Characteristics of children of the Microcephaly Epidemic Research Group Pediatric Cohort who developed postnatal microcephaly.

The number of studies published on postnatal microcephaly in children with Congenital Zika Syndrome is small, clinical presentations vary and aspects of the evolution of these children remain unclarified. The present case series examined clinical characteristics and assessed the growth velocity of the head circumference, weight and height Z-scores in 23 children who developed postnatal microcephaly during follow-up in the Microcephaly Epidemic Research Group Pediatric Cohort. To estimate the change in the head circumference, weight and height Z-scores over time and compare the mean difference between sexes, we used multilevel mixed-effects linear regressions with child-specific random effects. Among these children, 60.9% (n = 14/23) presented with craniofacial disproportion, 60.9% (n = 14/23) with strabismus, 47.8% (n = 11/23) with early onset seizures, 47.8% (n = 11/23) with dysphagia and 43.5% (n = 10/23) with arthrogryposis. Of the 82.7% (n = 19/23) children who underwent neuroimaging, 78.9% (n = 15/19) presented with alterations in the central nervous system. Monthly growth velocity, expressed in Z-scores, of the head circumference was - 0.098 (95% CI % - 0.117 to - 0.080), of weight was: - 0.010 (95%-CI - 0.033 to 0.014) and of height was: - 0.023 (95%-CI - 0.046 to 0.0001). Postnatal microcephaly occurred mainly in children who had already presented with signs of severe brain damage at birth; there was variability in weight and height development, with no set pattern.

Zika-Related Microcephaly and Its Repercussions for the Urinary Tract: Clinical, Urodynamic, Scintigraphic and Radiological Aspects.

AIMS: Describing the urodynamic parameters of children aged 3 to 5 years with microcephaly related to congenital Zika syndrome and verifying the association with clinical, imaging and neurological characteristics. METHODS: From October 2018 to March 2020, children with Zika-related microcephaly underwent urological, ultrasonographic and urodynamic evaluation. In selected cases, complementary exams such as urethrocystography and scintigraphy were performed. The children also underwent a complete neurological evaluation. To compare frequency between groups, we used Pearson's chi-squared test or Fisher's exact test. RESULTS: This study evaluated 40 children, of whom 85% were 4 years old, and all had abnormalities on the urodynamic study, with low bladder capacity (92.5%) and detrusor overactivity (77.5%) as the most frequent findings. Only three children had ultrasound abnormalities, but no child had cystographic or scintigraphic abnormalities, and the postvoid residual volume was normal in 80% of cases. In spite of a frequency of 67.5% of intestinal constipation, there was no record of febrile urinary tract infection after the first year of life. All children presented severe microcephaly and at least one neurological abnormality in addition to microcephaly. The homogeneity of the children in relation to microcephaly severity and neurological abnormalities limited the study of the association with the urodynamic parameters. CONCLUSIONS: Urodynamic abnormalities in children aged 3 to 5 years with Zika-related microcephaly do not seem to characterize a neurogenic bladder with immediate risks for the upper urinary tract. The satisfactory bladder emptying suggests that the voiding pattern is reflex.

The Microcephaly Epidemic Research Group Paediatric Cohort (MERG-PC): A Cohort Profile.

This cohort profile aims to describe the ongoing follow-up of children in the Microcephaly Epidemic Research Group Paediatric Cohort (MERG-PC). The profile details the context and aims of the study, study population, methodology including assessments, and key results and publications to date. The children that make up MERG-PC were born in Recife or within 120 km of the city, in Pernambuco/Brazil, the epicentre of the microcephaly epidemic. MERG-PC includes children from four groups recruited at different stages of the ZIKV microcephaly epidemic in Pernambuco, i.e., the Outpatient Group (OG/n = 195), the Microcephaly Case-Control Study (MCCS/n = 80), the MERG Pregnant Women Cohort (MERG-PWC/n = 336), and the Control Group (CG/n = 100). We developed a comprehensive array of clinical, laboratory, and imaging assessments that were undertaken by a 'task force' of clinical specialists in a single day at 3, 6, 12, 18 months of age, and annually from 24 months. Children from MCCS and CG had their baseline assessment at birth and children from the other groups, at the first evaluation by the task force. The baseline cohort includes 711 children born between February 2015 and February 2019. Children's characteristics at baseline, excluding CG, were as follows: 32.6% (184/565) had microcephaly, 47% (263/559) had at least one physical abnormality, 29.5% (160/543) had at least one neurological abnormality, and 46.2% (257/556) had at least one ophthalmological abnormality. This ongoing cohort has contributed to the understanding of the congenital Zika syndrome (CZS) spectrum. The cohort has provided descriptions of paediatric neurodevelopment and early epilepsy, including EEG patterns and treatment response, and information on the frequency and characteristics of oropharyngeal dysphagia; cryptorchidism and its surgical findings; endocrine dysfunction; and adenoid hypertrophy in children with Zika-related microcephaly. The study protocols and questionnaires were shared across Brazilian states to enable harmonization across the different studies investigating microcephaly and CZS, providing the opportunity for the Zika Brazilian Cohorts Consortium to be formed, uniting all the ZIKV clinical cohorts in Brazil.

Endocrine Dysfunction in Children with Zika-Related Microcephaly Who Were Born during the 2015 Epidemic in the State of Pernambuco, Brazil.

Congenital viral infections and the occurrence of septo-optic dysplasia, which is a combination of optic nerve hypoplasia, abnormal formation of structures along the midline of the brain, and pituitary hypofunction, support the biological plausibility of endocrine dysfunction in Zika-related microcephaly. In this case series we ascertained the presence and describe endocrine dysfunction in 30 children with severe Zika-related microcephaly from the MERG Pediatric Cohort, referred for endocrinological evaluation between February and August 2019. Of the 30 children, 97% had severe microcephaly. The average age at the endocrinological consultation was 41 months and 53% were female. The most frequently observed endocrine dysfunctions comprised short stature, hypothyroidism, obesity and variants early puberty. These dysfunctions occurred alone 57% or in combination 43%. We found optic nerve hypoplasia (6/21) and corpus callosum hypoplasia (20/21). Seizure crises were reported in 86% of the children. The most common-and clinically important-endocrine dysfunctions were pubertal dysfunctions, thyroid disease, growth impairment, and obesity. These dysfunctions require careful monitoring and signal the need for endocrinological evaluation in children with Zika-related microcephaly, in order to make early diagnoses and implement appropriate treatment when necessary.

Cryptorchidism in Children with Zika-Related Microcephaly.

The genitourinary tract was recently identified as a potential site of complications related to the congenital Zika syndrome (CZS). We provide the first report of a series of cryptorchidism cases in 3-year-old children with Zika-related microcephaly who underwent consultations between October 2018 and April 2019 as part of the follow-up of the children cohort of the Microcephaly Epidemic Research Group, Pernambuco, Brazil. Of the 22 males examined, eight (36.4%) presented with cryptorchidism. Among 14 undescended testis cases, 11 (78.6%) could be palpated in the inguinal region. Seven of the eight children had severe microcephaly. Conventional risk factors for cryptorchidism were relatively infrequent in these children. We hypothesize that cryptorchidism is an additional manifestation of CZS present in children with severe microcephaly. As in our cases, for most of the children, the testes were located in the inguinal region, and the possible mechanisms for cryptorchidism were gubernaculum disturbance or cremasteric abnormality.