Vitamin D supplementation in pregnancy, prenatal 25(OH)D levels, race, and subsequent asthma or recurrent wheeze in offspring: Secondary analyses from the Vitamin D Antenatal Asthma Reduction Trial.
J Allergy Clin Immunol. 2017 Mar 9. pii: S0091-6749(17)30217-8. doi:10.1016/j.jaci.2017.01.013. [Epub ahead of print]
- Pregnancies with a good level of vitamin D at 10-18 weeks had fewer asthmatic infants than those with low vitamin D who were then supplemented with 4400 IU of vitamin D – which would not be of much benefit (without loading dose) until 18 to 26 weeks – long after the lungs start to develop
- As is the case for many health problems: Need a good level of vitamin D as soon as possible
- Via loading dose (repleting vitamin D levels 3 months sooner) or perhaps even start supplementation before conception
- Overview Asthma and Vitamin D
- Childhood Asthma somewhat reduced by 2400 IU vitamin D late in pregnancy (néed more, earlier) March 2019
- Asthma in 3 year olds decreased somewhat with 4,000 IU during pregnancy – RCT Jan 2016 Started at 10-18 weeks, no loading dose
- Asthma reduced 31 percent when Omega-3 taken during pregnancy – RCT Dec 2016 Started Omega-3 at 24 weeks
- Risk of infant Asthma cut in half if mother supplemented Vitamin D to get more than 30 ng – RCT Oct 2017
- Babies 3.6X more likely to go to hospital for asthma if asthmatic mother had low vitamin D while pregnant – June 2019
Wolsk HM1, Harshfield BJ2, Laranjo N2, Carey VJ3, O'Connor G4, Sandel M5, Strunk RC6, Bacharier LB6, Zeiger RS7, Schatz M7, Hollis BW8, Weiss ST3, Litonjua AA9.
1 Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Mass; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
2 Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Mass.
3 Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass.
4 the Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, Mass.
5 Department of Pediatrics, Boston Medical Center, Boston, Mass.
6 Division of Pediatric Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Washington University School of Medicine and St Louis Children's Hospital, St Louis, Mo.
7 Department of Allergy and Research evaluation, Kaiser Permanente Southern California, San Diego and Pasadena, Calif.
8 Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina.
9 Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass. Electronic address: augusto.litonjua at channing.harvard.edu.
Nutrient trials differ from drug trials because participants have varying circulating levels at entry into the trial.
We sought to study the effect of a vitamin D intervention in pregnancy between subjects of different races and the association between 25-hydroxyvitamin D3 (25[OH]D) levels in pregnancy and the risk of asthma/recurrent wheeze in offspring.
The Vitamin D Antenatal Asthma Reduction Trial is a randomized trial of pregnant women at risk of having children with asthma randomized to 4400 international units/d vitamin D or placebo plus 400 international units/d vitamin D. Asthma and recurrent wheezing until age 3 years were recorded.
African American (AA) women (n = 312) had lower initial levels of 25(OH)D (mean [SD], 17.6 ng/mL [8.3 ng/mL]) compared with non-AA women (n = 400; 27.1 ng/mL [9.7 ng/mL], P < .001). No racial difference was found from vitamin D supplementation in pregnancy on asthma/recurrent wheezing in offspring (P for interaction = .77). Having an initial level of greater than 30 ng/mL and being randomized to the intervention group was associated with the lowest risk for asthma/recurrent wheeze by age 3 years compared with having an initial level of less than 20 ng/mL and receiving placebo (adjusted odds ratio, 0.42; 95% CI, 0.19-0.91).
We did not find differences between AA and non-AA mothers in the effect of maternal vitamin D supplementation and asthma/recurrent wheeze in offspring at 3 years. Maternal supplementation of vitamin D, particularly in mothers with initial 25(OH)D levels of greater than 30 ng/mL, reduced asthma/recurrent wheeze in the offspring through age 3 years, suggesting that higher vitamin D status beginning in early pregnancy is necessary for asthma/recurrent wheeze prevention in early life.
