Prevalence of lifestyle cardiovascular risk factors and estimated framingham 10-year risk scores of adults with psychotic disorders compared to controls at a referral hospital in Eldoret, Kenya.

INTRODUCTION: Lifestyle factors such as smoking, alcohol use, suboptimal diet, and inadequate physical activity have been associated with increased risk of cardiovascular diseases. There are limited data on these risk factors among patients with psychosis in low- and middle-income countries. OBJECTIVES: This study aimed to establish the prevalence of lifestyle cardiovascular risk factors, and the 10-year cardiovascular risk scores and associated factors in patients with psychosis compared to controls at Moi Teaching and Referral Hospital in Eldoret, Kenya. METHODS: A sample of 297 patients with schizophrenia, schizoaffective disorder, or bipolar mood disorder; and 300 controls matched for age and sex were included in this analysis. A study specific researcher-administered questionnaire was used to collect data on demographics, antipsychotic medication use, smoking, alcohol intake, diet, and physical activity. Weight, height, abdominal circumference, and blood pressure were also collected to calculate the Framingham 10-year Cardiovascular Risk Score (FRS), while blood was drawn for measurement of glucose level and lipid profile. Pearson's chi-squared tests and t-tests were employed to assess differences in cardiovascular risk profiles between patients and controls, and a linear regression model was used to determine predictors of 10-year cardiovascular risk in patients. RESULTS: Compared to controls, patients with psychosis were more likely to have smoked in their lifetimes (9.9% vs. 3.3%, p = 0.006) or to be current smokers (13.8% vs. 7%, p = 0.001). Over 97% of patients with psychosis consumed fewer than five servings of fruits and vegetables per week; 78% engaged in fewer than three days of vigorous exercise per week; and 48% sat for more than three hours daily. The estimated 10-year risk of CVD was relatively low in this study: the FRS in patients was 3.16, compared to 2.93 in controls. The estimated 10-year cardiovascular risk in patients was significantly associated with female sex (p = 0.007), older patients (p < 0.001), current tobacco smoking (p < 0.001), and metabolic syndrome (p < 0.001). CONCLUSION: In the setting of Eldoret, there is suboptimal physical exercise and intake of healthy diet among patients with psychosis and controls. While the estimated risk score among patients is relatively low in our study, these data may be useful for informing future studies geared towards informing interventions to promote healthy lifestyles in this population.

Evaluating construct and criterion validity of NeuroScreen in assessing neurocognition among hospitalized Ugandan first-episode psychosis patients.

Introduction: Neurocognitive impairment (NCI) is commonly exhibited among patients experiencing their first episode of psychosis. However, there are few resources in many low-income countries, such as Uganda, that allow for the administration of extensive neurocognitive test batteries for the detection of NCI. NeuroScreen is a brief tablet-based neurocognitive assessment battery that can be administered by all levels of healthcare staff. We examined the validity of NeuroScreen to assess neurocognition and detect NCI in first-episode psychosis (FEP) patients in Uganda. Methods: We enrolled 112 participants FEP patients and matched controls at Butabika Mental Referral Hospital. Each participant completed NeuroScreen and a traditionally administered neurocognitive battery: the MATRIC Consensus Cognitive Battery (MCCB). We examined correlations between participant performance on NeuroScreen and the MCCB. A ROC curve determined sensitivity and specificity of NeuroScreen to detect NCI as determined by MCCB criterion. Results: There was a large, statistically significant correlation between overall performance on NeuroScreen and the MCCB [r(112) = 0.64, p < .001]. Small to large correlations were found between tests in the MCCB and NeuroScreen batteries. The ROC curve of NeuroScreen performance to detect MCCB-defined NCI had an area under curve of 0.80 and optimal sensitivity and specificity of 83 % and 60 %, respectively. Conclusion: There was a moderate positive correlation between overall performance on both batteries. NeuroScreen shows promise as a valid assessment battery to assess neurocognition and detect NCI in FEP patients in Uganda. Further studies of NeuroScreen in healthy individuals and in a range of mental disorders are recommended.

