ORIGINAL ARTICLE
Maternal Vitamin D Status in Pregnancy and Risk of Lower
Respiratory Tract Infections, Wheezing, and Asthma in
Offspring
Eva Morales,
a,b,c
Isabelle Romieu,
d
Stefano Guerra,
a,b,c
Ferra ´n Ballester,
c,e,f
Marisa Rebagliato,
c,g
Jesu ´s Vioque,
c,h
Adonina Tardo ´n,
i
Cristina Rodriguez Delhi,
j
Leonor Arranz,
k,l
Maties Torrent,
c,m
Mercedes Espada,
n
Mikel Basterrechea,
c,o
and Jordi Sunyer
a,b,c
; on behalf of the INMA Project
Background: Adequate vitamin D status in mothers during preg-
nancy may influence the health status of the child later in life. We
assessed whether maternal circulating 25-hydroxyvitamin D
(25OHD) concentrations in pregnancy are associated with risk of
lower respiratory tract infections, wheezing, and asthma in the
offspring.
Methods: Data were obtained from 1724 children of the INfancia y
Medio Ambiente (INMA) Project, a population-based birth cohort
study. Maternal circulating 25(OH)D concentrations were measured
in pregnancy (mean gestational age = 12.6 SD = 2.5 weeks).
When the child was age 1 year, parents were asked if their child had
a physician-confirmed history of lower respiratory tract infections or
a history of wheezing. The questions about wheezing were repeated
annually thereafter. Asthma was defined as parental report of doctor
diagnosis of asthma or receiving treatment at the age of 4 – 6 years
or wheezing since the age of 4 years.
Results: The median maternal circulating 25(OH)D concentration in
pregnancy was 29.5 ng/mL (interquartile range, 22.5–37.1 ng/mL).
After multivariable adjustment, there was a trend for an independent
association between higher levels of maternal circulating 25(OH)D
levels in pregnancy and decreased odds of lower respiratory tract
infections in offspring (for cohort- and season-specific quartile Q4
vs. Q1, odds ratio = 0.67 95% confidence interval = 0.50 – 0.90;
test for trend, P = 0.016). We found no association between
25(OH)D levels in pregnancy and risk of wheezing at age 1 year or
4 years, or asthma at age 4 – 6 years.
Conclusions: Higher maternal circulating 25(OH)D concentrations
in pregnancy were independently associated with lower risk of lower
respiratory tract infections in offspring in the first year of life but not
with wheezing or asthma in childhood.
(Epidemiology 2012;23: 64 –71)
A
sthma has increased worldwide and remains the most
common chronic disease of childhood, with the highest
prevalence
1
in industrialized countries farthest from the equa-
tor (eg, Australia, New Zealand, and the United Kingdom).
Vitamin D insufficiency, defined as a circulating level
of 30 ng/mL of 25-hydroxyvitamin D (25OHD), is be-
coming a public health issue.
2
This phenomenon can be
attributed at least in part to dietary and behavior changes
during recent decades, especially in Western countries. Chil-
dren as well as pregnant and lactating women are identified as
vulnerable groups for vitamin D insufficiency.
3
In addition to
its crucial role in maintenance of musculoskeletal health,
vitamin D also has effects on the immune system and plays a
role in host defenses against respiratory-tract pathogens.
4
In
Submitted 4 February, 2011; accepted 6 September 2011; posted 14 November
2011.
From the
a
Center for Research in Environmental Epidemiology (CREAL),
Barcelona, Catalonia, Spain;
b
Hospital del Mar Research Institute (IMIM),
Barcelona, Catalonia, Spain;
c
CIBER Epidemiología y Salud Pu ´blica (CI-
BERESP), Barcelona, Catalonia, Spain;
d
National Institute of Public Health,
Cuernavaca, Mexico;
e
Center for Public Health Research (CSISP), Valencia,
Spain;
f
University of Valencia, Valencia, Spain;
g
Rey Juan Carlos Univer-
sity, Madrid, Spain;
h
Departmento de Salud Pu ´blica, Hospital San Agustín,
Servicio de Salud del Principado de Asturias (SESPA), Avile ´s, Asturias,
Spain;
i
Oviedo University, Asturias, Spain;
j
Hospital San Agustin, Servicio
de Salud del Principado de Asturias (SESPA), Avile ´s, Asturias, Spain;
k
Servicio de Pediatría, Hospital Universitario Donostia, Servicio Vasco de
Salud, Osakidetza, Euskadi, Spain;
l
Departamento de Pediatría, Facultad de
Medicina y Odontología, Universidad del País Vasco (UPV/EHU), Euskadi,
Spain;
m
Area de Salud de Menorca, IB-SALUT, Menorca, Spain;
n
Clinical
Chemistry Unity, Public Health Laboratory of Bilbao, Euskadi, Spain; and
o
Subdireccio ´n de Salud Pu ´blica de Gipuzkoa, Departamento de Sanidad del
Gobierno Vasco, Euskadi, Spain.
This study was funded by grants from Instituto de Salud Carlos III and
Spanish Ministry of Health (Red INMA G03/176; CB06/02/0041; FIS
97/0588; 00/0021-2, PI061756; PS0901958; FIS-FEDER 03/1615, 04/
1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, and 09/
02647; FIS-PI041436, FIS-PI081151, FIS-PI06/0867, and FIS-PS09/
00090), Conselleria de Sanitat Generalitat Valenciana, Generalitat de
Catalunya-CIRIT 1999SGR 00241, Department of Health of the Basque
Government (2005111093 and 2009111069), the Provincial Government
of Gipuzkoa (DFG06/004 and DFG08/001), and Fundacio ´ n Roger Torne ´.
The authors reported no other financial interests related to this research.
The above-mentioned funding agencies were not responsible for the design
and conduct of the study, for the collection, management, analysis, and
interpretation of the data; or in the preparation, review, or approval of the
manuscript.
Supplemental digital content is available through direct URL citations
in the HTML and PDF versions of this article (www.epidem.com).
Correspondence: Eva Morales, Centre for Research in Environmental Epidemi-
ology (CREAL), Parc de Recerca Biome `dica de Barcelona, Dr. Aiguader 88,
08003-Barcelona, Catalonia, Spain. E-mail: emorales1@creal.cat.
Copyright © 2011 by Lippincott Williams & Wilkins
ISSN: 1044-3983/12/2301-0064
DOI: 10.1097/EDE.0b013e31823a44d3
Epidemiology • Volume 23, Number 1, January 2012 64 | www.epidem.com