Early risk for child externalising symptoms: Examining genetic, prenatal, temperamental and parental influences.

This study utilized the Early Growth and Development Study (N = 561 adoptive children; 57.2% male, 55.3% White), a study of children adopted at birth, to examine heritable (birth parent psychopathology) and prenatal risk (prenatal maternal distress and smoking during pregnancy), infant negative affectivity, adoptive parent over-reactivity and warmth as independent predictors of childhood externalizing symptoms. The current study evaluated if: (1) infant negative affectivity and over-reactive parenting are candidate mediators for the effects of heritable and prenatal risk on externalizing symptoms and (2) parental warmth weakens the influence of heritable risk, prenatal risk, negative affectivity, and over-reactive parenting on externalizing symptoms. There were main effects of heritable risk, infant negative affectivity, and over-reactive parenting on child externalizing symptoms. The study found no support for the hypothesized mediation and moderation effects, suggesting that targeting parental over-reactivity rather than warmth would be more effective in reducing risk for childhood externalizing symptoms.

Maternal smoking during pregnancy is associated with DNA methylation in early adolescence: A sibling comparison design.

Maternal smoking during pregnancy (MSDP) may impact offspring biological (e.g., deoxyribonucleic acid methylation [DNAm]) and behavioral (e.g., attention-deficit/hyperactivity disorder hyperactive/impulsive [ADHD-HI] symptoms) development. There has been consistency in findings of differential methylation in global DNAm, and the specific genes AHRR, CYP1A1, CNTNAP2, MYO1G, and GFI1 in relation to MSDP. The current study aims to (a) replicate the associations of MSDP and DNAm in prior literature in middle childhood-adolescence (cross-sectionally) using a sibling-comparison design where siblings were discordant for MSDP (n = 328 families; Mage Sibling 1 = 13.02; Sibling 2 = 10.20), adjusting for prenatal and postnatal covariates in order to isolate the MSDP exposure on DNAm. We also (b) cross-sectionally explored the role of DNAm in the most robust MSDP-ADHD associations (i.e., with ADHD-HI) previously found in this sample. We quantified smoking exposure severity for each sibling reflecting time and quantity of MSDP, centered relative to the sibling pair's average (i.e., within-family centered, indicating child-specific effects attributable MSDP exposure) and controlling for the sibling average MSDP (i.e., between-family component, indicating familial confounding related to MSDP). We found that child-specific MSDP was associated with global DNAm, and CNTNAP2, CYP1A1, and MYO1G methylation after covariate adjustment, corroborating emerging evidence for a potentially causal pathway between MSDP and DNAm. There was some evidence that child-specific CNTNAP2 and MYO1G methylation partially explained associations between MSDP and ADHD-HI symptoms, though only on one measure (of two). Future studies focused on replication of these findings in a longitudinal genetic design could further solidify the associations found in the current study. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The roles of familial transmission and smoking during pregnancy on executive function skills: A sibling-comparison study.

This research examines maternal smoking during pregnancy and risk for poorer executive function in siblings discordant for exposure. Data (N = 173 families) were drawn from the Missouri Mothers and Their Children study, a sample, identified using birth records (years 1998-2005), in which mothers changed smoking behavior between two pregnancies (Child 1 [older sibling]: M age = 12.99; Child 2 [younger sibling]: M age = 10.19). A sibling comparison approach was used, providing a robust test for the association between maternal smoking during pregnancy and different aspects of executive function in early-mid adolescence. Results suggested within-family (i.e., potentially causal) associations between maternal smoking during pregnancy and one working memory task (visual working memory) and one response inhibition task (color-word interference), with increased exposure associated with decreased performance. Maternal smoking during pregnancy was not associated with stop-signal reaction time, cognitive flexibility/set-shifting, or auditory working memory. Initial within-family associations between maternal smoking during pregnancy and visual working memory as well as color-word interference were fully attenuated in a model including child and familial covariates. These findings indicate that exposure to maternal smoking during pregnancy may be associated with poorer performance on some, but not all skills assessed; however, familial transmission of risk for low executive function appears more important.

Analysis of Early-Life Growth and Age at Pubertal Onset in US Children.

