Therefore, HIV prevention programs should include substance use screening and intervention services. Medical mistrust has been associated with low intention of PrEP uptake and poor medication adherence. Medical mistrust is also a barrier to HIV testing and causes disruptions in HIV care. Study participants expressed a high level of mistrust toward medical providers and institutions. However, that did not seem to affect self-test kit ordering in our study. Additional research is needed to evaluate how medical mistrust may impact HIV testing and PrEP uptake. Regarding PrEP, participants reported being informed of its benefits, comfortable taking PrEP, and not embarrassed about taking PrEP; however, they did report concerns about the adverse effects and the cost of PrEP. Similar concerns have been reported by Kota et al in a cohort of MSM. Although PrEP is generally considered safe, public health messages should include more information about its low frequency of adverse effects and overall safety. Further awareness about access to low-cost PrEP might improve uptake and retention. There are established state-sponsored programs that offer low-cost or free PrEP through in-person or telemedicine visits or with simple delivery via regular mail. Additional efforts to promote those initiatives and programs in high-incidence areas, such as in the areas included in this study, may be necessary.Alcohol use during pregnancy has been related to poorer offspring postnatal health and cognitive and behavioral outcomes from birth through adulthood . The global prevalence rate of any alcohol use in pregnancy is approximately 10% . Factors such as dose and exposure patterns,vertical grow racks canada as well as accompanying environmental factors, likely contribute to the significant variability in the range and magnitude of adverse pregnancy outcomes associated with prenatal alcohol exposure.
One of the most disabling potential outcomes of drinking during pregnancy is fetal alcohol syndrome, which has an estimated global prevalence in the general population of 14.6 per 10,000 people . Fetal alcohol syndrome is associated with brain anomalies, postnatal growth restriction, and facial dysmorphology, as well as psychological, behavioral, and cognitive deficits . Fetal alcohol spectrum disorder is a more inclusive umbrella term used to describe individuals within the overarching category of prenatal alcohol exposure, including fetal alcohol syndrome, partial fetal alcohol syndrome, alcohol-related neurodevelopmental disorder, fetal alcohol effects, and alcohol-related birth defects. Estimates suggest that one of every 13 women who consumed alcohol during pregnancy delivered a child with fetal alcohol spectrum disorder, equivalent to 76.9 per 10,000 children in the general population . Children with fetal alcohol spectrum disorder exhibit poorer behavior and emotions, lower intelligence, cognitive deficits, and neurodevelopmental delays . Neuroimaging studies show that youths with fetal alcohol spectrum disorder, who were exposed to heavy alcohol use in utero , exhibit smaller cerebral surface area and aberrant cortical thickness and generally show widespread reductions in brain volume throughout cortical and subcortical regions when compared with unexposed youths , although other studies have reported increased gray matter in the parietal and temporal lobes . Youths with fetal alcohol spectrum disorder also exhibit reduced resting-state functional connectivity in the default, salience, dorsal and ventral attention, and executive control networks . Although there is an established literature on the adverse outcomes associated with heavy alcohol use in pregnancy, evidence of the effects of lighter alcohol use on offspring psychological, behavioral, and neurodevelopmental outcomes is sparse and inconsistent, perhaps because of sample size and inadequate adjustment for potential confounding factors in some studies . To fill these knowledge gaps, the present study utilized clinical interview, youth and parent self-report, cognitive tasks, and structural and resting-state functional MRI data from 9,719 community-based children ages 9–10 years in the Adolescent Brain Cognitive Development Study.
