Higher levels of prenatal C-reactive protein associated with childhood asthma, atopy
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Higher prenatal C-reactive protein levels and increases in these levels from early to late pregnancy were associated with childhood asthma, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice.
Systemic inflammation experienced during pregnancy may then be a factor in the risk for childhood asthma, the researchers wrote.
“Exposures in the womb set off processes that program an infant to either be at greater risk or be resilient to the development of diseases later in life, ie, the Developmental Origins of Health and Disease [theory],” Augusto A. Litonjua, MD, MPH, chief of the division of pediatric pulmonary medicine at Golisano Children’s Hospital of the University of Rochester Medical Center, told Healio.
“We know that inflammation is a part of asthma, and we wanted to see if inflammation in the pregnant mother increases the risk for asthma in the child after birth,” Litonjua said.
Study design, results
The study involved 522 pairs of mothers and children from the Vitamin D Antenatal Asthma Reduction Trial. Researchers obtained plasma samples from these mothers early (between 10 and 18 weeks of gestation) and later (between 32 and 38 weeks) in their pregnancies.
Also, the researchers assessed these children for asthma, eczema and allergic rhinitis each quarter from birth through age 6 years.
Children of mothers with elevated levels of log-transformed prenatal C-reactive protein (CRP) early (adjusted OR = 1.76; 95% CI, 1.12-2.82) and later (aOR = 2.45; 95% CI, 1.47-4.18) in pregnancy had higher risk for asthma by age 6 years.
Also, the children of mothers whose CRP increased from early to late pregnancy had a significantly increased risk for asthma (aOR = 2.06; 95% CI, 1.26-3.39) and eczema (aOR = 1.71; 95% CI, 1.11-2.66) at age 6 years compared with children of mothers whose CRP decreased.
These results appeared comparable in models that added maternal pre-pregnancy BMI or excluded the 35 children who were born prematurely from the analysis.
Additionally, researchers found significant associations between aeroallergen sensitization and prenatal CRP for all three measurements of prenatal CRP (P < .001).
Analysis also revealed that 39 of the 116 patients with aeroallergen sensitization also had atopic asthma, while 28 of the 162 patients without sensitization had nonatopic asthma.
However, the researchers found, the associations between prenatal CRP and childhood asthma only were maintained among those patients with atopic asthma, with adjusted ORs of 3.78 (95% CI, 1.49-10.64) for early elevated CRP, 4.84 (95% CI, 1.68-15.5) for late high CRP and 3.01 (95% CI, 1.06-9.16) for increases in CRP.
The researchers did not find any significant associations between prenatal CRP and asthma without concurrent atopy.
Further, log-transformed early elevated CRP mediated 96% of the effect of maternal pre-pregnancy BMI on childhood asthma (P = .02), with a corresponding rate of 86% for elevated CRP in late pregnancy (P < .002).
Similarly, the effect of early pregnancy vitamin D insufficiency on childhood asthma was mediated approximately 17% by log-transformed early elevated CRP (P = .04) and 20% by late elevated CRP (P = .06).
Conclusions, next steps
The researchers concluded that there is an association between childhood asthma and increases in systemic inflammation and innate immunity dysregulation during pregnancy, with failures to control this inflammation increasing the risk for asthma, particularly atopic asthma.
“We will need to validate these findings in a larger population. We also only measured CRP levels for this study. There are other biomarkers of inflammation that need to be studied to see whether any would be better than CRP,” Litonjua said.
“Next, we will need to see whether modifying some of the exposures during pregnancy can decrease the levels of these inflammatory biomarkers, and whether this will lead to better child health,” he continued.
Also, the researchers noted several maternal characteristics and exposures associated with higher CRP levels in pregnancy, such as low socioeconomic status, diets rich in processed foods, exposure to cigarette smoke, gestational diabetes and vitamin D insufficiency.
“Attention to some of the modifiable exposures during pregnancy could help in lowering the state of inflammation,” Litonjua said.
Based on indicators that vitamin D sufficiency in early pregnancy and normal pre-pregnancy BMI protect against elevated prenatal CRP, the researchers wrote, women should begin interventions that optimize maternal health and decrease childhood atopy before conception.
For more information:
Augusto A. Litonjua, MD, MPH, can be reached at augusto_litonjua@urmc.rochester.edu.
Perspective
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I think this is a significant study in that it demonstrates that inflammatory disease, as manifested by an elevated CRP, is associated with the development of childhood asthma in the presence of aeroallergen sensitization.
I do not have any experience with these findings myself, because maternal CRP is not information that I routinely have when evaluating children with asthma. But the key point here is that CRP is a marker of inflammation, and it should prompt a search for the underlying cause.
Ideally, research needs to identify the cause of the inflammation and whether it is amenable to treatment. In this study, maternal asthma was considered a potential confounder, but I did not see any comment on whether the addition of that to the model changed the outcome.
It would also be interesting to know if poorly controlled asthma or allergic disease is associated with an elevation of CRP, which is something that is not commonly measured, and whether that relationship is responsible for the CRP findings.
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