Importance: Earlier pubertal onset may be associated with an increased risk of chronic diseases. However, the extent to which growth in the first 5 years of life-an important developmental life stage that lays the foundation for later health outcomes-is associated with pubertal onset remains understudied. Objective: To assess whether changes in weight, length or height, and body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) during the first 5 years of life are associated with earlier pubertal onset. Design, Setting, and Participants: This cohort study used data from 36 cohorts participating in the Environmental Influences on Child Health Outcomes program from January 1, 1986, to December 31, 2015. Participant inclusion required at least 1 anthropometric measure in the first 5 years of life and at least 1 measure of pubertal onset. Data were analyzed from January 1 to June 30, 2021. Exposures: Standardized velocities of weight, length or height, and BMI gain in early infancy (0-0.5 years), late infancy (0.5-2 years), and early childhood (2-5 years). Main Outcomes and Measures: Markers of pubertal onset for boys and girls, including age at peak height velocity (APHV), time to puberty score greater than 1, time to Tanner pubic hair stage greater than 1, and time to menarche. Multivariable regression models were used to estimate mean differences in APHV by growth periods. Results: Of 7495 children included in the study, 3772 (50.3%) were girls, 4505 (60.1%) were White individuals, and 6307 (84.1%) were born during or after the year 2000. Girls had a younger APHV (10.8 vs 12.9 years) than boys. In boys, faster weight gain (per 1-SD increase) in early infancy (ß, -0.08 years; 95% CI, -0.10 to -0.06), late infancy (ß, -0.10 years; 95% CI, -0.12 to -0.08), and early childhood (ß, -0.07 years; 95% CI, -0.08 to -0.05) was associated with younger APHV after adjusting for the child's birth year, race, and Hispanic ethnicity as well as maternal age at delivery; educational level during pregnancy; annual household income during pregnancy; prenatal cigarette smoking; whether the mother was nulliparous; whether the mother had gestational diabetes, hypertension, or preeclampsia; mode of delivery; prepregnancy BMI; gestational weight gain; and gestational age at delivery. Similar associations were observed for length or height and BMI gains during the same age periods. In girls, faster gains (per 1-SD increase) in weight (ß, -0.03 years; 95% CI, -0.05 to -0.01) and height (ß, -0.02 years; 95% CI, -0.04 to 0.00) in early childhood were associated with younger APHV. Faster BMI gain in late infancy was associated with earlier time to menarche, whereas faster BMI gain in early childhood was associated with earlier time to Tanner pubic hair stage greater than 1. Conclusions and Relevance: This cohort study found that faster gains in weight, length or height, or BMI in early life were associated with earlier pubertal onset. The results suggest that children who experience faster early growth should be monitored closely for earlier onset of puberty and referred as appropriate for supportive services.

Interactions between Genetic, Prenatal, Cortisol, and Parenting Influences on Adolescent Substance Use and Frequency: A TRAILS Study.

INTRODUCTION: Dynamic relations between genetic, hormone, and pre- and postnatal environments are theorized as critically important for adolescent substance use but are rarely tested in multifactorial models. This study assessed the impact of interactions of genetic risk and cortisol reactivity with prenatal and parenting influences on both any and frequency of adolescent substance use. METHODS: Data are from the TRacking Adolescents' Individual Lives Survey (TRAILS), a prospective longitudinal, multi-rater study of 2,230 Dutch adolescents. Genetic risk was assessed via 3 substance-specific polygenic scores. Mothers retrospectively reported prenatal risk when adolescents were 11 years old. Adolescents rated their parents' warmth and hostility at age 11. Salivary cortisol reactivity was measured in response to a social stress task at age 16. Adolescents' self-reported cigarette, alcohol, and cannabis use frequency at age 16. RESULTS: A multivariate hurdle regression model showed that polygenic risk for smoking, alcohol, and cannabis predicted any use of each substance, respectively, but predicted more frequent use only for smoking. Blunted cortisol reactivity predicted any use and more frequent use for all 3 outcomes. There were 2 interactions: blunted cortisol reactivity exacerbated the association of polygenic risk with any smoking and the association of prenatal risk with any alcohol use. CONCLUSION: Polygenic risk seems of importance for early use but less so for frequency of use, whereas blunted cortisol reactivity was correlated with both. Blunted cortisol reactivity may also catalyze early risks for substance use, though to a limited degree. Gene-environment interactions play no role in the context of this multifactorial model.

Predictors and moderators of response to brief interventions among adolescents with risky alcohol and marijuana use.

