Metabolomic Profiles in Jamaican Children With and Without Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a wide range of behavioral and cognitive impairments. While genetic and environmental factors are known to contribute to its etiology, metabolic perturbations associated with ASD, which can potentially connect genetic and environmental factors, remain poorly understood. Therefore, we conducted a metabolomic case-control study and performed a comprehensive analysis to identify significant alterations in metabolite profiles between children with ASD and typically developing (TD) controls in order to identify specific metabolites that may serve as biomarkers for the disorder. We conducted metabolomic profiling on plasma samples from participants in the second phase of Epidemiological Research on Autism in Jamaica, an age and sex-matched cohort of 200 children with ASD and 200 TD controls (2-8 years old). Using high-throughput liquid chromatography-mass spectrometry techniques, we performed a targeted metabolite analysis, encompassing amino acids, lipids, carbohydrates, and other key metabolic compounds. After quality control and missing data imputation, we performed univariable and multivariable analysis using normalized metabolites while adjusting for covariates, age, sex, socioeconomic status, and child's parish of birth. Our findings revealed unique metabolic patterns in children with ASD for four metabolites compared to TD controls. Notably, three metabolites were fatty acids, including myristoleic acid, eicosatetraenoic acid, and octadecenoic acid. The amino acid sarcosine exhibited a significant association with ASD. These findings highlight the role of metabolites in the etiology of ASD and suggest opportunities for the development of targeted interventions.

JA KIDS - Jamaica's second national birth cohort study: aims and methods.

Birth cohort studies across the world have yielded information that has been used to inform policy and programme decisions that have improved the health and well-being of populations. A few such studies have been conducted in low- and middle-income countries due to funding, methodological and other challenges. This paper briefly reviews the methods of comprehensive birth cohort studies with extensive follow-up of participants through the life course conducted in low- and middle-income countries. It then reviews the first Jamaican birth cohort study of 1986 and discusses the methodological advances in implementing JA KIDS, the second Jamaican birth cohort study conducted in 2011. The aims and methods of JA KIDS are described in detail.

Does household size matter? Crowding and its effects on child development.

There is very little compelling evidence that household size negatively affects child development. In this study, the effects of household size on child development were analysed using data collected for a sample of 1311 four-year-old Jamaican children. Children's development was assessed using the Griffiths Mental Development Scales across six developmental domains: locomotor, personal-social, language, coordination, performance and practical reasoning. The findings suggest that children's locomotor and personal-social development are negatively affected by household crowding, with no significant effects observed for other domains. Additional results show that these adverse effects are strongest if the child lives in a single room compared to a separately detached house. This evidence speaks to the need to tailor policies towards access to good housing infrastructure and the provision of recreational spaces to encourage play and social interaction among children.

Epidemiology of violence against young children in Jamaica.

Violence against young children is known to have detrimental short and long-term effects. Yet, few studies investigate the prevalence of violence against young children, particularly very young children under the age of 2 years. This paper reports on the prevalence of violence against young children in Jamaica using data obtained from the JA KIDS birth cohort study that undertook pre-enrolment of pregnant mothers in the antenatal period and followed full or sub-samples of parents and children at 9-12 months, 18-22 months and 4-5 years. Violence in pregnancy was experienced by 6.1% of pre-enrolled mothers. As many as 43.1% of Jamaican children ages 9-12 months were shouted at, and almost 30% were slapped. Physical and emotional violence increased with age, and by 4-5 years, approximately 90% of children experienced physical and emotional violence. Non-violent methods, primarily explaining and reasoning with children, were also reported by more than 95% of parents at 4-5 years. Corporal punishment was the most common form of violence experienced, but young children also witnessed hurtful physical and emotional violence between mothers and their partners and lived in communities in which there were violent events. Strategies to reduce young children's experiences as victims and witnesses of violence are discussed.

Metabolomic profiles in Jamaican children with and without autism spectrum disorder.

