Low-to-moderate prenatal alcohol consumption and the risk of selected birth outcomes: a prospective cohort study.

PURPOSE: To estimate whether low-to-moderate prenatal alcohol exposure is associated with selected birth outcomes. METHODS: Low-to-moderate prenatal alcohol drinking and effects on low birthweight, preterm delivery, intrauterine growth restriction, and selected neonatal outcomes were evaluated among 4496 women and singleton infants. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable logistic regression, controlling for confounding variables. RESULTS: Early pregnancy drinking was associated with reduced odds of low birthweight, OR, 0.66 (95% CI, 0.46-0.96) and birth length less than 10th percentile, OR, 0.74 (95% CI, 0.56-0.97). Drinking during the first 3 months showed lower odds for birth length and head circumference less than 10th percentile, OR, 0.56 (95% CI, 0.36-0.87) and OR, 0.69 (95% CI, 0.50-0.96), respectively. Third trimester drinking was associated with lower odds for low birthweight, OR, 0.56 (95% CI, 0.34-0.94) and preterm delivery, OR, 0.60 (95% CI, 0.42-0.87). CONCLUSIONS: Our results suggest low-to-moderate alcohol exposure during early and late gestation is not associated with increased risk of low birthweight, preterm delivery, intrauterine growth restriction, and most selected perinatal outcomes.

Fine particulate matter and risk of preterm birth and pre-labor rupture of membranes in Perth, Western Australia 1997-2007: a longitudinal study.

OBJECTIVE: A recent longitudinal study reported an association between fine particulate (PM2.5) exposure and preterm birth (PTB) in a US cohort. We applied the same design to an Australian cohort to investigate associations with PTB and pre-labor rupture of membranes (PROM). METHODS: From 287,680 births, we selected 39,189 women who had singleton births at least twice in Western Australia in 1997-2007 (n=86,844 births). Analyses matched pregnancies to the same women with conditional logistic regression. RESULTS: For PROM adjusted odds ratios (ORs) for a 1 µg/m(3) increase in PM2.5 in the first trimester, second trimester, third trimester, and whole pregnancy were 1.00 (95% confidence interval (CI): 0.97, 1.03), 1.03 (95% CI: 1.00, 1.06), 1.02 (95% CI: 1.00, 1.05), and 1.02 (95% CI: 0.99, 1.05) respectively. For PTB, corresponding ORs were 1.00 (95% CI: 0.96, 1.04), 1.00 (95% CI: 0.96, 1.04), 0.98 (95% CI: 0.94, 1.02), and 0.99 (95% CI: 0.95, 1.04) respectively. CONCLUSION: Risk of PROM was greater for pregnancies with elevated PM2.5 exposure in the second trimester than were other pregnancies to the same Australian women at lower exposure. There was insufficient evidence for an association with PTB, indicating that a longer time period might be needed to observe an association if a causal effect exists.

Sources of fine particulate matter and risk of preterm birth in Connecticut, 2000-2006: a longitudinal study.

BACKGROUND: Previous studies have examined fine particulate matter (≤ 2.5 µm; PM2.5) and preterm birth, but there is a dearth of longitudinal studies on this topic and a paucity of studies that have investigated specific sources of this exposure. OBJECTIVES: Our aim was to assess whether anthropogenic sources are associated with risk of preterm birth, comparing successive pregnancies to the same woman. METHODS: Birth certificates were used to select women who had vaginal singleton live births at least twice in Connecticut during 2000-2006 (n = 23,123 women, n = 48,208 births). We procured 4,085 daily samples of PM2.5 on Teflon filters from the Connecticut Department of Environmental Protection for six cities in Connecticut. Filters were analyzed for chemical composition, and Positive Matrix Factorization was used to determine contributions of PM2.5 sources. Risk estimates were calculated with conditional logistic regression, matching pregnancies to the same women. RESULTS: Odds ratios of preterm birth per interquartile range increase in whole pregnancy exposure to dust, motor vehicle emissions, oil combustion, and regional sulfur PM2.5 sources were 1.01 (95% CI: 0.93, 1.09), 1.01 (95% CI: 0.92, 1.10), 1.00 (95% CI: 0.89, 1.12), and 1.09 (95% CI: 0.97, 1.22), respectively. CONCLUSION: This was the first study of PM2.5 sources and preterm birth, and the first matched analysis, that better addresses individual-level confounding potentially inherent in all past studies. There was insufficient evidence to suggest that sources were statistically significantly associated with preterm birth. However, elevated central estimates and previously observed associations with mass concentration motivate the need for further research. Future studies would benefit from high source exposure settings and longitudinal study designs, such as that adopted in this study.

