Qiuying Yang

Epidemiologic Evidence of Relationships Between Reproductive and Child Health Outcomes and Environmental Chemical Contaminants

This review summarizes the level of epidemiologic evidence for relationships between prenatal and/or early life exposure to environmental chemical contaminants and fetal, child, and adult health. Discussion focuses on fetal loss, intrauterine growth restriction, preterm birth, birth defects, respiratory and other childhood diseases, neuropsychological deficits, premature or delayed sexual maturation, and certain adult cancers linked to fetal or childhood exposures. Environmental exposures considered here include chemical toxicants in air, water, soil/house dust and foods (including human breast milk), and consumer products. Reports reviewed here included original epidemiologic studies (with at least basic descriptions of methods and results), literature reviews, expert group reports, meta-analyses, and pooled analyses. Levels of evidence for causal relationships were categorized as sufficient, limited, or inadequate according to predefined criteria. There was sufficient epidemiological evidence for causal relationships between several adverse pregnancy or child health outcomes and prenatal or childhood exposure to environmental chemical contaminants. These included prenatal high-level methylmercury (CH3Hg) exposure (delayed developmental milestones and cognitive, motor, auditory, and visual deficits), high-level prenatal exposure to polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans (PCDFs), and related toxicants (neonatal tooth abnormalities, cognitive and motor deficits), maternal active smoking (delayed conception, preterm birth, fetal growth deficit [FGD] and sudden infant death syndrome [SIDS]) and prenatal environmental tobacco smoke (ETS) exposure (preterm birth), low-level childhood lead exposure (cognitive deficits and renal tubular damage), high-level childhood CH3Hg exposure (visual deficits), high-level childhood exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (chloracne), childhood ETS exposure (SIDS, new-onset asthma, increased asthma severity, lung and middle ear infections, and adult breast and lung cancer), childhood exposure to biomass smoke (lung infections), and childhood exposure to outdoor air pollutants (increased asthma severity). Evidence for some proven relationships came from investigation of relatively small numbers of children with high-dose prenatal or early childhood exposures, e.g., CH3Hg poisoning episodes in Japan and Iraq. In contrast, consensus on a causal relationship between incident asthma and ETS exposure came only recently after many studies and prolonged debate. There were many relationships supported by limited epidemiologic evidence, ranging from several studies with fairly consistent findings and evidence of dose-response relationships to those where 20 or more studies provided inconsistent or otherwise less than convincing evidence of an association. The latter included childhood cancer and parental or childhood exposures to pesticides. In most cases, relationships supported by inadequate epidemiologic evidence reflect scarcity of evidence as opposed to strong evidence of no effect. This summary points to three main needs: (1) Where relationships between child health and environmental exposures are supported by sufficient evidence of causal relationships, there is a need for (a) policies and programs to minimize population exposures and (b) population-based biomonitoring to track exposure levels, i.e., through ongoing or periodic surveys with measurements of contaminant levels in blood, urine and other samples. (2) For relationships supported by limited evidence, there is a need for targeted research and policy options ranging from ongoing evaluation of evidence to proactive actions. (3) There is a great need for population-based, multidisciplinary and collaborative research on the many relationships supported by inadequate evidence, as these represent major knowledge gaps. Expert groups faced with evaluating epidemiologic evidence of potential causal relationships repeatedly encounter problems in summarizing the available data. A major driver for undertaking such summaries is the need to compensate for the limited sample sizes of individual epidemiologic studies. Sample size limitations are major obstacles to exploration of prenatal, paternal, and childhood exposures during specific time windows, exposure intensity, exposure–exposure or exposure–gene interactions, and relatively rare health outcomes such as childhood cancer. Such research needs call for investments in research infrastructure, including human resources and methods development (standardized protocols, biomarker research, validated exposure metrics, reference analytic laboratories). These are needed to generate research findings that can be compared and subjected to pooled analyses aimed at knowledge synthesis.

Adverse maternal outcomes in multifetal pregnancies

In this retrospective cohort of 165,188 singleton pregnancies and 44,674 multiple‐fetal pregnancies in Canada from 1984 to 2000, we compared the incidence of maternal complications. Multiple gestation pregnancies were associated with significant increases in cardiac morbidity, haematologic morbidity, amniotic fluid embolus, pre‐eclampsia, gestational diabetes, postpartum haemorrhage, prolonged hospital stay, the need for obstetric intervention, hysterectomy and blood transfusion. Multiple gestation pregnancies are associated with an increased risk of morbidity for the mother. This should be taken into consideration in antenatal care of these women.