Background:Brief interventions have shown promise in reducing adolescent alcohol and marijuana use. This manuscript presents a secondary analysis of a randomized trial that compared a brief parent motivational intervention (Family Check Up; FCU) to brief psychoeducation (PE) condition and found no effect of treatment condition on either binge drinking or marijuana use days. The current analyses explored whether the response to treatment may have varied as a function of six empirically-based baseline moderators and predictors: biological sex, age, race/ethnicity, mental health problems, parent-adolescent communication, and peer deviance. Methods: Data from the parent trial randomizing 102 parents to either the FCU (n = 51) or PE (n = 51) interventions were re-analyzed across four time points (baseline, 3-, 6-, and 12-months). Moderators and predictors were tested via a series of hierarchical linear models. Results: Parent-adolescent communication and peer deviance emerged as significant predictors of adolescent treatment response. Specifically, low-levels of parent-adolescent communication or peer deviance were associated with worse treatment response (i.e., significant increases in binge drinking days and marijuana use days) in the PE condition, but not in the FCU condition. Non-Hispanic Whites and girls had worse treatment response, regardless of treatment condition. Conclusions: The FCU condition appeared to mitigate risks of poor parent-adolescent communication and affiliation with deviant peers better than the PE condition. Clinical recommendations for decision-making around assignment to brief interventions are discussed.

A sibling-comparison study of smoking during pregnancy and risk for reading-related problems.

This research examines the relationship between smoking during pregnancy (SDP) and risk for reading related problems in siblings discordant for exposure to SDP. Data (N = 173 families) were drawn from the Missouri Mothers and Their Children study, a sample, identified using birth records (years 1998-2005), in which mothers changed her smoking behavior between two pregnancies (Child 1 [older sibling]: M = 12.99; Child 2 [younger sibling]: M = 10.19). A sibling comparison approach was used, providing a robust test for the association between SDP and reading related outcomes in school-aged children. Results suggested within-family (i.e., potentially causal) associations between SDP and reading and language/comprehension factor scores, as well as between SDP and specific reading-related skills, including reading accuracy and receptive language, with increased exposure to SDP associated with decreased performance. SDP was not associated with spelling, reading rate, or receptive vocabulary. Initial within-family associations between SDP and word-letter identification, phonetic/decoding skills, and reading comprehension were fully attenuated following partial control for genetic and environmental confounding of the associations. These findings indicate that exposure to SDP is associated with poorer performance on some, but not all skills assessed.

The Effect of Smoking during Pregnancy on Severity and Directionality of Externalizing and Internalizing Symptoms: A Genetically Informed Approach.

The objective was to examine the association between maternal smoking during pregnancy (SDP) and (I) severity and (II) directionality of externalizing and internalizing symptoms in a sample of sibling pairs while rigorously controlling for familial confounds. The Missouri Mothers and Their Children Study is a family study (N = 173 families) with sibling pairs (aged 7 to 16 years) who are discordant for exposure to SDP. This sibling comparison study is designed to disentangle the effects of SDP from familial confounds. An SDP severity score was created for each child using a combination of SDP indicators (timing, duration, and amount). Principal component analysis of externalizing and internalizing behavior, assessed with the Child Behavior Checklist and Teacher Report Form, was used to create symptom severity and directionality scores. The variance in severity and directionality scores was primarily a function of differences between siblings (71% and 85%, respectively) rather than differences across families (29% and 15%, respectively). The severity score that combines externalizing and internalizing symptom severity was not associated with SDP. However, a significant within-family effect of SDP on symptom directionality (b = 0.07, p = 0.04) was observed in the sibling comparison model. The positive directionality score indicates that SDP is associated with differentiation of symptoms towards externalizing rather than internalizing symptoms after controlling for familial confounds with a sibling comparison model. This supports a potentially causal relationship between SDP and externalizing behavior.

Maternal Consistency in Recalling Prenatal Experiences at 6 Months and 8 Years Postnatal.

