Development of negative and positive emotionality in irritable and nonirritable neonates.

OBJECTIVE: The current study compares the development of negative and positive emotionality of irritable and nonirritable neonates. BACKGROUND: Research indicates that the first few months of life are marked by decreases in negative emotionality and increases in positive emotionality. METHODS: The Neonatal Behavioural Assessment Scale (NBAS) was administered twice to 111 neonates at 3 and 4 weeks of age to select a sample of irritable neonates and a comparison group of nonirritable neonates. Mothers completed assessments of negative and positive emotionality at 1, 2, 4, and 9 months of age. RESULTS: Both irritable and nonirritable neonates demonstrate a significant decrease in frustration and a significant increase in positive emotionality from 2 to 4 months of age. Irritable neonates also demonstrate a significant decrease in negative emotionality from 4 to 9 months of age. Both irritable and nonirritable neonates demonstrate considerable stability in negative and positive emotionality. CONCLUSION: Implications of these results for parent education and early intervention are discussed.

The intersection of genome, epigenome and social experience in autism spectrum disorder: Exploring modifiable pathways for intervention.

The number of children diagnosed with autism spectrum disorder (ASD) has increased substantially over the past two decades. Current research suggests that both genetic and environmental risk factors are involved in the etiology of ASD. The goal of this paper is to examine how one specific environmental factor, early social experience, may be correlated with DNA methylation (DNAm) changes in genes associated with ASD. We present an innovative model which proposes that polygenic risk and changes in DNAm due to social experience may both contribute to the symptoms of ASD. Previous research on genetic and environmental factors implicated in the etiology of ASD will be reviewed, with an emphasis on the oxytocin receptor gene, which may be epigenetically altered by early social experience, and which plays a crucial role in social and cognitive development. Identifying an environmental risk factor for ASD (e.g., social experience) that could be modified via early intervention and which results in epigenetic (DNAm) changes, could transform our understanding of this condition, facilitate earlier identification of ASD, and guide early intervention efforts.

Parent mental health and child behavior during the COVID-19 pandemic.

Objective: Child behavior, which encompasses both internalizing and externalizing behaviors, is associated with many outcomes, including concurrent and future mental health, academic success, and social well-being. Thus, understanding sources of variability in child behavior is crucial for developing strategies aimed at equipping children with necessary resources. Parental mental health (PMH) difficulties and preterm birth may be risk factors for child behavior (CB) problems. Moreover, not only are PMH difficulties more common among parents of preterm children, but preterm children might also be more sensitive than full-term children to environmental stressors. In this study, we examined how PMH and CB changed during the COVID-19 pandemic, how change in PMH related to change in CB, and whether preterm children were more susceptible than full-term children to change in PMH. Methods: Parents that participated in a study prior to the pandemic were invited to complete follow-up questionnaires during the pandemic about PMH and CB. Forty-eight parents completed follow-up questionnaires. Results: Our results suggested that parental depression symptoms, children's internalizing symptoms, and children's externalizing symptoms significantly increased, and parental well-being significantly decreased during the pandemic. Change in parental depression symptoms, but not change in parental anxiety symptoms or parental well-being, was associated with change in children's internalizing and externalizing symptoms. Prematurity did not moderate change in PMH, change in CB, or the effect of change in PMH on change in CB. Conclusion: Our findings have the potential to inform efforts aimed at equipping children with behavioral resources.

Latent class analysis to characterize neonatal risk for neurodevelopmental differences.