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- Bisgaard, H., Szefler, S.J. Author's reply. Pediatr Pulmonol. 2007;42:1234. Crossref | Scopus (0)
- Bisgaard, H., Hermansen, M.N., Buchvald, F., Loland, L., Halkjaer, L.B., Bønnelykke, K. et al, Childhood asthma after bacterial colonization of the airway in neonates. N Engl J Med. 2007;357:1487–1495. Crossref | PubMed | Scopus (403)
- Henderson, A.J., Warner, J.O. Fetal origins of asthma. Semin Fetal Neonatal Med. 2012;17:82–91. Abstract | Full Text | Full Text PDF | PubMed | Scopus (27)
- Weiss, S.T., Tager, I.B., Speizer, F.E., Rosner, B. Persistent wheeze. Its relation to respiratory illness, cigarette smoking, and level of pulmonary function in a population sample of children. Am Rev Respir Dis. 1980;122:697–707. Crossref | PubMed
- Marks, G.B., Mihrshahi, S., Kemp, A.S., Tovey, E.R., Webb, K., Almqvist, C. et al, Prevention of asthma during the first 5 years of life: a randomized controlled trial. J Allergy Clin Immunol. 2006;118:53–61. Abstract | Full Text | Full Text PDF | PubMed | Scopus (179)
- Custovic, A., Simpson, B.M., Simpson, A., Kissen, P., Woodcock, A., NAC Manchester Asthma and Allergy Study Group. Effect of environmental manipulation in pregnancy and early life on respiratory symptoms and atopy during first year of life: a randomised trial. Lancet. 2001;358:188–193. Abstract | Full Text | Full Text PDF | PubMed | Scopus (227)
- Arshad, S.H., Bateman, B., Sadeghnejad, A., Gant, C., Matthews, S.M. Prevention of allergic disease during childhood by allergen avoidance: the Isle of Wight prevention study. J Allergy Clin Immunol. 2007;119:307–313. Abstract | Full Text | Full Text PDF | PubMed | Scopus (122)
- Litonjua, A.A., Carey, V.J., Laranjo, N., Harshfield, B.J., McElrath, T.F., O'Connor, G.T. et al, Effect of prenatal supplementation with vitamin D on asthma or recurrent wheezing in offspring by age 3 years: the VDAART randomized clinical trial. JAMA. 2016;315:362–370. Crossref | PubMed | Scopus (32)
- Heaney, R.P. Guidelines for optimizing design and analysis of clinical studies of nutrient effects. Nutr Rev. 2014;72:48–54. Crossref | PubMed | Scopus (68)
- Ng, K., Scott, J.B., Drake, B.F., Chan, A.T., Hollis, B.W., Chandler, P.D. et al, Dose response to vitamin D supplementation in African Americans: results of a 4-arm, randomized, placebo-controlled trial. Am J Clin Nutr. 2014;99:587–598. Crossref | PubMed | Scopus (30)
- Bhagatwala, J., Zhu, H., Parikh, S.J., Guo, D.-H., Kotak, I., Huang, Y. et al, Dose and time responses of vitamin D biomarkers to monthly vitamin D3 supplementation in overweight/obese African Americans with suboptimal vitamin D status: a placebo controlled randomized clinical trial. BMC Obes. 2015;2:27. Crossref | PubMed
- Wegienka, G., Havstad, S., Joseph, C.L., Zoratti, E., Ownby, D., Woodcroft, K. et al, Racial disparities in allergic outcomes in african americans emerge as early as age 2 years. Clin Exp Allergy. 2012;42:909–917. PubMed
- Litonjua, A.A., Lange, N.E., Carey, V.J., Brown, S., Laranjo, N., Harshfield, B.J. et al, The Vitamin D Antenatal Asthma Reduction Trial (VDAART): rationale, design, and methods of a randomized, controlled trial of vitamin D supplementation in pregnancy for the primary prevention of asthma and allergies in children. Contemp Clin Trials. 2014;38:37–50. Abstract | Full Text | Full Text PDF | PubMed | Scopus (31)
- Ersfeld, D.L., Rao, D.S., Body, J.-J., Sackrison, J.L. Jr., Miller, A.B., Parikh, N. et al, Analytical and clinical validation of the 25 OH vitamin D assay for the LIAISON® automated analyzer. Clin Biochem. 2004;37:867–874. Crossref | PubMed | Scopus (149)
- Hollis, B.W. Vitamin D requirement during pregnancy and lactation. J Bone Miner Res. 2007;22:V39–V44. Crossref | PubMed | Scopus (58)