DNA methylation as a potential mediator of the association between prenatal tobacco and alcohol exposure and child neurodevelopment in a South African birth cohort.

Prenatal tobacco exposure (PTE) and prenatal alcohol exposure (PAE) have been associated with an increased risk of delayed neurodevelopment in children as well as differential newborn DNA methylation (DNAm). However, the biological mechanisms connecting PTE and PAE, DNAm, and neurodevelopment are largely unknown. Here we aim to determine whether differential DNAm mediates the association between PTE and PAE and neurodevelopment at 6 (N = 112) and 24 months (N = 184) in children from the South African Drakenstein Child Health Study. PTE and PAE were assessed antenatally using urine cotinine measurements and the ASSIST questionnaire, respectively. Cord blood DNAm was measured using the EPIC and 450 K BeadChips. Neurodevelopment (cognitive, language, motor, adaptive behavior, socioemotional) was measured using the Bayley Scales of Infant and Toddler Development, Third Edition. We constructed methylation risk scores (MRS) for PTE and PAE and conducted causal mediation analysis (CMA) with these MRS as mediators. Next, we conducted a high-dimensional mediation analysis to identify individual CpG sites as potential mediators, followed by a CMA to estimate the average causal mediation effects (ACME) and total effect (TE). PTE and PAE were associated with neurodevelopment at 6 but not at 24 months. PTE MRS reached a prediction accuracy (R2) of 0.23 but did not significantly mediate the association between PTE and neurodevelopment. PAE MRS was not predictive of PAE (R2 = 0.006). For PTE, 31 CpG sites and eight CpG sites were identified as significant mediators (ACME and TE P < 0.05) for the cognitive and motor domains at 6 months, respectively. For PAE, 16 CpG sites and 1 CpG site were significant mediators for the motor and adaptive behavior domains at 6 months, respectively. Several of the associated genes, including MAD1L1, CAMTA1, and ALDH1A2 have been implicated in neurodevelopmental delay, suggesting that differential DNAm may partly explain the biological mechanisms underlying the relationship between PTE and PAE and child neurodevelopment.

In-utero exposure to indoor air pollution or tobacco smoke and cognitive development in a South African birth cohort study.

BACKGROUND AND AIMS: There is increasing evidence indicating that air pollution exposure is associated with neuronal damage. Since pregnancy is a critical window of vulnerability, air pollution exposure during this period could have adverse effects on neurodevelopment. This study aims 1) to analyze associations of prenatal exposure to indoor air pollution (particulate matter with diameters ≤10 µm, PM10) and tobacco smoke with neurodevelopment and 2) to determine whether these associations are mediated by deviations of epigenetic gestational age from chronological gestational age (ΔGA). METHODS: Data of 734 children from the South African Drakenstein Child Health Study were analyzed. Prenatal PM10 exposure was measured using devices placed in the families' homes. Maternal smoking during pregnancy was determined by maternal urine cotinine measures. The Bayley Scales of Infant and Toddler Development III (BSID-III) was used to measure cognition, language and motor development and adaptive behavior at two years of age. Linear regression models adjusted for maternal age, gestational age, sex of child, ancestry, birth weight/length, and socioeconomic status were used to explore associations between air pollutants and BSID-III scores. A mediation analysis was conducted to analyze if these associations were mediated by ΔGA using DNA methylation measurements from cord blood. RESULTS: An increase of one interquartile range in natural-log transformed PM10 (lnPM10; 1.58 µg/m3) was significantly associated with lower composite scores in cognition, language, and adaptive behavior sub-scores (composite score ß-estimate [95%-confidence interval]: -0.950 [-1.821, -0.120]). Maternal smoking was significantly associated with lower adaptive behavior scores (-3.386 [-5.632, -1.139]). Associations were not significantly mediated by ΔGA (e.g., for PM10 and cognition, proportion mediated [p-value]: 4% [0.52]). CONCLUSION: We found an association of prenatal exposure to indoor air pollution (PM10) and tobacco smoke on neurodevelopment at two years of age, particularly cognition, language, and adaptive behavior. Further research is needed to understand underlying biological mediators.

