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Background Infant HIV infection is associated with delayed milestone attainment. The extent to which effective antiretroviral therapy (ART) prevents these delays is not well defined. Methods Ages at attainment of milestones were compared between HIV-infected (initiated ART by age <5 months), and HIV-unexposed uninfected (HUU) infants. Kaplan Meier analyses were used to estimate and compare (log-rank tests) ages at milestones between groups. Adjusted analyses were performed using Cox proportional hazards models. Results Seventy-three HIV-infected on ART (median enrollment age 3.7 months) and 92 HUU infants (median enrollment age 1.6 months) were followed prospectively. HIV-infected infants on ART had delays in developmental milestone attainment compared to HUU: median age at attainment of sitting with support, sitting unsupported, walking with support, walking unsupported, monosyllabic speech and throwing toys were each delayed (all p -values <0.0005). Compared with HUU, the subset of HIV-infected infants with both virologic suppression and immune recovery at 6 months had delays for speech (delay: 2.0 months; P =  0.0002) and trend to later walking unsupported. Among HIV-infected infants with poor 6-month post-ART responses (lacking viral suppression and immune recovery) there were greater delays versus HUU for: walking unsupported (delay: 4.0 months; P =  0.0001) and speech (delay: 5.0 months; P  < 0.0001). Conclusions HIV infected infants with viral suppression on ART had better recovery of developmental milestones than those without suppression, however, deficits persisted compared to uninfected infants. Earlier ART may be required for optimized cognitive outcomes in perinatally HIV-infected infants. Trial registration NCT00428116 ; January 22, 2007.

Pregnant individuals with viral illness may experience significant morbidity and have higher rates of pregnancy and neonatal complications. With the growing number of viral infections and new viral pandemics, it is important to examine the effects of infection during pregnancy on both the gestational parent and the offspring. Febrile illness and inflammation during pregnancy are correlated with risk for autism, attention deficit/hyperactivity disorder, and developmental delay in the offspring in human and animal models. Historical viral epidemics had limited follow-up of the offspring of affected pregnancies. Infants exposed to seasonal influenza and the 2009 H1N1 influenza virus experienced increased risks of congenital malformations and neuropsychiatric conditions. Zika virus exposure in utero can lead to a spectrum of abnormalities, ranging from severe microcephaly to neurodevelopmental delays which may appear later in childhood and in the absence of Zika-related birth defects. Vertical infection with severe acute respiratory syndrome coronavirus-2 has occurred rarely, but there appears to be a risk for developmental delays in the infants with antenatal exposure. Determining how illness from infection during pregnancy and specific viral pathogens can affect pregnancy and neurodevelopmental outcomes of offspring can better prepare the community to care for these children as they grow. Impact Viral infections have impacted pregnant people and their offspring throughout history. Antenatal exposure to maternal fever and inflammation may increase risk of developmental and neurobehavioral disorders in infants and children. The recent SARS-CoV-2 pandemic stresses the importance of longitudinal studies to follow pregnancies and offspring neurodevelopment.

Congenital Zika virus infection has stimulated great international concern. A prospective case series of 87 infants with laboratory-confirmed congenital Zika syndrome (CZS) at the epicenter of the Brazilian Zika epidemic in Pernambuco state is presented. Mothers were interviewed for symptoms of possible Zika virus (ZIKV) infection during pregnancy, and fetal ultrasounds were obtained. Infant cerebrospinal fluid (CSF) samples were tested for ZIKV-specific antibodies, and sera were screened for other congenital infections. Neuroimaging and ophthalmologic evaluations were also performed. Sixty-six mothers (76%) reported symptoms of ZIKV infection during gestation. Fetal ultrasounds were available from 90% of the mothers, and all demonstrated brain structural abnormalities. All of the CSF samples tested positive for ZIKV immunoglobulin M. The majority of infants (89%) were term; the mean birth weight was 2577 ± 260 g, and the mean head circumference was 28.1 ± 1.8 cm. Severe microcephaly, defined as head circumference 3 SD below the mean for sex and gestational age, was found in 72 (82%) infants. All infants had an abnormal neurological exam, and 18 (20.7%) had arthrogryposis. The main abnormalities detected in computed tomography scans were calcifications (99%), followed by ventricular enlargement (94%), cortical hypogyration (81%), and less commonly, cerebellar hypoplasia (52%). Unilateral diaphragm paralysis was identified in 3 infants. Maternal young age, term infant, small for gestational age, and the presence of ophthalmologic abnormalities were significantly associated with a smaller head circumference Z score. Our findings, based on laboratory-confirmed ZIKV infection, add valuable evidence for the understanding of CZS.

