Adaptive, Externalizing, and Internalizing Behavior of Children with Prenatal Alcohol Exposure: A Comparison of Three Parent-Report Questionnaires.

This study compared the Behavior Assessment System for Children-Third Edition (BASC-3) to the Child Behavior Checklist (CBCL) and the Vineland Adaptive Behavior Scales-Third Edition (VABS-3) in children with and without histories of prenatal alcohol exposure. Data were collected from Collaborative Initiative on Fetal Alcohol Spectrum Disorders Phase 4 sites. Caregivers rated their child's behavior using three questionnaires: BASC-3, CBCL, and VABS-3. BASC-3 Adaptive Skills, Externalizing Problems, and Internalizing Problems scores were correlated with comparable scores from the CBCL (Externalizing and Internalizing Problems) and VABS-3 (Adaptive Skills) both within and across groups. Sensitivity, specificity, and positive and negative predictive values were calculated for the BASC-3. BASC-3 sensitivity rates were 78.1%, 80.5%, and 47.0% and specificity rates were 79.4%, 80.4%, and 81.5% for Adaptive Skills, Externalizing Problems, and Internalizing Problems, respectively. Positive predictive values were 87.1%, 88.0%, and 81.9% and negative predictive values were 67.0%, 69.8%, and 46.3% for Adaptive Skills, Externalizing Problems, and Internalizing Problems, respectively. Results replicated previous reports of behavioral and adaptive difficulties in children with prenatal alcohol exposure. These findings provide support for using the BASC-3 in this population.

Developmental, sensory and behavioral outcomes among infants and toddlers with prenatal alcohol exposure.

BACKGROUND: Prenatal alcohol exposure (PAE) can disrupt children's neurodevelopment and exert lasting influences on overall child well-being and family functioning. A comprehensive exploration of developmental outcomes in infants/toddlers with PAE seen for a diagnosis on the fetal alcohol spectrum can inform early identification and intervention. AIMS: To describe the prevalence and patterns of neurodevelopment, sensory processing, and emotional and behavioral functioning in a clinical sample of infants/toddlers with PAE. METHODS: In this retrospective analysis, clinical data from 125 infants/toddlers with PAE, aged 2-42 months, assessed at the University of Washington Fetal Alcohol Syndrome Diagnostic and Prevention Network clinic were analyzed. RESULTS: Seventy-four to 87% of infants/toddlers demonstrated delayed development in one or more domains of the Bayley Scales of Infant and Toddler Development (n = 125). Adverse developmental outcomes were significantly correlated with PAE and/or postnatal risk factors. All 93 infants/toddlers with a complete Infant/Toddler Sensory Profile obtained definite difference scores in at least one quadrant/section. Over half of infant/toddlers with a completed Child Behavior Checklist/1½- 5 had total problem scores in the borderline or clinical range. CONCLUSIONS: Findings suggest that several domains of child functioning may be vulnerable to the teratogenic impact of PAE, and that these delays are evident in the first years of life. Early screening, ongoing monitoring and comprehensive assessment is needed to facilitate earlier identification and guide clinical intervention.

Impaired vision in children prenatally exposed to methadone: an observational cohort study.

BACKGROUND/OBJECTIVES: To examine prevalence of failed visual assessment at 8-10 years in children born to methadone-maintained opioid dependent (MMOD) mothers and relate this to known in utero substance exposure. SUBJECTS/METHODS: Follow up of observational cohort study of methadone-exposed and comparison children matched for birthweight, gestation and postcode of residence at birth. Participants were 144 children (98 exposed, 46 comparison). Prenatal drug exposure was previously established via comprehensive maternal and neonatal toxicology. Children were invited to attend for visual assessment and casenotes were reviewed. Presence of acuity poorer than 0.2 logMAR, strabismus, nystagmus and/or impaired stereovision constituted a 'fail'. Fail rates were compared between methadone-exposed and comparison children after adjusting for known confounding variables. RESULTS: 33 children attended in person: data were also derived from casenote review for all children. After controlling for maternal reported tobacco use, methadone-exposed children were more likely to have a visual 'fail' outcome, adjusted odds ratio 2.6, 95% CI 1.1-6.2; adjusted relative risk 1.8 (95% CI 1.1-3.4). Visual 'fail' outcome rates did not differ between methadone-exposed children who had (n = 47) or had not (n = 51) received pharmacological treatment for neonatal abstinence/opioid withdrawal syndrome (NAS/NOWS); fail rate 62% vs 53% (95% CI of difference-11-27%). CONCLUSIONS: Children born to MMOD mothers are almost twice as likely as unexposed peers to have significant visual abnormalities at primary school age. Prenatal methadone exposure should be considered in the differential diagnosis of nystagmus. Findings support visual assessment prior to school entry for children with any history of prenatal opioid exposure. TRIAL REGISTRATION: The study was prospectively registered on ClinicalTrials.gov (NCT03603301), https://clinicaltrials.gov/ct2/show/NCT03603301 .

