Effects of Stress and Nativity on Maternal Antenatal Substance Use and Postnatal Mental Disorders.

Background: Maternal substance use and common mental disorders (CMDs) during or after pregnancy can lead to negative health outcomes among mothers and infants. We examined whether nativity (US-born versus foreign-born) and stress levels during pregnancy were associated with antenatal substance use and postnatal CMDs. Methods: We analyzed the Boston Birth Cohort, a racially diverse cohort recruited at birth with rolling enrollment since 1998. Information on antenatal substance use (tobacco and/or alcohol use) was obtained using an in-person postpartum questionnaire (n = 6,514). Information on postnatal CMDs (depression and/or anxiety) was obtained from medical records (n = 2,052). Nativity and stress during pregnancy were self-reported. We performed multivariate logistic regression to examine how nativity and stress levels were jointly associated with antenatal substance use and postnatal CMDs. We further investigated if blacks, Hispanics, and whites were differentially at risk. Results: We found that US-born mothers were at higher risk of substance use and CMDs than their foreign-born counterparts. In analyses combining nativity and stress, being US-born with high stress was associated with increased odds of antenatal substance use (adjusted odds ratio [aOR] = 14.91, 95% confidence interval [CI]: 12.09-18.39) and postnatal CMDs (aOR = 4.09, 95% CI: 2.72-6.15) compared with foreign-born mothers with low stress. The results of the subanalyses limited to black and Hispanic women separately were similar; high stress alone was associated with fourfold increased odds of CMDs among foreign-born Hispanic mothers (aOR = 4.27, 95% CI: 1.96-9.33). Conclusions: Findings suggest that identifying and alleviating high stress among pregnant women may reduce their risk of antenatal substance use and postnatal CMDs.

Maternal and cord plasma branched-chain amino acids and child risk of attention-deficit hyperactivity disorder: a prospective birth cohort study.

BACKGROUND: Branched-chain amino acids (BCAA: leucine, isoleucine, and valine) are essential amino acids involved in biological functions of brain development and recently linked with autism. However, their role in attention-deficit hyperactivity disorder (ADHD) is not well-studied. We investigated individual and combined relationships of maternal plasma and newborn cord plasma BCAAs with childhood development of ADHD. METHODS: We utilized the Boston Birth Cohort, a predominantly urban, low-income, US minority population. Child developmental outcomes were defined in three mutually exclusive groups - ADHD, neurotypical (NT), or other developmental disabilities based on physician diagnoses per ICD-9 or 10 in medical records. The final sample included 626 children (299 ADHD, 327 NT) excluding other developmental disabilities. BCAAs were measured by liquid chromatography-tandem mass spectrometry. We used factor analysis to create composite scores of maternal and cord BCAA, which we divided into tertiles. Logistic regressions analyzed relationships between maternal or cord BCAA tertiles with child ADHD risk, controlling for maternal race, age, parity, smoking, education, low birth weight, preterm birth, and child sex. Additionally, we analyzed maternal and cord plasma BCAAs jointly on child ADHD risk. RESULTS: Adjusted logistic regression found significantly increased odds of child ADHD diagnosis for the second (OR 1.63, 95% CI: 1.04, 2.54, p = .032) and third tertiles (OR 2.01, 95% CI: 1.28, 3.15, p = .002) of cord BCAA scores compared to the first tertile. This finding held for the third tertile when further adjusting for maternal BCAA score. There was no significant association between maternal BCAA score and child ADHD risk, nor a significant interaction between maternal and cord BCAA scores. CONCLUSIONS: In this prospective US birth cohort, higher cord BCAA levels were associated with a greater risk of developing ADHD in childhood. These results have implications for further research into mechanisms of ADHD development and possible early life screening and interventions.

Maternal persistent marijuana use and cigarette smoking are independently associated with shorter gestational age.