Pregnant women with posttraumatic stress disorder and risk of preterm birth.

IMPORTANCE: Posttraumatic stress disorder (PTSD) occurs in about 8% of pregnant women. Stressful conditions, including PTSD, are inconsistently linked to preterm birth. Psychotropic treatment has been frequently associated with preterm birth. Identifying whether the psychiatric illness or its treatment is independently associated with preterm birth may help clinicians and patients when making management decisions. OBJECTIVE: To determine whether a likely diagnosis of PTSD or antidepressant and benzodiazepine treatment during pregnancy is associated with risk of preterm birth. We hypothesized that pregnant women who likely had PTSD and women receiving antidepressant or anxiolytic treatment would be more likely to experience preterm birth. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal, prospective cohort study of 2654 women who were recruited before 17 completed weeks of pregnancy from 137 obstetrical practices in Connecticut and Western Massachusetts. EXPOSURES: Posttraumatic stress disorder, major depressive episode, and use of antidepressant and benzodiazepine medications. MAIN OUTCOMES AND MEASURES: Preterm birth, operationalized as delivery prior to 37 completed weeks of pregnancy. Likely psychiatric diagnoses were generated through administration of the Composite International Diagnostic Interview and the Modified PTSD Symptom Scale. Data on medication use were gathered at each participant interview. RESULTS: Recursive partitioning analysis showed elevated rates of preterm birth among women with PTSD. A further split of the PTSD node showed high rates for women who met criteria for a major depressive episode, which suggests an interaction between these 2 exposures. Logistic regression analysis confirmed risk for women who likely had both conditions (odds ratio [OR], 4.08 [95% CI, 1.27-13.15]). For each point increase on the Modified PTSD Symptom Scale (range, 0-110), the risk of preterm birth increased by 1% to 2%. The odds of preterm birth are high for women who used a serotonin reuptake inhibitor (OR, 1.55 [95% CI, 1.02-2.36]) and women who used a benzodiazepine medication (OR, 1.99 [95% CI, 0.98-4.03]). CONCLUSIONS AND RELEVANCE: Women with likely diagnoses of both PTSD and a major depressive episode are at a 4-fold increased risk of preterm birth; this risk is greater than, and independent of, antidepressant and benzodiazepine use and is not simply a function of mood or anxiety symptoms.

Birth cohorts in asthma and allergic diseases: report of a NIAID/NHLBI/MeDALL joint workshop.

Population-based birth cohorts on asthma and allergies increasingly provide new insights into the development and natural history of the diseases. More than 130 birth cohorts focusing on asthma and allergy have been initiated in the last 30 years. A National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute; Mechanisms of the Development of Allergy (MeDALL; Framework Programme 7 of the European Commission) joint workshop was held in Bethesda, Maryland, on September 11-12, 2012, with 3 objectives: (1) documenting the knowledge that asthma/allergy birth cohorts have provided, (2) identifying the knowledge gaps and inconsistencies, and (3) developing strategies for moving forward, including potential new study designs and the harmonization of existing asthma birth cohort data. The meeting was organized around the presentations of 5 distinct workgroups: (1) clinical phenotypes, (2) risk factors, (3) immune development of asthma and allergy, (4) pulmonary development, and (5) harmonization of existing birth cohorts. This article presents the workgroup reports and provides Web links (AsthmaBirthCohorts.niaid.nih.gov or www.medall-fp7.eu), where the reader will find tables describing the characteristics of the birth cohorts included in this report, the type of data collected at differing ages, and a selected bibliography provided by the participating birth cohorts.