- Castro, M., King, T.S., Kunselman, S.J., Cabana, M.D., Denlinger, L., Holguin, F. et al, Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels. JAMA. 2014;311:2083–2091. Crossref | PubMed | Scopus (81)
- Bodnar, L.M., Simhan, H.N., Powers, R.W., Frank, M.P., Cooperstein, E., Roberts, J.M. High prevalence of vitamin D insufficiency in black and white pregnant women residing in the northern united states and their neonates. J Nutr. 2007;137:447–452. PubMed
- Gallagher, J.C., Jindal, P.S., Smith, L.M. Vitamin D supplementation in young White and African American women. J Bone Miner Res. 2014;29:173–181. Crossref | PubMed | Scopus (16)
- Gallagher, J.C., Peacock, M., Yalamanchili, V., Smith, L.M. Effects of vitamin D supplementation in older African American women. J Clin Endocrinol Metab. 2013;98:1137–1146. Crossref | PubMed | Scopus (29)
- Zosky, G.R., Berry, L.J., Elliot, J.G., James, A.L., Gorman, S., Hart, P.H. Vitamin D deficiency causes deficits in lung function and alters lung structure. Am J Respir Crit Care Med. 2011;183:1336–1343. Crossref | PubMed | Scopus (151)
- Sharma, S., Chhabra, D., Kho, A.T., Hayden, L.P., Tantisira, K.G., Weiss, S.T. The genomic origins of asthma. Thorax. 2014;69:481–487. Crossref | PubMed | Scopus (19)
- Ferreira, G.B., Vanherwegen, A.-S., Eelen, G., Gutiérrez, A.C.F., Van Lommel, L., Marchal, K. et al, Vitamin D3 induces tolerance in human dendritic cells by activation of intracellular metabolic pathways. Cell Rep. 2015;10:711–725. Abstract | Full Text | Full Text PDF | Scopus (24) Boston, MA 02115 USA
The Vitamin D Antenatal Asthma Reduction Trial was supported by U01HL091528 from the National Heart, Lung, and Blood Institute. Additional support was provided by U54TR001012 from the National Centers for Advancing Translational Sciences for participant visits at Boston Medical Center. H.M.W. was supported by the Lundbeck Foundation (R191-2015-1571).
Disclosure of potential conflict of interest: N. Laranjo's institution received a grant from Brigham and Women's Hospital for this work. V. J. Carey's and B. W. Hollis' institutes have received a grant from the National Institutes of Health (NIH) for this work. G. O'Connor's institution has received a grant from the NIH for this work, has personally received consultancy fees from AstraZeneca, and has received grants from Jenssen Pharmaceuticals. M. Sandel's institution received a grant from Boston University School of Medicine for this work. L. B. Bacharier's institution has received a grant from the NIH/National Heart, Lung, and Blood Institute (NHLBI); has personally received consultancy fees and honoraria from Aerocrine, GlaxoSmithKline, and Genentech/Novartis; is a member of the Scientific Advisory Board and has received honoraria for lectures from Merck; consultancy fees from Cephalon; has board membership from DBV Technologies; is a consultant and has received honoraria for lectures from Teva and Boehringer Ingelheim; has received lectures fees from AstraZeneca; has received fees for development for educational tools from WebMD/Medscape; is a member of the Advisory Board membership for Sanofi and Vectura. R. S. Zeiger's institution received a grant from the NHLBI for this work and grants from Aerocrine, AstraZeneca, Genentech, MedImmune, and Merck for other works, and has personally received AstraZeneca, Genentech, Novartis, TEVA, GlaxoSmithKline, and Theravance. M. Schatz's institution received a grant from the NHLBI for this work. A. A. Litonjua's institution received a grant from the NIH for this work, has personally received consultancy fees from AstraZeneca, and has received royalties from UpToDate and Springer Humana Press. The rest of the authors declare that they have no relevant conflicts of interest.
Trial Registration: Clinicaltrials.gov Identifier NCT00920621.