BACKGROUND: Research assessing the effects of marijuana use on preterm birth has found mixed results, in part, due to lack of attention to the role of maternal tobacco smoking during pregnancy. OBJECTIVES: The study objective was to investigate whether maternal marijuana use was independently associated with gestational age, preterm birth, and two preterm birth subtypes (spontaneous vs clinician-initiated). METHODS: Participants included 8261 mother-newborn pairs from the Boston Birth Cohort. Information on gestational age was collected from electronic medical records. Marijuana use and tobacco smoking during pregnancy were assessed through a standard questionnaire after birth. Linear and log-linear regression models were used to assess associations between marijuana use with and without tobacco smoking during pregnancy and the outcomes of interest. RESULTS: Of the 8261 mothers, 27.5% had preterm births. About 3.5% of mothers with term deliveries and 5.2% of mothers with preterm births used marijuana during pregnancy. Marijuana use and cigarette smoking were independently associated with a decrease in gestational age by 0.50 weeks (95% confidence interval [CI] -0.87, -0.13) and 0.52 weeks (95% CI -0.76, -0.28), respectively. Marijuana use during early or late pregnancy was associated with a similar decrease in gestational age by 0.50 weeks. When we examined the effects on the preterm birth subtypes, simultaneous marijuana use and tobacco smoking were associated with higher risk of spontaneous preterm birth (RR 1.64, 95% CI 1.23, 2.18). The elevated risk was not observed with clinician-initiated preterm birth. CONCLUSIONS: In this high-risk US population, maternal marijuana use and cigarette smoking during pregnancy were independently associated with shorter gestational age. When we examined the effects on preterm birth subtypes, the elevated risk was only observed with spontaneous preterm birth.

Polydrug Use During Pregnancy and Preterm Birth in a Low-Income, Multiethnic Birth Cohort, Boston, 1998-2018.

OBJECTIVE: The opioid epidemic in the United States increasingly affects women of reproductive age and has resulted in a rise in concurrent polydrug use. The objective of this study was to investigate the effect of this polydrug use on preterm birth in a multiethnic birth cohort. METHODS: We analyzed data from 8261 mothers enrolled in the Boston Birth Cohort from 1998 to 2018 in Boston, Massachusetts. We grouped substances used during pregnancy based on their primary effects (stimulant or depressant) and assessed independent and combined associations with smoking on preterm birth. RESULTS: Of 8261 mothers, 131 used stimulant drugs and 193 used depressant drugs during pregnancy. The preterm birth rate was 27.5% (2271 of 8261) in the sample. Mothers who smoked had 35% increased odds of preterm birth across adjusted models. Mothers who used stimulant drugs without smoking were not at increased risk of preterm delivery compared with mothers who used neither (odds ratio [OR] = 0.69; 95% confidence interval [CI], 0.19-1.98), whereas mothers who used depressant drugs without smoking had more than twice the odds of having preterm delivery (OR = 2.31; 95% CI, 1.19-4.44), and infants were at risk of a 1-week reduction in gestational age (OR = -1.05; 95% CI, -2.07 to -0.03). Concurrently smoking and using depressant drugs was associated with increased odds of preterm birth (OR = 1.83; 95% CI, 1.28-2.61), as was concurrently smoking and using stimulant drugs (OR = 1.73; 95% CI, 1.14-2.59). CONCLUSIONS: Using stimulant drugs and depressant drugs during pregnancy is a risk factor for preterm birth. The individual and combined effects of using these drugs with smoking must be considered together to reduce the risk of preterm birth in the United States.

Association of Cord Plasma Biomarkers of In Utero Acetaminophen Exposure With Risk of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in Childhood.