The Association between Airborne PM2.5 Chemical Constituents and Birth Weight-Implication of Buffer Exposure Assignment.

Several papers reported associations between airborne fine particulate matter (PM2.5) and birth weight, though findings are inconsistent across studies. Conflicting results might be due to (1) different PM2.5 chemical structure across locations, and (2) various exposure assignment methods across studies even among the studies that use ambient monitors to assess exposure. We investigated associations between birth weight and PM2.5 chemical constituents, considering issues arising from choice of buffer size (i.e. distance between residence and pollution monitor). We estimated the association between each pollutant and term birth weight applying buffers of 5 to 30km in Connecticut (2000-2006), in the New England region of the U.S. We also investigated the implication of the choice of buffer size in relation to population characteristics, such as socioeconomic status. Results indicate that some PM2.5 chemical constituents, such as nitrate, are associated with lower birth weight and appear more harmful than other constituents. However, associations vary with buffer size and the implications of different buffer sizes may differ by pollutant. A homogeneous pollutant level within a certain distance is a common assumption in many environmental epidemiology studies, but the validity of this assumption may vary by pollutant. Furthermore, we found that areas close to monitors reflect more minority and lower socio-economic populations, which implies that different exposure approaches may result in different types of study populations. Our findings demonstrate that choosing an exposure method involves key tradeoffs of the impacts of exposure misclassification, sample size, and population characteristics.

Fine particulate matter and risk of preterm birth in Connecticut in 2000-2006: a longitudinal study.

Several studies have examined associations between particulate matter with aerodynamic diameter of 2.5 µm or less (PM2.5) and preterm birth, but it is uncertain whether results were affected by individual predispositions (e.g., genetic factors, social conditions) that might vary considerably between women. We tested the hypothesis that a woman is at greater risk of preterm delivery when she has had elevated exposure to ambient PM2.5 during a pregnancy than when she has not by comparing pregnancies in the same woman. From 271,204 births, we selected 29,175 women who had vaginal singleton livebirths at least twice in Connecticut in 2000-2006 (n = 61,688 births). Analyses matched pregnancies to the same woman. Adjusted odds ratios per interquartile range (2.33-µg/m(3)) increase in PM2.5 in the first trimester, second trimester, third trimester, and whole pregnancy were 1.07 (95% confidence interval (CI): 1.00, 1.15), 0.96 (95% CI: 0.90, 1.03), 1.03 (95% CI: 0.97, 1.08), and 1.13 (95% CI: 1.01, 1.28), respectively. Among Hispanic women, the odds ratio per interquartile range increase in whole-pregnancy exposure was 1.31 (95% CI: 1.00, 1.73). Pregnancies with elevated PM2.5 exposure were more likely to result in preterm birth than were other pregnancies to the same woman at lower exposure. Associations were most pronounced in the first trimester and among Hispanic women.

PM2.5 exposure and birth outcomes: use of satellite- and monitor-based data.

