

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9+ VitaminDWiki pages have MONGOLIA in the title

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