Health Care Utilization in the First 7 Years in Children with Fetal Growth Abnormalities: A Retrospective Cohort Study.

OBJECTIVE: To investigate the relationship between birth weight for gestational age and health care utilization of term offspring from birth to 7 years. STUDY DESIGN: We used a population-based retrospective cohort study of infants (≥37 weeks' gestational age) born between 2003 and 2007 in the Canadian province of Nova Scotia (n = 42 050). Perinatal records were linked to provincial administrative health data from birth to age 7 years. The primary outcome was health care utilization (physician visits and hospital admissions) and costs. Birth weight was categorized as small for gestational age (SGA, <10th percentile), appropriate for gestational age (AGA), or large for gestational age (LGA, >90th percentile). Regression models adjusted for potential confounders were used to investigate the associations. RESULTS: Children born SGA had a higher number of specialist visits and hospital admissions, a longer length of stay for the birth admission, and, as a result, higher physician and hospital costs amounting to a cost differential of Can $1222 during the first 7 years of life compared with children born AGA. By contrast, health care use and costs did not differ between children born LGA and AGA. CONCLUSION: Former SGA term infants have a moderate increase in health care use and costs in early childhood compared with former AGA infants, and LGA birth at term is not associated with higher health care utilization.

Neurodevelopmental outcomes of very preterm infants who received cord milking at birth: a randomized controlled trial.

Umbilical cord milking improves postnatal adaptation and short-term outcomes of very preterm infants compared to early cord clamping. Little is known about the impact of umbilical cord milking on long-term neurodevelopmental outcomes. The objective of this study is to compare the effects of intact umbilical cord milking (UCM) vs. early cord clamping (ECC) at birth on neurodevelopmental outcomes at 36 months' corrected age. Preterm infants < 31 weeks' gestation who were randomized at birth to receive three time milking of their attached cord or ECC (< 10 s) were evaluated at 36 months' corrected age. Neurodevelopmental outcomes were assessed by blinded examiners using Bayley Scales of Infant and Toddler Development (version III). Analysis was by intention to treat. Out of the 73 infants included in the original trial, 2 died and 65 (92%) infants were evaluated at 36 months' corrected age. Patient characteristics and short-term outcomes were similar in both study groups. There were no significant differences in the median cognitive, motor or language scores or in the rates of cerebral palsy, developmental impairment, deafness, or blindness between study groups. CONCLUSION: Neurodevelopmental outcomes at 36 months' corrected age of very preterm infants who received UCM were not shown to be significantly different from those who received ECC at birth. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01487187 What is Known: • Compared to early cord clamping, umbilical cord milking improves postnatal adaptation and short-term outcomes of very preterm infants compared to early cord clamping. • Little is known about the impact of umbilical cord milking on neurodevelopmental outcomes. WHAT IS NEW: • Neurodevelopmental outcomes at 3 years of age were not significantly different in very preterm infants who received cord milking vs. those who received early cord clamping at birth.

Compliance with Fetal Fibronectin Testing at a Canadian Tertiary Care Perinatal Centre.

OBJECTIVE: The purpose of this study was to assess compliance with fetal fibronectin (fFN) testing recommendations at a single tertiary care perinatal centre. The secondary objective was to identify factors associated with compliance with these recommendations. METHODS: A retrospective cohort study was conducted from January 1, 2016 to December 31, 2016 of all patients who presented to the IWK Health Centre with suspected preterm labour. Inclusion criteria included symptoms of preterm labour prior to 370 weeks gestation, singleton or multiple pregnancy, and established fetal wellbeing. Exclusion criteria included severe fetal anomaly, contraindications to tocolysis, transfer from community hospital, or inadequate documentation. Provider compliance was evaluated to determine: 1) whether the test was performed for appropriate indications according to provincial fFN guidelines; 2) whether fFN results were appropriately being used to inform patient care. Logistic regression was used to determine factors associated with compliance. RESULTS: A total of 528 patients presented with symptoms of preterm labour. The overall compliance with testing recommendations was 76.1%. Compliance for patients who met criteria for fFN testing was 73%, and compliance for those not meeting criteria was 76.4%. Of patients with a negative fFN result, 85.3% were appropriately discharged home without intervention. Gestational age, time of day, and non-obstetrician provider type were found to be associated with compliance. CONCLUSION: Despite regional and national guidelines, this study demonstrates a compliance rate of 76% in our centre, indicating a gap in provider knowledge regarding proper use and interpretation of fFN. Non-obstetrician provider type was associated with decreased compliance.