BACKGROUND: Air pollution may be related to adverse birth outcomes. Exposure information from land-based monitoring stations often suffers from limited spatial coverage. Satellite data offer an alternative data source for exposure assessment. METHODS: We used birth certificate data for births in Connecticut and Massachusetts, United States (2000-2006). Gestational exposure to PM2.5 was estimated from US Environmental Protection Agency monitoring data and from satellite data. Satellite data were processed and modeled by using two methods-denoted satellite (1) and satellite (2)-before exposure assessment. Regression models related PM2.5 exposure to birth outcomes while controlling for several confounders. Birth outcomes were mean birth weight at term birth, low birth weight at term (<2500 g), small for gestational age (SGA, <10th percentile for gestational age and sex), and preterm birth (<37 weeks). RESULTS: Overall, the exposure assessment method modified the magnitude of the effect estimates of PM2.5 on birth outcomes. Change in birth weight per interquartile range (2.41 µg/m) increase in PM2.5 was -6 g (95% confidence interval = -8 to -5), -16 g (-21 to -11), and -19 g (-23 to -15), using the monitor, satellite (1), and satellite (2) methods, respectively. Adjusted odds ratios, based on the same three exposure methods, for term low birth weight were 1.01 (0.98-1.04), 1.06 (0.97-1.16), and 1.08 (1.01-1.16); for SGA, 1.03 (1.01-1.04), 1.06 (1.03-1.10), and 1.08 (1.04-1.11); and for preterm birth, 1.00 (0.99-1.02), 0.98 (0.94-1.03), and 0.99 (0.95-1.03). CONCLUSIONS: Under exposure assessment methods, we found associations between PM2.5 exposure and adverse birth outcomes particularly for birth weight among term births and for SGA. These results add to the growing concerns that air pollution adversely affects infant health and suggest that analysis of health consequences based on satellite-based exposure assessment can provide additional useful information.

Household levels of nitrogen dioxide and pediatric asthma severity.

BACKGROUND: Adverse respiratory effects in children with asthma are associated with exposures to nitrogen dioxide (NO2). Levels indoors can be much higher than outdoors. Primary indoor sources of NO2 are gas stoves, which are used for cooking by one-third of U.S. households. We investigated the effects of indoor NO2 exposure on asthma severity among an ethnically and economically diverse sample of children, controlling for season and indoor allergen exposure. METHODS: Children 5-10 years of age with active asthma (n = 1,342) were recruited through schools in urban and suburban Connecticut and Massachusetts (2006-2009) for a prospective, year-long study with seasonal measurements of NO2 and asthma severity. Exposure to NO2 was measured passively for four, month-long, periods with Palmes tubes. Asthma morbidity was concurrently measured by a severity score and frequency of wheeze, night symptoms, and use of rescue medication. We used adjusted, hierarchical ordered logistic regression models to examine associations between household NO2 exposure and health outcomes. RESULTS: Every 5-fold increase in NO2 exposure above a threshold of 6 ppb was associated with a dose-dependent increase in risk of higher asthma severity score (odds ratio = 1.37 [95% confidence interval = 1.01-1.89]), wheeze (1.49 [1.09-2.03]), night symptoms (1.52 [1.16-2.00]), and rescue medication use (1.78 [1.33-2.38]). CONCLUSIONS: Asthmatic children exposed to NO2 indoors, at levels well below the U.S. Environmental Protection Agency outdoor standard (53 ppb), are at risk for increased asthma morbidity. Risks are not confined to inner city children, but occur at NO2 concentrations common in urban and suburban homes.

Implementing provider-based sampling for the National Children's Study: opportunities and challenges.

BACKGROUND: The National Children's Study (NCS) was established as a national probability sample of births to prospectively study children's health starting from in utero to age 21. The primary sampling unit was 105 study locations (typically a county). The secondary sampling unit was the geographic unit (segment), but this was subsequently perceived to be an inefficient strategy. METHODS AND RESULTS: This paper proposes that second-stage sampling using prenatal care providers is an efficient and cost-effective method for deriving a national probability sample of births in the US. It offers a rationale for provider-based sampling and discusses a number of strategies for assembling a sampling frame of providers. Also presented are special challenges to provider-based sampling pregnancies, including optimising key sample parameters, retaining geographic diversity, determining the types of providers to include in the sample frame, recruiting women who do not receive prenatal care, and using community engagement to enrol women. There will also be substantial operational challenges to sampling provider groups. CONCLUSION: We argue that probability sampling is mandatory to capture the full variation in exposure and outcomes expected in a national cohort study, to provide valid and generalisable risk estimates, and to accurately estimate policy (such as screening) benefits from associations reported in the NCS.