BACKGROUND: Neonatal risk factors, such as preterm birth and low birth weight, have been robustly linked to neurodevelopmental deficits, yet it is still unclear why some infants born preterm and/or low birth weight experience neurodevelopmental difficulties while others do not. The current study investigated this heterogeneity in neurodevelopmental abilities by examining additional neonatal morbidities as risk factors, utilizing latent class analysis to classify neonates into groups based on similar neonatal risk factors, and including neonates from the full spectrum of gestational age. METHODS: Neonates who received neonatal care at an academic public hospital during an almost 10-year period (n = 19,951) were included in the latent class analysis, and 21 neonatal indicators of health were used. Neonatal class, sex, and the interaction between neonatal class and sex were used to examine differences in neurodevelopment at 18 months of age in a typically developing population. RESULTS: The best fitting model included five infant classes: healthy, hypoxic, critically ill, minorly ill, and complicated delivery. Scores on the parent-rated neurodevelopmental measure differed by class such that infants in the critically ill, minorly ill, and complicated delivery classes had lower scores. There was no main effect of sex on the neurodevelopmental measure scores, but the interaction between sex and neonatal class was significant for three out of five neurodevelopmental domains. CONCLUSIONS: The current study extends the understanding of risk factors in neurodevelopment by including several neonatal medical conditions that are often overlooked and by using a person-centered, as opposed to variable-centered, approach. Future work should continue to examine risk factors, such as maternal health during pregnancy and medical interventions for newborns, in relation to neonatal risks and neurodevelopment by using a person-centered approach.

Association between perinatal depression and risk of attention deficit hyperactivity disorder among children: a retrospective cohort study.

PURPOSE: Perinatal depression has previously been identified as a risk factor for attention deficit hyperactivity disorder (ADHD) in the offspring. Population-based studies utilizing diagnosis data are needed to better understand the relationship between these two variables. The objective of this study was to examine the association between perinatal depression and the risk of ADHD among children born during a 5 or-more-year follow-up period. METHODS: The sample was drawn from a population-based cohort of privately insured mother-child pairs within the state of Iowa. Hazard ratios for risk of ADHD by exposure to perinatal depression were estimated using adjusted Cox proportional-hazard models. RESULTS: Among the 5,635 mother-child pairs, 484 mothers were diagnosed with depression during the perinatal period, and 269 children were diagnosed with ADHD. After adjustment for confounders, children born to mothers with perinatal depression were over three times more likely to be diagnosed with ADHD (HR 3.16 (95% CI 2.35, 4.23)). CONCLUSIONS: Children born to mothers with perinatal depression were found to be at increased risk of ADHD. This finding suggests that ADHD and its adverse sequelae could be mitigated by increasing maternal depression intervention efforts as well as ADHD screening and treatment efforts targeted to this vulnerable population.

Telomere Length and ADHD Symptoms in Young Adults.

Objective: Previous research examining telomeres in individuals with neuropsychiatric disorders shows that greater illness, symptoms, or cognitive impairment are linked with shorter telomeres. However, the relationships of telomere length and neuropsychological processes or psychiatric symptoms are not understood in individuals with Attention Deficit/Hyperactivity Disorder (ADHD). Method: 390 young adults with and without ADHD completed a multi-informant diagnostic assessment and neuropsychological testing battery. Participant DNA was isolated from saliva samples, and telomere length was determined using qPCR. Results: Linear regression models demonstrated the only significant association to survive correction for multiple testing was for childhood hyperactivity-impulsivity symptoms and longer telomere length. Conclusion: Contrary to expectations, longer telomere length in young adults was associated only with childhood ADHD symptoms, particularly hyperactivity-impulsivity, in this sample. These findings are an important demonstration that the neuropsychological deficits and symptoms experienced by individuals diagnosed with ADHD during adulthood may not be negatively associated with telomere length.

Neonatal Negative Emotionality and the Child Behavior Checklist-Dysregulation Profile (CBCL-DP) in middle childhood.

