Nonmicrocephalic Infants with Congenital Zika Syndrome Suspected Only after Neuroimaging Evaluation Compared with Those with Microcephaly at Birth and Postnatally: How Large Is the Zika Virus "Iceberg"?

BACKGROUND AND PURPOSE: Although microcephaly is the most prominent feature of congenital Zika syndrome, a spectrum with less severe cases is starting to be recognized. Our aim was to review neuroimaging of infants to detect cases without microcephaly and compare them with those with microcephaly. MATERIALS AND METHODS: We retrospectively evaluated all neuroimaging (MR imaging/CT) of infants 1 year of age or younger. Patients with congenital Zika syndrome were divided into those with microcephaly at birth, postnatal microcephaly, and without microcephaly. Neuroimaging was compared among groups. RESULTS: Among 77 infants, 24.6% had congenital Zika syndrome (11.7% microcephaly at birth, 9.1% postnatal microcephaly, 3.9% without microcephaly). The postnatal microcephaly and without microcephaly groups showed statistically similar imaging findings. The microcephaly at birth compared with the group without microcephaly showed statistically significant differences for the following: reduced brain volume, calcifications outside the cortico-subcortical junctions, corpus callosum abnormalities, moderate-to-severe ventriculomegaly, an enlarged extra-axial space, an enlarged cisterna magna (all absent in those without microcephaly), and polymicrogyria (the only malformation present without microcephaly). There was a trend toward pachygyria (absent in groups without microcephaly). The group with microcephaly at birth compared with the group with postnatal microcephaly showed significant differences for simplified gyral pattern, calcifications outside the cortico-subcortical junctions, corpus callosum abnormalities, moderate-to-severe ventriculomegaly, and an enlarged extra-axial space. CONCLUSIONS: In microcephaly at birth, except for polymicrogyria, all patients showed abnormalities described in the literature. In postnatal microcephaly, the only abnormalities not seen were a simplified gyral pattern and calcifications outside the cortico-subcortical junction. Infants with normocephaly presented with asymmetric frontal polymicrogyria, calcifications in the cortico-subcortical junction, mild ventriculomegaly, and delayed myelination.

Spectrum of Spinal Cord, Spinal Root, and Brain MRI Abnormalities in Congenital Zika Syndrome with and without Arthrogryposis.

BACKGROUND AND PURPOSE: Arthrogryposis is among the malformations of congenital Zika syndrome. Similar to the brain, there might exist a spectrum of spinal cord abnormalities. The purpose of this study was to explore and describe in detail the MR imaging features found in the spinal cords, nerve roots, and brains of children with congenital Zika syndrome with and without arthrogryposis. MATERIALS AND METHODS: Twelve infants with congenital Zika syndrome (4 with arthrogryposis and 8 without) who had undergone brain and spinal cord MR imaging were retrospectively selected. Qualitative and quantitative analyses were performed and compared between groups. RESULTS: At visual inspection, both groups showed reduced thoracic spinal cord thickness: 75% (6/8) of the group without arthrogryposis and 100% (4/4) of the arthrogryposis group. However, the latter had the entire spinal cord reduced and more severely reduced conus medullaris anterior roots (respectively, P = .002 and .007). Quantitative differences were found for conus medullaris base and cervical and lumbar intumescences diameters (respectively, P = .008, .048, .008), with more prominent reduction in arthrogryposis. Periventricular calcifications were more frequent in infants with arthrogryposis (P = .018). CONCLUSIONS: Most infants had some degree of spinal cord thickness reduction, predominant in the thoracic segment (without arthrogryposis) or in the entire spinal cord (with arthrogryposis). The conus medullaris anterior roots were reduced in both groups (thinner in arthrogryposis). A prominent anterior median fissure of the spinal cord was absent in infants without arthrogryposis. Brain stem hypoplasia was present in all infants with arthrogryposis, periventricular calcifications, in the majority, and polymicrogyria was absent.

The effect of brief neonatal exposure to cows' milk on atopic symptoms up to age 5.