We aimed to address four research questions critical for families, clinicians, and policy makers. First, do psychological, behavioral, and neurodevelopmental outcomes differ between youths prenatally exposed to alcohol and unexposed youths during preadolescence, before youths have initiated alcohol and other substance use? Second, is there a dose-dependent relationship between levels of alcohol exposure and outcomes of interest? Third, what are the common alcohol exposure patterns in the ABCD community sample, and are these patterns associated with adverse outcomes? And fourth, do structural and functional brain differences mediate the association between prenatal alcohol exposure and neurobehavioral outcomes? An examination of this large, diverse community sample of children in the United States, where patterns of exposure are more typical of the general population, is urgently needed. Prenatal alcohol exposure was measured using the modified Developmental History Questionnaire through parents’ retrospective report of maternal alcohol use before and after knowledge of pregnancy , the maximum number of drinks consumed on a single occasion, and the average number of drinks consumed per week during pregnancy. From this information, a dichotomous prenatal alcohol exposure variable was derived , an estimate of the total number of drinks consumed during pregnancy was calculated, and youths were categorized into common alcohol exposure patterns based on established prenatal alcohol use classification . Further details and relevant questions from the ABCD protocol are provided in the online supplement.Psychopathology was examined in children using the eight empirically based syndrome scales and higher-order factors of the parent-reported Child Behavior Checklist . Lifetime mental disorder diagnoses were determined using parent-reported responses on the Schedule for Affective Disorders and Schizophrenia for School-Age Children , based on DSM-5 criteria . Impulsivity was assessed using the 20-item Urgency, Premeditation, Perseverance, Sensation Seeking, Positive Urgency, Impulsive Behavior Scale for Children-Short Form .
Motivation was examined using the four subscales of the behavioral avoidance and behavioral inhibition scales .The single-item Cash Choice Task was utilized as a measure of delayed gratification, motivation, and impulsivity . All data were available for baseline assessment , and 1-year follow-up data were available for all psychopathology syndrome scales and higher-order factors as measured by the CBCL and for the externalizing disorders as measured by the K-SADS . We adjusted for fixed and random effects. Fixed covariates were chosen based on prior evidence of an association with the outcomes or because of statistically significant group differences in the present sample . Birth-related covariates included weight and whether the child was born prematurely . Genetic covariates included sex at birth and race/ethnicity . Youth age at time of assessment and school grade performance were also included. Maternal covariates included maternal age at birth, a history of maternal depression , and other substance use during pregnancy, with tobacco, cannabis, cocaine, and heroin use each included as separate variables. The highest level of parental education was used as an indicator of socioeconomic status . Random effects included nesting youths within families to account for sibling effects and nesting youths within MRI scanner site. Imaging acquisition and scanning parameters are described elsewhere . Briefly, all scans were uploaded to a shared server that is maintained by the Data Analysis, Informatics, and Resource Center of the ABCD Study. Brain data were collected on 3-T scanners, including the Siemens MAGNETOM Prisma, the GE Discovery MR750, and the Philips Achieva. The T1 images were corrected for gradient nonlinearity distortions using scanner-specific, nonlinear transformations. Cortical reconstruction and volumetric segmentation were performed by the Data Analysis, Informatics, and Resource Center using FreeSurfer, version 5.3.0. The Desikan-Killiany brain registration atlas was used in the present analyses to examine cortical thickness, surface area, and volume of 68 cortical regions, as well as volume in 40 subcortical segmentations. Participants also completed four 5-minute resting state blood-oxygen-level-dependent scans, with their eyes open and fixated on a crosshair. Resting-state images were acquired in the axial plane using an echo-planar imaging sequence. Using a functional atlas, cortical surface regions were grouped into 12 predefined large-scale networks : auditory, cingulo-opercular, cingulo-parietal, default-mode, dorsal-attention, fronto-parietal, retrosplenial-temporal, salience, sensorimotor-hand,sensorimotor-mouth, ventral-attention,2×4 grow rack and visual networks. Resting-state functional connectivity strength indices were then calculated using the Fisher r-to-z transformation of the average correlation values between pairs of regions within each large-scale network , between these 12 networks , and between the networks and 19 subcortical regions . The Data Analysis, Informatics, and Resource Center used a combination of automated and manual methods to review the data sets for quality control before sharing data via the National Institute of Mental Health Data Archive. First, prenatal alcohol exposure was examined as a dichotomous variable . Generalized additive mixed models exploring associations with psychological, behavioral, neural, and cognitive outcomes were run adjusting only for random effects and then were repeated after entering all covariates as fixed effects . Structural and functional neural indices found to be significantly associated with prenatal alcohol exposure when adjusting for fixed and random effects were identified as regions of interest for the remaining analyses. Follow-up analyses included intracranial volume as an additional covariate in statistically significant volumetric models. Considering the large number of functional indices explored and the strict multiple comparisons adjustment applied, uncorrected results were also reported for connectivity within and between a narrower selection of major networks previously associated with fetal alcohol spectrum disorder .