Relationship between birth weight and exposure to airborne fine particulate potassium and titanium during gestation.

Airborne particles are linked to numerous health impacts, including adverse pregnancy outcomes. Most studies of particles examined total mass, although the chemical structure of particles varies widely. We investigated whether mother's exposure to potassium (K) and titanium (Ti) components of airborne fine particulate matter (PM(2.5)) during pregnancy was associated with birth weight or risk of low birth weight (<2500 g) for term infants. The study population was 76,788 infants born in four counties in Connecticut and Massachusetts, US, for August 2000-February 2004. Both K and Ti were associated with birth weight. An interquartile range (IQR) increase K was associated with an 8.75% (95% confidence interval (CI): 1.24-16.8%) increase in risk of low birth weight. An IQR increase in Ti was associated with a 12.1% (95% CI: 3.55-21.4%) increase in risk of low birth weight, with an estimate of 6.41% (95% CI: -5.80-20.2%) for males and 16.4% (95% CI: 5.13-28.9%) for females. Results were robust to sensitivity analysis of first births only, but not adjustment by co-pollutants. Disentangling the effects of various chemical components is challenging because of the covariance among some components due to similar sources. Central effect estimates for infants of African-American mothers were higher than those of white mothers, although the confidence intervals overlapped. Our results indicate that exposure to airborne potassium and titanium during pregnancy is associated with lower birth weight. Associations may relate to chemical components of sources producing K and Ti.

Depression and serotonin reuptake inhibitor treatment as risk factors for preterm birth.

BACKGROUND: Major depressive disorder and the use of serotonin reuptake inhibitors (SRIs) in pregnancy have been associated with preterm birth. Studies that have attempted to separate effects of illness from treatment have been inconclusive. We sought to explore the separate effects of SRI use and major depressive episodes in pregnancy on risk of preterm birth. METHODS: We conducted a prospective cohort study of 2793 pregnant women, oversampled for a recent episode of major depression or use of an SRI. We extracted data on birth outcomes from hospital charts and used binary logistic regression to model preterm birth (<37 weeks' gestation). We used ordered logistic regression to model early (<34 weeks' gestation) or late (34-36 weeks) preterm birth, and we used nominal logistic regression to model preterm birth antecedents (spontaneous preterm labor/preterm premature rupture of membranes/preterm for medical indications/term). RESULTS: Use of an SRI, both with (odds ratio = 2.1 [95% confidence interval = 1.0-4.6]) and without (1.6 [1.0-2.5]) a major depressive episode, was associated with preterm birth. A major depressive episode without SRI use (1.2 [0.68-2.1]) had no clear effect on preterm birth risk. None of these exposures was associated with early preterm birth. Use of SRIs in pregnancy was associated with increases in spontaneous but not medically indicated preterm birth. CONCLUSIONS: SRI use increased risk of preterm birth. Although the effect of a major depressive episode alone was unclear, symptomatic women undergoing antidepressant treatment had elevated risk.

Review of research on residential mobility during pregnancy: consequences for assessment of prenatal environmental exposures.

Studies on environmental exposures during pregnancy often have limited residential history (e.g., at delivery), potentially introducing exposure misclassification. We reviewed studies reporting residential mobility during pregnancy to summarize current evidence and discuss research implications. A meaningful quantitative combination of results (e.g., meta-analysis), was infeasible owing to variation in study designs. Fourteen studies were identified, of which half were from the US. Most were case-control studies examining birth defects. Residential history was typically assessed after delivery. Overall mobility rates were 9-32% and highest in the second trimester. Mobility generally declined with age, parity, and socioeconomic status, although not consistently. Married mothers moved less frequently. Findings were dissimilar by race, smoking, or alcohol use. On the basis of the few studies reporting distance moved, most distances were short (median often <10 km). Results indicate potential misclassification for environmental exposures estimated with incomplete residential information. This misclassification could be associated with potential confounders, such as socioeconomics, thereby affecting risk estimates. As most moves were short distances, exposures that are homogenous within a community may be well estimated with limited residential data. Future research should consider the implications of residential mobility during pregnancy in relation to the exposure's spatial heterogeneity and factors associated with the likelihood of moving and distance moved.

