Neurodevelopmental Abnormalities In Children Research Articles

Outcomes up to age 36 months after congenital Zika virus infection-U.S. states.

To characterize neurodevelopmental abnormalities in children up to 36 months of age with congenital Zika virus exposure. From the U.S. Zika Pregnancy and Infant Registry, a national surveillance system to monitor pregnancies with laboratory evidence of Zika virus infection, pregnancy outcomes and presence of Zika associated birth defects (ZBD) were reported among infants with available information. Neurologic sequelae and developmental delay were reported among children with ≥1 follow-up exam after 14 days of age or with ≥1 visit with development reported, respectively. Among 2248 infants, 10.1% were born preterm, and 10.5% were small-for-gestational age. Overall, 122 (5.4%) had any ZBD; 91.8% of infants had brain abnormalities or microcephaly, 23.0% had eye abnormalities, and 14.8% had both. Of 1881 children ≥1 follow-up exam reported, neurologic sequelae were more common among children with ZBD (44.6%) vs. without ZBD (1.5%). Of children with ≥1 visit with development reported, 46.8% (51/109) of children with ZBD and 7.4% (129/1739) of children without ZBD had confirmed or possible developmental delay. Understanding the prevalence of developmental delays and healthcare needs of children with congenital Zika virus exposure can inform health systems and planning to ensure services are available for affected families. We characterize pregnancy and infant outcomes and describe neurodevelopmental abnormalities up to 36 months of age by presence of Zika associated birth defects (ZBD). Neurologic sequelae and developmental delays were common among children with ZBD. Children with ZBD had increased frequency of neurologic sequelae and developmental delay compared to children without ZBD. Longitudinal follow-up of infants with Zika virus exposure in utero is important to characterize neurodevelopmental delay not apparent in early infancy, but logistically challenging in surveillance models.

Neurodevelopmental Abnormalities in Patients with Familial Hypocalciuric Hypercalcemia Type 3

To evaluate the prevalence and degree of any neurodevelopmental abnormalities in children with familial hypocalciuric hypercalcemia type 3 (FHH3). A formal neurodevelopmental assessment was performed in children diagnosed with FHH3. The Vineland Adaptive Behavior Scales, which is a standardized parent report assessment tool for adaptive behavior, was used to assess communication, social skills, and motor function and to generate a composite score. Six patients were diagnosed with hypercalcemia between 0.1 and 8years of age. All had neurodevelopmental abnormalities in childhood consisting of either global developmental delay, motor delay, expressive speech disturbances, learning difficulties, hyperactivity, or autism spectrum disorder. Four out of the 6 probands had a composite Vineland Adaptive Behavior Scales SDS of<-2.0, indicating adaptive malfunctioning. Significant deficits were observed in the domains of communication (mean SDS: -2.0, P<.01), social skills (mean SDS: -1.3, P<.05), and motor skills (mean SDS: 2.6, P<.05). Individuals were equally affected across domains, with no clear genotype-phenotype correlation. All family members affected with FHH3 also described evidence of neurodevelopmental dysfunction, including mild-to-moderate learning difficulties, dyslexia, and hyperactivity. Neurodevelopmental abnormalities appear to be a highly penetrant and common feature of FHH3, and early detection is warranted to provide appropriate educational support. This case series also supports consideration of serum calcium measurement as part of the diagnostic work-up in any child presenting with unexplained neurodevelopmental abnormalities.