Association of Maternal Influenza Vaccination During Pregnancy With Early Childhood Health Outcomes.

Importance: Seasonal influenza vaccination in pregnancy can reduce influenza illness among pregnant women and newborns. Evidence is limited on whether seasonal influenza vaccination in pregnancy is associated with adverse childhood health outcomes. Objective: To assess the association between maternal influenza vaccination during pregnancy and early childhood health outcomes. Design, Setting, and Participants: Retrospective cohort study, using a birth registry linked with health administrative data. All live births in Nova Scotia, Canada, between October 1, 2010, and March 31, 2014, were included, with follow-up until March 31, 2016. Adjusted hazard ratios (HRs) and incidence rate ratios (IRRs) with 95% confidence intervals were estimated while controlling for maternal medical history and other potential confounders using inverse probability of treatment weighting. Exposures: Seasonal influenza vaccination during pregnancy. Main Outcomes and Measures: Childhood outcomes studied were immune-related (eg, asthma, infections), non-immune-related (eg, neoplasms, sensory impairment), and nonspecific (eg, urgent or inpatient health care utilization), measured from emergency department and hospitalization databases. Results: Among 28 255 children (49% female, 92% born at ≥37 weeks' gestation), 10 227 (36.2%) were born to women who received seasonal influenza vaccination during pregnancy. During a mean follow-up of 3.6 years, there was no significant association between maternal influenza vaccination and childhood asthma (incidence rate, 3.0 vs 2.5 per 1000 person-years; difference, 0.53 per 1000 person-years [95% CI, -0.15 to 1.21]; adjusted HR, 1.22 [95% CI, 0.94 to 1.59]), neoplasms (0.32 vs 0.26 per 1000 person-years; difference, 0.06 per 1000 person-years [95% CI, -0.16 to 0.28]; adjusted HR, 1.26 [95% CI, 0.57 to 2.78]), or sensory impairment (0.80 vs 0.97 per 1000 person-years; difference, -0.17 per 1000 person-years [95% CI, -0.54 to 0.21]; adjusted HR, 0.82 [95% CI, 0.49 to 1.37]). Maternal influenza vaccination in pregnancy was not significantly associated with infections in early childhood (incidence rate, 184.6 vs 179.1 per 1000 person-years; difference, 5.44 per 1000 person-years [95% CI, 0.01 to 10.9]; adjusted IRR, 1.07 [95% CI, 0.99 to 1.15]) or with urgent and inpatient health services utilization (511.7 vs 477.8 per 1000 person-years; difference, 33.9 per 1000 person-years [95% CI, 24.9 to 42.9]; adjusted IRR, 1.05 [95% CI, 0.99 to 1.16]). Conclusions and Relevance: In this population-based cohort study with mean follow-up duration of 3.6 years, maternal influenza vaccination during pregnancy was not significantly associated with an increased risk of adverse early childhood health outcomes.

The 3G Multigenerational Cohort of Nova Scotian women and their mothers and offspring.

