Can Asthma Be Prevented in Children Before Birth?

MARSEILLE, France — Controlling asthma in mothers-to-be, removing dust mites, taking probiotics and vitamin supplements...Is there any solid evidence showing that women's behavior during pregnancy could reduce the risk for asthma in their unborn children? At the 27th French-language convention on respiratory medicine, Cécile Chenivesse, MD, of the department of respiratory medicine, immunology, and allergies at Lille Regional University Hospital in France, answered this question using only well-supported scientific literature.

Risk Factors?

The risk factors of developing asthma differ with age. "During the fetal period, the first risk factor for asthma in unborn children is having asthmatic parents, especially an asthmatic mother," said Chenivesse. "A second important factor is smoking: first, having a mother who smokes during pregnancy, but this also refers to the environment surrounding the pregnant woman, including, but not exclusive to, the father."

Parental asthma, prenatal environmental tobacco smoke, and prematurity (especially in very premature births) are well-established risk factors of childhood asthma. What's more, current results suggest mild-to-moderate causal effects of certain behaviors or modifiable exposure during pregnancy (such as maternal weight gain or obesity, maternal use of antibiotics or paracetamol, and maternal stress); during the perinatal period (such as cesarean birth); or during the postnatal period (such as serious infection with respiratory syncytial virus, excess weight or obesity, exposure to moisture or mold in the home environment and to air pollution outside of it) on childhood asthma. These findings need to be confirmed via interventional studies or at least well-designed prospective studies.

Inhaled Corticosteroids

Can controlling a mother's asthma during pregnancy prevent asthma in her baby? "Yes," said Chenivesse. Taking inhaled corticosteroids (ICS) early on and making sure asthma is well controlled during pregnancy (this includes medication other than ICS too) reduces the risk for asthma in the child.

"It is logical to assume that exposure to Th2 inflammation during the fetal period could contribute to the risk of developing asthma," Chenivesse added. "A single center, double-blind, randomized, controlled Australian study carried out in 179 women recruited before 22 weeks' gestation confirms that FeNO-guided (fractional exhaled nitric oxide, an eosinophil inflammation marker) asthma treatment during pregnancy reduces the rate of asthma in children between 4 and 6 years of age (140 children; 36% asthmatic). This study already shows the protective effect of inhaled corticosteroids for everyone. They reduce the risk of asthma in the child."

The result was that patients enrolled in the FeNO group were started on and had their ICS dose adjusted much earlier on than those in the control group. "The benefit observed in the FeNO group is mainly down to how quickly the subjects were started on ICS," said Chenivesse. At the end of the study, there were more pregnant women taking ICS and long-acting beta-2 agonists, but with a lower dose of ICS in the FeNO-guided group.

"By increasing how often these patients take their medication, we can decrease the rate of occurrence of asthma in their offspring," said Chenivesse. The reduced asthma risk between 4 and 6 years of age goes from 43.2% to 25.9% (odds ratio [OR], 0.46). It isn't known whether or not this effect is maintained into adulthood.

Smoking, Dust Mites

Very few data on a multifaceted intervention approach exist. A study of this type conducted in 545 high-risk children (those with asthma in a first-degree relative or another IgE-mediated allergy in two first-degree relatives) implemented lifestyle measures from the first trimester of pregnancy up to the first year postpartum (dust mite avoidance, stopping smoking, exclusive breastfeeding encouraged, and supplementation with a partially hydrolyzed formula).

"We didn't get any results, because nobody stopped smoking," said Chenivesse, "and nobody was willing to give up their pets. The only outcome that's left is preventing exposure to dust mites. The reduction in the risk of asthma at 1 year of age is low (15.1% vs 20.2%) and is maintained at the age of 2 and 7 years (risk reduction of 14.9% vs 23% in the control group at 7 years)."

She concluded that "in at-risk situations, avoidance of dust mites during pregnancy and breastfeeding (exclusive or combined with a partially hydrolyzed formula) is recommended, considering the literature."

Vitamin D

Does taking a vitamin D supplement during pregnancy reduce the risk of asthma in unborn children? "We don't know," said Chenivesse. "In fact, it's difficult to give a definitive answer not only for vitamin D, but also for A and E, et cetera, since available studies are mostly cohort or case–control studies." A meta-analysis compiling 14 studies of this type (23,030 mother/child couples, 2073 cases of asthma) found a positive association between a diet rich in vitamin D and a lower risk of having a child with a persistent wheeze or asthma (OR, 0.78, P = .002).

But to go from that to saying that vitamin D supplementation can reduce the risk for asthma in unborn children would risk crossing a line, said Chevenisse.

Other Vitamins

"Taking a vitamin A supplement during pregnancy is associated with an increased risk of asthma in children, suggests a recent study," she added. Excess vitamin A (≥ 2.5 times the recommended intake) during pregnancy was associated with increased risk, whereas vitamin D intake close to recommendations was associated with a reduced risk of asthma in school-age children. No association for high intakes of both nutrients suggests antagonistic effects of vitamins A and D.

As for vitamin D and E supplementation during pregnancy and in children, a longitudinal study of 1924 children born to women enrolled during pregnancy provides us with some answers. Maternal vitamin D and E intake during pregnancy was assessed, and respiratory questionnaires were completed for the 10-year-old children.

Longitudinal analyses included data collected at 1, 2, 5, and 10 years. Low maternal vitamin D and E intakes during pregnancy are associated with increased risk of children developing asthma in the first 10 years of life.

Probiotics

"Although prenatal probiotic use is interesting on a conceptual level, a meta-analysis found no positive association, and even a negative association in some studies," said Chenivesse.

Therefore, no advice can be given at this time. The authors of the meta-analysis concluded that prenatal or early life probiotic administration (Lactobacillus acidophilus) reduces the risk for atopic sensitization and decreases the total IgE level in children but may not reduce the risk of asthma or wheeze. Future trials for asthma prevention should carefully select probiotic strain and consider longer follow-up.

Omega 3

Omega 3 "probably could be" effective, said Chenivesse, "but more so in women deficient in long-chain polyunsaturated fatty acids."

The only interventional study focusing on food intake during pregnancy and its impact on the risk of asthma in the child enrolled 736 pregnant women at 24 weeks' gestation. These women received 2.4 g of n-3 LCPUFA (fish oil) or placebo (olive oil) per day. According to the results from 695 children, fish oil supplementation reduces the risk for asthma (persistent wheeze or asthma) at 3 years of age. The risk for persistent wheeze or asthma in the treatment group was 16.9% vs 23.7% in the control group, corresponding to a relative reduction of 30.7%.

Yet although n-3 LCPUFA supplementation in the third trimester of pregnancy reduces the absolute risk for persistent wheeze or asthma and lower respiratory tract infections in the offspring, "by delving deeper into this study, it becomes clear that this beneficial effect is real but is only found in women who are deficient with extremely low levels of polyunsaturated fatty acids (EPA and DHA). It would be the correction of this deficiency that would reduce the risk of asthma," said Chenivesse.

Chenivesse declared having received research grants from Santelys and Novartis; funding from ALK-Abello, AstraZeneca, Boehringer Ingenheim, Chiesi, GSK, and Sanofi-Regeneron; and convention invitations from AstraZeneca, Novartis, and Boehringer Ingenheim.

This article was translated from the Medscape French Edition.

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