Original articleAsthma, lower airway diseaseAssociation of maternal anemia with increased wheeze and asthma in children
Introduction
Asthma and respiratory disease account for increasing childhood morbidity, placing a burden on the health care system and on affected individuals and families. In 2007, approximately 6.7 million children under the age of 18 had asthma,1 with rates increasing to nearly 7 million (9.4%) by 2008.2 As of 2008, more than 14% of children aged 0 to 17 years had been diagnosed with asthma,2 with children 0 to 4 years of age demonstrating the greatest use of health care services for asthma-related illness.1 Increases in childhood respiratory disease over the past decades have highlighted the need to identify specific factors associated with early childhood wheezing and childhood asthma. The rise in prevalence of asthma is too rapid to be attributable to genetic mutations, and air pollution has actually declined in many areas where asthma rates have been increasing.
Recent research has suggested that maternal dietary factors during pregnancy may influence the development of childhood asthma.3, 4 The intrauterine environment provides the substrate for many important processes, including lung and early immune system development, and support of optimal fetal growth requires adequate maternal nutritional status. Lung development in utero is apparent within 3 to 4 weeks after fertilization and continues throughout gestation and childhood.5, 6 Inadequate nutritional status during gestation may negatively impact childhood respiratory health,3, 4 particularly during critical periods of embryonic and fetal growth.
Maternal anemia, an indicator of overall nutritional status, has been linked to a number of adverse outcomes, including infant mortality, preterm delivery, poor gestational weight gain, low birth weight, and poor infant neurocognitive performance.7, 8, 9 Anemia is prevalent in the pregnant population in the United States (9.3% in the general pregnant population and up to 27% in low-income minority women7, 8, 10; up to 95% of anemia in pregnancy is attributable to iron deficiency11 resulting from inadequate iron intake or hemodilution of pregnancy.
Given the relatively high prevalence of maternal anemia in pregnancy, and its potential for influencing the respiratory health of offspring through fetal programming effects, further investigation into the role of maternal anemia on childhood respiratory outcomes is warranted. The current study examines the relationship of maternal anemia in pregnancy with patterns of wheezing and asthma in early childhood.
Section snippets
Study Population
The study population consists of families who participated in the Asthma in Pregnancy (AIP) Study and the Perinatal Risk of Asthma in Infants of Asthmatic Mothers Study. Methods have been described in detail previously12, 13 (see Fig. 1 and eMethods). The current analysis was restricted to 597 families, with information available on childhood wheeze patterns, asthma diagnosis, maternal hemoglobin (Hgb) measurements and International Statistical Classification of Diseases, 9th Revision (ICD-9)
Results
Table 1 presents population characteristics by maternal anemia status, recurrent wheeze in year 1, and current asthma for the cohort (n = 597). Slightly over half of the children were male (53%), and 76% were white, non-Hispanic. Mothers with asthma were, by design, overselected for the study (44% of the cohort had asthma), and an even greater frequency reported maternal allergies (67%). Frequencies of NICU placement at birth (18%), preterm delivery (9%) and intrauterine growth restriction (7%)
Discussion
Maternal anemia during pregnancy was associated with both short-term (recurrent wheeze in first year of life and wheeze by 3 years of age) and longer-term (asthma diagnosis ever and asthma at age 6) respiratory health outcomes in children. Maternal asthma status appears to modify these associations. Among mothers with asthma, maternal anemia is associated with an increase in odds of more persistent respiratory outcomes, including asthma and persistent wheeze in the children at age 6. Among
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Cited by (32)
Asthma in pregnancy – Management, maternal co-morbidities, and long-term health
2022, Best Practice and Research: Clinical Obstetrics and GynaecologyCitation Excerpt :Among infants born to mothers with asthma, the adjusted odds of recurrent wheeze at one year of age in association with anaemia in pregnancy was 4.78 (95% CI 1.75, 13.08), whereas there was no significant association in infants of mothers without asthma (aOR 1.64, 95% CI 0.58, 4.61). In addition, anaemia in pregnancy was associated with diagnosed asthma, and diagnosed asthma with wheeze or medication use at age 6 years, but only in children of mothers with asthma [49]. A high proportion of pregnant women with asthma have insufficient serum vitamin D levels.
Ameliorating Atopy by Compensating Micronutritional Deficiencies in Immune Cells: A Double-Blind Placebo-Controlled Pilot Study
2022, Journal of Allergy and Clinical Immunology: In PracticeCitation Excerpt :However, such a comparison, is weakened because our proof-of-concept pilot study was a relatively small single-center trial. Our data emphasize that micronutritional deficiencies are present in atopic individuals2,50,59–61 and that iron deficiency is sufficient to generate a TH2 milieu in vitro as well as in the preclinical16,33,53,62 and clinical settings,63 which are the prerequisites for allergy development. Immune resilience is a non–allergen specific phenomenon elicited by modulation of the innate immune system.
Maternal anemia and pediatric neurological morbidity in the offspring – Results from a population based cohort study
2019, Early Human DevelopmentCitation Excerpt :An association has been established between prenatal maternal anemia and small for gestational age newborns (SGA, i.e., <5th percentile of birthweight, per gender and gestational age), preterm births (PTB), low birthweight (LBW, i.e., birthweight < 2500 g.), stillbirth, and admission to neonatal intensive care [2,6,7,11–16]. Maternal anemia has also been associated with a variety of diseases in offspring later in life, including asthma [17,18], schizophrenia [19], allergies [20], and in animal studies, with decreased pulmonary function [7,19,20]. Based on the Developmental Origins of Adult Health and Disease theory, early life is considered a critical period of development, in which optimal environment is critical for long term health and development [22].
42 - The Epidemiology of Asthma
2019, Kendig's Disorders of the Respiratory Tract in ChildrenMaternal obesity affects inflammatory and iron indices in umbilical cord blood
2016, Journal of PediatricsMaternal hemoglobin levels during pregnancy and asthma in childhood: The Generation R Study
2014, Annals of Allergy, Asthma and Immunology
Disclosures: Michael Bracken and Paige Wickner work as occasional contractors for Pfizer, although the research in this paper is not related in any way to compensation received from this company. All other authors do not have any conflict of interest.
Funding Sources: This work was supported by grant # AI41040.