BACKGROUND: The negative impact of exposures such as maternal obesity, excessive gestational weight gain, and hypertension in pregnancy on the health of the next generation has been well studied. Evidence from animal studies suggests that the effects of in utero exposures may persist into the second generation, but the epidemiological literature on the influence of pregnancy-related exposures across three generations in humans is sparse. OBJECTIVES: This cohort was established to investigate associations between antenatal and perinatal exposures and health outcomes in women and their offspring. POPULATION: The cohort includes women who were born and subsequently had their own pregnancies in the Canadian province of Nova Scotia from 1980 onward. DESIGN: Intergenerational linkage of data in the Nova Scotia Atlee Perinatal Database was used to establish a population-based dynamic retrospective cohort. METHODS: The cohort has prospectively collected information on sociodemographics, maternal health and health behaviours, pregnancy health and complications, and obstetrical and neonatal outcomes for two generations of women and their offspring. PRELIMINARY RESULTS: As of October 2018, the 3G cohort included 14 978 grandmothers (born 1939-1986), 16 766 mothers or cohort women (born 1981-2003), and 28 638 children (born 1996-2018). The cohort women were generally younger than Nova Scotian women born after 1980, and as a result, characteristics associated with pregnancy at a younger age were more frequently seen in the cohort women; sampling weights will be created to account for this design effect. The cohort will be updated annually to capture future deliveries to women who are already in the cohort and women who become eligible for inclusion when they deliver their first child. CONCLUSIONS: The 3G Multigenerational Cohort is a population-based cohort of women and their mothers and offspring, spanning a time period of 38 years, and provides the opportunity to study inter- and transgenerational associations across the maternal line.

Maternal pre-pregnancy obesity and health care utilization and costs in the offspring.

BACKGROUND/OBJECTIVE: The association between maternal pre-pregnancy obesity and adverse child health outcomes is well described, but there are few data on the relationship with offspring health service use. We examined the influence of maternal pre-pregnancy obesity on offspring health care utilization and costs over the first 18 years of life. METHODS: This was a population-based retrospective cohort study of children (n = 35,090) born between 1989 and 1993 and their mothers, who were identified using the Nova Scotia Atlee Perinatal Database and linked to provincial administrative health data from birth through 2014. The primary outcome was health care utilization as determined by the number and cost of physician visits, hospital admissions and days, and high utilizer status (>95th percentile of physician visits). The secondary outcome was health care utilization by ICD chapter. Maternal pre-pregnancy weight was categorized as normal weight, overweight, or obese. Multivariable-adjusted regression models were used to examine the association between maternal weight status and offspring health care use. RESULTS: Children of mothers with pre-pregnancy obesity had more physician visits (10%), hospital admissions (16%), and hospital days (10%) than children from mothers of normal weight over the first 18 years of life. Offspring of mothers with obesity had C$356 higher physician costs and C$1415 hospital costs over 18 years than offspring of normal weight mothers. Children of mothers with obesity were 1.74 times more likely to be a high utilizer of health care and had higher rates of physician visits and hospital stays for nervous system and sense organ disorders, respiratory disorders, and gastrointestinal disorders compared to children of normal weight mothers. CONCLUSION: Our findings suggest that maternal pre-pregnancy overweight and obesity are associated with slightly higher offspring health care utilization and costs in the first 18 years of life.

Cesarean Delivery and Healthcare Utilization and Costs in the Offspring: A Retrospective Cohort Study.

OBJECTIVE: To examine the association between cesarean delivery and healthcare utilization and costs in offspring from birth until age 7 years. STUDY DESIGN: A retrospective cohort study of singleton term births in the Canadian province of Nova Scotia between 2003 and 2007 followed until age 7 years was conducted using data from the Nova Scotia Atlee Perinatal Database and administrative health data. The main exposure was mode of delivery (cesarean delivery vs vaginal birth); the outcome was healthcare utilization and costs during the first 7 years of life. Associations were modeled using multiple regression adjusting for maternal prepregnancy weight and sociodemographic factors. RESULTS: In total, 32 464 births were included in the analysis. Compared with children born by vaginal birth, children born by cesarean delivery had more physician visits (incidence rate ratio 1.06, 95% CI 1.05-1.08) and longer hospital stays (incidence rate ratio 1.12, 95% CI 1.03-1.21) and were more likely to be high utilizers of physician visits (OR 1.23, 95% CI 1.10-1.37). Physician and hospital costs were $775 higher for children born by cesarean delivery compared with vaginal birth. CONCLUSIONS: Cesarean delivery compared with vaginal birth is associated with small but statistically significant increases in healthcare utilization and costs during the first 7 years of life.

Association between gestational urinary bisphenol a concentrations and adiposity in young children: The MIREC study.