Importance: Prior studies have raised concern about maternal acetaminophen use during pregnancy and increased risk of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in their children; however, most studies have relied on maternal self-report. Objective: To examine the prospective associations between cord plasma acetaminophen metabolites and physician-diagnosed ADHD, ASD, both ADHD and ASD, and developmental disabilities (DDs) in childhood. Design, Setting, and Participants: This prospective cohort study analyzed 996 mother-infant dyads, a subset of the Boston Birth Cohort, who were enrolled at birth and followed up prospectively at the Boston Medical Center from October 1, 1998, to June 30, 2018. Exposures: Three cord acetaminophen metabolites (unchanged acetaminophen, acetaminophen glucuronide, and 3-[N-acetyl-l-cystein-S-yl]-acetaminophen) were measured in archived cord plasma samples collected at birth. Main Outcomes and Measures: Physician-diagnosed ADHD, ASD, and other DDs as documented in the child's medical records. Results: Of 996 participants (mean [SD] age, 9.8 [3.9] years; 548 [55.0%] male), the final sample included 257 children (25.8%) with ADHD only, 66 (6.6%) with ASD only, 42 (4.2%) with both ADHD and ASD, 304 (30.5%) with other DDs, and 327 (32.8%) who were neurotypical. Unchanged acetaminophen levels were detectable in all cord plasma samples. Compared with being in the first tertile, being in the second and third tertiles of cord acetaminophen burden was associated with higher odds of ADHD diagnosis (odds ratio [OR] for second tertile, 2.26; 95% CI, 1.40-3.69; OR for third tertile, 2.86; 95% CI, 1.77-4.67) and ASD diagnosis (OR for second tertile, 2.14; 95% CI, 0.93-5.13; OR for third tertile, 3.62; 95% CI, 1.62-8.60). Sensitivity analyses and subgroup analyses found consistent associations between acetaminophen buden and ADHD and acetaminophen burden and ASD across strata of potential confounders, including maternal indication, substance use, preterm birth, and child age and sex, for which point estimates for the ORs vary from 2.3 to 3.5 for ADHD and 1.6 to 4.1 for ASD. Conclusions and Relevance: Cord biomarkers of fetal exposure to acetaminophen were associated with significantly increased risk of childhood ADHD and ASD in a dose-response fashion. Our findings support previous studies regarding the association between prenatal and perinatal acetaminophen exposure and childhood neurodevelopmental risk and warrant additional investigations.

Maternal smoking during pregnancy and cord blood DNA methylation: new insight on sex differences and effect modification by maternal folate levels.

Maternal smoking during pregnancy may affect newborn DNA methylation (DNAm). However, little is known about how these associations vary by a newborn's sex and/or maternal nutrition. To fill in this research gap, we investigated epigenome-wide DNAm associations with maternal smoking during pregnancy in African American mother-newborn pairs. DNAm profiling in cord (n = 379) and maternal blood (n = 300) were performed using the Illumina HumanMethylation450 BeadChip array. We identified 12 CpG sites whose DNAm levels in cord blood were associated with maternal smoking, at a false discovery rate <5%. The identified associations in the GFI1 gene were more pronounced in male newborns than in females (P = 0.002 for maternal smoking × sex interaction at cg18146737). We further observed that maternal smoking and folate level may interactively affect cord blood DNAm level at cg05575921 in the AHRR gene (P = 5.0 × 10-4 for interaction): compared to newborns unexposed to maternal smoking and with a high maternal folate level (>19.2 nmol/L), the DNAm level was about 0.03 lower (P = 3.6 × 10-4) in exposed newborns with a high maternal folate level, but was 0.08 lower (P = 1.2 × 10-8) in exposed newborns with a low maternal folate level. Our data suggest that adequate maternal folate levels may partly counteract the impact of maternal smoking on DNAm. These findings may open new avenues of inquiry regarding sex differences in response to environmental insults and novel strategies to mitigate their intergenerational health effects through optimization of maternal nutrition.

Differential effects of stress and African ancestry on preterm birth and related traits among US born and immigrant Black mothers.

Preterm birth (PTB, <37 weeks of gestation) is influenced by a wide range of environmental, genetic and psychosocial factors, and their interactions. However, the individual and joint effects of genetic factors and psychosocial stress on PTB have remained largely unexplored among U.S. born versus immigrant mothers.We studied 1121 African American women from the Boston Birth Cohort enrolled from 1998 to 2008. Regression-based analyses were performed to examine the individual and joint effects of genetic ancestry and stress (including lifetime stress [LS] and stress during pregnancy [PS]) on PTB and related traits among U.S. born and immigrant mothers.Significant associations between LS and PTB and related traits were found in the total study population and in immigrant mothers, including gestational age, birthweight, PTB, and spontaneous PTB; but no association was found in U.S. born mothers. Furthermore, significant joint associations of LS (or PS) and African ancestral proportion (AAP) on PTB were found in immigrant mothers, but not in U.S. born mothers.Although, overall, immigrant women had lower rates of PTB compared to U.S. born women, our study is one of the first to identify a subset of immigrant women could be at significantly increased risk of PTB and related outcomes if they have high AAP and are under high LS or PS. In light of the growing number of immigrant mothers in the U.S., our findings may have important clinical and public health implications.