It is unclear if SARS CoV-2 infection during pregnancy is associated with adverse neurodevelopmental repercussions to infants. We assessed pediatric neurodevelopmental outcomes in children born to mothers with laboratory-confirmed SARS CoV-2 infection during pregnancy. Neurodevelopmental outcomes of in-utero exposed children were compared to that of pre-pandemic control children in Los Angeles (LA), CA, USA and Rio de Janeiro, Brazil. Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III), the gold standard tool for evaluating neurodevelopment until 36 months of age and Ages and Stages Questionnaires (ASQ-3), a frequently used screening instrument for evaluating neurodevelopment in this same age group were the assessment tools used. Developmental delay (DD) was defined as having a score < − 2 SD below the norm (< 70) in at least one of three Bayley-III domains, (cognitive, motor or language) or a score below the cut-off (dark zone) in at least one of five ASQ-3 domains (communication, gross motor, fine motor, problem solving, personal-social). Exposed children were born between April 2020 and December 2022 while control children were born between January 2016 to December 2019. Neurodevelopmental testing was performed in 300 children total: 172 COVID-19 exposed children between 5–30 months of age and 128 control children between 6–38 months of age. Bayley-III results demonstrated that 12 of 128 exposed children (9.4%) had DD versus 2 of 128 controls (1.6%), p  = 0.0007. Eight of 44 additional exposed children had DD on ASQ-3 testing. Fully, 20 of 172 exposed children (11.6%) and 2 of 128 control children (1.6%), p  = 0.0006 had DD. In Rio, 12% of exposed children versus 2.6% of controls, p  = 0.02 had DD. In LA, 5.7% of exposed children versus 0 controls, p  = 0.12 had DD. Severe/critical maternal COVID-19 predicted below average neurodevelopment in the exposed cohort (OR 2.6, 95% CI 1.1–6.4). Children exposed to antenatal COVID-19 have a tenfold higher frequency of DD as compared to controls and should be offered neurodevelopmental follow-up.

Exposure to Zika virus in utero has been associated with neurodevelopmental abnormalities. In this letter, the results of long-term follow-up of Brazilian children exposed to ZIKV in utero are reported.

Little is known about the neurocognitive outcome in children exposed to perinatal mother-to-child Chikungunya virus (p-CHIKV) infection. The CHIMERE ambispective cohort study compared the neurocognitive function of 33 p-CHIKV-infected children (all but one enrolled retrospectively) at around two years of age with 135 uninfected peers (all enrolled prospectively). Psychomotor development was assessed using the revised Brunet-Lezine scale, examiners blinded to infectious status. Development quotients (DQ) with subscores covering movement/posture, coordination, language, sociability skills were calculated. Predictors of global neurodevelopmental delay (GND, DQ ≤ 85), were investigated using multivariate Poisson regression modeling. Neuroradiologic follow-up using magnetic resonance imaging (MRI) scans was proposed for most of the children with severe forms. The mean DQ score was 86.3 (95%CI: 81.0-91.5) in infected children compared to 100.2 (95%CI: 98.0-102.5) in uninfected peers (P<0.001). Fifty-one percent (n = 17) of infected children had a GND compared to 15% (n = 21) of uninfected children (P<0.001). Specific neurocognitive delays in p-CHIKV-infected children were as follows: coordination and language (57%), sociability (36%), movement/posture (27%). After adjustment for maternal social situation, small for gestational age, and head circumference, p-CHIKV infection was found associated with GND (incidence rate ratio: 2.79, 95%CI: 1.45-5.34). Further adjustments on gestational age or breastfeeding did not change the independent effect of CHIKV infection on neurocognitive outcome. The mean DQ of p-CHIKV-infected children was lower in severe encephalopathic children than in non-severe children (77.6 versus 91.2, P<0.001). Of the 12 cases of CHIKV neonatal encephalopathy, five developed a microcephaly (head circumference <-2 standard deviations) and four matched the definition of cerebral palsy. MRI scans showed severe restrictions of white matter areas, predominant in the frontal lobes in these children. The neurocognitive outcome of children exposed to perinatal mother-to-child CHIKV infection is poor. Severe CHIKV neonatal encephalopathy is associated with an even poorer outcome.