Objective: Determine whether an association exists between neonatal negative emotionality and childhood emotional dysregulation. Background: The Child Behaviour Checklist-Dysregulation Profile (CBCL-DP) has been used as a measure of emotional dysregulation in childhood. Although there is now good evidence that the CBCL-DP predicts later psychopathology, little is known about what factors predict elevations on the CBCL-DP. Methods: 30 mother-child dyads who previously participated in a study of neonatal temperament were recruited to a follow-up study of emotional dysregulation during middle childhood. The Neonatal Behaviour Assessment Scale (NBAS) and the Infant Characteristics Questionnaire (ICQ) were utilised as observer and maternal measures of neonatal negative emotionality, respectively. Maternal post-partum depression was also measured during the neonatal period using the Edinburgh Post-Partum Depression Scale (EPDS). The Child Behaviour Checklist-Dysregulation Profile (CBCL-DP) was used as a measure of childhood emotional dysregulation. Results: The ICQ fussy-difficult scale was significantly correlated with the CBCL-DP score (r = .46, p = .010), and this correlation remained significant after controlling for maternal EPDS score (CBCL-DP r = .51, p = .01). The NBAS irritability score was not associated with the CBCL-DP score. Conclusions: This association provides preliminary results that neonates rated as having high negative emotionality may indeed experience chronic difficulties with emotional dysregulation.

Genetic variants associated with patent ductus arteriosus in extremely preterm infants.

OBJECTIVE: Patent ductus arteriosus (PDA) is a commonly observed condition in preterm infants. Prior studies have suggested a role for genetics in determining spontaneous ductal closure. Using samples from a large neonatal cohort we tested the hypothesis that common genetic variations are associated with PDA in extremely preterm infants. STUDY DESIGN: Preterm infants (n = 1013) enrolled at NICHD Neonatal Research Network sites were phenotyped for PDA. DNA was genotyped for 1634 single nucleotide polymorphisms (SNPs) from candidate genes. Analyses were adjusted for ancestral eigenvalues and significant epidemiologic variables. RESULTS: SNPs in several genes were associated with the clinical diagnosis of PDA and with surgical ligation in extremely preterm neonates diagnosed with PDA (p < 0.01). None of the associations were significant after correction for multiple comparisons. CONCLUSION: We identified several common genetic variants associated with PDA. These findings may inform further studies on genetic risk factors for PDA in preterm infants.

Sluggish Cognitive Tempo Symptoms Contribute to Heterogeneity in Adult Attention-Deficit Hyperactivity Disorder.

Attention-deficit hyperactivity disorder (ADHD) persists into adulthood in over 50% of cases, although its associated symptom profiles, comorbid problems, and neuropsychological deficits change substantially across development. Sluggish cognitive tempo (SCT) symptoms may contribute to associations between ADHD and comorbid problems and may partially explain the substantial heterogeneity observed in its correlates. 349 adults aged 18-38 years (M = 23.2, SD = 4.5, 54.7% male, 61.03% with ADHD) completed a multi-informant diagnostic procedure and a comprehensive neuropsychological battery. Adults with ADHD (n = 213) were retained for analyses. Latent class analyses (LCA) revealed three profiles of SCT symptoms among those with ADHD, which we classified as minimal, moderate, or severe SCT. Multiple analysis of covariance (MANCOVA) revealed significant differences among these profiles, which remained when controlling for persistence of ADHD symptoms and sex. In general, adults with ADHD combined with SCT symptoms (moderate and severe) had significantly more symptoms of anxiety, depression, and persistent inattention, and had more severe professional and relational impairment compared to ADHD adults without SCT. Compared to those with moderate or minimal SCT symptoms, the severe SCT group had the most symptoms of depression and internalizing disorders, and the most impairment in the domain of daily responsibility. No significant differences based on externalizing symptoms emerged when controlling for sex and persistence of inattention symptoms, suggesting the moderate and severe SCT groups do not simply reflect more symptoms. Moreover, follow-up mediation analyses revealed that SCT might at least partially explain the heterogeneity in ADHD. Findings have implications for refinement of etiological conceptualization, assessment methods, and intervention strategies.

A Meta-Analysis of the Association Between Birth Weight and Attention Deficit Hyperactivity Disorder.