Maternal preconception body mass index and offspring cord blood DNA methylation: exploration of early life origins of disease.

Maternal obesity is associated with a variety of common diseases in the offspring. One possible underlying mechanism could be maternal obesity induced alterations in DNA methylation. However, this hypothesis is yet to be tested. We performed epigenomic mapping of cord blood among 308 Black mother-infant pairs delivered at term at the Boston Medical Center using the Illumina HumanMethylation27 BeadChip. Linear regression and pathway analyses were conducted to evaluate the associations between DNA methylation levels and prepregnancy maternal BMI (<25, 25-30, ≥30 kg/m(2) ). The methylation levels of 20 CpG sites were associated with maternal BMI at a significance level of P-value <10(-4) in the overall sample, and boys and girls, separately. One CpG site remained statistically significant after correction for multiple comparisons (FDR corrected P-value = 0.04) and was annotated to a potential cancer gene, ZCCHC10. Some of the other CpG site annotated genes appear to be critical to the development of cancers and cardiovascular diseases (i.e., WNT16, C18orf8, ANGPTL2, SAPCD2, ADCY3, PRR16, ERBB2, DOK2, PLAC1). Significant findings from pathway analysis, such as infectious and inflammatory and lipid metabolism pathways, lends support for the potential impact of maternal BMI on the above stated disorders. This study demonstrates that prepregnancy maternal BMI might lead to alterations in offspring DNA methylation in genes relevant to the development of a range of complex chronic diseases, providing evidence of trans-generational influence on disease susceptibility via epigenetic mechanism.

Placental weight mediates the effects of prenatal factors on fetal growth: the extent differs by preterm status.

OBJECTIVE: Elevated pre-pregnancy BMI, excessive gestational weight gain (GWG), and gestational diabetes mellitus (GDM) are known determinants of fetal growth. The role of placental weight is unclear. We aimed to examine the extent to which placental weight mediates the associations of pre-pregnancy BMI, GWG, and GDM with birth weight-for-gestational age, and whether the relationships differ by preterm status. DESIGN AND METHODS: We examined 1,035 mother-infant pairs at birth from the Boston Birth Cohort. Data were collected by questionnaire and clinical measures. Placentas were weighed without membranes or umbilical cords. We performed sequential models excluding and including placental weight, stratified by preterm status. RESULTS: We found that 21% of mothers were obese, 42% had excessive GWG, and 5% had GDM. Forty-one percent were preterm. Among term births, after adjustment for sex, gestational age, maternal age, race, parity, education, smoking, and stress during pregnancy, birth weight-for-gestational age z-score was 0.55 (0.30, 0.80) units higher for pre-pregnancy obesity vs. normal weight. It was 0.34 (0.13, 0.55) higher for excessive vs. adequate GWG, 0.67 (0.24, 1.10) for GDM vs. no DM, with additional adjustment for pre-pregnancy BMI. Adding placental weight to the models attenuated the estimates for pre-pregnancy obesity by 20%, excessive GWG by 32%, and GDM by 21%. Among preterm infants, GDM was associated with 0.67 (0.34, 1.00) higher birth weight-for-gestational age z-score, but pre-pregnancy obesity and excessive GWG were not. Attenuation by placental weight was 36% for GDM. CONCLUSIONS: These results suggest that placental weight partially mediates the effects of pre-pregnancy obesity, GDM, and excessive GWG on fetal growth among term infants.

Role of African ancestry and gene-environment interactions in predicting preterm birth.