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a wide range of behavioral and cognitive impairments. While genetic and environmental factors are known to contribute to its etiology, the underlying metabolic perturbations associated with ASD which can potentially connect genetic and environmental factors, remain poorly understood. Therefore, we conducted a metabolomic case-control study and performed a comprehensive analysis to identify significant alterations in metabolite profiles between children with ASD and typically developing (TD) controls. Objective: To elucidate potential metabolomic signatures associated with ASD in children and identify specific metabolites that may serve as biomarkers for the disorder. Methods: We conducted metabolomic profiling on plasma samples from participants in the second phase of Epidemiological Research on Autism in Jamaica (ERAJ-2), which was a 1:1 age (±6 months)-and sex-matched cohort of 200 children with ASD and 200 TD controls (2-8 years old). Using high-throughput liquid chromatography-mass spectrometry techniques, we performed a targeted metabolite analysis, encompassing amino acids, lipids, carbohydrates, and other key metabolic compounds. After quality control and imputation of missing values, we performed univariable and multivariable analysis using normalized metabolites while adjusting for covariates, age, sex, socioeconomic status, and child's parish of birth. Results: Our findings revealed unique metabolic patterns in children with ASD for four metabolites compared to TD controls. Notably, three of these metabolites were fatty acids, including myristoleic acid, eicosatetraenoic acid, and octadecenoic acid. Additionally, the amino acid sarcosine exhibited a significant association with ASD. Conclusions: These findings highlight the role of metabolites in the etiology of ASD and suggest opportunities for the development of targeted interventions.

Factors associated with blood mercury concentrations and their interactions with three glutathione S-transferase genes (GSTT1, GSTM1, and GSTP1): an exposure assessment study of typically developing Jamaican children.

BACKGROUND: Jamaican soil is abundant in heavy metals including mercury (Hg). Due to availability and ease of access, fish is a traditional dietary component in Jamaica and a significant source of Hg exposure. Mercury is a xenobiotic and known neuro-toxicant that affects children's neurodevelopment. Human glutathione S-transferase (GST) genes, including GSTT1, GSTM1, and GSTP1, affect Hg conjugation and elimination mechanisms. METHODS: In this exposure assessment study we used data from 375 typically developing (TD) 2-8-year-old Jamaican children to explore the association between environmental Hg exposure, GST genes, and their interaction effects on blood Hg concentrations (BHgCs). We used multivariable general linear models (GLMs). RESULTS: We identified the child's age, consumption of saltwater fish, canned fish (sardine, mackerel), string beans, grain, and starches (pasta, macaroni, noodles) as the environmental factors significantly associated with BHgCs (all P < 0.05). A significant interaction between consumption of canned fish (sardine, mackerel) and GSTP1 in relation to BHgC using either a co-dominant or recessive genetic model (overall interaction P = 0.01 and P < 0.01, respectively) indicated that consumption of canned fish (sardine, mackerel) was significantly associated with higher mean BHgC only among children with the GSTP1 Ile105Val, Ile/Ile [Ratio of mean Hg (95% CI) = 1.59 (1.09, 2.32), P = 0.02] and Ile/Val [Ratio of mean Hg (95% CI) = 1.46 (1.12, 1.91), P = 0.01] genotypes. CONCLUSIONS: Since this is the first study from Jamaica to report these findings, replication in other populations is recommended.

Neonatal Outcome of Babies Born to Women 40 Years and Older in a Jamaican Birth Cohort.

