M.P. Vélez

Cohort Profile: The Maternal-Infant Research on Environmental Chemicals Research Platform

BACKGROUND The Maternal-Infant Research on Environmental Chemicals (MIREC) Study was established to obtain Canadian biomonitoring data for pregnant women and their infants, and to examine potential adverse health effects of prenatal exposure to priority environmental chemicals on pregnancy and infant health. METHODS Women were recruited during the first trimester from 10 sites across Canada and were followed through delivery. Questionnaires were administered during pregnancy and post-delivery to collect information on demographics, occupation, life style, medical history, environmental exposures and diet. Information on the pregnancy and the infant was abstracted from medical charts. Maternal blood, urine, hair and breast milk, as well as cord blood and infant meconium, were collected and analysed for an extensive list of environmental biomarkers and nutrients. Additional biospecimens were stored in the studys Biobank. The MIREC Research Platform encompasses the main cohort study, the Biobank and follow-up studies. RESULTS Of the 8716 women approached at early prenatal clinics, 5108 were eligible and 2001 agreed to participate (39%). MIREC participants tended to smoke less (5.9% vs. 10.5%), be older (mean 32.2 vs. 29.4 years) and have a higher education (62.3% vs. 35.1% with a university degree) than women giving birth in Canada. CONCLUSIONS The MIREC Study, while smaller in number of participants than several of the international cohort studies, has one of the most comprehensive datasets on prenatal exposure to multiple environmental chemicals. The biomonitoring data and biological specimen bank will make this research platform a significant resource for examining potential adverse health effects of prenatal exposure to environmental chemicals.

Temporal trends of preterm birth subtypes and neonatal outcomes.

OBJECTIVE: To describe temporal trends of preterm birth subtypes, neonatal morbidity, and hospital neonatal mortality. METHODS: A database of 1.7 million births that occurred in 51 maternity hospitals in Latin America from 1985 to 2003 was studied. Subgroups of preterm births were classified according to the presence or absence of maternal medical or obstetric complications, spontaneous labor, preterm labor after premature rupture of membranes, induction of labor, or elective cesarean. Outcomes studied, for different periods, were prevalence of small for gestational age, neonatal morbidity, and neonatal mortality. RESULTS: Spontaneous preterm labor without maternal complications was the most frequent subtype of preterm birth (60%), followed by premature rupture of membranes without maternal complications. Preterm births due to elective induction and delivery by elective cesarean increased markedly in the last 20 years, from 10% in 1985–1990 to 18.5% in recent years. Neonates born after spontaneous labor without maternal complications had the lowest mortality rate, but their large numbers made them responsible for one half of the preterm mortality. The induction followed by elective cesarean subgroups accounted for 13.4% of the preterm deaths between 1985 and 1990 and increased to 21.2% between 1996 and 2003. CONCLUSION: Spontaneous labor in mothers without maternal complications is the most frequent cause of preterm births and is also the most important subgroup related to neonatal mortality. However, preterm births due to induction of labor or elective cesarean are increasing in Latin America and are becoming important contributors to neonatal mortality. LEVEL OF EVIDENCE: II-2

Female exposure to phenols and phthalates and time to pregnancy: the Maternal-Infant Research on Environmental Chemicals (MIREC) Study

OBJECTIVE To assess the potential effect of bisphenol A (BPA), triclosan (TCS), and phthalates on womens fecundity, as measured by time to pregnancy (TTP). DESIGN Pregnancy-based retrospective TTP study. SETTING Not applicable. PATIENT(S) A total of 2,001 women during the first trimester of pregnancy recruited between 2008 and 2011 (the Maternal-Infant Research on Environmental Chemicals (MIREC) Study), with 1,742 women included in the BPA analysis, 1,699 in the TCS analysis, and 1,597 in the phthalates analysis. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Fecundability odds ratios (FORs) estimated using the Cox model modified for discrete time data. RESULT(S) The BPA concentrations were not statistically significantly associated with diminished fecundity either in crude or adjusted models. Women in the highest quartile of TCS (>72 ng/mL) had evidence of decreased fecundity (FOR 0.84; 95% confidence interval, 0.72-0.97) compared with the three lower quartiles as the reference group. Exposure to phthalates was suggestive of a shorter TTP, as indicated by FORs greater than 1, although the 95% confidence interval always included 1. CONCLUSION(S) Elevated TCS exposure may be associated with diminished fecundity. BPA and phthalates showed no negative impact; on the contrary, some phthalates might be associated with a shorter time to pregnancy. A major limitation of the study was that only one measurement of exposure was available for each woman after conception. Further research is necessary to test these findings.