OBJECTIVE: To estimate whether African ancestry, specific gene polymorphisms, and gene-environment interactions could account for some of the unexplained preterm birth variance within African American women. METHODS: We genotyped 1,509 African ancestry-informative markers, cytochrome P450 1A1 (CYP1A1), and glutathione S-transferases Theta 1 (GSTT1) variants in 1,030 self-reported African American mothers. We estimated the African ancestral proportion using the ancestry-informative markers for all 1,030 self-reported African American mothers. We examined the effect of African ancestry and CYP1A1- and GSTT1-smoking interactions on preterm birth cases as a whole and within its subgroups: very preterm birth (gestational age less than 34 weeks); and late preterm birth (gestational age greater than 34 and less than 37 weeks). We applied logistic regression and receiver operating characteristic curve analysis, separately, to evaluate whether African ancestry and CYP1A1- and GSTT1-smoking interactions could make additional contributions to preterm birth beyond epidemiologic factors. RESULTS: We found significant associations of African ancestry with preterm birth (22% compared with 31%, odds ratio [OR] 1.11, 95% confidence interval [CI] 1.02-1.20) and very preterm birth (23% compared with 33%, OR 1.17, 95% CI 1.03-1.33), but not with late preterm birth (22% compared with 29%, OR 1.06, 95% CI 0.97-1.16). In addition, the receiver operating characteristic curve analysis suggested that African ancestry and CYP1A1- and GSTT1-smoking interactions made substantial contributions to very preterm birth beyond epidemiologic factors. CONCLUSION: Our data underscore the importance of simultaneously considering epidemiologic factors, African ancestry, specific gene polymorphisms, and gene-environment interactions to better understand preterm birth racial disparity and to improve our ability to predict preterm birth, especially very preterm birth.

Translating scientific advances to improved outcomes for children with sickle cell disease: a timely opportunity.

Despite the recent advances made in the care of children with sickle cell disease (SCD), premature mortality, especially among older children and young adults, remains a hallmark of this disease. The lack of survival gains highlights the translational gap of implementing innovations found efficacious in the controlled trial setting into routine clinical practice. Health services research (HSR) examines the most effective ways to finance, organize, and deliver high quality care in an equitable manner. To date, HSR has been underutilized as a means to improve the outcomes for children with SCD. Emerging national priorities in health care delivery, new sources of funding, and evolving electronic data collection systems for patients with SCD have provided a unique opportunity to overcome the translational gap in pediatric SCD. The purpose of this article is to provide a comprehensive HSR agenda to create patient-specific evidence of clinical effectiveness for interventions used in the routine care setting, understand the barriers faced by clinicians to providing high quality care, assess and improve the interactions of patients with the health care system, and measure the quality of care delivered to increase survival for all children and young adults with SCD.

Who rules the roost?

CASE: Adam's mother was concerned about her 3-year-old son's hyperactivity, violence, and activity level. Adam and his mom had recently moved into a shelter for pregnant women. The rest of the residents are primarily in their early 20s, whereas Adam's mom is 42. She had found about 3 months ago that she was pregnant. This was her fourth pregnancy, second with this father, and he had recently left her when she refused an abortion. Her other children are 22 and 24 and live out of state. She has a history of opioid addiction. She had been on methadone during Adam's gestation and had recently started on buprenorphine to treat her addiction during this pregnancy as well. Adam is here today for his 3-year-old checkup and you had not seen him for a year. Mom states that he has been healthy but has become progressively active over the last year. He is very angry about his dad leaving, and according to Adam's mother "blames her" for sending him away. They are living in 1 room at the shelter, and mom is finding it increasingly difficult to keep him busy all day. When she goes out looking for a job, he is very challenging at the shelter, and she constantly receives complaints that he is "too loud" in the common rooms. She feels like she is at the end of her rope with him, he is constantly climbing, bolting from her, and taking risks.When you examine Adam, you find a robust, healthy young boy. His eye contact is good, and he is socially related but does actively explore your office. When he begins taking the instruments off your wall, his mother sits passively watching him. When he begins playing with the faucet, she half heartedly tells him to "stop" but he looks at her and continues splashing. He then begins flicking the light switch on and off in the room with no response from mom. When you ask about discipline, mom states "nothing works." When you ask about supports, she states "I have nobody except Adam and the new baby now."Adam was born after an uneventful full-term pregnancy with his mother on 100 mg methadone daily. She denies cigarette smoking, drugs, alcohol, or other medications. Urine testing throughout was positive only for opioids. Motor milestones were achieved at the appropriate time. Language milestones at the 2-year-old visit consisted of 10 single words. Now, he has a 50 single-word vocabulary but no 2-word combinations. He primarily takes whatever he wants and has a tantrum if mom cannot figure out what he desires. Adam's medical history is unremarkable. Family history is significant for drug abuse by her father and mother; mental illness in the father's family consisting of bipolar disorder in several uncles. Where do you go from here?