OBJECTIVE: Mothers are known to be reliable reporters of smoking during pregnancy, type of delivery, and birth weight when compared with medical records. Few studies have considered whether the timing of retrospective collection affects the mother's retrospective self-report. We examined the consistency of maternal retrospective recall of prenatal experiences, behaviors, and basic birth outcomes between 6 months and 8 years postpartum. METHOD: We examined 117 mothers (62% White, 44% living in a committed relationship, median high school education) from the Early Growth and Development Study (EGDS). EGDS is a longitudinal adoption study that includes birth mothers of children born between 2003 and 2009 who were involved in a domestic adoption. Using the modified life history calendar and a pregnancy screener, mothers reported on their prenatal health behaviors, prenatal substance use, and labor and delivery at 6 months and 8 years postpartum. Cohen κ was calculated to examine consistency, and χ tests were used to test differences by parity and maternal education. RESULTS: Mothers' recall was very good for recall of the type of delivery and good for smoking during pregnancy, medicine used for labor induction, and specific medical problems (i.e., pre-eclampsia, sexually transmitted infections, and kidney infections). Recall consistency was poor for illicit drug use, specific prenatal tests performed (i.e., amniocentesis and emergency room visits), and using drugs other than an epidural during delivery. CONCLUSION: This study provides support for using retrospective collection of maternal self-report on some prenatal experiences up to 8 years postpartum and offers a potential way to more accurately collect self-reported prenatal experiences.

Lability in Parent- and Child-Based Sources of Parental Monitoring Is Differentially Associated with Adolescent Substance Use.

Parental knowledge about adolescents' whereabouts and activities remains one of the strongest predictors of reduced adolescent substance use. A recent study found that across middle childhood and adolescence, parental knowledge is characterized by fluctuations on a year-to-year basis, termed lability, even more-so than by linear trends, and that lability too is a predictor of adolescent substance use (Lippold et al., Dev. Psychol. 17, 274-283, 2016). The present study replicates Lippold et al. (Dev. Psychol. 17, 274-283, 2016) by quantifying developmental change and lability in parental knowledge across adolescence and examining associations with drinking, smoking, and other drug use later in adolescence, and extends the study by examining the sources of knowledge: child disclosure, parental solicitation, and parental control, separately. Using a community-based sample of 1023 youth in the Northeastern region of the USA, all three sources of knowledge were characterized by developmental change and lability. In general, higher levels and steeper developmental declines in knowledge were associated with substance use outcomes. Findings for child disclosure replicated the prior findings: increased lability of child disclosure predicted substance use. Unexpectedly, decreased lability of parental solicitation and control was associated with worse substance use outcomes. Findings suggest different mechanisms by which lability in child- and parent-driven cultivation of knowledge is associated with substance use. If replicated in studies that address causality, these mechanisms could be leveraged for prevention/intervention efforts. For example, increasing the consistency of child disclosure may help prevent substance use, but teaching parents to be more responsive to time-specific challenges with adolescents may be more effective than increasing the consistency of parents' knowledge-building parenting behaviors.

Developmental Pathways from Genetic, Prenatal, Parenting and Emotional/Behavioral Risk to Cortisol Reactivity and Adolescent Substance Use: A TRAILS Study.

Cortisol reactivity is a frequently studied biomarker of substance use, though infrequently examined in adolescence. However, past research provides evidence that multiple developmental influences, including genetics and both prenatal and postnatal environmental influences, contribute both to cortisol reactivity and adolescent substance use. The aim of this study was to assess the impact of these earlier developmental influences on cortisol reactivity to a social stress challenge and adolescent substance use (smoking, alcohol, and marijuana use frequency assessed at age 16 years), using data from the TRacking Adolescents' Individual Lives Survey (TRAILS; N= 2230 adolescents, 51% female). Developmental pathways included polygenic risk, prenatal stress, warm parenting (age 11), and internalizing and externalizing problems (intercepts and change from 11-16 years). Cortisol reactivity was associated with smoking but not alcohol or marijuana use. Externalizing problems were the stronger predictor of adolescent substance use, but internalizing problems also had an important role. Prenatal stress and middle childhood parenting operated via middle childhood externalizing problems, and parenting also operated via trajectories of growth of externalizing problems in predicting adolescent substance use outcomes. Further, there were protective effects of internalizing problems for alcohol and marijuana use in the context of a more comprehensive model. These developmental influences did not attenuate the association of cortisol reactivity and smoking. These findings suggest a need to understand the broader developmental context regarding the impact of internalizing pathways to substance use, and that it is unlikely that cortisol reactivity and smoking are associated solely because of common developmental influences.

Disruptive Behavior in Siblings Discordant for Exposure to Maternal Smoking During Pregnancy: A Multi-rater Approach.