Association between maternal depression during pregnancy and newborn DNA methylation.

Around 15-65% of women globally experience depression during pregnancy, prevalence being particularly high in low- and middle-income countries. Prenatal depression has been associated with adverse birth and child development outcomes. DNA methylation (DNAm) may aid in understanding this association. In this project, we analyzed associations between prenatal depression and DNAm from cord blood from participants of the South African Drakenstein Child Health Study. We examined DNAm in an epigenome-wide association study (EWAS) of 248 mother-child pairs. DNAm was measured using the Infinium MethylationEPIC (N = 145) and the Infinium HumanMethylation450 (N = 103) arrays. Prenatal depression scores, obtained with the Edinburgh Postnatal Depression Scale (EPDS) and the Beck Depression Inventory-II (BDI-II), were analyzed as continuous and dichotomized variables. We used linear robust models to estimate associations between depression and newborn DNAm, adjusted for measured (smoking status, household income, sex, preterm birth, cell type proportions, and genetic principal components) and unmeasured confounding using Cate and Bacon algorithms. Bonferroni correction was used to adjust for multiple testing. DMRcate and dmrff were used to test for differentially methylated regions (DMRs). Differential DNAm was significantly associated with BDI-II variables, in cg16473797 (Δ beta = -1.10E-02, p = 6.87E-08), cg23262030 (Δ beta per BDI-II total IQR = 1.47E-03, p = 1.18E-07), and cg04859497 (Δ beta = -6.42E-02, p = 1.06E-09). Five DMRs were associated with at least two depression variables. Further studies are needed to replicate these findings and investigate their biological impact.

Maternal psychosocial risk factors and child gestational epigenetic age in a South African birth cohort study.

Accelerated epigenetic aging relative to chronological age has been found to be associated with higher risk of mortality in adults. However, little is known about whether and how in utero exposures might shape child gestational epigenetic age (EA) at birth. We aimed to explore associations between maternal psychosocial risk factors and deviation in child gestational EA at birth (i.e., greater or lower EA relative to chronological age) in a South African birth cohort study-the Drakenstein Child Health Study. Maternal psychosocial risk factors included trauma/stressor exposure; posttraumatic stress disorder (PTSD); depression; psychological distress; and alcohol/tobacco use. Child gestational EA at birth was calculated using an epigenetic clock previously devised for neonates; and gestational EA deviation was calculated as the residuals of the linear model between EA and chronological gestational age. Bivariate linear regression was then used to explore unadjusted associations between maternal/child risk factors and child gestational EA residuals at birth. Thereafter, a multivariable regression method was used to determine adjusted associations. Data from 271 maternal-child dyads were included in the current analysis. In the multivariable regression model, maternal PTSD was significantly and negatively associated with child gestational EA residuals at birth (ß = -1.95; p = 0.018), controlling for study site, sex of the child, head circumference at birth, birthweight, mode of delivery, maternal estimated household income, body mass index (BMI) at enrolment, HIV status, anaemia, psychological distress, and prenatal tobacco or alcohol use. Given the novelty of this preliminary finding, and its potential translational relevance, further studies to delineate underlying biological pathways and to explore clinical implications of EA deviation are warranted.

Genetic susceptibility to asthma increases the vulnerability to indoor air pollution.