Association of variants in innate immune genes with asthma and eczema.

BACKGROUND: The innate immune pathway is important in the pathogenesis of asthma and eczema. However, only a few variants in these genes have been associated with either disease. We investigate the association between polymorphisms of genes in the innate immune pathway with childhood asthma and eczema. In addition, we compare individual associations with those discovered using a multivariate approach. METHODS: Using a novel method, case control based association testing (C2BAT), 569 single nucleotide polymorphisms (SNPs) in 44 innate immune genes were tested for association with asthma and eczema in children from the Boston Home Allergens and Asthma Study and the Connecticut Childhood Asthma Study. The screening algorithm was used to identify the top SNPs associated with asthma and eczema. We next investigated the interaction of innate immune variants with asthma and eczema risk using Bayesian networks. RESULTS: After correction for multiple comparisons, 7 SNPs in 6 genes (CARD25, TGFB1, LY96, ACAA1, DEFB1, and IFNG) were associated with asthma (adjusted p-value<0.02), while 5 SNPs in 3 different genes (CD80, STAT4, and IRAKI) were significantly associated with eczema (adjusted p-value < 0.02). None of these SNPs were associated with both asthma and eczema. Bayesian network analysis identified 4 SNPs that were predictive of asthma and 10 SNPs that predicted eczema. Of the genes identified using Bayesian networks, only CD80 was associated with eczema in the single-SNP study. Using novel methodology that allows for screening and replication in the same population, we have identified associations of innate immune genes with asthma and eczema. Bayesian network analysis suggests that additional SNPs influence disease susceptibility via SNP interactions. CONCLUSION: Our findings suggest that innate immune genes contribute to the pathogenesis of asthma and eczema, and that these diseases likely have different genetic determinants.

Effects of endotoxin exposure on childhood asthma risk are modified by a genetic polymorphism in ACAA1.

BACKGROUND: Polymorphisms in the endotoxin-mediated TLR4 pathway genes have been associated with asthma and atopy. We aimed to examine how genetic polymorphisms in innate immunity pathways interact with endotoxin to influence asthma risk in children. METHODS: In a previous analysis of 372 children from the Boston Home Allergens and the Connecticut Childhood Asthma studies, 7 SNPs in 6 genes (CARD15, TGFB1, LY96, ACAA1, DEFB1 and IFNG) involved in innate immune pathways were associated with asthma, and 5 SNPs in 3 genes (CD80, STAT4, IRAK2) were associated with eczema. We tested these SNPs for interaction with early life endotoxin exposure (n = 291), in models for asthma and eczema by age 6. RESULTS: We found a significant interaction between endotoxin and a SNP (rs156265) in ACAA1 (p = 0.0013 for interaction). Increased endotoxin exposure (by quartile) showed protective effects for asthma in individuals with at least one copy of the minor allele (OR = 0.39 per quartile increase in endotoxin, 95% CI 0.15 to 1.01). Endotoxin exposure did not reduce the risk of asthma in children homozygous for the major allele. CONCLUSION: Our findings suggest that protective effects of endotoxin exposure on asthma may vary depending upon the presence or absence of a polymorphism in ACAA1.

Does antidepressant use attenuate the risk of a major depressive episode in pregnancy?