INTRODUCTION: Maternal smoking during pregnancy (SDP) is associated with disruptive behavior. However, there is debate whether the SDP-disruptive behavior association is a potentially causal pathway or rather a spurious effect confounded by shared genetic and environmental factors. AIMS AND METHODS: The Missouri Mothers and Their Children Study is a sibling comparison study that includes families (n = 173) selected for sibling pairs (aged 7-16 years) discordant for SDP. Critically, the sibling comparison design is used to disentangle the effects of SDP from familial confounds on disruptive behavior. An SDP severity score was created for each child using a combination of SDP indicators (timing, duration, and amount of SDP). Multiple informants (parents and teachers) reported on disruptive behavior (i.e., DSM-IV semi-structured interview, the Child Behavior Checklist, and Teacher Report Form). RESULTS: The variability in disruptive behavior was primarily a function of within-family differences (66%-100%). Consistent with prior genetically informed approaches, the SDP-disruptive behavior association was primarily explained by familial confounds (genetic and environmental). However, when using a multi-rater approach (parents and teachers), results suggest a potentially causal effect of SDP on disruptive behavior (b = 0.09, SE = 0.04, p = 0.03). The potentially causal effect of SDP remained significant in sensitivity analyses. DISCUSSION: These findings suggest that familial confounding likely plays a complex role in the SDP-disruptive behavior association when examining both parent and teacher reports of behavior. Importantly, the current study highlights the importance of multiple raters, reflecting a more comprehensive measure of complex behaviors (e.g., disruptive behavior) to examine the teratogenic effects of SDP. IMPLICATIONS: Our study provides additional evidence that controlling for genetic and family factors is essential when examining the effect of SDP on later behavioral problems, as it explains a portion of the association between SDP and later behavioral problems. However, we found a significant association between SDP and disruptive behavior when using a multi-rater approach that capitalizes on both parent and teacher report, suggesting that parent and teacher ratings capture a unique perspective that is important to consider when examining SDP-behavior associations.

Parenting and prenatal risk as moderators of genetic influences on conduct problems during middle childhood.

This study examines interactions of heritable influences, prenatal substance use, and postnatal parental warmth and hostility on the development of conduct problems in middle childhood for boys and girls. Participants are 561 linked families, collected in 2 cohorts, including birth parents, adoptive parents, and adopted children. Heritable influences on internalizing and externalizing (including substance use) problems were derived from birth mothers' and fathers' symptoms, diagnoses, and age of onset from diagnostic interviews, and the proportion of first-degree relatives with the same type of problems. Smoking during pregnancy (SDP) and alcohol use during pregnancy were assessed retrospectively from birth mothers at 5 months postpartum. Earlier externalizing problems and parental warmth and hostility and were assessed at 1 assessment prior to the outcome (Cohort II: 4.5 years; Cohort I: 7 years). Conduct problems were symptoms from a diagnostic interview assessed at age 6 (Cohort II) or 8 (Cohort I). Findings from regression analyses suggest that (a) SDP plays an important role for the development of conduct problems, (b) some relatively well-accepted effects (e.g., parental hostility) were less important when simultaneously considering multiple factors influencing the development of conduct problems, and (c) main effects of genetic risk and SDP, and interactions among genetic risk and postnatal warmth, SDP and postnatal warmth, and genetic risk, SDP, and postnatal hostility for conduct problems were important for boys' but not girls' conduct problems. Replication is needed, but the current results provide preliminary but empirically grounded hypotheses for future research testing complex developmental models of conduct problems. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Prenatal substance exposure and offspring development: Does DNA methylation play a role?

The period of in utero development is one of the most critical windows during which adverse conditions and exposures may influence the growth and development of the fetus as well as its future postnatal health and behavior. Maternal substance use during pregnancy remains a relatively common but nonetheless hazardous in utero exposure. For example, previous epidemiological studies have associated prenatal substance exposure with reduced birth weight, poor developmental and psychological outcomes, and increased risk for diseases and behavioral disorders (e.g., externalizing behaviors like ADHD, conduct disorder, and substance use) later in life. Researchers are now learning that many of the mechanisms whereby adverse in utero exposures may affect key pathways crucial for proper fetal growth and development are epigenetic in nature, with the majority of work in humans considering DNA methylation specifically. This review will explore the research to date on epigenetic alterations tied to maternal substance use during pregnancy and will also discuss the possible role of DNA methylation in the robust relationship between maternal substance use and later behavioral and developmental sequelae in offspring.