INTRODUCTION: Indoor air pollution and maternal smoking during pregnancy are associated with respiratory symptoms in infants, but little is known about the direct association with lung function or interactions with genetic risk factors. We examined associations of exposure to indoor particulate matter with a 50% cut-off aerodynamic diameter of 10 µm (PM10) and maternal smoking with infant lung function and the role of gene-environment interactions. METHODS: Data from the Drakenstein Child Health Study, a South African birth cohort, were analysed (n=270). Lung function was measured at 6 weeks and 1 year of age, and lower respiratory tract infection episodes were documented. We measured pre- and postnatal PM10 exposures using devices placed in homes, and prenatal tobacco smoke exposure using maternal urine cotinine levels. Genetic risk scores determined from associations with childhood-onset asthma in the UK Biobank were used to investigate effect modifications. RESULTS: Pre- and postnatal exposure to PM10 as well as maternal smoking during pregnancy were associated with reduced lung function at 6 weeks and 1 year as well as with lower respiratory tract infection in the first year. Due to a significant interaction between the genetic risk score and prenatal exposure to PM10, infants carrying more asthma-related risk alleles were more susceptible to PM10-associated reduced lung function (pinteraction=0.007). This interaction was stronger in infants with Black African ancestry (pinteraction=0.001) and nonexistent in children with mixed ancestry (pinteraction=0.876). CONCLUSIONS: PM10 and maternal smoking exposures were associated with reduced lung function, with a higher susceptibility for infants with an adverse genetic predisposition for asthma that also depended on the infant's ancestry.

Maternal health and birth outcomes in a South African birth cohort study.

BACKGROUND: Maternal physical and mental health during pregnancy are key determinants of birth outcomes. There are relatively few prospective data that integrate physical and mental maternal health measures with birth outcomes in low- and middle-income country settings. We aimed to investigate maternal health during pregnancy and the impact on birth outcomes in an African birth cohort study, the Drakenstein Child Health Study. METHODS: Pregnant women attending 2 public health clinics, Mbekweni (serving a predominantly black African population) and TC Newman (predominantly mixed ancestry) in a poor peri-urban area of South Africa were enrolled in their second trimester and followed through childbirth. All births occurred at a single public hospital. Maternal sociodemographic, physical and psychosocial characteristics were comprehensively assessed. Multivariable linear regression models were used to explore associations between maternal health and birth outcomes. RESULTS: Over 3 years, 1137 women (median age 25.8 years; 21% HIV-infected) gave birth to 1143 live babies. Most pregnancies were uncomplicated but gestational diabetes (1%), anaemia (22%) or pre-eclampsia (2%) occurred in a minority. Most households (87%) had a monthly income of less than USD 350; only 27% of moms were employed and food insecurity was common (37%). Most babies (80%) were born by vaginal delivery at full term; 17% were preterm, predominantly late preterm. Only 74 (7%) of babies required hospitalisation immediately after birth and only 2 babies were HIV-infected. Food insecurity, socioeconomic status, pregnancy-associated hypertension, pre-eclampsia, gestational diabetes and mixed ancestry were associated with lower infant gestational age while maternal BMI at enrolment was associated with higher infant gestational age. Primigravida or alcohol use during pregnancy were negatively associated with infant birth weight and head circumference. Maternal BMI at enrolment was positively associated with birth weight and gestational diabetes was positively associated with birth weight and head circumference for gestational age. Smoking during pregnancy was associated with lower infant birth weight. CONCLUSION: Several modifiable risk factors including food insecurity, smoking, and alcohol consumption during pregnancy were identified as associated with negative birth outcomes, all of which are amenable to public health interventions. Interventions to address key exposures influencing birth outcomes are needed to improve maternal and child health in low-middle income country settings.

Risk and protective factors for child development: An observational South African birth cohort.