A large body of work has investigated the association between birth weight and ADHD and has resulted in mixed findings with regard to the direction and magnitude of this association. Despite the vast amount of research on this topic, a comprehensive and systematic quantification of the association between birth weight and ADHD has yet to be undertaken. A meta-analysis of 88 unique studies (N = 4,645,482) was conducted to quantify the overall effect size of birth weight on ADHD symptoms. Several variables were examined as moderators that may contribute to systematic variation in effect sizes. Overall, birth weight was found to have a small, but significant, association with ADHD symptoms such that individuals born at lower birth weights manifested greater symptoms of ADHD (r = -0.15). Sample type, mean birth weight of the sample, geographic region, the informant of ADHD symptoms, ADHD symptom measurement method, and race were all found to contribute significantly to heterogeneity in effect sizes. Notably, several early life risk factors previously found to be associated with both ADHD and birth weight, gestational age and prenatal smoking exposure, were not found to contribute to heterogeneity in effect sizes. The findings of the current analyses align with the growing recognition that early life adversity contributes to neurodevelopmental difficulties, and the findings highlight the importance of a better understanding of the mechanisms underlying the association between early life risk factors and adverse neurodevelopmental sequela, such as that observed in ADHD.

A meta-analytic review of the association between cortisol reactivity in response to a stressor and attention-deficit hyperactivity disorder.

A substantial literature suggests that abnormal cortisol reactivity may be a vulnerability for deleterious mental health outcomes, including ADHD. ADHD has been linked with difficulty in emotion regulation and increased risk of experiencing stressors, both of which may be related to psychobiological abnormalities (e.g., abnormal cortisol reactivity). Research has been mixed regarding the association between cortisol reactivity and ADHD. Therefore, the present meta-analytic review (k = 12) sought to quantify this association and review the relevant methodological issues and theoretical implications of this area of research. Overall, no effect was found between cortisol reactivity and ADHD (r = 0), although significant heterogeneity in the analyses suggested that there might be moderators of this association, if one does exist. Results highlight the importance of addressing limitations of the current literature on cortisol reactivity and ADHD and exploring additional indices of emotion regulation that may be associated with ADHD. Implications for future research efforts are discussed.

Genetic Associations with Gestational Duration and Spontaneous Preterm Birth.

BACKGROUND: Despite evidence that genetic factors contribute to the duration of gestation and the risk of preterm birth, robust associations with genetic variants have not been identified. We used large data sets that included the gestational duration to determine possible genetic associations. METHODS: We performed a genomewide association study in a discovery set of samples obtained from 43,568 women of European ancestry using gestational duration as a continuous trait and term or preterm (<37 weeks) birth as a dichotomous outcome. We used samples from three Nordic data sets (involving a total of 8643 women) to test for replication of genomic loci that had significant genomewide association (P<5.0×10-8) or an association with suggestive significance (P<1.0×10-6) in the discovery set. RESULTS: In the discovery and replication data sets, four loci (EBF1, EEFSEC, AGTR2, and WNT4) were significantly associated with gestational duration. Functional analysis showed that an implicated variant in WNT4 alters the binding of the estrogen receptor. The association between variants in ADCY5 and RAP2C and gestational duration had suggestive significance in the discovery set and significant evidence of association in the replication sets; these variants also showed genomewide significance in a joint analysis. Common variants in EBF1, EEFSEC, and AGTR2 showed association with preterm birth with genomewide significance. An analysis of mother-infant dyads suggested that these variants act at the level of the maternal genome. CONCLUSIONS: In this genomewide association study, we found that variants at the EBF1, EEFSEC, AGTR2, WNT4, ADCY5, and RAP2C loci were associated with gestational duration and variants at the EBF1, EEFSEC, and AGTR2 loci with preterm birth. Previously established roles of these genes in uterine development, maternal nutrition, and vascular control support their mechanistic involvement. (Funded by the March of Dimes and others.).

Association of candidate gene polymorphisms with clinical subtypes of preterm birth in a Latin American population.