Within-Family Effects of Smoking during Pregnancy on ADHD: the Importance of Phenotype.

We sought to test within- and between- family associations of smoking during pregnancy (SDP) and attention deficit-hyperactivity disorder (ADHD) symptoms using a structured interview based on the conventional Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) symptoms and the Strengths and Weaknesses of ADHD-Symptoms and Normal-Behavior (SWAN) scale, which is a population based measure that grew out of the notion that an ADHD diagnosis exists on the extreme end of a continuum of normative behaviors and includes both above- and below- average performance on attention and activity. We used a sibling-comparison approach in a sample of 173 families including siblings aged 7-16 years (52% male) drawn from the state of Missouri, USA, wherein mothers smoked during one pregnancy but not the other. There was a within-family effect of smoking during pregnancy on SWAN hyperactivity/impulsivity and SWAN total ADHD behaviors. The associations between SDP and DSM-IV-based ADHD symptom dimensions as well as SWAN inattention were explained by familial confounds. These findings suggest that SDP exerts a potentially causal effect on increased ADHD hyperactive/impulsive behaviors and that this SDP effect is best captured when hyperactivity/impulsivity is assessed more normatively across the population, rather than specifically assessing problematic behaviors via DSM symptoms. Thus, any potentially causal effect of SDP on ADHD symptom dimensions may be restricted to hyperactive/impulsive behaviors rather than inattention, and normative, non-DSM-IV based behavioral measures may provide a more sensitive test of mechanisms of SDP-ADHD symptom associations, particularly in non-clinical samples.

Inhibitory control in siblings discordant for exposure to maternal smoking during pregnancy.

Maternal smoking during pregnancy (SDP) has been linked to poorer offspring executive function across development, but SDP does not occur independent of other familial risk factors. As such, poor and inconsistent control for potential confounds, notably shared familial (i.e., genetic and environmental) confounds, preclude concluding causal effects of SDP on child outcomes. We examined the within-family association between SDP and one component of executive function, inhibitory control, in a sample of families (N = 173) specifically selected for sibling pairs discordant for exposure to SDP. Thus, the present study examines if the SDP-inhibitory control association withstands rigorous control for potential child and familial confounds. 79% of the variation in child inhibitory control was attributable to within-family differences and 21% was attributable to differences between families, indicating that the variability in inhibitory control was primarily a function of differences between siblings rather than differences across families. Further, the association between SDP and inhibitory control was fully attenuated when confounds were considered. These findings suggest that co-occurring vulnerabilities act as more salient risk factors for poorer child inhibitory control than SDP and may serve as effective targets of interventions seeking to improve children's inhibitory control in families with nicotine dependent mothers. (PsycINFO Database Record

Prenatal Exposure Effects on Early Adolescent Substance Use: Preliminary Evidence From a Genetically Informed Bayesian Approach.

OBJECTIVE: Given the controversy surrounding the question of whether there are direct or causal effects of exposure to maternal smoking during pregnancy (SDP) on offspring outcomes such as substance use during the adolescent years, we sought to test, on a preliminary basis, within- and between-family associations of SDP and initiation of substance use early in adolescence (by age 15 years) using a discordant sibling design. METHOD: We used a sibling-comparison approach in a sample of 173 families drawn from the state of Missouri, wherein mothers were discordant for smoking behaviors between two different pregnancies, to test for associations of SDP and initiation of substance use in a younger adolescent cohort. The discordant sibling comparison approach allows for disentangling familial effects from direct effects of SDP through the purposeful collection of data from siblings within the same family with differential exposure. RESULTS: There were no between- or within-family effects of SDP on initiation of any type of substance use (alcohol, marijuana, smoking, and other drug classes), suggesting that SDP does not exert a direct effect on substance use in early adolescence. CONCLUSIONS: Preliminary findings did not support an association of SDP and initiation of substance use in this younger adolescent sample. Studies such as this one can help build a body of evidence to explain whether associations of SDP and adolescent outcomes reflect a direct effect of SPD or may instead be attributable to familial confounders that are controlled in the discordant sibling design.

Smoking during pregnancy and ADHD risk: A genetically informed, multiple-rater approach.