To describe the neurological and neurodevelopmental outcomes of children with Congenital Zika Syndrome (CZS) associated microcephaly beyond 2 years of age. We followed children with CZS-associated microcephaly in an outpatient clinic in Salvador, Brazil. Neurological and neurodevelopmental assessments were performed using the Hammersmith Infant Neurological Examination (HINE) and Bayley Scales of Infant and Toddler Neurodevelopment (Bayley-III) respectively. Of the 42 children included, 19 were male (45.2%); median (interquartile range) age at neurological evaluation was 28 (25-32) months, and 36 (85.7%) had severe microcephaly. HINE and Bayley-III results were completed for 35/42 (83.3%) and 33/42 (78.5%) children respectively. Bayley-III identified a severe developmental delay in 32/33 (97.0%) children while 1/33 (3.0%) had only a mild delay. In the multivariable analysis, we found that Bayley-III and HINE scores were correlated. Better HINE scores were associated with higher Bayley-III cognitive raw scores (β = 0.29; CI 95% = 0.02-0.57) and motor raw scores (β = 0.43; CI 95% = 0.04-0.82) after adjusting for head circumference, prematurity, and age at neurodevelopmental evaluation. Furthermore, we found that greater head circumference at follow up was associated with higher cognitive (β = 1.27; CI 95% = 0.01-2.53) and motor raw scores (β = 2.03; CI 95% = 0.25-3.81). Children with CZS-associated microcephaly demonstrate severe neurodevelopmental delays and slower growth rates than their peers over time. Still, they have remarkably heterogeneous neurodevelopmental profiles according to neurological exam scores which correlate with their long-term outcomes. We found that HINE scores effectively captured the heterogeneity of neurological capabilities among these children and could be predictive of cognitive and motor development progress.

Delays in development that occur during early childhood can have long-lasting consequences, potentially leading to poor academic achievement. Research has shown that the human immunodeficiency virus can have neurotropic effects, which may impact the development of the brain in infected children. However, there is a scarcity of evidence regarding developmental delays among children with human immunodeficiency virus in the study area. This study aimed to determine the prevalence of developmental delay and associated factors among children with the human immunodeficiency virus in southern Ethiopia. A cross-sectional study was undertaken among 422 children aged below five during October 30 to December 30, 2021, who acquired the human immunodeficiency virus at public hospitals. A pretested tool anthropometric measurements were utilized. To examine developmental delay, the age and stage questionnaires (version 3) were used. Descriptive statistics were performed. Bivariable and multivariable binary logistic regression models were fitted to identify potential factors associated with delays in child development. The analysis was performed using STATA version 14.2. Adjusted odds ratios with 95% confidence intervals and variables with p-values less than 0.05 were considered to be significantly associated with global developmental delay. A total of 413 under-five children with human immune virus participated, with a 97.9% response rate. Of all children, 222 (53.75%) were male, and the mean age of children was 3.5 ± 1 (± SD) years. Overall global developmental delay was 41.89% [95% CI 37–47%]. Maternal age 35 and older [AOR 2.2; 95% CI (1.11–4.3)], maternal educational status [AOR 0.47; 95% CI (0.23–0.96)], higher birth order [AOR 3; 95% CI (1.5–4)], and stunting [AOR 2.2; 95% CI (1.4–3.42)] were significant factors associated with global developmental delay. Half of the children examined demonstrated delayed development across domains. The global developmental delay constitutes a significant public health concern, underscoring the necessity for early detection initiatives including developmental screening, diagnostic evaluations, and therapeutic interventions. We found significant associations between the developmental status of the children and the maternal age, educational level of mothers, higher birth order, and stunting of under-five children. Policies should aim to enhance mother and child health services, expand access to early intervention programs, and incorporate developmental surveillance into routine pediatric care. Additional research may be necessary to elucidate the underlying causes of the high prevalence of Global developmental delay, evaluate the efficacy of current interventions, and investigate innovative approaches to mitigate developmental delays.

The coronavirus (COVID-19) pandemic has affected, and will continue to affect, every aspect of the intellectual and developmental disabilities (IDD) community. We provide recommendations to (a) support people with IDD and the broader of field of IDD during the course of the pandemic, and (b) place the IDD community in a strong position when the health threats associated with the pandemic abate and post-pandemic social and policy structures are formed.

PurposeDue to the severe risk of long-term sequelae, prenatal cytomegalovirus infection is of particular importance amongst intrauterine viral infections. This review summarizes the current knowledge about CMV infection in pregnancy.MethodsA search of the Medline and Embase database was done for articles about CMV infection in pregnany. We performed a detailed review of the literature in view of diagnosis, epidemiology and management of CMV infection in pregnancy.ResultsThe maternal course of the infection is predominantly asymptomatic; the infection often remains unrecognized until the actual fetal manifestation. Typical ultrasound signs that should arouse suspicion of intrauterine CMV infection can be distinguished into CNS signs such as ventriculomegaly or microcephaly and extracerebral infection signs such as hepatosplenomegaly or hyperechogenic bowel. Current treatment strategies focus on hygienic measures to prevent a maternal CMV infection during pregnancy, on maternal application of hyperimmunoglobulines to avoid materno-fetal transmission in case of a maternal seroconversion, and on an antiviral therapy in case the materno-fetal transmission have occurred.ConclusionCMV infection in pregnancy may result in a severe developmental disorder of the newborn. This should be taken into account in the treatment of affected and non-affected pregnant women.