BACKGROUND: Many women become pregnant while undergoing antidepressant treatment and are concerned about continuing antidepressant medication. However, antidepressant discontinuation may increase the risk of a new episode of major depressive disorder. We sought to estimate differences in the risk of developing a new major depressive episode among pregnant and postpartum women with recurrent illness who either did or did not use antidepressants. METHODS: Participants were recruited from obstetrical settings; we analyzed a subgroup of 778 women with a history of a depressive disorder. Diagnoses were determined by the Composite International Diagnostic Interview administered twice in pregnancy and once after delivery. We used Cox Regression to model onset of a major depressive episode with a time-dependent predictor of antidepressant use. RESULTS: There was no clear difference in risk of a major depressive episode between women who took antidepressants and women who did not (hazard ratio [HR] = 0.88; 95% CI = 0.51-1.50). After accounting for antidepressant use, clearly hazardous factors included 4 or more depressive episodes before pregnancy (HR = 1.97; 95% CI = 1.09-3.57), black race (HR = 3.69; 95% CI = 2.16-6.30), and Hispanic ethnicity (HR = 2.33; 95% CI = 1.47-3.69). CONCLUSIONS: Failure to use or discontinuation of antidepressants in pregnancy did not have a strong effect on the development of a major depressive episode. Women with 4 or more episodes before pregnancy were at high risk of a major depressive episode, independent of antidepressant use. Black and Hispanic women also were at high risk of a major depressive episode, but it is possible that this effect is attributable to unmeasured factors.

Indications contributing to the increasing cesarean delivery rate.

OBJECTIVE: To examine physician-documented indications for cesarean delivery in order to investigate the specific factors contributing to the increasing cesarean delivery rate. METHODS: We analyzed rates of primary and repeat cesarean delivery, including indications for the procedure, among 32,443 live births at a major academic hospital between 2003 and 2009. Time trends for each indication were modeled to estimate the absolute and cumulative annualized relative risk of cesarean by indication over time and the relative contribution of each indication to the overall increase in primary cesarean delivery rate. RESULTS: The cesarean delivery rate increased from 26% to 36.5% between 2003 and 2009; 50.0% of the increase was attributable to an increase in primary cesarean delivery. Among the documented indications, nonreassuring fetal status, arrest of dilation, multiple gestation, preeclampsia, suspected macrosomia, and maternal request increased over time, whereas arrest of descent, malpresentation, maternal-fetal indications, and other obstetric indications (eg, cord prolapse, placenta previa) did not increase. The relative contributions of each indication to the total increase in primary cesarean rate were: nonreassuring fetal status (32%), labor arrest disorders (18%), multiple gestation (16%), suspected macrosomia (10%), preeclampsia (10%), maternal request (8%), maternal-fetal conditions (5%), and other obstetric conditions (1%). CONCLUSION: Primary cesarean births accounted for 50% of the increasing cesarean rate. Among primary cesarean deliveries, more subjective indications (nonreassuring fetal status and arrest of dilation) contributed larger proportions than more objective indications (malpresentation, maternal-fetal, and obstetric conditions).

Urban land-use and respiratory symptoms in infants.

BACKGROUND: Children's respiratory health has been linked to many factors, including air pollution. The impacts of urban land-use on health are not fully understood, although these relationships are of key importance given the growing populations living in urban environments. OBJECTIVES: We investigated whether the degree of urban land-use near a family's residence is associated with severity of respiratory symptoms like wheeze among infants. METHODS: Wheeze occurrence was recorded for the first year of life for 680 infants in Connecticut for 1996-1998 from a cohort at risk for asthma development. Land-use categories were obtained from the National Land Cover Database. The fraction of urban land-use near each subject's home was related to severity of wheeze symptoms using ordered logistic regression, adjusting for individual-level data including smoking in the household, race, gender, and socio-economic status. Nitrogen dioxide (NO(2)) exposure was estimated using integrated traffic exposure modeling. Different levels of urban land-use intensity were included in separate models to explore intensity-response relationships. A buffer distance was selected based on the log-likelihood value of models with buffers of 100-2000 m by 10 m increments. RESULTS: A 10% increase in urban land-use within the selected 1540 m buffer of each infant's residence was associated with 1.09-fold increased risk of wheeze severity (95% confidence interval, 1.02-1.16). Results were robust to alternate buffer sizes. When NO(2), representing traffic pollution, was added to the model, results for urban land-use were no longer statistically significant, but had similar central estimates. Higher urban intensity showed higher risk of prevalence and severity of wheeze symptoms. CONCLUSIONS: Urban land-use was associated with severity of wheeze symptoms in infants. Findings indicate that health effect estimates for urbanicity incorporate some effects of traffic-related emissions, but also involve other factors. These may include differences in housing characteristics or baseline healthcare status.

