Harnessing the power of telemedicine to accomplish international pediatric outcome research during the COVID-19 pandemic

The COVID-19 pandemic occurred during planned neurodevelopmental follow-up of Colombian children with antenatal Zika-virus exposure. The objective of the study was to leverage the institution's telemedicine infrastructure to support international clinical child outcome research. In a prospective cohort study of child neurodevelopment (NCT04398901), we used synchronous telemedicine to remotely train a research team and perform live observational assessments of children in Sabanalarga, Colombia. An observational motor and conceptional standardized tool kit was mailed to Colombia; other materials were translated and emailed; team training was done virtually. Children were recruited by team on the ground. Synchronous activities were video-recorded directly to two laptops, each with a telehealth Zoom link to allow simultaneous evaluation of “table” and “standing” activities, and backup recordings were captured directly on the device in Colombia. The U.S. team attended live over Zoom from four states and five distinct locations, made observational notes, and provided real-time feedback. Fifty-seven, 3–4-year-old children with Zika-virus exposure and 70 non-exposed controls were studied during 10 daytrips. Direct laptop recording ensured complete record of child activities due to internet outages. Telemedicine can be used to successfully perform international neurodevelopmental outcome research in children during the COVID-19 pandemic. Telemedicine can benefit global health studies.

Family Mindfulness Training for Childhood ADHD: Short- and Long-Term Effects on Children, Fathers and Mothers

Objectives We evaluated the effects of the family mindfulness-based intervention (MBI) “MYmind” for children with ADHD and their parents, and examined child and parent predictors of child outcome. Methods Using a pragmatic quasi-experimental waitlist design, children aged 7–19 years (n = 167), clinically referred with a DSM-IV ADHD diagnosis, and both their parents completed waitlist (average waiting time was 8 weeks), pre-test, post-test, 8-week, and 1-year follow-up measurements. MYmind consisted of eight weekly 1.5-h mindfulness-based group sessions for children and parallel for parents, and a follow-up session. We assessed children’s and both parents’ ADHD symptoms and other psychopathology, child executive function, parental stress, parental overreactivity, and mindful parenting. Results Multilevel analyses revealed medium-to-large effect-sized reduced child ADHD symptoms between pre- and post-test, becoming stronger at follow-ups, while no waitlist effects occurred. Parents above the ADHD threshold improved on adult ADHD symptoms with similar sized effects. Children’s and parents’ other psychopathology, child executive function, parental overreactivity, and mindful parenting improved, whereas parental stress only improved at 1-year follow-up. Child age, child gender, ADHD medication, parental ADHD, and parent participation did not predict child outcome. Parent gender however interacted with parental ADHD to predict child outcome; children of fathers (but not mothers) above the ADHD threshold improved more than children of fathers below the ADHD threshold at post-test and at 8-week follow-up. Reduced paternal ADHD from pre- to post-test mediated this effect. Conclusions Family MBI (MYmind) may reduce childhood ADHD and improve parental functioning. Fathers with ADHD symptoms appear important in helping offspring with ADHD.

Expression changes in immune and epigenetic gene pathways associated with nutritional metabolites in maternal blood from pregnancies resulting in autism and atypical neurodevelopment

BackgroundThe prenatal period is a critical window to study factors involved in the development of autism spectrum disorder (ASD). Environmental factors, especially in utero nutrition, can interact with genetic risk for ASD, but how specific prenatal nutrients in mothers of children later diagnosed with ASD or non-typical development (Non-TD) associate with gestational gene expression is poorly understood. Maternal blood collected prospectively during pregnancy provides a new opportunity to gain insights into nutrition, particularly one-carbon metabolites, on gene pathways and neurodevelopment.MethodsGenome-wide transcriptomes were measured using microarrays in 300 maternal blood samples from all three trimesters in the Markers of Autism Risk in Babies - Learning Early Signs (MARBLES) study. Sixteen different one-carbon metabolites, including folic acid, betaine, 5’-methyltretrahydrofolate (5-MeTHF), and dimethylglycine (DMG) were measured. Differential expression analysis and weighted gene correlation network analysis (WGCNA) were used to compare gene expression between children later diagnosed as typical development (TD), Non-TD and ASD, and to nutrient metabolites.ResultsUsing differential gene expression analysis, six transcripts associated with four genes (TGR-AS1, SQSTM1, HLA-C and RFESD) showed genome-wide significance (FDR q < 0.05) with child outcomes. Genes nominally differentially expressed compared to TD specifically in ASD, but not Non-TD, significantly overlapped with seven high confidence ASD genes. 218 transcripts in common to ASD and Non-TD differential expression compared to TD were significantly enriched for functions in immune response to interferon-gamma, apoptosis, and metal ion transport. WGCNA identified co-expressed gene modules significantly correlated with 5-MeTHF, folic acid, DMG, and betaine. A module enriched in DNA methylation functions showed a protective association with folic acid/5-MeTHF concentrations and ASD risk. Independent of child outcome, maternal plasma betaine and DMG concentrations associated with a block of co-expressed genes enriched for adaptive immune, histone modification, and RNA processing functions.LimitationsBlood contains a heterogeneous mixture of cell types, and many WGCNA modules correlated with cell type and/or nutrient concentrations, but not child outcome. Gestational age correlated with some co-expressed gene modules in addition to nutrients.ConclusionsThese results support the premise that the prenatal maternal blood transcriptome is a sensitive indicator of gestational nutrition and children’s later neurodevelopmental outcomes.