Maternal smoking during pregnancy (SDP) is a significant public health concern with adverse consequences to the health and well-being of the developing child, including behavioral outcomes such as Attention-Deficit Hyperactivity Disorder (ADHD). There is substantial interest in understanding the nature of this reported association, particularly in light of more recent genetically informed studies that suggest that the SDP-ADHD link is less clear than once thought. In a sample of families (N = 173) specifically selected for sibling pairs discordant for prenatal smoking exposure, we use a sibling-comparison approach that controls for shared genetic and familial influences to assess the effects of SDP on ADHD symptom dimensions. ADHD was measured by both parent and teacher report on the Conners report forms and the Child Behavior Checklist/Teacher Report Form (CBCL/TRF). Results for the CBCL/TRF Total ADHD score are consistent with prior genetically informed approaches and suggest that previously reported associations between SDP and ADHD are largely due to familial confounding rather than causal teratogenic effects. However, results from the Conners parent report suggest a potentially causal effect of SDP on hyperactive/impulsive and, to a lesser extent, total ADHD symptoms; SDP results in increased parent-reported hyperactive/impulsive and total ADHD symptoms even after accounting for genetic and familial confounding factors. This suggests that the Conners assessment (parent-report) may provide a sensitive measure for use in studies examining child specific SDP effects on continuous and dimensional aspects of ADHD. © 2016 Wiley Periodicals, Inc.

Passive rGE or Developmental Gene-Environment Cascade? An Investigation of the Role of Xenobiotic Metabolism Genes in the Association Between Smoke Exposure During Pregnancy and Child Birth Weight.

There is considerable evidence that smoke exposure during pregnancy (SDP) environmentally influences birth weight after controlling for genetic influences and maternal characteristics. However, maternal smoking during pregnancy-the behavior that leads to smoke exposure during pregnancy-is also genetically-influenced, indicating the potential role of passive gene-environment correlation. An alternative to passive gene-SDP correlation is a cascading effect whereby maternal and child genetic influences are causally linked to prenatal exposures, which then have an 'environmental' effect on the development of the child's biology and behavior. We describe and demonstrate a conceptual framework for disentangling passive rGE from this cascading GE effect using a systems-based polygenic scoring approach comprised of genes shown to be important in the xenobiotic (substances foreign to the body) metabolism pathway. Data were drawn from 5044 families from the Avon Longitudinal Study of Parents and Children with information on maternal SDP, birth weight, and genetic polymorphisms in the xenobiotic pathway. Within a k-fold cross-validation approach (k = 5), we created weighted maternal and child polygenic scores using 18 polymorphisms from 10 genes that have been implicated in the xenobiotic metabolism pathway. Mothers and children shared variation in xenobiotic metabolism genes. Amongst mothers who smoked during pregnancy, neither maternal nor child xenobiotic metabolism polygenic scores were associated with a higher likelihood of smoke exposure during pregnancy, or the severity of smoke exposure during pregnancy (and therefore, neither proposed mechanism was supported), or with child birth weight. SDP was consistently associated with lower child birth weight controlling for the polygenic scores, maternal educational attainment, social class, psychiatric problems, and age. Limitations of the study design and the potential of the framework using other designs are discussed.

Maternal Smoking During Pregnancy and Offspring Birth Weight: A Genetically-Informed Approach Comparing Multiple Raters.

Maternal smoking during pregnancy (SDP) is a significant public health concern with adverse consequences to the health and well-being of the fetus. There is considerable debate about the best method of assessing SDP, including birth/medical records, timeline follow-back approaches, multiple reporters, and biological verification (e.g., cotinine). This is particularly salient for genetically-informed approaches where it is not always possible or practical to do a prospective study starting during the prenatal period when concurrent biological specimen samples can be collected with ease. In a sample of families (N = 173) specifically selected for sibling pairs discordant for prenatal smoking exposure, we: (1) compare rates of agreement across different types of report-maternal report of SDP, paternal report of maternal SDP, and SDP contained on birth records from the Department of Vital Statistics; (2) examine whether SDP is predictive of birth weight outcomes using our best SDP report as identified via step (1); and (3) use a sibling-comparison approach that controls for genetic and familial influences that siblings share in order to assess the effects of SDP on birth weight. Results show high agreement between reporters and support the utility of retrospective report of SDP. Further, we replicate a causal association between SDP and birth weight, wherein SDP results in reduced birth weight even when accounting for genetic and familial confounding factors via a sibling comparison approach.