BACKGROUND: Bisphenol A (BPA) is a high production volume chemical and because of its use in many consumer products, exposure is ubiquitous. Gestational BPA exposure has been associated with excess adiposity in rodent studies, but not consistently in human studies. We investigated the relation between gestational BPA exposure and early childhood adiposity in a prospective cohort study of 719 mother-child pairs. METHODS: We used data from the MIREC Study, a prospective Pan-Canadian pregnancy and birth cohort study. We measured BPA in urine samples collected at an average of 12.1 weeks (range: 6.3-15 weeks) gestation and measured children's weight, height, waist/hip circumference, and subscapular/triceps skinfold thickness at an average age of 3.5 years (range: 1.9-6.2). We estimated covariate-adjusted associations of log2-transformed BPA concentrations with child adiposity measures and examined whether these associations differed in boys and girls. RESULTS: Median BPA concentrations were 0.8 ng/mL (IQR: 0.5-1.4). Among both boys and girls, each 2-fold increase in BPA concentrations was associated with higher waist-to-hip ratio (ß: 0.003; 95% CI: 0.001, 0.005). The association of BPA with waist circumference and subscapular skinfold thickness was modified by sex (sex x BPA interaction p-values<0.2). In girls, each 2-fold increase in BPA concentrations was associated with a 0.2 cm (95% CI: 0.0, 0.5) and 0.15 mm (95% CI: 0.01, 0.30) increase in waist circumference and subscapular skinfolds, respectively. Associations were generally null or slightly inverse in boys. CONCLUSIONS: In this cohort, gestational urinary BPA concentrations were associated with subtle increases in girl's central adiposity during early childhood.

Blood metal levels and early childhood anthropometric measures in a cohort of Canadian children.

Fetal exposure to some toxic metals has been associated with reduced fetal growth, but the impact of contemporary, low-level metals on anthropometric measures in childhood is not well understood. Our primary objective was to quantify associations between childhood levels of toxic metals and concurrently measured body mass index (BMI) in a population of Canadian preschool-aged children. We collected biomonitoring data and anthropometric measures on 480 children between the ages of two and five years in the Maternal-Infant Research on Environmental Chemicals (MIREC) Child Development Plus study. Concentrations of four toxic metals (lead, arsenic, cadmium, and mercury) were measured in whole blood collected from pregnant women and their children. Blood levels of key essential elements were also measured in children. Children's weight, height, and BMI z-scores were calculated using the World Health Organization growth standards. We used a series of linear regression models, adjusted for potential parental confounders, concurrently measured metals and elements, and prenatal blood metal levels, to evaluate associations between tertiles of each toxic metal and anthropometric measures. We tested for effect modification by sex. Of the 480 children, 449 (94%) were singleton births and had complete biomonitoring and anthropometric data. The majority of children had detectable concentrations of metals. In the adjusted models, girls with blood lead concentrations in the highest tertile (>0.82 µg/dL) had, on average, 0.26 (95% Cl: -0.55, 0.03) lower BMI z-scores than those in the referent category. In contrast, boys with lead levels in the highest tertile had, on average, 0.14 higher BMI z-scores (95% Cl: -0.14, 0.41) (p-value heterogeneity = 0.04). In this population of Canadian preschool-aged children with low-level blood lead concentrations, we observed effect modification by sex in the association between Pb and BMI but no statistically significant associations in the sex-specific strata. Child blood levels of As, Cd, and Hg were not associated with childhood BMI, weight, or height in boys or girls.

Do stressful life events during pregnancy modify associations between phthalates and anogenital distance in newborns?