BackgroundPreterm birth (PTB) is the leading cause of neonatal mortality and morbidity. PTB is often classified according to clinical presentation as follows: idiopathic (PTB-I), preterm premature rupture of membranes (PTB-PPROM), and medically induced (PTB-M). The aim of this study was to evaluate the associations between specific candidate genes and clinical subtypes of PTB.MethodsTwenty-four single-nucleotide polymorphisms (SNPs) were genotyped in 18 candidate genes in 709 infant triads. Of them, 243 were PTB-I, 256 were PTB-PPROM, and 210 were PTB-M. These data were analyzed with a Family-Based Association.ResultsPTB was nominally associated with rs2272365 in PON1, rs883319 in KCNN3, rs4458044 in CRHR1, and rs610277 in F3. Regarding clinical subtypes analysis, three SNPs were associated with PTB-I (rs2272365 in PON1, rs10178458 in COL4A3, and rs4458044 in CRHR1), rs610277 in F3 was associated with PTB-PPROM, and rs883319 in KCNN3 and rs610277 in F3 were associated with PTB-M.ConclusionOur study identified polymorphisms potentially associated with specific clinical subtypes of PTB in this Latin American population. These results could suggest a specific role of such genes in the mechanisms involved in each clinical subtype. Further studies are required to confirm our results and to determine the role of these genes in the pathophysiology of clinical subtypes.

DRD4 Variants Moderate the Impact of Parental Characteristics on Child Attention-Deficit Hyperactivity Disorder: Exploratory Evidence from a Multiplex Family Design.

Parental ADHD symptomatology and related impairments have been robustly associated with youth ADHD across decades of work. Notably, these factors may impede typical development of child self-regulation capabilities through both neurobiological and interpersonal processes. High heritability of estimates for the disorder further suggest that these effects are likely genetically-mediated, at least in part. Variation within the dopamine D4 receptor gene (DRD4) has been shown to moderate parental influences on youth ADHD. Use of a multiplex family design (i.e., samples of families that included multiple affected members) may facilitate identification of additional gene variants of interest and advance understanding of gene-environment interplay in regard to parenting. Thirty multiplex families consisting of 114 individuals (66 youth, 48 parents) completed a multi-stage, multi-informant diagnostic and neurocognitive assessment, measures of parenting, and provided saliva samples for DNA analyses. Sanger sequencing of the DRD4 gene yielded 16 rare variants; a polygenic risk score was computed for both parents and youth. Generalized estimating equations (GEE) examined the predictive effects of parental ADHD symptoms, parental neurocognitive functioning, and poor parenting dimensions on youth ADHD as well as moderation of these effects by parental and youth DRD4 variants. Findings indicated that parental DRD4 variants moderated the impact of parental ADHD and neurocognitive functioning on youth ADHD symptoms. Youth DRD4 variants moderated the impact of parental inconsistent discipline on child ADHD. In all cases, stronger associations were observed for those individuals with more risk variants. These exploratory findings highlight the potential utility of a multiplex family design for examining the interplay between parent and child characteristics in predicting youth outcomes.

Sex moderates the impact of birth weight on child externalizing psychopathology.

Low birth weight (LBW) has consistently been associated with childhood attention deficit/hyperactivity disorder (ADHD), and a similar association has been found for childhood externalizing disorders, such as oppositional defiant disorder (ODD) and conduct disorder (CD), albeit to a lesser degree. Although the association between LBW and these disorders has been robustly replicated, few studies have adequately controlled for confounding variables, such as parental age at birth and prenatal tobacco use, examined the specificity of the risk of LBW for ADHD symptoms, or investigated potential nonlinear (i.e., quadratic) effects of birth weight (BW). Additionally, the extent to which LBW confers risk for these disorders depending on childhood sex has rarely been examined. The current study examined associations between BW and ADHD, ODD, and CD symptom dimensions as well as the extent to which such associations are moderated by child sex, while also controlling for confounding variables. Significant interactions between sex and BW emerged across all analyses predicting ADHD and externalizing psychopathology, such that associations were stronger in males relative to females. Results remained when controlling for a number of confounds, including parental age, prenatal tobacco use, comorbid psychopathology, as well as other indicators of maternal and child health during the pre- and perinatal period. Both linear and quadratic associations emerged between BW and both hyperactivity and CD symptoms, whereas BW predicted inattention and ODD symptoms in a linear fashion. Future research should continue to investigate the impact of BW on ADHD and externalizing psychopathology, in particular, the biological mechanisms underlying this association. (PsycINFO Database Record

Genetic Modifiers of Patent Ductus Arteriosus in Term Infants.

