ABSTRACT
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.
Subject(s)
Microcephaly , Nervous System Malformations , Pregnancy Complications, Infectious , Zika Virus Infection , Zika Virus , Brazil/epidemiology , Child , Cohort Studies , Female , Humans , Infant , Infant, Newborn , Microcephaly/diagnosis , Microcephaly/epidemiology , Neuroimaging , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Zika Virus Infection/complications , Zika Virus Infection/congenital , Zika Virus Infection/epidemiologyABSTRACT
BACKGROUND: While Zika virus (ZIKV) is now widely recognized as a teratogen, the frequency and full spectrum of adverse outcomes of congenital ZIKV infection remains incompletely understood. METHODS: Participants in the MERG cohort of pregnant women with rash, recruited from the surveillance system from December/2015-June/2017. Exposure definition was based on a combination of longitudinal data from molecular, serologic (IgM and IgG3) and plaque reduction neutralization tests for ZIKV. Children were evaluated by a team of clinical specialists and by transfontanelle ultrasound and were classified as having microcephaly and/or other signs/symptoms consistent with congenital Zika syndrome (CZS). Risks of adverse outcomes were quantified according to the relative evidence of a ZIKV infection in pregnancy. FINDINGS: 376 women had confirmed and suspected exposure to ZIKV. Among evaluable children born to these mothers, 20% presented with an adverse outcome compatible with exposure to ZIKV during pregnancy. The absolute risk of microcephaly was 2.9% (11/376), of calcifications and/or ventriculomegaly was 7.2% (13/180), of additional neurologic alterations was 5.3% (13/245), of ophthalmologic abnormalities was 7% (15/214), and of dysphagia was 1.8% (4/226). Less than 1% of the children experienced abnormalities across all of the domains simultaneously. Interpretation: Although approximately one-fifth of children with confirmed and suspected exposure to ZIKV in pregnancy presented with at least one abnormality compatible with CZS, the manifestations presented more frequently in isolation than in combination. Due to the rare nature of some outcomes and the possibility of later manifestations, large scale individual participant data meta-analysis and the long-term evaluation of children are imperative to identify the full spectrum of this syndrome and to plan actions to reduce damages.
Subject(s)
Central Nervous System Diseases/virology , Pregnancy Complications, Infectious/virology , Pregnancy Outcome , Zika Virus Infection/pathology , Adult , Brazil/epidemiology , Central Nervous System Diseases/congenital , Female , Humans , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Zika Virus , Zika Virus Infection/congenitalABSTRACT
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.
Subject(s)
Endocrine System Diseases/epidemiology , Endocrine System Diseases/etiology , Microcephaly/epidemiology , Microcephaly/etiology , Pregnancy Complications, Infectious/epidemiology , Zika Virus Infection/complications , Zika Virus Infection/epidemiology , Zika Virus , Biomarkers , Brazil/epidemiology , Child, Preschool , Female , Humans , Infant , Male , Microcephaly/diagnosis , Microcephaly/metabolism , Pregnancy , Public Health Surveillance , Symptom Assessment , Zika Virus Infection/diagnosis , Zika Virus Infection/virologySubject(s)
Humans , Infant, Newborn , Immunoglobulin M/cerebrospinal fluid , Zika Virus/isolation & purification , Zika Virus Infection/diagnosis , Hearing Loss, Sensorineural/diagnosis , Microcephaly/virology , Brain Stem/diagnostic imaging , Tomography Scanners, X-Ray Computed , Infectious Disease Transmission, Vertical , Hearing Loss, Sensorineural/virologyABSTRACT
BACKGROUND: In Brazil, in October 2015, an outbreak of Zika virus (ZIKV) infection and an increase in newborns with microcephaly suggested a relationship between maternal infection and microcephaly in children. OBJECTIVE: First, to assess the presence of dental bud sin 13 infants with a confirmed diagnosis of congenital ZIKV syndrome, born to mothers infected with the virus during pregnancy; second, to evaluate the dental development of these children at a 36-month follow-up. DESIGN: Case-based longitudinal study. RESULTS: Dental radiographs in the first semester showed that all children had dental buds. Along with the study, the individuals presented with various dental disturbances. At the end of the evaluation period, some children still had incomplete deciduous dentition. CONCLUSION: The abnormal chronology of dental eruption and dental development disturbances in children with microcephaly infected with ZIKV born to infected mothers indicate a possible role of the virus in odontogenesis.