Prenatal Exposure to Nonpersistent Environmental Chemicals and Postpartum Depression.

Importance: Postpartum depression (PPD) affects up to 20% of childbearing individuals, and a significant limitation in reducing its morbidity is the difficulty in modifying established risk factors. Exposure to synthetic environmental chemicals found in plastics and personal care products, such as phenols, phthalates, and parabens, are potentially modifiable and plausibly linked to PPD and have yet to be explored. Objective: To evaluate associations of prenatal exposure to phenols, phthalates, parabens, and triclocarban with PPD symptoms. Design, Setting, and Participants: This was a prospective cohort study from 5 US sites, conducted from 2006 to 2020, and included pooled data from 5 US birth cohorts from the National Institutes of Health Environmental Influences on Child Health Outcomes (ECHO) consortium. Participants were pregnant individuals with data on urinary chemical concentrations (phenols, phthalate metabolites, parabens, or triclocarban) from at least 1 time point in pregnancy and self-reported postnatal depression screening assessment collected between 2 weeks and 12 months after delivery. Data were analyzed from February to May 2022. Exposures: Phenols (bisphenols and triclosan), phthalate metabolites, parabens, and triclocarban measured in prenatal urine samples. Main Outcomes and Measures: Depression symptom scores were assessed using the Edinburgh Postnatal Depression Scale (EPDS) or the Center for Epidemiologic Studies Depression Scale (CES-D), harmonized to the Patient-Reported Measurement Information System (PROMIS) Depression scale. Measures of dichotomous PPD were created using both sensitive (EPDS scores ≥10 and CES-D scores ≥16) and specific (EPDS scores ≥13 and CES-D scores ≥20) definitions. Results: Among the 2174 pregnant individuals eligible for analysis, nearly all (>99%) had detectable levels of several phthalate metabolites and parabens. PPD was assessed a mean (SD) of 3 (2.5) months after delivery, with 349 individuals (16.1%) and 170 individuals (7.8%) screening positive for PPD using the sensitive and specific definitions, respectively. Linear regression results of continuous PROMIS depression T scores showed no statistically significant associations with any chemical exposures. Models examining LMW and HMW phthalates and di (2-ethylhexyl) phthalate had estimates in the positive direction whereas all others were negative. A 1-unit increase in log-transformed LMW phthalates was associated with a 0.26-unit increase in the PROMIS depression T score (95% CI, -0.01 to 0.53; P = .06). This corresponded to an odds ratio (OR) of 1.08 (95% CI, 0.98-1.19) when modeling PPD as a dichotomous outcome and using the sensitive PPD definition. HMW phthalates were associated with increased odds of PPD (OR, 1.11; 95% CI, 1.00-1.23 and OR, 1.10; 95% CI, 0.96-1.27) for the sensitive and specific PPD definitions, respectively. Sensitivity analyses produced stronger results. Conclusions and Relevance: Phthalates, ubiquitous chemicals in the environment, may be associated with PPD and could serve as important modifiable targets for preventive interventions. Future studies are needed to confirm these observations.

Effects of prenatal alcohol exposition on cognitive outcomes in childhood and youth: a longitudinal analysis based on meconium ethyl glucuronide.

