Interdisciplinary-driven hypotheses on spatial associations of mixtures of industrial air pollutants with adverse birth outcomes.

BACKGROUND: Adverse birth outcomes (ABO) such as prematurity and small for gestational age confer a high risk of mortality and morbidity. ABO have been linked to air pollution; however, relationships with mixtures of industrial emissions are poorly understood. The exploration of relationships between ABO and mixtures is complex when hundreds of chemicals are analyzed simultaneously, requiring the use of novel approaches. OBJECTIVE: We aimed to generate robust hypotheses spatially linking mixtures and the occurrence of ABO using a spatial data mining algorithm and subsequent geographical and statistical analysis. The spatial data mining approach aimed to reduce data dimensionality and efficiently identify spatial associations between multiple chemicals and ABO. METHODS: We discovered co-location patterns of mixtures and ABO in Alberta, Canada (2006-2012). An ad-hoc spatial data mining algorithm allowed the extraction of primary co-location patterns of 136 chemicals released into the air by 6279 industrial facilities (National Pollutant Release Inventory), wind-patterns from 182 stations, and 333,247 singleton live births at the maternal postal code at delivery (Alberta Perinatal Health Program), from which we identified cases of preterm birth, small for gestational age, and low birth weight at term. We selected secondary patterns using a lift ratio metric from ABO and non-ABO impacted by the same mixture. The relevance of the secondary patterns was estimated using logistic models (adjusted by socioeconomic status and ABO-related maternal factors) and a geographic-based assignment of maternal exposure to the mixtures as calculated by kernel density. RESULTS: From 136 chemicals and three ABO, spatial data mining identified 1700 primary patterns from which five secondary patterns of three-chemical mixtures, including particulate matter, methyl-ethyl-ketone, xylene, carbon monoxide, 2-butoxyethanol, and n-butyl alcohol, were subsequently analyzed. The significance of the associations (odds ratio > 1) between the five mixtures and ABO provided statistical support for a new set of hypotheses. CONCLUSION: This study demonstrated that, in complex research settings, spatial data mining followed by pattern selection and geographic and statistical analyses can catalyze future research on associations between air pollutant mixtures and adverse birth outcomes.

A Randomized Controlled Trial of the Safety and Immunogenicity of Tetanus, Diphtheria, and Acellular Pertussis Vaccine Immunization During Pregnancy and Subsequent Infant Immune Response.

Background: Immunization of pregnant women with tetanus-diphtheria-acellular pertussis vaccine (Tdap) provides protection against pertussis to the newborn infant. Methods: In a randomized, controlled, observer-blind, multicenter clinical trial, we measured the safety and immunogenicity of Tdap during pregnancy and the effect on the infant's immune response to primary vaccination at 2, 4, and 6 months and booster vaccination at 12 months of age. A total of 273 women received either Tdap or tetanus-diphtheria (Td) vaccine in the third trimester and provided information for the safety analysis and samples for the immunogenicity analyses; 261 infants provided serum for the immunogenicity analyses. Results: Rates of adverse events were similar in both groups. Infants of Tdap recipients had cord blood levels that were 21% higher than maternal levels for pertussis toxoid (PT), 13% higher for filamentous hemagglutinin (FHA), 4% higher for pertactin (PRN), and 7% higher for fimbriae (FIM). These infants had significantly higher PT antibody levels at birth and at 2 months and significantly higher FHA, PRN, and FIM antibodies at birth and 2 and 4 months, but significantly lower PT and FHA antibody levels at 6 and 7 months and significantly lower PRN and FIM antibody levels at 7 months than infants whose mothers received Td. Differences persisted prebooster at 12 months for all antigens and postbooster 1 month later for PT, FHA, and FIM. Conclusions: This study demonstrated that Tdap during pregnancy results in higher levels of antibodies early in infancy but lower levels after the primary vaccine series. Clinical Trials Registration: NCT00553228.

Epidural analgesia in labour and neonatal respiratory distress: a case-control study.