Association of caesarean delivery for first birth with placenta praevia and placental abruption in second pregnancy

Objective  To quantify the risk of placenta praevia and placental abruption in singleton, second pregnancies after a caesarean delivery of the first pregnancy.

Association Between Ozone and Respiratory Admissions Among Children and the Elderly in Vancouver, Canada

In this study, we examine the impact of ozone on daily respiratory admissions in both young children and the elderly in greater Vancouver, British Columbia. Study subjects included children less than 3 yr of age and adults 65 yr of age or over living in greater Vancouver who had acute hospital admissions for any respiratory diseases (ICD-9 codes 460–519) during the 13-yr period 1986–1998. Bidirectional case-crossover analysis was used to investigate associations between ambient ozone and respiratory hospitalizations after adjustment for other pollutants, including carbon monoxide, nitrogen dioxide, sulfur dioxide, and coefficient of haze. Potential effect modification by socioeconomic status as measured by household income was also examined. Respiratory admissions were associated with ozone levels 2, 3, 4, and 5 days prior to admission in both children and the elderly, with the strongest association observed at a lag of 4 days. Odds ratios for hospital admission of 1.22 (95% CI: 1.15–1.30) for children and 1.13 (1.09–1.18) for the elderly, respectively, were found, based on an increment in exposure corresponding to the interquartile range for ozone. Adjusting for other pollutants did not attenuate the ozone effect on respiratory admissions. Nor did socioeconomic status appear to modify the association between ozone and respiratory admissions in either children or the elderly. We concluded that ambient ozone is positively associated with respiratory hospital admission among young children and the elderly in Vancouver, British Columbia. These associations persisted after adjustment for both copollutant exposures and socioeconomic status.

Paternal age and adverse birth outcomes: teenager or 40+, who is at risk?

BACKGROUND Most previous studies on the effect of paternal age have focused on the association of advanced paternal age with congenital anomalies. The objective of this study was to determine whether paternal age is associated with the risk of adverse birth outcomes, independent of maternal confounders. METHODS We carried out a retrospective cohort study of 2 614 966 live singletons born to married, nulliparous women aged 20-29 years between 1995 and 2000 in the USA. Multiple logistic regressions were applied to estimate the independent effect of paternal age on adverse birth outcomes. RESULTS Compared with infants born to fathers aged 20-29 years, infants fathered by teenagers (<20 years old) had an increased risk of preterm birth [odds ratio (OR) = 1.15, 95% confidence interval (CI): 1.10, 1.20], low birth weight (OR = 1.13, 95% CI: 1.08, 1.19), small-for-gestational-age births (OR = 1.17, 95% CI: 1.13, 1.22), low Apgar score (OR = 1.13, 95% CI: 1.01, 1.27), neonatal mortality (OR = 1.22, 95% CI: 1.01, 1.49) and post-neonatal mortality (OR = 1.41, 95% CI: 1.09, 1.82). Advanced paternal age (> or =40 years) was not associated with the risk of adverse birth outcomes. CONCLUSIONS Teenage fathers carry an increased risk of adverse birth outcomes that is independent of maternal confounders, whereas advanced paternal age is not an independent risk factor for adverse birth outcomes.

Influence of Relatively Low Level of Particulate Air Pollution on Hospitalization for COPD in Elderly People

To assess the association between relatively low levels of size-fractioned particulate matter (PM) and hospitalization for chronic obstructive pulmonary disease (COPD), we conducted a time-series analysis among elderly people 65 yr of age or more living in Vancouver between June 1995 and March 1999. Measures of thoracic PM (PM10), fine PM (PM2.5), coarse PM (PM10−2.5), and coefficient of haze (COH) were examined over periods varying from 1 to 7 days prior to hospital admissions. Generalized additive models (GAMs; general linear models, GLMs) were used, and temporal trends and seasonal and subseasonal cycles in COPD hospitalizations were removed by using GLM with parametric natural cubic splines. The relative risks were calculated based on an incremental exposure corresponding to the interquartile range of these measures, and were adjusted for daily weather conditions and gaseous pollutants. PM measures had a positive effect on COPD hospitalization, especially 0 to 2 days prior to the admissions, before copollutants were accounted for. For 3-day average levels of exposure the relative risk estimates were 1.13 (95% confidence interval: 1.05–1.21) for PM10, 1.08 (1.02–1.15) for PM2.5, 1.09 (1.03–1.16) for PM10−2.5, and 1.05 (1.01–1.09) for COH. The associations were no longer significant when NO2 was included in the models. We concluded that the particle-related measures were significantly associated with COPD hospitalization in the Vancouver area, where the level of air pollution is relatively low, but the effects were not independent of other air pollutants.