BACKGROUND: Approximately 250 million (43%) children under the age of 5 years in low- and middle-income countries (LMICs) are failing to meet their developmental potential. Risk factors are recognised to contribute to this loss of human potential. Expanding understanding of the risks that lead to poor outcomes and which protective factors contribute to resilience in children may be critical to improving disparities. METHODS AND FINDINGS: The Drakenstein Child Health Study is a population-based birth cohort in the Western Cape, South Africa. Pregnant women were enrolled between 20 and 28 weeks' gestation from two community clinics from 2012 to 2015; sociodemographic and psychosocial data were collected antenatally. Mothers and children were followed through birth until 2 years of age. Developmental assessments were conducted by trained assessors blinded to background, using the Bayley-III Scales of Infant and Toddler Development (BSID-III), validated for use in South Africa, at 24 months of age. The study assessed all available children at 24 months; however, some children were not able to attend, because of loss to follow-up or unavailability of a caregiver or child at the correct age. Of 1,143 live births, 1,002 were in follow-up at 24 months, and a total of 734 children (73%) had developmental assessments, of which 354 (48.2%) were girls. This sample was characterised by low household employment (n = 183; 24.9%) and household income (n = 287; 39.1% earning 1 domain affected, and 75 (10.2%) had delay in all domains. Bivariate and multivariable analyses revealed several factors that were associated with developmental outcomes. These included protective factors (maternal education, higher birth weight, and socioeconomic status) and risk factors (maternal anaemia in pregnancy, depression or lifetime intimate partner violence, and maternal HIV infection). Boys consistently performed worse than girls (in cognition [ß = -0.74; 95% CI -1.46 to -0.03, p = 0.042], receptive language [ß = -1.10; 95% CI -1.70 to -0.49, p < 0.001], expressive language [ß = -1.65; 95% CI -2.46 to -0.84, p < 0.001], and fine motor [ß = -0.70; 95% CI -1.20 to -0.20, p = 0.006] scales). There was evidence that child sex interacted with risk and protective factors including birth weight, maternal anaemia in pregnancy, and socioeconomic factors. Important limitations of the study include attrition of sample from birth to assessment age and missing data in some exposure areas from those assessed. CONCLUSIONS: This study provides reliable developmental data from a sub-Saharan African setting in a well-characterised sample of mother-child dyads. Our findings highlight not only the important protective effects of maternal education, birth weight, and socioeconomic status for developmental outcomes but also sex differences in developmental outcomes and key risk and protective factors for each group.

Perinatal depression among mothers in a South African birth cohort study: Trajectories from pregnancy to 18 months postpartum.

BACKGROUND: Perinatal depression affects 21-50% of women in South Africa and poses significant health risks to mothers and children. Trajectories of depressive symptoms change over time and have not been well characterized during the perinatal period in low and middle-income countries. METHODS: Data from women enrolled in a population-based birth cohort study in Paarl, South Africa with at least 3 depression measures from pregnancy through 18 months postpartum (N = 831) were analyzed. Depressive symptoms were measured continuously using the Edinburgh Postnatal Depression Scale (EPDS). Group-based trajectory models were used to estimate trajectories of depressive symptoms during the perinatal period and multinomial multivariable models to identify predictors of trajectory group membership. RESULTS: Five distinct trajectory patterns of depressive symptoms were identified: moderate levels of depressive symptoms during pregnancy but minimal postpartum (3.5%), minimal levels during pregnancy and increasing postpartum (3.7%), unstable levels peaking at 12 months postpartum (6.6%), mild levels with slight decrease postpartum (82.9%), and severe levels during pregnancy and postpartum (3.1%). Membership in the chronic severe symptom group was associated with stressful life events, sexual intimate partner violence and tobacco use. LIMITATIONS: Modeling limitations prevented determining how changes in psychosocial predictors over time may influence depressive symptom trajectories. CONCLUSIONS: Mild to severe depressive symptoms during pregnancy/postpartum were common among this South African cohort. Interventions to treat women with severe chronic depressive symptoms with co-occurring psychosocial issues are urgently needed.

Effect of Hazardous Alcohol Use During Pregnancy on Growth Outcomes at Birth: Findings from a South African Cohort Study.