AIMS: To determine the effect of brief early exposure to cows' milk on the expression of atopy during the first five years of life. METHODS: Follow up analysis of a double blind, placebo controlled, randomised feeding intervention trial (BOKAAL study). Subjects were 1108 children from 1533 initially randomised breast fed neonates in the Netherlands. Atopic disease and prevalence of allergic symptoms at age 1, 2, and 5, and specific IgE at age 1 and 5 were determined. RESULTS: Atopic disease in the first year was found in 10.0% (cows' milk) versus 9.3% (placebo) of the children, with a relative risk (RR) of 1.07. No differences were found in the second year either. At age 5, atopic disease was found in 26.3% (cows' milk) versus 25.0% (placebo), RR 1.05. There was no difference in the prevalence of allergic symptoms. Specific IgE to cows' milk (RAST positive 2+ or more) was 5.8% (cows' milk) versus 4.1% (placebo) at age 1 (RR 1.43), and 5.3% versus 3.0% at age 5 (RR 1.77). There was no difference in sensitisation to other common allergens between the two groups. CONCLUSION: Early, brief exposure to cows' milk in breast fed children is not associated with atopic disease or allergic symptoms up to age 5.

Relation between IgG antibodies to foods and IgE antibodies to milk, egg, cat, dog and/or mite in a cross-sectional study.

BACKGROUND: Because IgG antibodies to foods can be detected before IgE antibodies to inhalants, increased levels of IgG antibodies to foods might be used as a predictor of IgE-mediated allergy in initially nonatopic children. OBJECTIVE: To examine the cross-sectional relation between IgG to foods (i.e. mixture of wheat and rice, mixture of soybean and peanut, egg white, cow's milk, meat, orange and potato) and specific IgE to cat, dog, mite, milk and egg white in 1-year-old children. METHODS: All atopic children (n = 120; 58 with and 62 without eczema) and a random sample of the nonatopic children (n = 144) of the Bokaal study were tested on their IgG response to foods. The IgG results of the food assays were dichotomized high or low using the 66th centile as a cut-off value. RESULTS: Atopic children more often had high IgG levels to foods than nonatopic children. IgG to egg white (OR = 7.50) and mixture of wheat and rice (OR = 4.79) were most strongly associated with positive specific IgE. In a stepwise logistic regression analysis egg white, mixture of wheat and rice, and orange were selected (OR = 3.76, OR = 2.43, and OR = 2.11, respectively). In children without eczema higher levels of IgG to foods were still significantly associated with atopy, which was most prominent for egg white, orange and cow's milk. CONCLUSION: An increased IgG antibody level to foods, especially to egg white, orange, and mixture of wheat and rice, indicates an increased risk of having IgE to cat, dog, mite, egg and/or milk allergens, even in the noneczematous group. Therefore, in another prospective study we are currently investigating the usefulness of IgG in early identification, i.e. before IgE antibodies can be detected, of children with an increased risk of developing allergic diseases in the future.

Randomised controlled trial of brief neonatal exposure to cows' milk on the development of atopy.

OBJECTIVE: To determine the effect of brief early exposure to cows' milk on atopy in the first 2 years of life. DESIGN: Double blind, placebo controlled, randomised feeding intervention trial (Bokaal study). SETTING: Dutch midwifery practices. PARTICIPANTS: 1533 breast fed neonates. INTERVENTION: Exposure to cows' milk protein (n = 758) or a protein free placebo (n = 775) during the first 3 days of life. MAIN OUTCOME MEASURES: Clinical atopic disease and any positive radioallergosorbent (RAST) tests at 1 year of age. RESULTS: Atopic disease in the first year was found in 10.0% (cows' milk) v 9.3% (placebo) of the children, with a relative risk of 1.07; in the second year, atopic disease was found in 9.6% v 10.2%, respectively, with a relative risk of 0.94. Per protocol analysis showed similar results. Any RAST positive test was found in 9.4% (cows' milk) v 7.9% (placebo) of children, with a relative risk of 1.19. Stratified analysis for high family risk of allergy showed a doubled incidence of atopic disease but no effect from the intervention. CONCLUSION: Early and brief exposure to cows' milk in breast fed children does not increase the risk of atopic disease in the first 2 years.