OBJECTIVE: The study aimed to determine the outcome of babies born to women ≥40 years in a Jamaican birth cohort. STUDY DESIGN: Maternal demographic data and neonatal data for women ≥40 years who delivered live singleton babies and their younger counterparts aged 20 30 years were extracted from the JA KIDS birth cohort dataset. Outcome measures were preterm birth, low birth weight, very low birth weight, extremely low birth weight, macrosomia, a low 5-minute Apgar score <7, admission to the neonatal unit, and neonatal death. Descriptive analyses were performed; statistical significance was taken at the level p <0.05. RESULTS: A total of 5,424 women and their babies were entered into the study, 5,099 (94%) women were aged 20 to 30 years (mean age ± standard deviation [SD]: 24.5 ± 3.2 years) and 325 (6%) were aged ≥40 years (mean age ± SD: 41.5 ± 1.6 years). A greater percentage of preterm babies (18%) were born to women ≥40 years than to their younger counterparts (14%; p = 0.04). There was no difference in the proportion of low birth weight infants, very low birth weight infants, or extremely low birth weight infants born between the two groups (p > 0.05). There was also no significant difference in the proportion of babies who were macrosomic and in those who had a low 5-minute Apgar score <7. There were 866 (16%) neonatal admissions, 67/325 (21%) of these babies were born to women aged ≥40 years and 799/5,099 (16%) were born to their younger counterparts (p = 0.01). The commonest reason for admission was prematurity. While 60 babies died, there was no significant difference between both groups with 56 (1%) born to women 20 to 30 years and 4 (1%) born to women ≥40 years (p = 0.48). CONCLUSION: Adverse outcomes noted for babies born to women ≥40 years were prematurity and the need for neonatal admission. However, no excess mortality was recorded. KEY POINTS: · Women 40 years and older are more likely to have a chronic illness such as hypertension and diabetes and to have an operative delivery.. · Babies born to women 40 years and older are more likely to be late premature infants and require neonatal admission.. · However, there is no increased risk of neonatal mortality..

Additive or Interactive Associations of Food Allergies with Glutathione S-Transferase Genes in Relation to ASD and ASD Severity in Jamaican Children.

To investigate additive and interactive associations of food allergies with three glutathione S-transferase (GST) genes in relation to ASD and ASD severity in Jamaican children. Using data from 344 1:1 age- and sex-matched ASD cases and typically developing controls, we assessed additive and interactive associations of food allergies with polymorphisms in GST genes (GSTM1, GSTP1 and GSTT1) in relation to ASD by applying conditional logistic regression models, and in relation to ASD severity in ASD cases as measured by the Autism Diagnostic Observation Schedule-2nd Edition (ADOS-2) total and domains specific comparison scores (CSs) by fitting general linear models. Although food allergies and GST genes were not associated with ASD, ASD cases allergic to non-dairy food had higher mean ADOS-2 Restricted and Repetitive Behaviors (RRB) CS (8.8 vs. 8.0, P = 0.04). In addition, allergy to dairy was associated with higher mean RRB CS only among ASD cases with GSTT1 DD genotype (9.9 vs. 7.8, P < 0.01, interaction P = 0.01), and GSTP1 Val/Val genotype under a recessive genetic model (9.8 vs. 7.8, P = 0.02, interaction P = 0.06). Our findings are consistent with the role for GST genes in ASD and food allergies, though require replication in other populations.

Interactions between Environmental Factors and Glutathione S-Transferase (GST) Genes with Respect to Detectable Blood Aluminum Concentrations in Jamaican Children.

Aluminum (Al) is a metallic toxicant at high concentrations following natural or unnatural exposures. Dietary intake is considered as the main source of aluminum exposure in children. We used data from 366 typically developing (TD) children (ages 2−8 years) who participated as controls in an age- and sex-matched case−control study in Jamaica. We investigated additive and interactive associations among environmental factors and children's genotypes for glutathione S-transferase (GST) genes (GSTT1, GSTM1, GSTP1), in relation to having a detectable blood aluminum concentration (BAlC) of >5.0 µg/L, using multivariable logistic regression models. Findings from interactive models revealed that the odds of having a detectable BAlC was significantly higher among children who ate string beans (p ≤ 0.01), whereas about 40% lower odds of having a detectable BAlC was observed in children with higher parental education level, (p = 0.02). A significant interaction between consumption of saltwater fish and GSTP1 in relation to having a detectable BAlC using either co-dominant or dominant genetic models (overall interaction p = 0.02 for both models) indicated that consumption of saltwater fish was associated with higher odds of having a detectable BAlC only among children with the GSTP1 Ile105Val Ile/Ile genotype using either co-dominant or dominant models [OR (95% CI) = 2.73 (1.07, 6.96), p = 0.04; and OR (95% CI) = 2.74 (1.08, 6.99), p = 0.03]. Since this is the first study from Jamaica that reports such findings, replication in other populations is warranted.