Neurodevelopmental Abnormalities in Children Associated with Maternal Use of Psychoactive Medication

Background: Due to its negative effects on the unborn child and the mother as a consumer, pregnant women's intake of psychoactive substances has become a public health concern. Additionally, consuming these chemicals has been linked to several neurological development changes in children, including behavioral issues (such as attention deficit hyperactivity disorder and autism spectrum disorder), cognitive issues, and sensory and motor function changes. Objectives: To perform a thorough, comprehensive study of the neurodevelopmental problems in children linked to maternal drug use. Method: A search of the scientific literature on studies about neurodevelopmental abnormalities linked to maternal use of psychoactive medications during pregnancy and published in the previous ten years up to June 2022 was conducted from PubMed, Google Scholar, and Directory open access Journals. Results: The initial screening identified 380 articles. We excluded 50 unaccessible articles and 160 articles due to publication dates and study types; after that, 62 articles were also discarded because they were duplicates, and 68 were excluded because the information was irrelevant or systemic reviews, so we finally obtained 40 articles for full-text reading distributed as follows: 18 from PubMed, 12 from Directory Open Access Journal, and 10 from Google scholar

Association Between Antenatal Exposure to Zika Virus and Anatomical and Neurodevelopmental Abnormalities in Children

Zika virus (ZIKV) is a mosquito-borne flavivirus recognized as teratogenic since the 2015 to 2016 epidemic. Antenatal ZIKV exposure causes brain anomalies, yet the full spectrum has not been delineated. To characterize the clinical features of ZIKV infection at a pediatric referral center in Rio de Janeiro, Brazil, among children with antenatal ZIKV exposure. Retrospective cohort study conducted from May to July 2019 of a prospective cohort of 296 infants with antenatal ZIKV exposure followed up since December 2015 at a tertiary maternity-pediatric hospital. Zika virus infection during pregnancy. Characterization of clinical features with anthropometric, neurologic, cardiologic, ophthalmologic, audiometric, and neuroimaging evaluations in infancy and neurodevelopmental assessments (Bayley Scales of Infant and Toddler Development, Third Edition) from 6 to 42 months of age, stratified by head circumference at birth (head circumference within the reference range, or normocephaly [NC] vs microcephaly [MC]). Antenatal exposure to ZIKV was confirmed for 219 of 296 children (74.0%) referred to Instituto Fernandes Figueira with suspected ZIKV infection through positive maternal or neonatal polymerase chain reaction analysis or IgM serology results. Of these children, 110 (50.2%) were boys, ages ranged from 0 to 4 years, and 53 (24.2%) had congenital microcephaly. The anomalies observed in ZIKV-exposed children with MC or NC were failure to thrive (MC: 38 of 53 [71.7%]; NC: 73 of 143 [51.0%]), cardiac malformations (MC: 19 of 46 [41.3%]; NC: 20 of 100 [20.0%]), excess nuchal skin (MC: 16 of 22 [72.7%]; NC: 35 of 93 [37.6%]), auditory abnormalities (MC: 13 of 50 [26.0%]; NC: 14 of 141 [9.9%]), and eye abnormalities (MC: 42 of 53 [79.2%]; NC: 28 of 158 [17.7%]). Although they experienced fewer neurologic abnormalities than children born with MC, those with NC also had frequent neurologic abnormalities (109 of 160 [68.1%]), including hyperreflexia (36 of 136 [26.5%]), abnormal tone (53 of 137 [38.7%]), congenital neuromotor signs (39 of 93 [41.9%]), feeding difficulties (15 of 143 [10.5%]), and abnormal brain imaging results (44 of 150 [29.3%]). Among 112 children with NC with Bayley-III evaluations, 72 (64.3%) had average or above-average scores; 30 (26.8%) scored 1 SD below average in at least 1 domain; and 10 (8.9%) scored 2 SD below average in at least 1 domain. Among 112 children with NC, a smaller head circumference at birth was significantly associated with subsequent below-average cognitive scores (U = 499.5; z = -2.833; P = .004) and language scores (U = 235.5; z = -2.491; P = .01). Children without MC who were exposed to ZIKV in utero had a high frequency of anatomical and neurodevelopmental abnormalities. The head circumference at birth for children with NC was associated with neurocognitive development. Recognition of the wide spectrum of clinical phenotypes is critical to ensure early referral to rehabilitative interventions.