BACKGROUND: Prenatal alcohol exposure (PAE) has been linked to severe, adverse child outcomes. However, little is known regarding subclinical outcomes of low/moderate PAE and its longitudinal consequences, especially regarding neurophysiological and neurocognitive development. A newborn biomarker of PAE, meconium ethyl glucuronide (EtG), has been shown to predict cognitive impairments in primary-school-aged children. The current study investigated the ongoing effects of subclinical PAE in adolescence. METHODS: A sample of n = 96 mother-child dyads of the FRAMES/FRANCES cohort were classified into PAE/no PAE using EtG with a 10 ng/g cutoff. Mothers were recruited during pregnancy and children were assessed during primary-school age (M = 7.57, SD = 0.65, range: 6.00-9.92 years) and adolescence (M = 13.26, SD = 0.31, range: 12.79-14.20 years) on three levels: clinical (ADHD rating), neuropsychological (IQ score and performance in a go/nogo task), and neurophysiological (analysis of P3 event-related potentials (ERP) during said go/nogo task). Developmental outcomes and courses following PAE were assessed using rmANCOVAs, controlling for relevant confounders (socioeconomic status (SES), birth weight, and maternal psychopathology). RESULTS: Neurophysiological impairments emerged for exposed children in the form of diminished attentional resource recruiting in childhood and adolescence (reduced go-P3 amplitudes) with no differences in performance. Neuropsychological testing showed a reduced IQ score for both time points with dose-dependent effects in childhood. Clinical ADHD symptoms were not significantly affected. CONCLUSION: Subclinical PAE, as determined by meconium EtG, has negative developmental consequences on cognitive function that persist from childhood to adolescence. These findings suggest that there is no safe limit for alcohol consumption during pregnancy and that more thorough screening of alcohol consumption during pregnancy is necessary for early identification and treatment of at-risk children.

Dentofacial characteristics of children and adolescents with foetal alcohol spectrum disorders: a comparison with matched controls.

BACKGROUND: Foetal alcohol spectrum disorders (FASD) include somatic and neurological developmental disturbances after prenatal alcohol exposure, including facial anomalies. However, the knowledge of the orthodontic skeletal and dental cephalometric relations in this group is limited. The aim of the study was to assess the dentofacial characteristics of children and adolescents with FASD and to compare them with a matched control group. METHODS: The study group comprised all available children and adolescents diagnosed with FASD (> 7 years of age) in whom good quality cephalograms were available. The control group comprised non-syndromic, orthodontically untreated children with normal occlusion and skeletal relations matched with age and gender. Cephalometric analysis included eighteen linear and angular measurements. The general linear model for repeated measures regarding age, gender and the type of FASD was applied. RESULTS: The group with FASD included 35 individuals (21 girls and 14 boys) aged 7-18 years including 21 with foetal alcohol syndrome. The mean age in the study and the control group was 12.8 years (SD, range 3.2, 7.1-18.1) and 13.0 (SD, range 2.9, 9.1-18.1), respectively. Statistically significant differences between the groups were found in 15 out of 18 of the cephalometric measurements (83%). In children with FASD the mandible was more retrusive, the incisors were more proclined and the mandibular incisors and the lips were more protruded when compared with controls. There was no significant evidence of an influence of age, gender or FASD type. CONCLUSIONS: Dentofacial characteristics of children and adolescents with FASD significantly differ from controls. Early orthodontic diagnosis and prophylaxis should play a part of the interdisciplinary care of patients in this group.

Pattern of Visual-Motor Integration, Visual Perception, and Fine Motor Coordination Abilities in Children Being Assessed for Fetal Alcohol Spectrum Disorder.

OBJECTIVE: Motor skill assessment is part of the fetal alcohol spectrum disorder (FASD) multidisciplinary assessment. Some clinicians opt to exclude assessment of the subcomponents of visual-motor integration (visual perception and motor coordination), on the assumption that challenges will be revealed based on the assessment of visual-motor integration. The objective is to describe the visual-motor integration, visual perception, and fine motor coordination pattern of abilities in children with confirmed prenatal alcohol exposure being assessed for fetal alcohol spectrum disorder. METHODS: This cross-sectional study included 91 children (65 males; mean age: 10 years, 6 months SD = 2 years, 10 months) undergoing assessment for FASD. Friedman and Wilcoxon statistics were used to compare mean visual-motor integration, visual perception, and fine motor coordination percentiles from the Beery-Buktenica Developmental Test of Visual-Motor Integration, Sixth Edition (Beery-6). RESULTS: Children being assessed for FASD (n = 91) had the highest normative scores in visual perception, followed by visual-motor integration and fine motor coordination (mean percentiles (SD): 35.9 (24.9), 20.6 (18.3), and 13.8 (15.5), respectively) (χ 2 distribution = 46.909, p ≤ 0.001). CONCLUSION: Children being assessed for FASD experience more challenges with fine motor coordination compared with visual-motor integration and visual perception tasks. This pattern differs from the pattern established for the general population in which tasks that require visual-motor integration are more challenging than tasks that isolate visual perception and fine motor coordination. These results suggest that fine motor coordination should be included in FASD diagnostic assessments and considered as an area for intervention.

Identifying Prenatal Alcohol Exposure and Children Affected by It: A Review of Biomarkers and Screening Tools.

