Abstract
Gestational hypertension may confer risk of atopic disease in offspring through a direct biological mechanism, but another possibility is that risk is mediated through complications of pregnancy. To explore these associations, we conducted an analysis of a nationally representative birth cohort based in the UK involving children born 2000–2002. We included 12,450 mother-child pairs. We used logistic regression to estimate the association between hypertensive disease and asthma, hay fever, or eczema by age 5, and parentally reported early wheeze and severe wheeze. Mediation by gestation at delivery and caesarean delivery was explored using causal mediation analysis. Odds ratios (95% CI) for gestational hypertension and childhood asthma, hay fever, and eczema were 1.32 (1.09, 1.59), 1.22 (0.97, 1.55), and 1.12 (0.96, 1.32) respectively, adjusted for confounding. The population attributable fractions were 2.4% (1.0–3.8%), 0.9% (−0.3% to 2.1%), and 1.8% (0.0–3.7%), respectively. Accounting for mediation by gestational age and caesarean delivery, odds ratios (95% CI) for the potential direct effects of gestational hypertension were 1.21 (0.97, 1.50), 1.17 (0.91, 1.49), and 1.11 (0.94, 1.31) for the same.Conclusion: Gestational hypertension was weakly positively associated with asthma and this was partly mediated by earlier delivery. Only a small proportion of early childhood asthma was attributable to gestational hypertensive disease in this representative UK-based birth cohort.What is known:• Gestational hypertension has been shown to be an inconsistent risk factor for the atopic diseases.• The in utero immune environment may modify the risk of atopy in offspring; alternatively, complications of pregnancy including caesarean delivery and prematurity may explain an association between hypertensive disease and atopy.What is new:• Self-reported gestational hypertension was a weak risk factor for asthma and wheeze in the Millennium Cohort Study.• Part of the association between gestational hypertensive disease and asthma was explained by earlier delivery.
Highlights
Atopy describes the tendency to develop allergic diseases like atopic eczema, asthma, hay fever, and food allergy, which often occur in those with elevated immunoglobulin E (IgE) levels
Gestational hypertension was weakly positively associated with asthma and this was partly mediated by earlier delivery
The in utero immune environment may modify the risk of atopy in offspring; alternatively, complications of pregnancy including caesarean delivery and prematurity may explain an association between hypertensive disease and atopy
Summary
Atopy describes the tendency to develop allergic diseases like atopic eczema, asthma, hay fever, and food allergy, which often occur in those with elevated immunoglobulin E (IgE) levels. As our knowledge of the genetic determinants of atopic disease has advanced, so has our knowledge that atopic disease encompasses an array of allergic phenotypes in which elevated IgE. Dysregulation of communication at the maternal decidual and fetal trophoblastic interface is recognized as an antecedent of PET, which may reduce immune tolerance of the fetus [7] and produce inflammation characterized by decreased regulatory T-cells and anti-inflammatory cytokines [8, 9], features of both PET and atopic disease [10,11,12,13]. Determining the direction and strength of the association between gestational hypertensive disease and individual atopic diseases may help to characterize the atopic phenotypes and inform pre-conception or antenatal prevention strategies
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