Neurodevelopmental Abnormalities in Children With In Utero Zika Virus Exposure Without Congenital Zika Syndrome

The number of children who were born to mothers with Zika virus (ZIKV) infection during pregnancy but who did not have apparent disability at birth is large, warranting the study of the risk for neurodevelopmental impairment in this population without congenital Zika syndrome (CZS). To investigate whether infants without CZS but who were exposed to ZIKV in utero have normal neurodevelopmental outcomes until 18 months of age. This cohort study prospectively enrolled a group of pregnant women with ZIKV in Atlántico Department, Colombia, and in Washington, DC. With this cohort, we performed a longitudinal study of infant neurodevelopment. Infants born between August 1, 2016, and November 30, 2017, were included if they were live born, had normal fetal brain findings on magnetic resonance imaging and ultrasonography, were normocephalic at birth, and had normal examination results without clinical evidence of CZS. Seventy-seven infants born in Colombia, but 0 infants born in the United States, met the inclusion criteria. Prenatal ZIKV exposure. Infant development was assessed by the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA) and the Alberta Infant Motor Scale (AIMS) at 1 or 2 time points between 4 and 18 months of age. The WIDEA and AIMS scores were converted to z scores compared with normative samples. Longitudinal mixed-effects regression models based on bootstrap resampling methods estimated scores over time, accounting for gestational age at maternal ZIKV infection and infant age at assessment. Results were presented as slope coefficients with 2-tailed P values based on z statistics that tested whether the coefficient differed from 0 (no change). Of the 77 Colombian infants included in this cohort study, 70 (91%) had no CZS and underwent neurodevelopmental assessments. Forty infants (57%) were evaluated between 4 and 8 months of age at a median (interquartile range [IQR]) age of 5.9 (5.3-6.5) months, and 60 (86%) underwent assessment between 9 and 18 months of age at a median (IQR) age of 13.0 (11.2-16.4) months. The WIDEA total score (coefficients: age = -0.227 vs age2 = 0.006; P < .003) and self-care domain score (coefficients: age = -0.238 vs age2 = 0.01; P < .008) showed curvilinear associations with age. Other domain scores showed linear declines with increasing age based on coefficients for communication (-0.036; P = .001), social cognition (-0.10; P < .001), and mobility (-0.14; P < .001). The AIMS scores were similar to the normative sample over time (95% CI, -0.107 to 0.037; P = .34). Nineteen of 57 infants (33%) who underwent postnatal cranial ultrasonography had a nonspecific, mild finding. No difference was found in the decline of WIDEA z scores between infants with and those without cranial ultrasonography findings except for a complex interactive relationship involving the social cognition domain (P < .049). The AIMS z scores were lower in infants with nonspecific cranial ultrasonography findings (-0.49; P = .07). This study found that infants with in utero ZIKV exposure without CZS appeared at risk for abnormal neurodevelopmental outcomes in the first 18 months of life. Long-term neurodevelopmental surveillance of all newborns with ZIKV exposure is recommended.

Vital Signs: Zika-Associated Birth Defects and Neurodevelopmental Abnormalities Possibly Associated with Congenital Zika Virus Infection - U.S. Territories and Freely Associated States, 2018.

IntroductionZika virus infection during pregnancy causes serious birth defects and might be associated with neurodevelopmental abnormalities in children. Early identification of and intervention for neurodevelopmental problems can improve cognitive, social, and behavioral functioning.MethodsPregnancies with laboratory evidence of confirmed or possible Zika virus infection and infants resulting from these pregnancies are included in the U.S. Zika Pregnancy and Infant Registry (USZPIR) and followed through active surveillance methods. This report includes data on children aged ≥1 year born in U.S. territories and freely associated states. Receipt of reported follow-up care was assessed, and data were reviewed to identify Zika-associated birth defects and neurodevelopmental abnormalities possibly associated with congenital Zika virus infection.ResultsAmong 1,450 children of mothers with laboratory evidence of confirmed or possible Zika virus infection during pregnancy and with reported follow-up care, 76% had developmental screening or evaluation, 60% had postnatal neuroimaging, 48% had automated auditory brainstem response-based hearing screen or evaluation, and 36% had an ophthalmologic evaluation. Among evaluated children, 6% had at least one Zika-associated birth defect identified, 9% had at least one neurodevelopmental abnormality possibly associated with congenital Zika virus infection identified, and 1% had both.ConclusionOne in seven evaluated children had a Zika-associated birth defect, a neurodevelopmental abnormality possibly associated with congenital Zika virus infection, or both reported to the USZPIR. Given that most children did not have evidence of all recommended evaluations, additional anomalies might not have been identified. Careful monitoring and evaluation of children born to mothers with evidence of Zika virus infection during pregnancy is essential for ensuring early detection of possible disabilities and early referral to intervention services.

