Original article
Asthma, lower airway disease
Association of maternal anemia with increased wheeze and asthma in children

https://doi.org/10.1016/j.anai.2010.11.007Get rights and content

Background

Increasing interest has focused on maternal nutrition and micronutrient status during pregnancy and respiratory disease development in the offspring.

Objective

To examine the relationship between maternal anemia in pregnancy with wheeze and asthma in early childhood.

Methods

The cohort included children of women followed through pregnancy and recontacted when the child was 6 years of age to evaluate respiratory health. Exposure was assessed using maternal anemia diagnosis and hemoglobin (Hgb) < 11 during delivery hospitalization. Study outcomes include wheezing in early childhood; patterns of wheeze from birth to age 6 (early-onset transient wheeze; late-onset wheeze; early-onset persistent wheeze); and diagnosis of childhood asthma.

Results

Maternal anemia was reported by 11.9% of mothers and was associated with recurrent infant wheeze in the first year (adjusted odds ratio [ORa] = 2.17, 95% confidence interval [CI] 1.18, 4.00), wheezing before age 3 (Ora = 2.42, 95% CI 1.38, 4.23), and early-onset transient and early-onset persistent wheeze patterns (Ora = 2.81, 95%CI 1.38, 5.72, and Ora = 2.07, 95% CI 1.02, 4.22), respectively. Among children of mothers with asthma, maternal anemia was associated with recurrent wheeze in year 1 (Ora = 4.22, 95% CI 1.65, 10.80) and wheeze before age 3 (Ora = 2.73, 95% CI 1.17, 6.35). Offspring of mothers with asthma also had increased odds of asthma diagnosis (Ora = 2.53, 95% CI 1.04, 6.17) and current asthma (Ora = 3.46, 95% CI 1.45, 8.26).

Conclusions

Maternal anemia during pregnancy is associated with infant respiratory health outcomes. If this observation is replicated, maternal anemia may be a target for intervention and future research.

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

References (45)

  • A.A. Litonjua et al.

    Gold, Maternal antioxidant intake in pregnancy and wheezing illnesses in children at 2 y of age

    Am J Clin Nutr

    (2006)
  • P. Chanmugam et al.

    Did fat intake in the United States really decline between 1989–1991 and 1994–1996?

    J Am Diet Assoc

    (2003)
  • L.J. Akinbami et al.

    Status of childhood asthma in the United States, 1980–2007

    Pediatrics

    (2009)
  • B. Bloom et al.

    Summary health statistics for U.S. children: National Health Interview Survey, 2007

    Vital Health Stat

    (2009)
  • G. Devereux

    Early life events in asthma: diet

    Pediatr Pulmonol

    (2007)
  • P.H. Burri

    Structural aspects of prenatal and postnatal development and growth of the lung

  • ACOG Practice Bulletin No. 95: anemia in pregnancy

    Obstet Gynecol

    (2008)
  • F.C. Bruce et al.

    Maternal morbidity rates in a managed care population

    Obstet Gynecol

    (2008)
  • Anemia in Pregnancy

  • E.M. Kang et al.

    Prenatal exposure to acetaminophen and asthma in children

    Obstet Gynecol

    (2009)
  • Iron Deficiency Anaemia: Assessment, Prevention and Control

    (2001)
  • F. Martinez et al.

    Asthma and wheezing in the first six years of life

    N Engl J Med

    (1995)
  • Cited by (32)

    • Asthma in pregnancy – Management, maternal co-morbidities, and long-term health

      2022, Best Practice and Research: Clinical Obstetrics and Gynaecology
      Citation 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 Practice
      Citation 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 Development
      Citation 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 Children
    View all citing articles on Scopus

    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.

    View full text