Cerebral palsy and developmental intellectual disability in children younger than 5 years: Findings from the GBD-WHO Rehabilitation Database 2019.

Objective: Children with developmental disabilities are associated with a high risk of poor school enrollment and educational attainment without timely and appropriate support. Epidemiological data on cerebral palsy and associated comorbidities required for policy intervention in global health are lacking. This paper set out to report the best available evidence on the global and regional prevalence of cerebral palsy (CP) and developmental intellectual disability and the associated "years lived with disability" (YLDs) among children under 5 years of age in 2019. Methods: We analyzed the collaborative 2019 Rehabilitation Database of the Global Burden of Disease (GBD) Study and World Health Organization for neurological and mental disorders available for 204 countries and territories. Point prevalence and YLDs with 95% uncertainty intervals (UI) are presented. Results: Globally, 8.1 million (7.1-9.2) or 1.2% of children under 5 years are estimated to have CP with 16.1 million (11.5-21.0) or 2.4% having intellectual disability. Over 98% resided in low-income and middle-income countries (LMICs). CP and intellectual disability accounted for 6.5% and 4.5% of the aggregate YLDs from all causes of adverse health outcomes respectively. African Region recorded the highest prevalence of CP (1.6%) while South-East Asia Region had the highest prevalence of intellectual disability. The top 10 countries accounted for 57.2% of the global prevalence of CP and 62.0% of the global prevalence of intellectual disability. Conclusion: Based on this Database, CP and intellectual disability are highly prevalent and associated with substantial YLDs among children under 5 years worldwide. Universal early detection and support services are warranted, particularly in LMICs to optimize school readiness for these children toward inclusive education as envisioned by the United Nations' Sustainable Development Goals.

Detoxification Role of Metabolic Glutathione S-Transferase (GST) Genes in Blood Lead Concentrations of Jamaican Children with and without Autism Spectrum Disorder.

Glutathione S-transferases (GST) are involved in the detoxification of exogenous chemicals including lead (Pb). Using data from 344 pairs of autism spectrum disorder (ASD) cases and age- and sex-matched typically developing (TD) controls (2−8 years old) from Jamaica, we investigated the interaction between three GST genes and ASD status as determinants of blood Pb concentrations (BPbCs). We found that ASD cases had lower geometric mean BPbCs than TD children (1.74 vs. 2.27 µg/dL, p < 0.01). Using a co-dominant genetic model, ASD cases with the Ile/Val genotype for the GSTP1 Ile105Val polymorphism had lower GM BPbCs than TD controls, after adjusting for a known interaction between GSTP1 and GSTT1, child's parish, socioeconomic status, consumption of lettuce, fried plantains, and canned fish (Ile/Val: 1.78 vs. 2.13 µg/dL, p = 0.03). Similarly, among carriers of the I/I or I/D (I*) genotype for GSTT1 and GSTM1, ASD cases had lower adjusted GM BPbCs than TD controls (GSTT1 I*: 1.61 vs. 1.91 µg/dL, p = 0.01; GSTM1 I*: 1.71 vs. 2.04 µg/dL, p = 0.01). Our findings suggest that genetic polymorphisms in GST genes may influence detoxification of Pb by the enzymes they encode in Jamaican children with and without ASD.

Additive and Interactive Associations of Environmental and Sociodemographic Factors with the Genotypes of Three Glutathione S-Transferase Genes in Relation to the Blood Arsenic Concentrations of Children in Jamaica.