Assessment of neurodevelopmental abnormalities in children with severe acute malnutrition between the age of 6 months to 30 months

Objectives : To assess the developmental abnormalities in Severe Acute Malnutrition using Developmental Assessment Scale for Indian Infants (DASII). Design: Hospital based Prospective Analytical Study. Setting : Department of Pediatrics, Kamla Raja Hospital, Gajra Raja Medical College, Gwalior. Participants: Children with severe acute malnutrition as per criteria of WHO between the age of 6 months and 30 months admitted in the hospital between March 2015 to January 2017. Method: Patients were first managed as per WHO guidelines of SAM. At the end of stabilization phase detailed neurological examination was done to look for neurological deficits by Development Assessment Scale for Indian Infants (DASII). Results: A total of 70 cases were enrolled. Mean Development Quotient for cases was 79.7(23.5) against a population mean of 112.28(10.7) (p 11.5cm [91.5(16.4)]. On analyzing patients having stunting, it was found that a significant proportion of them had low Motor DQ (chi 2 4.1, p value 0.023), low Mental DQ (chi 2 2.9, p value 0.038), and low Mean DQ (chi 2 3.1, p value 0.036) when compared to patients not having stunting. Conclusions : SAM patients have both low Mental DQ and Motor DQ. Low MUAC is associated with Low Motor DQ. Stunting is associated with low Motor and Mental DQ.

Effect of General Anesthesia on Neurodevelopmental Abnormalities in Children Undergoing Treatment of Vascular Anomalies With Laser Surgery: A Retrospective Review.

Multiple exposures to general anesthesia may be neurotoxic to the developing brain. This relationship has not been evaluated in children undergoing laser surgery for vascular anomalies. To evaluate the prevalence of neurodevelopmental abnormalities in children who received multiple laser procedures under general anesthesia before the age of 4 years for the treatment of vascular anomalies. Retrospective chart review of patients with contact of parents for telephone interview. Thirty-three patients were eligible. Average age at the time of survey was 7.8 years. Twenty-three (84.8%) patients were female, with average age at the time of first treatment at 1.9 years. Average number of treatments received before the age of 4 years was 6.7. Anesthetics included inhalational nitrous oxide and isoflurane and intravenous propofol. Seven patients carried one or more of the following diagnoses: attention-deficit hyperactivity disorder (3.0%), anxiety (6.1%), behavioral disorder (3.0%), language disorder (3.0%), speech disorder (3.0%), and motor disorder (6.1%). These prevalence rates are similar to those found in the US population. This is the first report on the prevalence of neurodevelopmental disorders in children undergoing multiple laser treatments under general anesthesia. Although the study sample is small, no increased risks when comparing with prevalence rates reported in the literature were noted.