To examine dose-dependent relationships, spline models with 1.5% winsorization to convert outliers were conducted to flexibly fit associations between the estimated total number of drinks consumed during pregnancy and outcomes of interest, adjusting for fixed and random effects. Next, the prevalence of alcohol exposure patterns was estimated, and the effect of these patterns of drinking in pregnancy on the outcomes of interest was examined using generalized additive mixed models. The week of maternal pregnancy awareness was added as an additional covariate. Follow-up analyses examined whether there were differential effects associated with varying gradations of alcohol use throughout pregnancy. Sensitivity analyses were conducted, where the dichotomous prenatal alcohol exposure groups were demographically matched on all covariates after excluding rarer cases on which groups were mismatched, including youths with other in utero substance use exposure and positive reports of maternal depression . The aforementioned association analyses were then repeated with this more homogeneous sub-sample . Results of unadjusted models and effect sizes are provided in Tables S2–S5 in the online supplement. In covariate adjusted models, youths prenatally exposed to alcohol exhibited significantly greater psychopathology, impulsivity, and cognitive functioning compared with unexposed youths . Exposed youths were more likely to have a lifetime diagnosis of separation anxiety disorder and oppositional defiant disorder relative to unexposed youths. Exposed youths also exhibited greater total cerebral volume and greater regional cortical volume and surface area throughout the temporal, occipital, and parietal lobes, relative to unexposed youths. Regional cortical volume differences in the left inferior temporal lobe passed false-discovery-rate correction when intracranial volume was included as an additional covariate . No significant differences between exposed and unexposed youths were observed for cortical thickness. Compared with unexposed youths, exposed youths exhibited hypoconnectivity between the auditory network and the right ventral diencephalon, and hyper connectivity between the sensorimotor hand and salience networks . Connectivity within and between the other networks and sub-cortical indices was not significantly associated with prenatal alcohol exposure . Considering that no significant associations were observed within or between established networks previously associated with fetal alcohol spectrum disorder, no further results of functional analyses are presented here .In covariate-adjusted models, linear and nonlinear associations were observed between the estimated total number of drinks consumed during pregnancy and total psychological problems, internalizing psychopathology and somatic complaints, attention deficits, sensation-seeking behavior, and performance on the Flanker Task, which measured attention and inhibitory control . The total number of drinks was linearly associated with greater cerebral volume . Both linear and nonlinear associations were observed between the total number of drinks and regional volume throughout the temporal, occipital, and parietal lobes . Dose-dependent responses were not observed for any other outcome of interest.Six patterns of parent-reported alcohol use in pregnancy were identified . Because of sample size, exposure pattern analyses were limited to abstinent mothers, light reducers, light, stable users, and heavier reducers, accounting for 98.1% of the sample. On average, light reducer mothers consumed 2.3 drinks/week for the first 7 weeks of pregnancy . Light stable-drinking mothers consumed approximately 1.1 drinks/week throughout pregnancy , while heavier reducer mothers consumed approximately 5.3 drinks/week for the first 7 weeks of pregnancy . Participant characteristics for each group are provided in Table S9 in the online supplement. Covariate-adjusted models showed that, compared with unexposed youths, all exposure groups exhibited greater psychopathology and behavioral problems, varying mental disorders , and greater cognitive functioning.