PURPOSE: Early identification of prenatal alcohol exposure (PAE) and of those in need of services resulting from this exposure is an important public health concern. This study reviewed the existing literature on potential biomarkers and screening tools of PAE and its impact. SEARCH METHODS: Electronic databases were searched for articles published between January 1, 1996, and November 30, 2021, using the following search terms: ("fetal alcohol" or "prenatal alcohol" or "FASD" or "alcohol-related neurodevelopmental disorder" or "ARND" or "ND-PAE") and ("screening" or "identification" or "biomarker"). Duplicate articles were electronically eliminated. Titles and abstracts were reviewed for appropriateness, and selected articles were retrieved for further analysis. Additional articles were added that were referenced in the reviewed articles or identified from expert knowledge. Information about the characteristics of the sample, the biomarker or screening tool, and the predictive validity outcome data were abstracted. A narrative analysis of the studies was then performed on the data. SEARCH RESULTS: A total of 3,813 articles were initially identified, and 1,215 were removed as duplicates. Of the remaining articles, 182 were identified as being within the scope of the review based on title and abstract inspection, and 181 articles were successfully retrieved. Of these, additional articles were removed because they were preclinical (3), were descriptive only (13), included only self-report of PAE (42), included only mean group comparison (17), were additional duplicates (2), focused on cost analysis (9), missed predictive validity data (24), or for other reasons (23). The remaining articles (n = 48) were abstracted. An additional 13 manuscripts were identified from these articles, and two more from expert knowledge. A total of 63 articles contributed to the review. DISCUSSION AND CONCLUSIONS: Biomarkers and screening tools of PAE and its impact fall short of ideal predictive validity characteristics. Higher specificity than sensitivity was found for many of the biomarkers and screening tools used to identify PAE and its impact, suggesting that current methods continue to under-identify the full range of individuals impacted by PAE. Exceptions to this were found in recent investigations using microRNAs related to growth and vascular development, proteomic changes associated with PAE, and combinations of markers estimating levels of various cytokines. Replications of these findings are needed across other samples to confirm the limited data available. Future research on biomarkers and screening tools should attend to feasibility and scalability of implementation. This article also recommends a systematic process of evaluation to improve early identification of individuals impacted by PAE so that harm reduction and habilitative care efforts can be implemented.

Effect of Neonatal Abstinence Syndrome Treatment Status and Maternal Depressive Symptomatology on Maternal Reports of Infant Behaviors.

OBJECTIVE: The objective of this study is to investigate the effects of maternal perinatal depression symptoms and infant treatment status for neonatal abstinence syndrome (NAS) on maternal perceptions of infant regulatory behavior at 6 weeks of age. METHODS: Mothers and their infants (N = 106; 53 dyads) were recruited from a rural, White cohort in Northeast Maine. Mothers in medication-assisted treatment (methadone) and their infants (n = 35 dyads) were divided based on the infant's NAS pharmacological treatment (n = 20, NAS+ group; n = 15, NAS- group) and compared with a demographically similar, nonexposed comparison group (n = 18 dyads; COMP group). At 6 weeks postpartum, mothers reported their depression symptoms Beck Depression Inventory-2nd Edition) and infant regulatory behaviors [Mother and Baby Scales (MABS)]. Infant neurobehavior was assessed during the same visit using the Neonatal Network Neurobehavioral Scale (NNNS). RESULTS: Mothers in the NAS+ group showed significantly higher depression scores than the COMP group (p < .05) while the NAS- group did not. Across the sample, mothers with higher depression scores reported higher infant "unsettled-irregularity" MABS scores, regardless of group status. Agreement between maternal reports of infant regulatory behaviors and observer-assessed NNNS summary scares was poor in both the NAS+ and COMP groups. CONCLUSIONS: Postpartum women in opioid recovery with infants requiring pharmacological intervention for NAS are more at risk for depression which may adversely influence their perceptions of their infants' regulatory profiles. Unique, targeted attachment interventions may be needed for this population.

Sex-related differences among individuals assessed for fetal alcohol spectrum disorder in Canada.