OBJECTIVE: To identify single-nucleotide polymorphisms (SNPs) in specific candidate genes associated with patent ductus arteriosus in term infants. STUDY DESIGN: We conducted an initial family-based, candidate gene study to analyze genotype data from DNA samples obtained from 171 term infants and their parents enrolled in the National Birth Defects Prevention Study (NBDPS). We performed transmission disequilibrium testing (TDT) using a panel of 55 SNPs in 17 genes. Replication of SNPs with P < .1 in the NBDPS trios was performed with a case-control strategy in an independent population. RESULTS: TDT analysis of the NBDPS trios resulted in 6 SNPs reaching the predetermined cutoff (P < .1) to be included in the replication study. These 6 SNPs were genotyped in the independent case-control population. A SNP in TGFBR2 was found to be associated with term patent ductus arteriosus in both populations after we corrected for multiple comparisons. (rs934328, TDT P = 2 × 10(-4), case-control P = 6.6 × 10(-5)). CONCLUSIONS: These findings confirm the importance of the transforming growth factor-beta pathway in the closure of the term ductus arteriosus and may suggest new therapeutic targets.

Polymorphisms in NR5A2, gene encoding liver receptor homolog-1 are associated with preterm birth.

BACKGROUND: Preterm birth (PTB) is a major cause of neonatal mortality and morbidity. There is strong evidence of genetic susceptibility. Objective of this study was to identify genetic variants contributing to PTB. METHODS: Genotyping was performed for 24 single nucleotide polymorphisms (SNPs) in 4 candidate genes (NR5A2, FSHR, FOXP3, and SERPINH1). Genotyping was completed on 728 maternal triads (mother and maternal grandparents of a preterm infant). Data were analyzed with Family Based Association Test. RESULTS: For all maternal triads rs2737667 of NR5A2 showed significant association at P = 0.02. When stratifying by gestational age three SNPs in NR5A2 had P values <0.05 in the <32-wk gestational age group (rs12131233, P = 0.007; rs2737667, P = 0.04; rs2816949, P = 0.02). When preterm premature rupture of membranes cases were excluded rs2737667 of NR5A2 showed the strongest association with a P value <0.0002. This association remained significant after correction for multiple testing. CONCLUSION: This study suggests a potential association between intronic SNPs in the NR5A2 gene and PTB. NR5A2 gene encodes for the liver receptor homolog-1 protein, which plays a critical role in regulation of cholesterol metabolism, steroidogenesis, and progesterone synthesis. These findings suggest that NR5A2 may be important in the pathophysiology of PTB and exploring noncoding regulators of NR5A2 is warranted.

Maternal and neonatal epidemiological features in clinical subtypes of preterm birth.

OBJECTIVE: This study was designed to characterize and compare the maternal and newborn epidemiological characteristics through analysis of environmental factors, sociodemographic characteristics and clinical characteristics between the different clinical subtypes of preterm birth (PTB): Idiopathic (PTB-I), premature rupture of the membranes (PTB-PPROM) and medically indicated (PTB-M). The two subtypes PTB-I and PTB-PPROM grouped are called spontaneous preterm births (PTB-S). METHODS: A retrospective, observational study was conducted in 1.291 preterm nonmalformed singleton live-born children to nulliparous and multiparous mother's in Tucumán-Argentina between 2005 and 2010. Over 50 maternal variables and 10 newborn variables were compared between the different clinical subtypes. The comparisons were done to identify heterogeneity between subtypes of preterm birth: (PTB-S) versus (PTB-M), and within spontaneous subtype: (PTB-I) versus (PTB-PPROM). In the same way, two conditional logistic multivariate regressions were used to compare the odds ratio (OR) between PTB-S and PTB-M, as well as PTB-I and PTB-PPROM. We matched for maternal age when comparing maternal variables and gestational age when comparing infant variables. RESULTS: The PTB-I subtype was characterized by younger mothers of lower socio-economic status, PTB-PPROM was characterized by environmental factors resulting from inflammatory processes, and PTB-M was characterized by increased maternal or fetal risk pregnancies. CONCLUSIONS: The main risk factor for PTB-I and PTB-M was having had a prior preterm delivery; however, previous spontaneous abortion was not a risk factor, suggesting a reproductive selection mechanism.