Anogenital distance (AGD) has been used as a marker of fetal androgen action to identify endocrine disrupting chemicals. A US study (TIDES) has reported that the association between some phthalates and reduced AGD in males was only apparent in sons of mothers reporting no stressful life events (SLEs) during pregnancy. The objective of the current study was to examine the potential modifying effect of SLEs and their subjective impact on associations between prenatal phthalates and AGD. First trimester urines from the MIREC Study were analysed for phthalate metabolites and AGD was measured in neonates. Post-delivery, the women answered questions on SLEs during the pregnancy. Women reporting 1 or more SLEs during pregnancy were considered a "higher stressor" group, whereas women reporting no SLEs or who reported a SLE that was perceived as not at all stressful were considered a "lower stressor" group. Multivariable linear regression models were fit stratified by stressor group. Maternal stressor, AGD and phthalates results were available for 153 females and 147 males. A summary measure of androgen-disrupting phthalates (Σ AD) was associated with significantly longer AGDs in females from the higher stressor group. These effect sizes were increased when the perceived impact was restricted to moderately or very much stressful. In males, all phthalates were associated with longer anopenile distance (APD), regardless of stressor group; however, higher Σ AD was associated with significantly longer APD in the lower stressor group. In contrast to the TIDES study, we did not observe shorter AGDs in male infants prenatally exposed to di-(2-ethylhexyl) phthalates, regardless of maternal stressor level. In conclusion, we were unable to replicate the findings of the TIDES study, but did find some evidence that prenatal SLEs may modify associations between phthalates and female AGD. Further research with other populations and measures of prenatal stress may shed more light on whether prenatal stress is an important effect modifier of associations between phthalates (or other chemicals) and anogenital distance.

Maternal pre-pregnancy weight status and health care use for mental health conditions in the offspring.

The objective of this study was to examine the relationship between pre-pregnancy maternal weight status and offspring physician visits for mental health conditions in childhood and adolescence. We conducted a population-based retrospective cohort study of singleton infants born between the years of 1989 and 1993 using a linkage of the Nova Scotia Atlee Perinatal Database with administrative health data. Offspring were followed from birth to age 18 years. Maternal weight status was categorized according to WHO body mass index cutoffs. The number of physician visits for any mental health condition, mood, anxiety, and adjustment disorders, conduct disorder, and attention-deficit hyperactivity disorder (ADHD) from age 0-18 years was determined from ICD codes in physician billings and hospital discharge abstract data. Negative binomial regression adjusting for sociodemographics, maternal psychiatric disorders and smoking was used to model the association. In total, 38,211 mother-offspring pairs were included in the cohort. Within the first 18 years of life, offspring of mothers with obesity had significantly more physician visits for any mental health condition [adjusted incidence rate ratio (IRR) 1.26, 95% CI 1.19-1.34], mood, anxiety, and adjustment disorders (IRR 1.16, 95% CI 1.07-1.25), conduct disorder (IRR 1.25, 95% CI 1.08-1.45), and ADHD (IRR 1.45, 95% CI 1.24-1.69) compared to mothers of normal weight. Associations for mood, anxiety, and adjustment disorders and conduct disorder were strongest at 13-18 years. Offspring of mothers with obesity appear to use health care for mental health conditions more frequently than offspring of normal weight mothers.

Associations between maternal triclosan concentrations in early pregnancy and gestational diabetes mellitus, impaired glucose tolerance, gestational weight gain and fetal markers of metabolic function.

BACKGROUND: Triclosan is a phenolic biocide used in a multitude of consumer products and in health care settings. It is widely detected in the American and Canadian populations and has been shown in animal models to act as an endocrine disrupting agent. However, there has been little examination to date of the effects of triclosan exposure in pregnancy on perinatal metabolic outcomes in human populations. METHODS: Using data from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a Canadian pregnancy cohort, we measured associations of first-trimester urinary triclosan concentrations with total gestational weight gain, gestational diabetes mellitus and impaired glucose tolerance in pregnancy, and fetal markers of metabolic function. Leptin and adiponectin were measured in plasma from umbilical cord blood samples in term neonates and categorized into low (< 10th percentile), intermediate (10th-90th percentile) and high (> 90th percentile) levels. Triclosan concentrations were grouped into quartiles and associations with study outcomes were examined using logistic regression models with adjustment for maternal age, race/ethnicity, pre-pregnancy BMI, education and urinary specific gravity. Restricted cubic spline analysis was performed to help assess linearity and shape of any dose-response relationships. All analyses for leptin and adiponectin levels were performed on the entire cohort as well as stratified by fetal sex. RESULTS: Triclosan measures were available for 1795 MIREC participants with a live born singleton birth. Regression analyses showed a non-significant inverse association between triclosan concentrations and leptin levels above the 90th percentile that was restricted to female fetuses (OR for highest quartile of triclosan compared to lowest quartile = 0.4 (95% CI 0.2-1.1), p-value for trend across quartiles = 0.02). Triclosan concentrations in the second quartile were associated with elevated odds of adiponectin below the 10th percentile in male fetuses (OR for Q2 compared to Q1 = 2.5, 95% CI 1.1-5.9, p-value for trend across quartiles = 0.93). No significant linear associations between triclosan concentrations and leptin or adiponectin levels in overall or sex-specific analyses were observed from restricted cubic spline analyses. No significant associations were observed in adjusted analyses between triclosan concentrations and gestational diabetes mellitus, impaired glucose tolerance or gestational weight gain. CONCLUSIONS: This study does not support an association between triclosan concentrations in pregnancy and fetal metabolic markers, glucose disorders of pregnancy, or excessive gestational weight gain.