BACKGROUND: Consideration of sex- and gender-related factors is critical for understanding and supporting health and wellbeing. Although both sex and gender influence people with developmental disabilities, there is relatively little research on these factors and their influences among individuals with fetal alcohol spectrum disorder (FASD), a complex neurodevelopmental disability impacting an estimated 4%-5% of the population. Understanding sex- and gender-related differences in FASD is needed to facilitate evidence-informed assessment, treatment planning, and advocacy. To begin unpacking these factors, we investigated sex-based differences in clinical presentation and experiences among individuals assessed for FASD across the lifespan. METHODS: We analyzed 2574 clinical records from 29 FASD diagnostic centers in Canada. Participants ranged in age from 1 to 61 years (mean 15.2 years), and more than half (58.3%) were male at birth. Study variables included participant demographics, physical indicators of prenatal alcohol exposure (PAE), neurodevelopmental impairment, FASD diagnosis, co-occurring physical and mental health diagnoses, and environmental adversity. RESULTS: There were no significant differences between males and females with respect to FASD diagnostic outcome or physical indicators of PAE. However, males experienced significantly more neurodevelopmental impairment. Females experienced higher rates of endocrine problems, anxiety, and depressive/mood disorders, whereas males had higher rates of attention deficit-hyperactivity disorder, conduct disorder, and oppositional defiant disorder. Adversity also differed by sex, with females experiencing higher rates of trauma and legal problems with victimization/custody, and males having more difficulties with school and offending/incarceration. Sex-based differences were most apparent in adolescents (13-17 years) and adults (≥25 years). CONCLUSIONS: Individuals with PAE/FASD experience notable sex-related differences in clinical presentation and experiences across the lifespan. Findings from this study should help to guide researchers, service providers, and policy makers to improve FASD screening, diagnosis, and intervention and better address the needs of individuals with PAE/FASD of all genders.

An investigation of the utility of the Australian Guide to the Diagnosis of Fetal Alcohol Spectrum Disorder in young children.

BACKGROUND: Early diagnosis of children with fetal alcohol spectrum disorder (FASD) assists in implementing critical early support. The challenge lies in having a diagnostic process that enables valid and reliable assessment of domains of functioning in young children, with the added complexity that many children will also have co-occurring exposure to childhood adversity that is likely to impact these domains. METHODS: The aim of this study was to test a diagnostic assessment of FASD in young children using the Australian Guide to the Diagnosis of FASD. Ninety-four children (aged 3 to 7 years) with confirmed or suspected prenatal alcohol exposure were referred to two specialist FASD clinics for assessment in Queensland, Australia. RESULTS: There was a significant risk profile with 68.1% (n = 64) children having had contact with child protection services, and most children living in kinship (n = 22, 27.7%) or foster (n = 36, 40.4%) care. Forty-one percent of the children were Indigenous Australians. The majority (64.9%, n = 61) of children met criteria for FASD, 30.9% were classified as "At Risk" for FASD (n = 29), and 4.3% received no FASD diagnosis (n = 4). Only 4 (4%) children were rated as severe for the brain domain. Over 60% of children (n = 58) had two or more comorbid diagnoses. Sensitivity analyses indicated that the removal of comorbid diagnoses in the Attention, Affect Regulation, or Adaptive Functioning domains resulted in a change in 7 of 47 cases (15%) to an "At Risk" designation. CONCLUSIONS: These results highlight the complexity of presentation and the extent of impairment in the sample. The use of comorbid diagnoses to substantiate a "severe" designation in specific neurodevelopmental domains raises the question of whether there were false-positive diagnoses. The complexity of determining causal relationships between exposure to PAE and early life adversity on developmental outcomes continues to be a challenge in this young population.

Latent classes of neurodevelopmental profiles and needs in children and adolescents with prenatal alcohol exposure.

BACKGROUND: Fetal alcohol spectrum disorder (FASD) resulting from prenatal alcohol exposure (PAE) is a common neurodevelopmental disorder, but substantial interindividual heterogeneity complicates timely and accurate assessment, diagnosis, and intervention. The current study aimed to identify classes of children and adolescents with PAE assessed for FASD according to their pattern of significant neurodevelopmental functioning across 10 domains using latent class analysis (LCA), and to characterize these subgroups across clinical features. METHODS: Data from the Canadian National FASD Database, a large ongoing repository of anonymized clinical data received from diagnostic clinics across Canada, was analyzed using a retrospective cross-sectional cohort design. The sample included 1440 children and adolescents ages 6 to 17 years (M = 11.0, SD = 3.5, 41.7% female) with confirmed PAE assessed for FASD between 2016 and 2020. RESULTS: Results revealed an optimal four-class solution. The Global needs group was characterized by high overall neurodevelopmental impairment considered severe in nature. The Regulation and Cognitive needs groups presented with moderate but substantively distinguishable patterns of significant neurodevelopmental impairment. The Attention needs group was characterized by relatively low probabilities of significant neurodevelopmental impairment. Both the Global and Regulation needs groups also presented with the highest probabilities of clinical needs, further signifying potential substantive differences in assessment and intervention needs across classes. CONCLUSIONS: Four relatively distinct subgroups were present in a large heterogeneous sample of children and adolescents with PAE assessed for FASD in Canada. These findings may inform clinical services by guiding clinicians to identify distinct service pathways for these subgroups, potentially increasing access to a more personalized treatment approach and improving outcomes.