BACKGROUND: Cohort studies have noted associations between hazardous alcohol use during pregnancy and infant growth outcomes, but many have not controlled for potential psychosocial confounders. To assess the unique contribution of hazardous alcohol use, we examined its effect on infant growth outcomes while controlling for maternal psychosocial stressors and hazardous tobacco and drug use in a cohort of 986 pregnant South African women enrolled into the Drakenstein Child Health Study between 2012 and 2015. METHODS: Data on psychosocial stressors and maternal risk behaviors were collected between 28 and 32 weeks of gestation. Participants were categorized as hazardous alcohol users if they obtained moderate or high scores (>10) on the Alcohol, Smoking and Substance Involvement Screening Test at this assessment or retrospectively reported drinking at least 2 drinks weekly during any trimester of pregnancy. Infant growth outcomes were recorded at delivery. Multivariable regression models examined correlates of hazardous alcohol use and associations between hazardous alcohol use and birth outcomes. RESULTS: Overall, 13% of mothers reported hazardous alcohol use. Recent exposure to intimate partner violence (adjusted odds ratio (aOR) = 2.08; 95% confidence interval (CI): 1.37, 3.18) and hazardous tobacco use (aOR = 5.03; 95% CI: 2.97, 8.52) were significant correlates of hazardous alcohol use. After controlling for potential psychosocial confounders, hazardous alcohol use remained associated with lower infant weight-for-age (B = -0.35, 95% CI: -0.56, -0.14), height-for-age (B = -0.46, 95% CI: -0.76, -0.17), and head-circumference-for-age z-scores (B = -0.43, 95% CI: -0.69, -0.17). CONCLUSIONS: Interventions to reduce hazardous alcohol use among pregnant women in South Africa are needed to prevent alcohol-related infant growth restrictions. As these growth deficits may lead to neurodevelopmental consequences, it is critical to identify alcohol-related growth restrictions at birth and link exposed infants to early interventions for neurodevelopment.

The developmental effects of HIV and alcohol: a comparison of gestational outcomes among babies from South African communities with high prevalence of HIV and alcohol use.

BACKGROUND: There is growing evidence of the negative impact of alcohol on morbidity and mortality of individuals living with HIV but limited evidence of in utero effects of HIV and alcohol on exposure on infants. METHODS: We conducted a population-based birth cohort study (N = 667 mother-infant dyads) in South Africa to investigate whether maternal alcohol use and HIV affected gestational outcomes. Descriptive data analysis was conducted for all variables using frequency distributions, measures of central tendency, and estimates of variance. Hierarchical multiple regression was conducted to determine whether maternal alcohol use, maternal HIV status and other risk factors (socioeconomic status, smoking, depression) predicted infant outcomes. RESULTS: Our results showed severity of recent alcohol use and lifetime alcohol use predicted low birth weight. Similarly lifetime alcohol use predicted shorter infant length, smaller head length, smaller head circumference, and early gestational age. However, HIV status was not a significant predictor of gestational outcomes. CONCLUSIONS: The unexpected finding that maternal HIV status did not predict any of the gestational outcomes may be due to high rates of ART usage among HIV-infected mothers. The potentially negative effects of HIV on gestational outcomes may have been attenuated by improved maternal health due to high coverage of antiretroviral treatment in South Africa. Interventions are needed to reduce alcohol consumption among pregnant mothers and to support healthy growth and psychosocial development of infants.

Determinants of early-life lung function in African infants.