Maternal Concentrations of Perfluoroalkyl Substances and Fetal Markers of Metabolic Function and Birth Weight.

Perfluoroalkyl substances (PFAS) are ubiquitous, persistent chemicals that have been widely used in the production of common household and consumer goods for their nonflammable, lipophobic, and hydrophobic properties. Inverse associations between maternal or umbilical cord blood concentrations of perfluorooctanoic acid and perfluorooctanesulfonate and birth weight have been identified. This literature has primarily examined each PFAS individually without consideration of the potential influence of correlated exposures. Further, the association between PFAS exposures and indicators of metabolic function (i.e., leptin and adiponectin) has received limited attention. We examined associations between first-trimester maternal plasma PFAS concentrations and birth weight and cord blood concentrations of leptin and adiponectin using data on 1,705 mother-infant pairs from the Maternal Infant Research on Environmental Chemicals (MIREC) Study, a trans-Canada birth cohort study that recruited women between 2008 and 2011. Bayesian hierarchical models were used to quantify associations and calculate credible intervals. Maternal perfluorooctanoic acid concentrations were inversely associated with birth weight z score, though the null value was included in all credible intervals (log10 ß = −0.10, 95% credible interval: −0.34, 0.13). All associations between maternal PFAS concentrations and cord blood adipocytokine concentrations were of small magnitude and centered around the null value. Follow-up in a cohort of children is required to determine how the observed associations manifest in childhood.

Birth Weight for Gestational Age, Anthropometric Measures, and Cardiovascular Disease Markers in Children.

OBJECTIVE: To examine the association of birth weight for gestational age with anthropometric measures and cardiometabolic markers in a population-based sample of Canadian children. STUDY DESIGN: The study used data from 2016 children aged 6-12 years from the first 2 cycles of the Canadian Health Measures Survey, a population-based survey of Canadian residents. The main exposure was birth weight for gestational age (small [SGA], large [LGA], and appropriate for gestational age [AGA]). The outcomes were anthropometric measures, blood pressure, and laboratory cardiovascular disease markers. The association between the exposure and the outcomes was examined using multiple regression. Analyses were weighted to account for the complex sampling design and for nonresponse. RESULTS: SGA infants had lower and LGA infants had higher z scores for anthropometric measures compared with the AGA group but most differences were not statistically significant. There were no differences between the SGA or LGA infants and the AGA group in blood pressure or individual cardiometabolic markers but SGA infants were significantly less likely to have elevated levels of 3 or more components of the metabolic syndrome compared with their AGA peers. CONCLUSIONS: Former SGA and LGA infants have lower (SGA) and higher (LGA) body mass index and waist circumference, respectively, than their AGA peers. The known long-term increased cardiovascular disease risk among SGA or LGA infants was not reflected in the blood pressure and laboratory measurements at age 6-12 years.

Examining the provisional guidelines for weight gain in twin pregnancies: a retrospective cohort study.

