Acute respiratory infections during pregnancy and congenital abnormalities: a population‐based case‐control study

Abstract

Diseases of respiratory system caused by acute infections are among the most common maternal diseases during pregnancy. The objective of the study was to estimate the association between congenital abnormalities and acute respiratory infections during the first trimester of pregnancy. The data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities including 22 843 cases with congenital abnormalities, 38 151 population controls without congenital abnormalities and 834 malformed controls with Down syndrome between 1980 and 1996 was evaluated. 2118 cases with congenital abnormalities (9.3%), 3455 population controls (9.1%) and 92 malformed controls with Down syndrome (11.0%) had mothers with acute respiratory infections. Of 25 different congenital abnormality groups, esophageal atresia/stenosis showed a high adjusted prevalence odds ratios (POR) with 95% confidence interval (CI) for acute respiratory infections during the first trimester of pregnancy in case mothers compared with population controls (3.6, 1.4-9.1) and malformed controls (1.9, 1.0-3.5), respectively. In addition there was an association between medically recorded acute respiratory infections during the first trimester of pregnancy and a higher risk for some other congenital abnormalities, such as posterior cleft palate and multiple congenital abnormalities. In conclusion a possible association between some congenital abnormalities, particularly esophageal atresia/stenosis and maternal acute respiratory infections cannot be excluded due to the interactions of the microbial agents, related drug treatments and last but not least the indirect effect of maternal diseases, such as fever-hyperthermia, hypoxia and dietary deficiency. However, periconceptional multivitamin/folic acid supplementation during the early pregnancy was able to reduce the acute respiratory infection related risk for congenital abnormalities.

Maternal fever during early pregnancy and the risk of oral clefts

“…These results support previous studies that reported an increased risk of birth defects following an illness usually associated with fever (Zhang and Cai, 1993;Acs et al, 2005Acs et al, , 2006aAcs et al, , 2006b. Of interest is a recent set of studies analyzing data from the Hungarian Congenital Abnormalities Registry (HCAR; Acs et al, 2005Acs et al, , 2006aAcs et al, , 2006b.…”

“…Of interest is a recent set of studies analyzing data from the Hungarian Congenital Abnormalities Registry (HCAR; Acs et al, 2005Acs et al, , 2006aAcs et al, , 2006b. These studies used a large dataset to evaluate the associations among maternal cold (Acs et al, 2006a), maternal influenza (Acs et al, 2005), maternal acute respiratory illnesses (ARI) (including bronchitis, sinusitis, pharyngitis, etc.)…”

“…These studies used a large dataset to evaluate the associations among maternal cold (Acs et al, 2006a), maternal influenza (Acs et al, 2005), maternal acute respiratory illnesses (ARI) (including bronchitis, sinusitis, pharyngitis, etc.) (Acs et al, 2006b), and a group of birth defects including isolated ''cleft lip with or without cleft palate'' and ''posterior cleft palate'', which are analogous to our CL1/2P and CP categories, respectively. Twofold to threefold increases were reported for CL1/2P after exposure to maternal influenza (OR, 3.2; 95% CI, 2.0-5.3; Acs et al, 2005), common cold (OR, 2.3; 95% CI, 1.5-3.6; Acs et al, 2006a) and ARI (OR, 1.9; 95% CI, 1.3-2.8; Acs et al, 2006b).…”

“…Possible confounders were selected based on previously reported associations with oral clefts and biologically plausible associations with infection or fever (Acs et al, 2005(Acs et al, , 2006bHashmi et al, 2005;Krost and Schubert, 2006;Villamor et al, 2008). Based on these criteria, the following potential covariates were examined: maternal body mass index (BMI), age, education, race/ethnicity, parity, and season of conception (winter, December to February; spring, March to May; summer, June to August; fall, September to November).…”

Reduction in orofacial clefts following folic acid fortification of the U.S. grain supply

“…Recent studies have shown that influenza and in particular a fever (hyperthermia) associated with the influenza may play an etiologic role in the origin of orofacial clefts (Acs et al, 2006;Metneki et al, 2005). One study found that there was a decrease in the prevalence of orofacial clefts among women with influenza who took an antifever medication; when folic acid was taken in addition to the antifever medication, a preventative effect was seen (Acs et al, 2005).…”