Improving Pediatric Hearing Testing for Children with Developmental Delays: The Effects of Video Modeling on Child Compliance and Caregiver Stress

Background For children with developmental delays (DDs) of any kind (e.g., global DDs, autism spectrum disorder, and Down syndrome), it is essential to understand if a hearing loss may be contributing to these delays. However, toddlers with DDs may have difficulty understanding directions, may be uncomfortable with a new situation, or may simply not want to complete the hearing testing tasks. Regardless of the reasons, noncompliant behaviors have a negative impact on hearing testing, which requires reliable behavioral responses from the child. Purpose The purpose of this study was to test a video intervention to improve hearing testing compliance in toddlers with developmental disabilities. Research Design Double-blind randomized clinical trial. Study Sample Twenty-four children with DDs between 24 and 36 months of age. Intervention Video model of the hearing testing procedures. Data Collection and Analysis The primary child outcome measure was the number of hearing tests completed by the audiologist. Caregiver outcome included a parent survey of perceived stress level before and after the evaluation. Results There was no significant difference between treatment and control groups regarding the number of hearing tests that were completed. Parents in the treatment group reported less stress following the evaluation as compared with parents of children in the control group. Conclusions Pre-exposure to the hearing testing procedures did not significantly improve patient compliance but may reduce caregiver stress. Given the high rates of noncompliance in toddlers with DDs, audiologists may benefit from multiple strategies to help improve testing compliance.

Placental DNA methylation levels at CYP2E1 and IRS2 are associated with child outcome in a prospective autism study

DNA methylation acts at the interface of genetic and environmental factors relevant for autism spectrum disorder (ASD). Placenta, normally discarded at birth, is a potentially rich source of DNA methylation patterns predictive of ASD in the child. Here, we performed whole methylome analyses of placentas from a prospective study MARBLES (Markers of Autism Risk in Babies—Learning Early Signs) of high-risk pregnancies. A total of 400 differentially methylated regions (DMRs) discriminated placentas stored from children later diagnosed with ASD compared to typically developing controls. These ASD DMRs were significantly enriched at promoters, mapped to 596 genes functionally enriched in neuronal development, and overlapped genetic ASD risk. ASD DMRs at CYP2E1 and IRS2 reached genome-wide significance, replicated by pyrosequencing and correlated with expression differences in brain. Methylation at CYP2E1 associated with both ASD diagnosis and genotype within the DMR. In contrast, methylation at IRS2 was unaffected by within DMR genotype but modified by preconceptional maternal prenatal vitamin use. This study therefore identified two potentially useful early epigenetic markers for ASD in placenta.

Placental DNA methylation levels at CYP2E1 and IRS2 are associated with child outcome in a prospective autism study

DNA methylation acts at the interface of genetic and environmental factors relevant for autism spectrum disorder (ASD). Placenta, normally discarded at birth, is a potentially rich source of DNA methylation patterns predictive of ASD in the child. Here, we performed whole methylome analyses of placentas from a prospective study of high-risk pregnancies. 400 differentially methylated regions (DMRs) discriminated placentas stored from children later diagnosed with ASD compared to typical controls. These ASD DMRs were significantly enriched at promoters, mapped to 596 genes functionally enriched in neuronal development, and overlapped genetic ASD risk. ASD DMRs at CYP2E1 and IRS2 reached genome-wide significance, replicated by pyrosequencing, and correlated with expression. Methylation at CYP2E1 associated with both ASD diagnosis and cis genotype, while methylation at IRS2 was unaffected by cis genotype but modified by preconceptional maternal prenatal vitamin use. This study therefore identified two potentially useful early epigenetic markers for ASD in placenta.

Perinatal Outcome in Women with a Vietnamese Migration Background – Retrospective Comparative Data Analysis of 3000 Deliveries

Introduction Perinatal data of women with a Vietnamese migration background have not been systematically studied in Germany to date. Numerous details of important maternal and child outcomes were compared and analysed. The studyʼs primary parameters were the frequency of and indication for c-section. Methodology The perinatal data from a Berlin hospital were analysed retrospectively. The women (Vietnamese migration background vs. autochthonous) were grouped using name analysis. Datasets of 3002 women giving birth, including 999 women with a Vietnamese migration background, were included. The associations between primary or secondary cesarean delivery and different child outcomes depending on the migration background (exposure) were studied using logistical regression analysis. Results Women with a Vietnamese migration background have a lower c-section rate of 8.0% for primary and 12.6% for secondary c-section than women without a migration background (11.1% primary and 16.4% secondary c-section respectively). Regression analysis shows that the odds that women with a Vietnamese migration background will have a primary (OR 0.75; p = 0.0884) or secondary c-section (OR 0.82; p = 0.1137) are not significantly lower. A Vietnamese migration background was associated with higher odds for an episiotomy but not for a grade 3 – 4 perineal tear. A Vietnamese migration background does not have a significant influence on poor 5-min Apgar scores ≤ 7 and low umbilical cord arterial pH values ≤ 7.10. Newborns of mothers with a Vietnamese migration background have higher odds of a relatively higher birth weight (> 3110 g). Summary There was no evidence that women with a Vietnamese migration background are delivered more often by caesarean section. There were also no differences as regards important child outcome data from women in the comparator group. Overall, the results do not provide any evidence for poorer quality of care of women with a Vietnamese migration background in Berlin despite the cultural and communication barriers in the reality of care provision.