Risk of birth defects increased in pregnancies conceived by assisted human reproduction

OBJECTIVE To assess the risk of birth defects in infants born after assisted human reproduction (AHR). DESIGN Retrospective cohort study. SETTING Niday Perinatal Database for the province of Ontario, 82 sites, both primary and tertiary centers. PATIENT(S) In 2005, information about reproductive assistance was reported for 61,569 deliveries. INTERVENTION(S) The prevalence of birth defects diagnosed in the prenatal period or at birth was estimated for all types of AHR together and then by type of procedure. MAIN OUTCOME MEASURE(S) The excess risks of birth defects by AHR were calculated by unconditional logistic regressions using spontaneously conceived pregnancies as the reference and were expressed by odds ratio and 95% confidence intervals and adjusted for maternal age, smoking, infant gender, gestation, and parity. RESULT(S) The prevalence of birth defects with AHR procedures was 2.91%, which was 1.55-fold higher (95% confidence interval [CI], 1.03-2.38) than in the non-AHR population (1.86%). Specific anomalies that increased with AHR were gastrointestinal (odds ratio [OR], 9.85; 95% CI, 3.44-28.44), cardiovascular (OR, 2.30; 95% CI, 1.11-4.77), and musculoskeletal defects (OR, 1.54; 95% CI, 0.48-4.94). The risks of birth defects by types of AHR were 2.35% for ovulation induction, 2.89% for IUI, and 3.45% for IVF. CONCLUSION(S) There is a significant increased risk of birth defects associated with AHR, and the risk is higher in IVF and IUI. The potential risk of anomalies associated with AHR may be considered in the counseling that is offered to infertile couples.

SHORT COMMUNICATION: Adverse maternal outcomes in multifetal pregnancies

In this retrospective cohort of 165,188 singleton pregnancies and 44,674 multiple‐fetal pregnancies in Canada from 1984 to 2000, we compared the incidence of maternal complications. Multiple gestation pregnancies were associated with significant increases in cardiac morbidity, haematologic morbidity, amniotic fluid embolus, pre‐eclampsia, gestational diabetes, postpartum haemorrhage, prolonged hospital stay, the need for obstetric intervention, hysterectomy and blood transfusion. Multiple gestation pregnancies are associated with an increased risk of morbidity for the mother. This should be taken into consideration in antenatal care of these women.

Adequacy of prenatal care and neonatal mortality in infants born to mothers with and without antenatal high-risk conditions

Background:  Previous studies have found that inadequate prenatal care was associated with increased neonatal mortality in the general pregnant women.

Increased risks of neonatal and postneonatal mortality associated with teenage pregnancy had different explanations

OBJECTIVE To determine the potential pathway of the association between teenage pregnancy and neonatal and postneonatal mortality. STUDY DESIGN AND SETTING We carried out a retrospective cohort study of 4,037,009 nulliparous pregnant women under 25 years old who had a live singleton birth during 1995 to 2000, based on linked birth and infant death data set of the United States. RESULTS Teenage pregnancy (10-19 years old) was associated with increased neonatal mortality (odds ratio [OR]: 1.20, 95% confidence interval [CI]=1.16-1.24) and postneonatal mortality (OR: 1.47, 95% CI=1.41-1.54) after adjustment for potential confounders. With further adjustment for weight gain during pregnancy, teenage pregnancy was still associated with increased risk of neonatal (OR: 1.23, 95% CI=1.19-1.28) and postneonatal mortality (OR: 1.48, 95% CI=1.42-1.55). When adjustment was made for gestational age at birth, there was no association of teenage pregnancy with neonatal mortality (OR: 0.98, 95% CI=0.95-1.02), whereas there was significant association with postneonatal mortality (OR: 1.40, 95% CI=1.34-1.46). CONCLUSION The increased risk of neonatal death associated with teenage pregnancy is largely attributable to higher risk of preterm births, whereas increased postneonatal mortality is independent of the known confounders and gestational age at birth.