Validation of the FASD-Tree as a screening tool for fetal alcohol spectrum disorders.

BACKGROUND: As many as 80% of individuals with fetal alcohol spectrum disorders (FASD) are misdiagnosed or not diagnosed. This study tests the accuracy and validity of a web-based screening tool (the FASD-Tree) for identifying children and adolescents with FASD. METHODS: Children with histories of prenatal alcohol exposure (PAE) and controls (N = 302, including 224 with PAE and 78 controls) were examined for physical signs of fetal alcohol syndrome (FAS), and parents completed behavioral questionnaires. Data were entered into the FASD-Tree, a web-based decision tree application. The FASD-Tree provided two outcomes: a dichotomous indicator (yes/no) and a numeric risk score (0 to 5), which have been shown separately to identify children with PAE and neurobehavioral impairment and to correlate with neurobehavioral outcomes. Overall accuracy (ACC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the decision tree, risk score, and their combination. Misclassified cases were examined for systematic bias. RESULTS: The FASD-Tree was successful in accurately identifying youth with histories of PAE and the subgroup of individuals with FASD, indicating its validity as an FASD screening tool. Overall accuracy rates for FASD-Tree components ranged from 75.0% to 84.1%, and both the decision tree outcome and risk score, and their combination, resulted in fair to good discrimination (area under the curve = 0.722 to 0.862) of youth with histories of PAE or FASD. While most participants were correctly classified, those who were misclassified differed in IQ and attention. Race, ethnicity, and sex did not affect the results. CONCLUSION: The FASD-Tree is not a biomarker of PAE and does not provide definitive evidence of prenatal alcohol exposure. Rather it is an accurate and valid screening tool for FASD and can be used by clinicians who suspect that a patient has a history of PAE, even if the exposure is unknown.

Fetal alcohol spectrum disorders.

Alcohol readily crosses the placenta and may disrupt fetal development. Harm from prenatal alcohol exposure (PAE) is determined by the dose, pattern, timing and duration of exposure, fetal and maternal genetics, maternal nutrition, concurrent substance use, and epigenetic responses. A safe dose of alcohol use during pregnancy has not been established. PAE can cause fetal alcohol spectrum disorders (FASD), which are characterized by neurodevelopmental impairment with or without facial dysmorphology, congenital anomalies and poor growth. FASD are a leading preventable cause of birth defects and developmental disability. The prevalence of FASD in 76 countries is >1% and is high in individuals living in out-of-home care or engaged in justice and mental health systems. The social and economic effects of FASD are profound, but the diagnosis is often missed or delayed and receives little public recognition. Future research should be informed by people living with FASD and be guided by cultural context, seek consensus on diagnostic criteria and evidence-based treatments, and describe the pathophysiology and lifelong effects of FASD. Imperatives include reducing stigma, equitable access to services, improved quality of life for people with FASD and FASD prevention in future generations.

Eye Abnormalities in Children with Fetal Alcohol Spectrum Disorders: A Systematic Review.

PURPOSE: Although eye abnormalities are reported in fetal alcohol spectrum disorders (FASD), no systematic review based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines has been undertaken. Our aim was to document the range and prevalence of eye abnormalities reported in children with prenatal alcohol exposure (PAE) and/or FASD. METHODS: Searches of electronic databases and manual searches. Eligible articles were observational studies in children with PAE and/or FASD; peer reviewed journal articles in the English language; and studies reporting quantitative or frequency data on functional/structural eye abnormalities. Pooled prevalence, odds ratio, and mean differences were calculated. RESULTS: Of the 1,068 retrieved articles 36 were eligible, including articles on children with diagnosed fetal alcohol syndrome/FASD (N = 31); PAE (N = 3); and FASD or PAE without FASD (N = 2). Structural and functional eye abnormalities were identified, the most prevalent being short palpebral fissure length (66.1%), visual impairment (55.5%), epicanthus (53.5%), subnormal stereoacuity (53.0%), abnormal retinal tortuosity (50.5%), impaired fixation ability (33.3%), telecanthus (31.7%), optic nerve hypoplasia (30.2%), and small optic discs (27.0%). Compared to non-exposed controls, strabismus, subnormal vision, ptosis, short palpebral fissure length, microphthalmos, smaller optic disc area, and retinal vessel tortuosity were more prevalent in children with FASD. CONCLUSIONS: Examination of eyes and vision should be considered in children with PAE and suspected or diagnosed FASD to enable early identification and optimal management. This first comprehensive, systematic literature review demonstrates the variety and frequency of eye abnormalities reported in PAE/FASD.