Differential patterns of 27 cord blood immune biomarkers across gestational age.

OBJECTIVES: Inflammation has been associated with preterm delivery and adverse neonatal outcomes such as cerebral palsy and chronic lung disease. However, no study to date has simultaneously examined a wide range of inflammatory mediators and their relationship to gestational age. We sought to describe the distribution of immune biomarkers in cord blood across gestational age and to investigate the association between biomarker level patterns and preterm birth. PATIENTS AND METHODS: As part of a large-scale molecular epidemiological study of preterm birth conducted at Boston Medical Center, this study analyzed both clinical and biomarker data from 927 births. Twenty-seven biomarkers were simultaneously quantified by immunoassay. The associations between the quartiles of 27 biomarkers and 3 gestational groups (< or =32, 33-36, and > or =37 weeks) were analyzed. Biomarkers found to be significant were further analyzed for dose-response correlation with preterm birth by logistic regression, adjusted for pertinent demographic and clinical factors. RESULTS: The 27 biomarkers could be classified into 1 of 3 groups: (1) biomarkers increased in preterm birth (interleukin [IL]-2, IL-4, IL-5, IL-8, IL-10, monocyte chemoattractant protein 1, macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, soluble IL-6 receptor alpha, tumor necrosis factor alpha, soluble tumor necrosis factor receptor I, and TREM-1 [triggering receptor expressed on myeloid cells 1]); (2) biomarkers decreased in preterm birth (brain-derived neurotrophic factor, IL-1beta, IL-18, matrix metalloproteinase 9, and neurotrophin 3); and (3) biomarkers not associated with preterm birth (IL-6, IL-12, IL-17, granulocyte/macrophage colony-stimulating factor, interferon gamma, macrophage migration inhibitory factor, neurotrophin 4, RANTES [regulated on activation, normal T-cell expressed and secreted], transforming growth factor beta, and tumor necrosis factor beta). CONCLUSIONS: Biomarkers have different directions of association with prematurity; for significant biomarkers, the strength of association increases with biomarker concentration. Our results provide important information that could be used to guide additional studies aimed at determining mechanisms that contribute to preterm birth.

Association of genetic ancestry with preterm delivery and related traits among African American mothers.

OBJECTIVE: In the United States, the rate of preterm delivery (PTD) is higher in African Americans (17.8%) than non-Hispanic whites (11.5%). Such disparity cannot be fully explained by differences in socioenvironmental factors. STUDY DESIGN: We genotyped 812 mothers in a case-control PTD study at Boston Medical Center who self-reported their ethnicity as "black." Regression analysis and Wilcoxon rank-sum test were applied to evaluate ancestral distribution and the association between genetic ancestry and PTD-related traits, as well as the potential confounding effect of population stratification. RESULTS: The estimated African ancestral proportion was 0.90 +/- 0.13. We found significant associations of ancestral proportion with PTD as a whole and PTD subgrouped by the presence of maternal hypertensive disorders. We did not observe significant confounding as a result of population stratification in this case-control PTD study. CONCLUSION: Our data underline the need for more intensive investigation of genetic admixture in African Americans to identify novel susceptibility genes of PTD.

The joint association between F5 gene polymorphisms and maternal smoking during pregnancy on preterm delivery.

Factor V (F5) genetic variants and maternal smoking during pregnancy individually has been associated with increased risk of preterm delivery (PTD). We hypothesize that F5 gene and maternal smoking may synergistically increase the risk of PTD. Three single nucleotide polymorphisms (SNPs) in F5 gene (rs6019, rs2213869 and rs6022) were genotyped in 542 mothers with PTD and 1,141 mothers with term deliveries at the Boston Medical Center. The individual and interactive effects of F5 SNPs and maternal smoking on PTD and gestational age were examined, respectively. The results suggested that maternal smoking, three F5 SNPs and F5 haplotype were individually associated with PTD and gestational age. More importantly, we found significant interactions between the two F5 SNPs (rs6019 and rs6022) and maternal smoking on PTD and gestational age. Compared with non-smoking mothers carrying rs6019 GG genotype, persistently smoking mothers carrying genotypes GC or CC were associated with significantly increased risk of PTD (OR(95% CI): 2.1(1.2-3.6) for GC; 5.7(2.1-15.0) for CC; p-interaction = 0.02). A significant interaction was also observed for gestational age. Similar pattern of interactions was found between rs6022 and maternal smoking on PTD. In summary, our data indicated that F5 gene variants and maternal smoking may synergistically increase the risk of PTD.