Universal coverage of IVF pays off

STUDY QUESTION What was the clinical and economic impact of universal coverage of IVF in Quebec, Canada, during the first calendar year of implementation of the public IVF programme? SUMMARY ANSWER Universal coverage of IVF increased access to IVF treatment, decreased the multiple pregnancy rate and decreased the cost per live birth, despite increased costs per cycle. WHAT IS KNOWN ALREADY Public funding of IVF assures equality of access to IVF and decreases multiple pregnancies resulting from this treatment. Public IVF programmes usually mandate a predominant SET policy, the most effective approach for reducing the incidence of multiple pregnancies. STUDY DESIGN, SIZE, DURATION This prospective comparative cohort study involved 7364 IVF cycles performed in Quebec during 2009 and 2011 and included an economic analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS IVF cycles performed in the five centres offering IVF treatment in Quebec during 2009, before implementation of the public IVF programme, were compared with cycles performed at the same centres during 2011, the first full calendar year following implementation of the programme. Data were obtained from the Canadian Assisted Reproductive Technologies Register (CARTR). Comparisons were made between the two periods in terms of utilization, pregnancy rates, multiple pregnancy rates and costs. MAIN RESULTS AND THE ROLE OF CHANCE The number of IVF cycles performed in Quebec increased by 192% after the new policy was implemented. Elective single-embryo transfer was performed in 1.6% of the cycles during Period I (2009), and increased to 31.6% during Period II (2011) (P < 0.001). Although the clinical pregnancy rate per embryo transfer was lower in 2011 than in 2009 (24.9 versus 39.9%, P < 0.001), the multiple pregnancy rate was greatly reduced (6.4 versus 29.4%, P < 0.001). The public IVF programme increased government costs per IVF treatment cycle from CAD

Maternal exposure to perfluorinated chemicals and reduced fecundity: the MIREC study

3730 to CAD

The influence of poverty and social support on the perceived health of children born to minority migrant mothers.

4759. Despite increased costs per cycle, the efficiency defined by the cost per live birth, which factored in downstream health costs up to 1 year post delivery, decreased from CAD

Life course socioeconomic adversity and age at natural menopause in women from Latin America and the Caribbean.

49 517 to CAD

Rapid policy change to single-embryo transfer while maintaining pregnancy rates per initiated cycle

43 362 per baby conceived by either fresh and frozen cycles. LIMITATIONS, REASONS FOR CAUTION The costs described in the economic model are likely an underestimate as they do not factor in many of the long-term costs that can occur after 1 year of age. The information collected in the Canadian ART register precludes the calculation of cumulative pregnancy rates. WIDER IMPLICATIONS OF THE FINDINGS Our study confirms that the implementation of a public IVF programme favouring eSET not only sharply decreases the incidence of multiple pregnancy, but also reduces the cost per live birth. STUDY FUNDING/COMPETING INTEREST(S) M.P.V. holds a fellowship award from the Canadian Institutes of Health Research (CIHR). The economic analysis performed by M.P.C. was supported by an unrestricted grant from Ferring Pharmaceutical.

