Maternal Cytokine Profiles during Pregnancy Predict Asthma in Children of Mothers without Asthma

Abstract

Little is known about whether maternal immune status during pregnancy influences asthma development in the child. We measured cytokine production in supernatants from mitogen-stimulated peripheral blood immune cells collected during and after pregnancy from the mothers of children enrolled in the Tucson Infant Immune Study, a nonselected birth cohort. Physician-diagnosed active asthma in children through age 9 and a history of asthma in their mothers were assessed through questionnaires. Maternal production of each of the cytokines IL-13, IL-4, IL-5, IFN-γ, IL-10, and IL-17 during pregnancy was unrelated to childhood asthma. However, IFN-γ/IL-13 and IFN-γ/IL-4 ratios during pregnancy were associated with a decreased risk of childhood asthma (n = 381; odds ratio [OR], 0.33; 95% confidence interval [CI], 0.17-0.66; P = 0.002; and n = 368; OR, 0.36; 95% CI, 0.18-0.71; P = 0.003, respectively). The inverse relations of these two ratios with childhood asthma were only evident in mothers without asthma (n = 309; OR, 0.18; 95% CI, 0.08-0.42; P = 0.00007; and n = 299; OR, 0.17; 95% CI, 0.07-0.39; P = 0.00003, respectively) and not in mothers with asthma (n = 72 and 69, respectively; P for interaction by maternal asthma = 0.036 and 0.002, respectively). Paternal cytokine ratios were unrelated to childhood asthma. Maternal cytokine ratios in mothers without asthma were unrelated to the children's skin-test reactivity, total IgE, physician-confirmed allergic rhinitis at age 5, or eczema in infancy. To our knowledge, this study provides the first evidence that cytokine profiles in pregnant mothers without asthma relate to the risk for childhood asthma, but not allergy, and suggests a process of asthma development that begins in utero and is independent of allergy.

Keywords: asthma; children; cytokines; maternal; pregnancy.

Figure 1.

Percent childhood asthma by quartiles of maternal IFN-γ/IL-13 ratios of pregnant mothers without asthma (solid bars) and pregnant mothers with asthma (open bars). Minimum and maximum values for the ratio quartiles: 0.6–11.7, 11.8–20.4, 20.5–38.0, and 38.1–231.

Figure 2.

Receiver operating characteristic (ROC) curves for reduced risk of childhood asthma attributable to the IFN-γ/IL-13 ratios of the children and pregnant mothers without asthma. The naive model includes only the children’s 3-month ratio (blue). The full model (red) including the IFN-γ/IL-13 ratios of the pregnant mothers shows a significant increase in the area under the curve (P = 0.02).