Accuracy of diagnostic codes for prenatal opioid exposure and neonatal opioid withdrawal syndrome.

OBJECTIVE: Determine the accuracy of diagnostic codes in identifying Prenatal Opioid Exposure (POE) and Neonatal Opioid Withdrawal Syndrome (NOWS). STUDY DESIGN: A cross-sectional study of 374,222 mother-infant dyads with delivery from 01/01/2010 to 12/31/2019. We ascertained maternal diagnostic codes for opioid use during pregnancy and infant diagnostic codes for drug exposure and withdrawal. We assessed sensitivity and positive predictive value (PPV) for POE and NOWS, defined using laboratory, pharmacy, and clinical data. RESULTS: Maternal codes had low sensitivity (36.4%) and PPV (34.7%) for POE. Infant codes for drug exposure were neither sensitive for POE (14%) nor NOWS (31.6%) and had low PPV. Codes for newborn withdrawal had low sensitivity (31.6%) for detecting NOWS, but high PPV (85%). Sensitivity improved (95.1%) for NOWS requiring pharmacologic treatment. CONCLUSIONS: Diagnostic codes identify POE and NOWS poorly. Improved case identification would include pharmacy and laboratory results, and clearly defined criteria for evidence of withdrawal.

Association of Prenatal Exposure to Benzodiazepines and Z-Hypnotics With Risk of Attention-Deficit/Hyperactivity Disorder in Childhood.

Importance: Evidence is limited regarding the safety of prenatal benzodiazepine and z-hypnotic exposure and its association with long-term neurodevelopment in childhood. Objective: To quantify the associations of the timing and number of intervals of prenatal exposure to benzodiazepines and/or z-hypnotics with the risk of attention-deficit/hyperactivity disorder (ADHD) in childhood. Design, Setting, and Participants: This cohort study used data from the 1999 to 2008 population-based Norwegian Mother, Father and Child Cohort Study, which are linked to the Medical Birth Registry of Norway, Norwegian Patient Registry, and Norwegian Prescription Database. Two populations of participants were created: a full sample and a mental health sample. The full sample included mothers and their live-born singletons, whereas the mental health sample was restricted to offspring of mothers who reported anxiety, depression, or sleeping problems during pregnancy or 6 months before pregnancy. Data were analyzed from September 2021 to February 2022. Exposures: Maternal self-report of benzodiazepine and/or z-hypnotic use during pregnancy was grouped into early pregnancy exposure and middle and/or late pregnancy exposure for analysis of the association with timing of exposure, and number of 4-week intervals of exposure was classified (single [1] vs multiple [≥2]) for analysis of the association with number of exposed intervals. Main Outcome and Measures: The outcome was ADHD, defined as time to ADHD diagnosis or filled prescription for ADHD medication. To control for confounding, inverse probability of treatment-weighted Cox proportional hazards regression models were used. Hazard ratios and 95% CIs were estimated. The weights were derived from propensity score modeling of the probability of benzodiazepine and/or z-hypnotic exposure as a function of potential confounders between the exposure and the outcome, including maternal symptoms of depression and anxiety. Results: The full sample comprised 82 201 pregnancies, and the mental health sample included 19 585 pregnancies. In total, 681 offspring (0.8%) in the full sample and 468 offspring (2.4%) in the mental health sample were prenatally exposed to benzodiazepines and/or z-hypnotics. After weighting, exposure in early (hazard ratio, 0.74; 95% CI, 0.39-1.94) and middle and/or late (hazard ratio, 0.76; 95% CI, 0.35-1.61) pregnancy was not associated with increased risk of childhood ADHD. There was no evidence of substantial association between the number of exposed intervals during pregnancy and childhood ADHD. Conclusions and Relevance: Results of this study suggest that there may be no increased risk of childhood ADHD associated with prenatal exposure to benzodiazepines and/or z-hypnotics, regardless of timing of exposure and number of exposed intervals. However, these findings should be interpreted with caution due to low study power.

Alcohol-related dysmorphic features as predictors of neurodevelopmental delay in infants and preschool-aged children: Results from a birth cohort in Ukraine.