Arsenic (As) is a metalloid that has been classified as a xenobiotic with toxic effects on human beings, especially on children. Since the soil in Jamaica contains As, dietary intake is considered the main source of As exposure in Jamaicans. In addition, glutathione S-transferase (GST) genes, including GSTT1, GSTP1, and GSTM1, play an important role in the metabolism of xenobiotics including As in humans. Using data from 375 typically developing children (2-8 years) in Jamaica, we investigated the environmental and sociodemographic factors, as well as their possible interactions with the children's genotype for GST genes in relation to having a detectable level of blood As concentration (i.e., >1.3 µg/L). Using multivariable logistic regression, we have identified environmental factors significantly associated with blood As concentrations that include a child's age, parental education levels, and the consumption of saltwater fish, cabbage, broad beans, and avocado (all p < 0.01). Based on the multivariable analysis including gene x environment interactions, we found that among children with the Ile/Ile genotype for GSTP1 Ile105Val, children who consumed avocado had higher odds of having a detectable blood As concentration compared to children who did not eat avocado.

Correlation between concentrations of four heavy metals in cord blood and childhood blood of Jamaican children.

This study investigated whether the concentrations of four metals [lead (Pb), mercury (Hg), manganese (Mn), and aluminum (Al)] are correlated in cord blood and childhood blood samples from Jamaican children. Cord blood samples were obtained from 21 pregnant women enrolled in the second Jamaican Birth Cohort Study from July 1, 2011 to September 30, 2011, and blood samples were drawn from their children who participated in a follow up study when the children were 4-8 years old. Correlations were assessed by the Pearson or the Spearman's rank correlation coefficient. The mean ages of children at the childhood visit and their mother at the child's birth were 5.5 years and 29.8 years, respectively. About 47.6% of children were male. Statistically significant correlations between cord blood and childhood blood concentrations of Pb (rSpearman =0.45; P = 0.04) and Mn (rPearson=0.48; P = 0.03) were found, and these remained significant when adjusted for the child's sex, age, or both. For Al and Hg, rSpearman=0.29 and 0.08, respectively, but the correlations were not statistically significant (both P ≥ 0.20). A significant correlation between cord blood and childhood blood Pb concentrations for children 4-8 years old has not been previously reported.

Neonatal morbidity in the 2011 JAKIDS Jamaican birth cohort.

This study reports the spectrum of discharge diagnoses in a national cohort of newborns admitted during a 3-month period to hospitals across Jamaica. The data were analyzed using measures of central tendency and risk assessed using odds ratio. Data on 1607 admissions were used to describe the spectrum of morbidity in hospitalized infants. Eight hundred and seven (50%) male and 754 (48%) female neonates were admitted. There was a 15% (240) readmission rate during the neonatal period. Infants of diabetic mothers were almost three times as likely to be admitted as infants whose mothers were not diabetic OR 2.89 (CI 1.96 - 4.13). Infants of women who were hypertensive were 1.5 times more likely to be admitted than infants of non-hypertensive women OR 1.56 (CI 1.56-1.9). The odds ratio for admission of an infant born to a woman delivered by caesarean section was 2.1 (CI: 1.67-2.38). Premature infants constituted 50% of admissions. The most prevalent discharge diagnosis included presumed sepsis, respiratory distress and neonatal jaundice in both preterm and term neonates. In the extreme preterm infant respiratory distress syndrome was the most predominant discharge diagnosis. Multiple gestation was a significant risk for admission OR 2.7 (CI 1.8 to 3.9). Prematurity, multiple gestation, macrosomia, maternal diabetes, maternal hypertension and low 5 minute Apgar score < 7 were all found to be independent predictors of neonatal admission in a logistic regression model (p < 0.001). The recognition of the discharge morbidity is useful for future health planning for the most vulnerable in our population.

Measurement invariance of the Childhood Autism Rating Scale (CARS) across six countries.