Association of maternal anemia with increased wheeze and asthma in children.

BACKGROUND: Increasing interest has focused on maternal nutrition and micronutrient status during pregnancy and respiratory disease development in the offspring. OBJECTIVE: To examine the relationship between maternal anemia in pregnancy with wheeze and asthma in early childhood. METHODS: The cohort included children of women followed through pregnancy and recontacted when the child was 6 years of age to evaluate respiratory health. Exposure was assessed using maternal anemia diagnosis and hemoglobin (Hgb) < 11 during delivery hospitalization. Study outcomes include wheezing in early childhood; patterns of wheeze from birth to age 6 (early-onset transient wheeze; late-onset wheeze; early-onset persistent wheeze); and diagnosis of childhood asthma. RESULTS: Maternal anemia was reported by 11.9% of mothers and was associated with recurrent infant wheeze in the first year (adjusted odds ratio [ORa] = 2.17, 95% confidence interval [CI] 1.18, 4.00), wheezing before age 3 (Ora = 2.42, 95% CI 1.38, 4.23), and early-onset transient and early-onset persistent wheeze patterns (Ora = 2.81, 95%CI 1.38, 5.72, and Ora = 2.07, 95% CI 1.02, 4.22), respectively. Among children of mothers with asthma, maternal anemia was associated with recurrent wheeze in year 1 (Ora = 4.22, 95% CI 1.65, 10.80) and wheeze before age 3 (Ora = 2.73, 95% CI 1.17, 6.35). Offspring of mothers with asthma also had increased odds of asthma diagnosis (Ora = 2.53, 95% CI 1.04, 6.17) and current asthma (Ora = 3.46, 95% CI 1.45, 8.26). CONCLUSIONS: Maternal anemia during pregnancy is associated with infant respiratory health outcomes. If this observation is replicated, maternal anemia may be a target for intervention and future research.

Antibiotic exposure by 6 months and asthma and allergy at 6 years: Findings in a cohort of 1,401 US children.

Many studies have reported that antibiotic use may be associated with increased risk of childhood asthma. Respiratory tract infections in small children may be difficult to distinguish from early symptoms of asthma, and studies may have been confounded by "protopathic" bias, where antibiotics are used to treat early symptoms of asthma. These analyses of a cohort including 1,401 US children assess the association between antibiotic use within the first 6 months of life and asthma and allergy at 6 years of age between 2003 and 2007. Antibiotic exposure was associated with increased risk of asthma (adjusted odds ratio = 1.52, 95% confidence interval (CI): 1.07, 2.16). The odds ratio if asthma was first diagnosed after 3 years of age was 1.66 (95% CI: 0.99, 2.79) and, in children with no history of lower respiratory infection in the first year of life, the odds ratio was 1.66 (95% CI: 1.12, 3.46). The adverse effect of antibiotics was particularly strong in children with no family history of asthma (odds ratio = 1.89, 95% CI: 1.00, 3.58) (P(interaction) = 0.03). The odds ratio for a positive allergy blood or skin test was 1.59 (95% CI: 1.10, 2.28). The results show that early antibiotic use was associated with asthma and allergy at 6 years of age, and that protopathic bias was unlikely to account for the main findings.