BACKGROUND: Cardinal and non-cardinal dysmorphic features are associated with prenatal alcohol exposure (PAE); however, their association with neurodevelopment is less clear. The objective of this study was to determine whether alcohol-related dysmorphic features predict neurodevelopmental delay in infants and toddlers. METHODS: We analyzed a prospective pregnancy cohort in western Ukraine enrolled between 2008 and 2014. A dysmorphology examination comprising body size and three cardinal and 14 non-cardinal dysmorphic features was performed at approximately 6 to 12 months of age. PAE was self-reported and operationalized as absolute ounces of alcohol per day around the time of conception. Neurodevelopment was assessed at 6 to 12 months with the Bayley Scales of Infant Development-II (BSID-II), and at 3.5 to 4.5 years of age with the Differential Ability Scales-II, the Child Behavior Checklist, and multiple measures that were used to create an executive functioning factor score. We performed logistic regression to predict children's neurodevelopment from dysmorphic features, growth measures, sex, and PAE. RESULTS: From an analytic sample of 582 unique children, 566 had BSID-II scores in infancy, and 289 completed the preschool battery. Models with all cardinal and non-cardinal dysmorphic features, growth measures, sex, and PAE performed better than models with subsets of those inputs. In general, models had poor performance classifying delays in infancy (area under the curve (AUC) <0.7) and acceptable performance on preschool-aged outcomes (AUC ~0.75). When the sample was limited to children with moderate-to-high PAE, predictive ability improved on preschool-aged outcomes (AUC 0.76 to 0.89). Sensitivity was relatively low for all models (12% to 63%), although other metrics of performance were higher. CONCLUSION: Predictive analysis based on dysmorphic features and measures of growth performed modestly in this sample. As these features are more reliably measured than neurodevelopment at an earlier age, the inclusion of dysmorphic features and measures of growth in predictive models should be further explored and validated in different settings and populations.

Association of advanced paternal age with lung function at school age.

BACKGROUND: Epidemiological studies suggest that advanced paternal age impact offspring health, but its impact on respiratory health is unclear. This study aimed to investigate the association of paternal age with lung function and fraction of exhaled nitric oxide (FeNO) in children. METHODS: We analyzed data from 1330 single-born children (576 girls, 43.3%; mean age, 6.4 years), who participated in the Longitudinal Investigation of Global Health in Taiwanese Schoolchildren (LIGHTS) cohort and received measurements of lung function and FeNO at 6-year follow-up visits. Covariate-adjusted regression analyses were applied. RESULTS: Every 5-year increase in paternal age at birth was associated with 0.51% decrease in FEV1/FVC ratio (95% CI - 0.86 to - 0.15; p = 0.005) and 19.86 mL/s decrease in FEF75 (95% CI: - 34.07 to - 5.65; p = 0.006). Stratified analyses revealed that increasing paternal age at birth was associated with decreasing FEV1/FVC ratio and FEF75 only among children with prenatal exposure to environmental tobacco smoke (ETS) or not being breastfed. Sensitivity analyses using paternal age as a categorical variable found decreasing FEV1/FVC ratio and FEF75 in the groups of paternal age 35-39 and ≥ 40 years. There was no association of paternal age at birth with FeNO. CONCLUSION: Our findings provide novel evidence linking advanced paternal age at birth with decreasing lung function in children at school age. Children with prenatal exposure to ETS or not being breastfed are more vulnerable to the adverse effect of advanced paternal age on childhood lung function. Further studies are warranted to confirm this novel adverse effect of advanced paternal age.

Direct and indirect effects on child neurocognitive development when maternal cancer is diagnosed during pregnancy: What do we know so far?

Cancer during pregnancy threatens the lives of mother and foetus and its incidence is rising, making it an emerging medical challenge. Evidence on the direct impact of cancer therapies on neonatal outcomes resulted in general guidelines for maternal treatment that safeguards foetal development. Less focus has been placed on indirect factors, in pre- and postnatal periods, that may exert long-term impacts specifically on child neurocognition. Foetal development, in the context of maternal cancer during pregnancy, may be influenced directly by exposure to cancer diagnostics and (co-)treatment, or indirectly through maternal inflammation, malnutrition, hormonal fluctuations, prematurity, and psycho-biological stress. Maternal stress and insecure mother-infant bonding related to postpartum cancer treatment may further impact child cognitive-behavioural development. Understanding the independent and synergistic effects of the factors impacting neurocognitive development creates the opportunity to intervene during the oncological treatment to improve the child's long-term outcome, both by medical and psychosocial care and support.