Female digit length ratio (2D:4D) and time-to-pregnancy

STUDY QUESTION What is the effect of maternal exposure to perfluorooctane sulfonate (PFOS), perflurooctanoic acid (PFOA) and perfluorohexane sulfonate (PFHxS) on female fecundity? SUMMARY ANSWER Increasing concentrations of PFOA or PFHxS in maternal plasma were associated with reduced fecundability and infertility. WHAT IS KNOWN ALREADY Perfluorinated chemicals (PFCs) are a group of synthetic compounds used in industrial production. There is a concern about the effect of PFCs on fecundity, as measured by time-to-pregnancy (TTP). Although some recent studies suggest that increasing concentrations of PFCs may decrease fecundity, divergence in the methodological approaches used to evaluate this association have prevented firm conclusions being reached. STUDY DESIGN, SIZE, DURATION The Maternal-Infant Research on Environmental Chemicals (MIREC) Study is a cohort study of 2,001 women recruited before 14 weeks of gestation in 10 cities across Canada between 2008 and 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS A questionnaire was administered and medical chart data and biospecimens were collected from participants. After excluding women who withdrew, those for whom data were incomplete, those whose pregnancies followed birth control failure, and accounting for male fertility, 1743 participants remained. TTP was defined as the number of months of unprotected intercourse needed to become pregnant in the current pregnancy, as self-reported in the first trimester of pregnancy. Plasma concentrations of PFOA, PFOS and PFHxS measured in the first trimester were considered as a surrogate of preconception exposure. Fecundability odds ratios (FORs) were estimated using Cox proportional hazard models for discrete time. FOR < 1 denote a longer TTP and FORs >1 denote a shorter TTP. The odds of infertility (TTP > 12 months or infertility treatment in the index pregnancy) were estimated using logistic regression. Each chemical concentration (ng/ml) was log-transformed and divided by its SD. MAIN RESULTS AND THE ROLE OF CHANCE The cumulative probabilities of pregnancy at 1, 6 and 12 months were 0.42 (95% confidence interval (CI) 0.40–0.45), 0.81 (95% CI 0.79–0.83) and 0.90 (95% CI 0.89–0.92), respectively. The mean maternal age was 32.8 (SD 5.0) years. The geometric means (ng/ml) of PFOA, PFOS and PFHxS were 1.66 (95% CI 1.61–1.71), 4.59 (95% CI 4.46–4.72) and 1.01 (95% CI 0.97–1.05), respectively. After adjustment for potential confounders, PFOA and PFHxS were associated with a 11 and 9% reduction in fecundability per one SD increase (FOR = 0.89; 95% CI 0.83–0.94; P < 0.001 for PFOA and FOR = 0.91; 95% CI 0.86–0.97; P = 0.002 for PFHxS), while no significant association was observed for PFOS (FOR = 0.96; 95% CI 0.91–1.02; P = 0.17). In addition, the odds of infertility increased by 31% per one SD increase of PFOA (odds ratio (OR) = 1.31; 95% CI 1.11–1.53; P = 0.001) and by 27% per one SD increase of PFHxS (OR = 1.27; 95% CI 1.09–1.48; P = 0.003), while no significant association was observed for PFOS (OR = 1.14; 95% CI 0.98–1.34; P = 0.09). LIMITATIONS, REASONS FOR CAUTION Women with the highest concentrations of PFCs might have been excluded from the study if there is a causal association with infertility. The MIREC study did not assess concentrations of PFCs in males, semen quality, menstrual cycle characteristics or intercourse frequency. WIDER IMPLICATIONS OF THE FINDINGS Our results add to the evidence that exposure to PFOA and PFHxS, even at lower levels than previously reported, may reduce fecundability. STUDY FUNDING/COMPETING INTEREST(S) The MIREC study is supported by the Chemicals Management Plan of Health Canada, the Canadian Institutes for Health Research (CIHR, grant no. MOP – 81285) and the Ontario Ministry of the Environment. M.P.V. was supported by a CIHR Fellowship Award, and a CIHR-Quebec Training Network in Perinatal Research (QTNPR) Ph.D. scholarship. W.D.F. is supported by a CIHR Canada Research Chair. There are no conflicts of interest to declare.

Surgically retrieved spermatozoa versus ejaculated spermatozoa in modified natural IVF-ICSI cycles

Objective. Poverty and low social support are common among minority migrant families. Little is known about their impact on the health of children of minority migrants to Canada. This study examined the associations between maternal perception of childs health and migration status, and examined the specific role of poverty and low social support in these associations. Design. Data from the first two rounds of the Quebec Longitudinal Study of Child Development (QLSCD) were analysed. The sample included 1990 children at 17 months of age, classified according to their mothers migration status: children of minority migrant mothers (n=165) and Canadian-born mothers (n=1825). Maternal perception of childs health status and social support were measured at 17 months, household income was measured at 5 and 17 months. Multivariable logistic regressions were performed; interactions of migration status with poverty and social support were tested. Results. Poverty and low social support were more common among minority migrant mothers than among Canadian-born mothers. Children of minority migrant mothers who were ‘never poor’ and reported high levels of social support were perceived in better health (OR 0.42; 95% confidence interval (CI): 0.19–0.91) than children of Canadian-born mothers (reference group). In contrast, children of minority migrant mothers who were ‘always poor’ and reported low social support were perceived in worse health (OR 6.32; 95% CI: 1.69–23.71) compared to the reference group. Conclusion. In Quebec, economic hardship and lack of social support are common realities among minority migrants with young children. Combined exposure to poverty and low social support is most detrimental to the perceived health of children of minority migrants.