Acquired Mutations Link Congenital Heart Disease, Neurodevelopmental Disorders

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessAcquired Mutations Link Congenital Heart Disease, Neurodevelopmental DisordersNick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:4 Feb 2016https://doi.org/10.1176/appi.pn.2016.1b16AbstractAbout 20 percent of children with severe congenital heart disease have an excess of mutations that are also commonly found in children with developmental problems such as autism.A study published December 4 in Science suggests that neurodevelopmental abnormalities in children with congenital heart disease may arise from the acquisition of harmful de novo gene mutations. These are not inherited but rather spontaneously occur during fetal development. These abnormalities include cognitive, motor, social, and language impairments.Michelle Massi“Finding this strong association between the developing heart and brain was a bit surprising, for while the heart and brain are both complex organs, they do separate early in the development process,” said study coauthor Jonathan Kaltman, M.D., who is the administrator of the National Heart, Lung, and Blood Institute’s (NHLBI) Bench to Bassinet Program, which funded this study.“At the same time, it makes sense clinically, given that there are several inherited disorders such as Down’s syndrome or DiGeorge syndrome, which feature both cardiac and neurological problems.”Investigators from the NHLBI’s Pediatric Cardiac Genomics Consortium used a technique known as exome sequencing to scan all the protein-encoding regions of the genome in over 1,200 affected family trios (a child with congenital heart disease [CHD] and his or her parents) along with 900 control trios without CHD.They uncovered almost 400 potentially harmful de novo mutations that significantly contribute to the risk of co-occurring CHD and neurodevelopmental disorders.While an excess number of these harmful mutations were found in only 2 percent of patients who had isolated CHD, the prevalence rose in children with more complications. The mutations were present in about 10 percent of patients who also had neurodevelopmental disorders or other extracardiac congenital anomalies (such as limb or kidney defects), and 20 percent of patients who had both.When the researchers compared the genetic data from children with CHD and children with neurodevelopmental disorders but no heart problems, they found 85 mutations were present in both groups—more than twice as many as would be expected by random chance.“These findings show enough statistical risk of developing neurodevelopmental disabilities when these particular gene mutations are present that we might consider developing a genetic test for patients with CHD,” Kaltman told Psychiatric News. Such a test could help to identify high-risk children for early interventions that might help to limit developmental delays and improve functioning, he said.In addition to the NHLBI, this study was supported in part by the National Human Genome Research Institute, the Howard Hughes Medical Institute, and Simons Foundation for Autism Research. ■An abstract of “De Novo Mutations in Congenital Heart Disease With Neurodevelopmental and Other Congenital Anomalies” can be accessed here. ISSUES NewArchived

Neurodevelopmental Abnormalities in Children With PHACE Syndrome

Prior case reports have identified neurodevelopmental abnormalities in children with PHACE syndrome, a neurocutaneous disorder first characterized in 1996. In this multicenter, retrospective study of a previously identified cohort of 93 children diagnosed with PHACE syndrome from 1999 to 2010, 29 children had neurologic evaluations at ≥ 1 year of age (median age: 4 years, 2 months). In all, 44% had language delay, 36% gross motor delay, and 8% fine motor delay; 52% had an abnormal neurological exam, with speech abnormalities as the most common finding. Overall, 20 of 29 (69%) had neurodevelopmental abnormalities. Cerebral, but not posterior fossa, structural abnormalities were identified more often in children with abnormal versus normal neurodevelopmental outcomes (35% vs. 0%, P = .04). Neurodevelopmental abnormalities in young children with PHACE syndrome referred to neurologists include language and gross motor delay, while fine motor delay is less frequent. Prospective studies are needed to understand long-term neurodevelopmental outcomes.

Hypothyroxinemia: a subclinical condition affecting neurodevelopment

Hypothyroxinemia with low levels of circulating free thyroxine and normal levels of thyrotropin, which is usually caused by iodine deficiency, may affect pregnant women even in apparently iodine-sufficient areas, and it is debated whether it increases the risk of neurodevelopmental abnormalities in children born to them. Epidemiological observations indeed indicate that this is the case. Animal models show abnormal brain cortical cytoarchitecture in pups born to mildly hypothyroxinemic dams. In regions where the availability and use of iodized salt is inadequate (where <90% of households use iodized salt), the WHO and the International Council for Control of Iodine Deficiency Disorders (ICCIDD) recommend iodine supplementation so that the total iodine intake is 250 µg/day to prevent iodine deficiency during gestation and lactation.