BACKGROUND: Low lung function in early life is associated with later respiratory illness. There is limited data on lung function in African infants despite a high prevalence of respiratory disease. AIM: To assess the determinants of early lung function in African infants. METHOD: Infants enrolled in a South African birth cohort, the Drakenstein child health study, had lung function measured at 6-10 weeks of age. Measurements, made with the infant breathing via a facemask during natural sleep, included tidal breathing, sulfur hexafluoride multiple breath washout and the forced oscillation technique. Information on antenatal and early postnatal exposures was collected using questionnaires and urine cotinine. Household benzene exposure was measured antenatally. RESULTS: Successful tests were obtained in 645/675 (95%) infants, median (IQR) age of 51 (46-58) days. Infant size, age and male gender were associated with larger tidal volume. Infants whose mothers smoked had lower tidal volumes (-1.6 mL (95% CI -3.0 to -0.1), p=0.04) and higher lung clearance index (0.1 turnovers (95% CI 0.01 to 0.3), p=0.03) compared with infants unexposed to tobacco smoke. Infants exposed to alcohol in utero or household benzene had lower time to peak tidal expiratory flow over total expiratory time ratios, 10% (95% CI -15.4% to -3.7%), p=0.002) and 3.0% (95% CI -5.2% to -0.7%, p=0.01) lower respectively compared with unexposed infants. HIV-exposed infants had higher tidal volumes (1.7 mL (95% CI 0.06 to 3.3) p=0.04) compared with infants whose mothers were HIV negative. CONCLUSION: We identified several factors including infant size, sex, maternal smoking, maternal alcohol, maternal HIV and household benzene associated with altered early lung function, many of which are factors amenable to public health interventions. Long-term study of lung function and respiratory disease in these children is a priority to develop strategies to strengthen child health.

Toward a Global Roadmap for Precision Medicine in Psychiatry: Challenges and Opportunities.

Mental disorders represent a major public health burden worldwide. This is likely to rise in the next decade, with the highest increases predicted to occur in low- and middle-income countries. Current psychotropic medication treatment guidelines focus on uniform approaches to the treatment of heterogeneous disorders and achieve only partial therapeutic success. Developing a global precision medicine approach in psychiatry appears attractive, given the value of this approach in other fields of medicine, such as oncology and infectious diseases. In this horizon scanning analysis, we review the salient opportunities and challenges for precision medicine in psychiatry over the next decade. Variants within numerous genes involved in a range of pathways have been implicated in psychotropic drug response and might ultimately be used to guide choice of pharmacotherapy. Multipronged approaches such as multi-omics (genomics, proteomics, metabolomics) analyses and systems diagnostics together with high-throughput sequencing and genotyping technologies hold promise for identifying precise and targeted treatments in mental disorders. To date, however, the vast majority of pharmacogenomics work has been undertaken in high-income countries on a relatively small proportion of the global population, and many other challenges face the field. Opportunities and challenges for establishing a global roadmap for precision medicine in psychiatry are discussed in this article.

Alcohol exposure in utero is associated with decreased gray matter volume in neonates.

Neuroimaging studies have indicated that prenatal alcohol exposure is associated with alterations in the structure of specific brain regions. However, the temporal specificity of such changes and their behavioral consequences are less known. Here we explore the brain structure of infants with in utero exposure to alcohol shortly after birth. T2 structural MRI images were acquired from 28 alcohol-exposed infants and 45 demographically matched healthy controls at 2-4 weeks of age on a 3T Siemens Allegra system as part of large birth cohort study, the Drakenstein Child Health Study (DCHS). Neonatal neurobehavior was assessed at this visit; early developmental outcome assessed on the Bayley Scales of Infant Development III at 6 months of age. Volumes of gray matter regions were estimated based on the segmentations of the University of North Carolina neonatal atlas. Significantly decreased total gray matter volume was demonstrated for the alcohol-exposed cohort compared to healthy control infants (p < 0.001). Subcortical gray matter regions that were significantly different between groups after correcting for overall gray matter volume included left hippocampus, bilateral amygdala and left thalamus (p < 0.01). These findings persisted even when correcting for infant age, gender, ethnicity and maternal smoking status. Both early neurobehavioral and developmental adverse outcomes at 6 months across multiple domains were significantly associated with regional volumes primarily in the temporal and frontal lobes in infants with prenatal alcohol exposure. Alcohol exposure during the prenatal period has potentially enduring neurobiological consequences for exposed children. These findings suggest the effects of prenatal alcohol exposure on brain growth is present very early in the first year of life, a period during which the most rapid growth and maturation occurs.