BACKGROUND: Epidural analgesia is the commonest mode for providing pain relief in labour, with a combination of bupivacaine and fentanyl most often used in practice. OBJECTIVE: To test whether late-preterm and term neonates exposed to opioids in epidural analgesia in labour are more likely to develop respiratory distress in the immediate neonatal period. METHODS: A case-control study was conducted of singleton infants born during January 2006 to December 2010. Cases were neonates ≥34 weeks gestation, who developed respiratory distress within 24 h of life requiring supplemental oxygen ≥2 h and/or positive pressure ventilation in the neonatal intensive care unit. Controls were gestation and site-matched neonates who did not develop any respiratory distress within the same period. The information on exposure to epidural analgesia and on potential confounding variables was obtained from the standardised delivery record, routinely filled out on all women admitted to the labour wards. RESULTS: In our study, 206 cases and 206 matched controls were enrolled. Exposure to epidural analgesia was present in 146 (70.9%) cases as compared with 131 (63.6%) of the controls. The association between exposure to epidural analgesia and respiratory distress in neonates was statistically significant upon adjustment for all potential confounders (adjusted OR: 1.75, 95% CI 1.03 to 2.99; p = 0.04). When data was separately analysed for term and late-preterm infants, the results were consistent across these subpopulations, showing no interaction effect. CONCLUSIONS: Late-preterm and term infants exposed to maternal epidural analgesia in labour are more likely to develop respiratory distress in the immediate neonatal period.

Corticosteroids for HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome in pregnancy.

BACKGROUND: Pre-eclampsia is a relatively common complication of pregnancy. HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome is a severe manifestation of pre-eclampsia with significant morbidity and mortality for pregnant women and their children. Corticosteroids are commonly used in the treatment of HELLP syndrome in the belief that they improve outcomes. OBJECTIVES: To determine the effects of corticosteroids on women with HELLP syndrome and their children. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2010). SELECTION CRITERIA: Randomized controlled trials comparing any corticosteroid with placebo, no treatment, or other drug; or comparing one corticosteroid with another corticosteroid or dosage in women with HELLP syndrome. DATA COLLECTION AND ANALYSIS: Two review authors assessed trial quality and extracted data independently. MAIN RESULTS: Eleven trials (550 women) compared corticosteroids with placebo or no treatment. There was no difference in the risk of maternal death (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.28 to 3.21), maternal death or severe maternal morbidity (RR 0.27, 95% CI 0.03 to 2.12), or perinatal/infant death (RR 0.64, 95% CI 0.21 to 1.97). The only clear effect of treatment on individual outcomes was improved platelet count (standardized mean difference (SMD) 0.67, 95% CI 0.24 to 1.10). The effect on platelet count was strongest for women who commenced treatment antenatally (SMD 0.80, 95% CI 0.25 to 1.35).Two trials (76 women) compared dexamethasone with betamethasone. There was no clear evidence of a difference between groups in respect to perinatal/infant death (RR 0.95, 95% CI 0.15 to 6.17) or severe perinatal/infant morbidity or death (RR 0.64, 95% CI 0.27 to 1.48). Maternal death and severe maternal morbidity were not reported. In respect to platelet count, dexamethasone was superior to betamethasone (MD 6.02, 95% CI 1.71 to 10.33), both when treatment was commenced antenatally (MD 8.10, 95% CI 6.23 to 9.97) and postnatally (MD 3.70, 95% CI 0.96 to 6.44). AUTHORS' CONCLUSIONS: There was no clear evidence of any effect of corticosteroids on substantive clinical outcomes. Those receiving steroids showed significantly greater improvement in platelet counts which was greater for those receiving dexamethasone than those receiving betamethasone. There is to date insufficient evidence of benefits in terms of substantive clinical outcomes to support the routine use of steroids for the management of HELLP. The use of corticosteroids may be justified in clinical situations in which increased rate of recovery in platelet count is considered clinically worthwhile.