Determining the prevalence of cytomegalovirus infection in a cohort of preterm infants.

BACKGROUND: Preterm birth is a global public health problem that is a significant cause of infant morbidity and mortality. Congenital cytomegalovirus (CMV) infection has been proposed as a risk factor for preterm birth, but the rate of CMV in infants born preterm is unclear. CMV is the leading infectious cause of sensorineural hearing loss, which will affect 15% - 20% of congenitally infected infants later in their childhood. 90% of infected infants are asymptomatic at birth and are not recognized as at risk for CMV-associated deficits. OBJECTIVE: To determine the prevalence of CMV infection in a large cohort of preterm infants. METHODS: DNA was extracted from cord blood, peripheral blood, saliva, and buccal swab samples collected from preterm infants. A total of 1200 unique DNA samples were tested for CMV using a nested PCR protocol. The proportions of preterm infants with CMV was compared by sample collection type, race, gender, and gestational age. RESULTS: A total of 37 infants tested positive for CMV (3.08%). After excluding twins, siblings, and infants older than two weeks at the time of sample collection, two out of 589 infants were CMV positive (0.3%), which was lower than the proportion of CMV observed in the general population. All positive samples came from buccal swabs. CONCLUSIONS: Our work suggests that while CMV infection may not be greater in preterm infants than in the general population, given the neurologic consequences of CMV in preterm infants, screening of this population may still be warranted. If so, our results suggest buccal swabs, collected at pregnancy or at birth, may be an ideal method for such a program.

Effects of Advancing Gestation and Non-Caucasian Race on Ductus Arteriosus Gene Expression.

OBJECTIVE: To identify genes affected by advancing gestation and racial/ethnic origin in human ductus arteriosus (DA). STUDY DESIGN: We collected 3 sets of DA tissue (n = 93, n = 89, n = 91; total = 273 fetuses) from second trimester pregnancies. We examined four genes, with DNA polymorphisms that distribute along racial lines, to identify "Caucasian" and "non-Caucasian" DA. We used real time polymerase chain reaction to measure RNA expression of 48 candidate genes involved in functional closure of the DA, and used multivariable regression analyses to examine the relationships between advancing gestation, "non-Caucasian" race, and gene expression. RESULTS: Mature gestation and non-Caucasian race are significant predictors for identifying infants who will close their patent DA when treated with indomethacin. Advancing gestation consistently altered gene expression in pathways involved with oxygen-induced constriction (eg, calcium-channels, potassium-channels, and endothelin signaling), contractile protein maturation, tissue remodeling, and prostaglandin and nitric oxide signaling in all 3 tissue sets. None of the pathways involved with oxygen-induced constriction appeared to be altered in "non-Caucasian" DA. Two genes, SLCO2A1 and NOS3, (involved with prostaglandin reuptake/metabolism and nitric oxide production, respectively) were consistently decreased in "non-Caucasian" DA. CONCLUSIONS: Prostaglandins and nitric oxide are the most important vasodilators opposing DA closure. Indomethacin inhibits prostaglandin production, but not nitric oxide production. Because decreased SLCO2A1 and NOS3 expression can lead to increased prostaglandin and decreased nitric oxide concentrations, we speculate that prostaglandin-mediated vasodilation may play a more dominant role in maintaining the "non-Caucasian" patent DA, making it more likely to close when inhibited by indomethacin.