The Childhood Autism Rating Scale (CARS) is a simple and inexpensive tool for Autism spectrum disorder (ASD) assessments, with evidenced psychometric data from different countries. However, it is still unclear whether ASD symptoms are measured the same way across different societies and world regions with this tool, since data on its cross-cultural validity are lacking. This study evaluated the cross-cultural measurement invariance of the CARS among children with ASD from six countries, for whom data were aggregated from previous studies in India (n = 101), Jamaica (n = 139), Mexico (n = 72), Spain (n = 99), Turkey (n = 150), and the United States of America (n = 186). We analyzed the approximate measurement invariance based on Bayesian structural equation modeling. The model did not fit the data and its measurement invariance did not hold, with all items found non-invariant across the countries. Items related to social communication and interaction (i.e., relating to people, imitation, emotional response, and verbal and nonverbal communication) displayed lower levels of cross-country non-invariance compared to items about stereotyped behaviors/sensory sensitivity (i.e., body and object use, adaptation to change, or taste, smell, and touch response). This study found that the CARS may not provide cross-culturally valid ASD assessments. Thus, cross-cultural comparisons with the CARS should consider first which items operate differently across samples of interest, since its cross-cultural measurement non-invariance could be a source of cross-cultural variability in ASD presentations. Additional studies are needed before drawing valid recommendations in relation to the cultural sensitivity of particular items.

Neonatal mortality in the 2011 JAKIDS birth cohort.

This study aimed to determine the mortality in a Jamaican birth cohort over a 3-month period. Data on the outcome of 87.5% of all births in Jamaica between July and September 2011 were used to determine trends in and determinants of neonatal mortality. There were 9650 live births and 144 neonatal deaths yielding a Neonatal Mortality Rate of 14.9/1000 (95% CI: 12.6-17.52/1000) livebirths. One hundred and twenty-one (84%) deaths occurred within the first seven days of life giving an Early Neonatal Mortality Rate of 12.5/1000 (95%CI: 10.4-15.0/1000) livebirths and a Late Neonatal Mortality Rate of 2.38/1000 (95%CI: 1.51-3.57/1000) live births. Sixty-nine (48%) deaths occurred within the first 24 hours. Thirty-eight neonates (26%) died prior to being admitted to a neonatal unit, approximately within 2 hours of life.Maternal age <15 years, decreasing birthweight, prematurity, male gender, multiple gestation and birth by caesarean section were associated with an increased risk of mortality p < 0.05. In order for Jamaica to experience further decline in its Neonatal Mortality Rate to meet the Sustainable Developmental Goal of at least as low as 12 per 1,000 live births by 2030 the focus must be on decreasing mortality in the very low birth weight infants who disproportionally contribute to mortality as well as continuing to implement measures to further decrease mortality in the larger infants.

ECD - Pregnancy outcomes of a birth cohort. Are adolescent mothers really at more risk?

This sub-study within the JAKIDS longitudinal cohort study compares medical and psychosocial outcomes of pregnancy in younger adolescent mothers (<16 years), older adolescent mothers (16-19 years) and adult mothers (>19 years) in Jamaica. Participants were recruited from July to September 2011 and included 9521 mother-infant dyads; mean maternal age 26.0 years (SD 6.8). Adolescent mothers represented 19.1% (n = 1822) of the sample - 1704 older adolescent mothers (17.9%) and 118 younger adolescent mothers (1.2%). Participants completed interviewer-administered questionnaires regarding their sexual and reproductive health history, feelings about the current pregnancy, and presence of anxious and depressive symptoms. Data on delivery and perinatal and neonatal outcomes were extracted from hospital charts. Younger adolescent mothers were more likely to deliver preterm (p < 0.001) and low birth weight infants (p < 0.001) than older adolescent and adult mothers. Younger adolescent mothers had lower levels of antenatal anxiety regarding the pregnancy and its outcome (p < 0.001) while prevalence of elevated depressive symptoms antenatally (EPDS ≥11) was similar across age groups. Older adolescent mothers with significant depressive symptoms had increased odds of preterm delivery. These findings call for close antenatal monitoring of younger adolescent mothers and highlight the need for psychological services for all mothers.