Delineation of a multiple congenital abnormality syndrome in the offspring of pregnant women affected with high fever-related disorders: a population-based study.

Our previous study showed an association between high fever-related maternal diseases during the second and/or third gestational months and a higher risk of multiple congenital abnormalities (MCA) in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities. The objective of our analysis is to attempt the delineation of the spectrum of the characteristic component defects of an MCA syndrome associated with high fever-related maternal diseases. Of 1349 cases with MCA without recognized genetic and teratogenic syndromes in the total dataset, 181 had a possible association with influenza, common cold with secondary complications, tonsillitis and recurrent orofacial herpes with high fever in the second and/or third gestational months. At the evaluation of component defects in these 181 MCA cases, an association was found between the components of the so-called two schisis-type defects, such as neural-tube defects and orofacial cleft, in addition to microphthalmos, neurogenic limb contractures, and indeterminate sex (i.e. maldevelopment of male external genital organs, such as hypoplasia of the penis and pseudohermaphroditism). In addition, previous findings that showed an association between high fever and facial anomalies (micrognathia and midfacial hypoplasia), microcephaly and defects of external ears, were confirmed in our dataset. Thus, we delineated the maternal high fever-related MCA syndrome, including the above component defects and this MCA syndrome was identified in 38 MCA (21.0%) among 181 MCA babies born to mothers with high fever-related diseases. In the total dataset of 1349 MCA, 2.8% of cases can be associated with high fever.