Maternal cigarette smoking, metabolic gene polymorphisms, and preterm delivery: new insights on GxE interactions and pathogenic pathways.

Preterm delivery (PTD, <37 weeks of gestation) is a significant clinical and public health problem. Previously, we reported that maternal smoking and metabolic gene polymorphisms of CYP1A1 MspI and GSTT1 synergistically increase the risk of low birth weight. This study investigates the relationship between maternal smoking and metabolic gene polymorphisms of CYP1A1 MspI and GSTT1 with preterm delivery (PTD) as a whole and preterm subgroups. This case-control study included 1,749 multi-ethnic mothers (571 with PTD and 1,178 controls) enrolled at Boston Medical Center. After adjusting covariates, regression analyses were performed to identify individual and joint associations of maternal smoking, two functional variants of CYP1A1 and GSTT1 with PTD. We observed a moderate effect of maternal smoking on PTD (OR = 1.6; 95% CI: 1.1-2.2). We found that compared to non-smoking mothers with low-risk genotypes, there was a significant joint association of maternal smoking, CYP1A1 (Aa/aa) and GSTT1 (absent) genotypes with gestational age (beta = -3.37; SE = 0.86; P = 9 x 10(-5)) and with PTD (OR = 5.8; 95% CI: 2.0-21.1), respectively. Such joint association was particularly strong in certain preterm subgroups, including spontaneous PTD (OR = 8.3; 95% CI: 2.7-30.6), PTD < 32 weeks (OR = 11.1; 95% CI: 2.9-47.7), and PTD accompanied by histologic chorioamnionitis (OR = 15.6; 95% CI: 4.1-76.7). Similar patterns were observed across ethnic groups. Taken together, maternal smoking significantly increased the risk of PTD among women with high-risk CYP1A1 and GSTT1 genotypes. Such joint associations were strongest among PTD accompanied by histologic chorioamnionitis.

Prevalence and correlates of high-quality basic pediatric preventive care.

BACKGROUND: The list of recommended pediatric preventive services has grown considerably in the past decade, and clinician variability, clinician distribution, and other correlates of provision of these basic preventive services (BPS) are not known. OBJECTIVE: To describe the proportion of high-quality basic pediatric preventive services, exclusive of immunizations, reported by parents and to identify sociodemographic and health system predictors and health service correlates of provision of these services. STUDY DESIGN: The study used cross-sectional data on 2041 children, 4 to 35 months of age, in the 2000 National Survey of Early Childhood Health. OUTCOME MEASURES: The BPS measure assesses the receipt of (1) developmental assessment, (2) injury prevention counseling, (3) screening for parental smoking, (4) guidance on reading to the child, and (5) guidance on 14 other topics (assessed as a composite score). The BPS scale categorizes the receipt of services as excellent, good, fair, or poor. RESULTS: Most children received excellent (34.9%) or good (31.5%) care, but many received fair (24.9%) or poor (8.7%) care. Sociodemographic and health care factors such as race/ethnicity, insurance, and practice setting were not associated with BPS levels. Higher BPS scores were associated with parental reports of longer well-child visits, more counseling regarding family and community risk factors, lower rates of delayed or missed care, and greater satisfaction. CONCLUSIONS: Two thirds of children receive good or excellent basic preventive care, as determined with this composite, and no disparities according to race/ethnicity, income, or health insurance status of families (which are often found to be associated with health care access) were found. This equitable distribution of high-quality care suggests a high level of clinician professionalism. Duration of visits may be a key factor to improve quality of care. Because of its association with other services, processes, and outcomes of care, the BPS scale may serve as a useful construct for monitoring quality and stimulating efforts to improve national pediatric preventive care.