Subject(s)
Odontogenesis , Pregnancy Complications, Infectious , Zika Virus Infection , Brazil , Child , Female , Humans , Infant , Infant, Newborn , Longitudinal Studies , Mothers , Pregnancy , Syndrome , Zika Virus Infection/complications , Zika Virus Infection/congenitalSubject(s)
Hearing Loss, Sensorineural/diagnosis , Immunoglobulin M/cerebrospinal fluid , Microcephaly/virology , Zika Virus Infection/diagnosis , Zika Virus/isolation & purification , Brain Stem/diagnostic imaging , Hearing Loss, Sensorineural/virology , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Tomography Scanners, X-Ray ComputedABSTRACT
OBJECTIVES: To describe sleep EEG patterns of neonates, and infants with microcephaly due to congenital Zika virus (ZikV) syndrome. METHODS: A descriptive case series of EEGs performed in a cohort of neonates with microcephaly monitored from October 2015 to February 2016 at a University Hospital in Northeast Brazil. Infants were investigated following an established protocol that includes EEG, neuroimaging studies, PCR and specific antibodies for ZikV detection. RESULTS: EEGs (n=37) from 37 infants were reviewed. Age at investigation varied from 1 to 5months (mean=2.6). Diffuse low voltage (n=7), background asymmetry (n=6) and modified hypsarrhythmia with or without burst-suppression (n=11), were the main background abnormalities identified. Interictal EEG abnormalities were identified in 23 recordings (62%) and localized as focal frontal (n=8) or occipital (n=2) spikes/sharp, multifocal spikes/sharp waves (n=13). Electrographic seizures without clinical manifestation were identified in 4 recordings and characterized as focal pseudo rhythmic pattern. Further findings were focal high amplitude slow waves that were registered in the frontal (n=3) or occipital (n=1) regions. CONCLUSIONS: Different types of EEG abnormalities were encountered with a predominance of interictal epileptogenic activity and hypsarrhythmia. SIGNIFICANCE: Sleep EEGs in congenital Zika virus syndrome are consistently abnormal even in infants who have not yet developed epilepsy.
Subject(s)
Electroencephalography/methods , Microcephaly/physiopathology , Sleep Wake Disorders/physiopathology , Sleep , Zika Virus Infection/physiopathology , Zika Virus , Cohort Studies , Female , Humans , Infant , Male , Microcephaly/diagnosis , Microcephaly/etiology , Sleep/physiology , Sleep Wake Disorders/diagnosis , Zika Virus Infection/complications , Zika Virus Infection/diagnosisABSTRACT
OBJECTIVES: To provide an initial description of the congenital syndrome presumably associated with infection by Zika virus compared with other syndromes including congenital infections of established etiologies. METHODS: We provide an overview of a published case series of 35 cases, a clinical series of 104 cases, and published and unpublished reports of clinical and laboratory findings describing cases diagnosed since the beginning of the epidemic of microcephaly in Brazil. RESULTS: About 60% to 70% of mothers report rash during pregnancy; mainly in the first trimester. Principal features are microcephaly, facial disproportionality, cutis girata, hypertonia/spasticity, hyperreflexia, and irritability; abnormal neuroimages include calcifications, ventriculomegaly, and lissencephaly. Hearing and visual abnormalities may be present. CONCLUSIONS: Preliminary data suggest that severe congenital abnormalities are linked to Zika virus infection. Cases have severe abnormalities, and although sharing many characteristics with congenital abnormalities associated with other viral infections, abnormalities presumably linked to the Zika virus may have distinguishing characteristics. These severe neurologic abnormalities may result in marked mental retardation and motor disabilities for many surviving offspring. POLICY IMPLICATIONS: Affected nations need to prepare to provide complex and costly multidisciplinary care that children diagnosed with this new congenital syndrome will require.
Subject(s)
Infectious Disease Transmission, Vertical , Microcephaly/etiology , Pregnancy Complications, Infectious , Zika Virus Infection/congenital , Brazil , Exanthema , Female , Humans , Infant, Newborn , Intellectual Disability/etiology , Neuroimaging , Pregnancy , Syndrome , Zika Virus/isolation & purification , Zika Virus Infection/transmissionABSTRACT
É descrito o caso de uma paciente do sexo feminino, 12 anos com alterações características da Síndrome de Sturge-Weber (nevus angiomatoso, cefaléia e retardo mental). No caso em estudo, há, no entanto, hemiparesia espástica trofomotora ipsilateral ao angioma, ausência de calcificações intracranianas e sinais sequelares de acidente vascular cerebral, achados não usuais nessa síndrome