BACKGROUND: Weight gain during pregnancy has an important impact on maternal and neonatal health. Unlike the Institute of Medicine (IOM) recommendations for weight gain in singleton pregnancies, those for twin gestations are termed "provisional", as they are based on limited data. The objectives of this study were to determine the neonatal and maternal outcomes associated with gaining weight below, within and above the IOM provisional guidelines on gestational weight gain in twin pregnancies, and additionally, to explore ranges of gestational weight gain among women who delivered twins at the recommended gestational age and birth weight, and those who did not. METHODS: A retrospective cohort study of women who gave birth to twins at ≥20 weeks gestation, with a birth weight ≥ 500 g was conducted in Nova Scotia, Canada (2003-2014). Our primary outcome of interest was small for gestational age (<10th percentile). In order to account for gestational age at delivery, weekly rates of 2nd and 3rd trimester weight gain were used to categorize women as gaining below, within, or above guidelines. We performed traditional regression analyses for maternal outcomes, and to account for the correlated nature of the neonatal outcomes in twins, we used generalized estimating equations (GEE). RESULTS: A total of 1482 twins and 741 mothers were included, of whom 27%, 43%, and 30% gained below, within, and above guidelines, respectively. The incidence of small for gestational age in these three groups was 30%, 21%, and 20%, respectively, and relative to gaining within guidelines, the adjusted odds ratios were 1.44 (95% CI 1.01-2.06) for gaining below and 0.92 (95% CI 0.62-1.36) for gaining above. The gestational weight gain in women who delivered twins at 37-42 weeks with average birth weight ≥ 2500 g and those who delivered twins outside of the recommend ranges were comparable to each other and the IOM recommendations. CONCLUSIONS: While gestational weight gain below guidelines for twins was associated with some adverse neonatal outcomes, additional research exploring alternate ranges of gestational weight gain in twin pregnancies is warranted, in order to optimize neonatal and maternal outcomes.

Predicting the Risk of Macrosomia at Mid-Pregnancy Among Non-Diabetics: A Retrospective Cohort Study.

OBJECTIVE: To identify factors known in mid-pregnancy to be associated with risk of macrosomia (≥4000 g) among non-diabetic women and to develop a risk score to allow early identification of women at high risk. METHODS: Data were obtained from a population-based perinatal database and a hospital laboratory database in Nova Scotia, Canada. The study included singleton live births born to non-diabetic women between 1998 and 2005. Logistic regression was used to identify risk factors significantly associated with macrosomia. Risk scoring systems were developed for nulliparous and parous women separately and validated using the C-statistic. RESULTS: Of the 23 857 mother-infant pairs included in the study, 16.7% of the infants were macrosomic. In nulliparous women, seven risk factors were identified, of which pre-pregnancy weight ≥90 kg with an OR of 4.8 (95% CI: 3.9 to 6.0) contributed a greater number of points to the risk score. The resulting risk score corresponded to a range of estimated risk of 0.2% to 47.0% and had a C-statistic of 0.70. In parous women, the most points were assigned to women with a previous large birth (OR: 3.7; 95% CI: 3.2-4.0) and a pre-pregnancy weight ≥90 kg (OR: 3.8; 95% CI: 3.1-4.7). The resulting risk score corresponded to a range of estimated risk of 0.4% to 88.0% and had a C-statistic of 0.75. CONCLUSIONS: Macrosomia risk can be estimated by a simple calculation based on a woman's risk factor profile at mid-pregnancy.

The next vaccine-autism question: Are school-aged youth with autism spectrum disorder undervaccinated and, if so, why?

Over the past two decades, the words 'autism' and 'vaccination' have often been linked and mired in controversy. In this commentary, we raise a different question about autism spectrum disorder (ASD) and vaccines: Are school-aged youth with ASD undervaccinated and, if so, why? There are several reasons why youth with ASD might be undervaccinated, including: belief in a vaccine-ASD link, challenges faced by youth with ASD when seeking health care and vaccine hesitancy factors that affect the general population. Possible undervaccination in this group is concerning given the prevalence of ASD and the key role of vaccinations in preventing infectious diseases. More research is needed to establish definitively whether youth with ASD are undervaccinated and to understand facilitators and barriers to vaccination for this population. This would help public health officials to develop and implement targeted policy and practice changes to increase vaccination uptake in youth with ASD, thereby increasing immunization equity.

Air Pollution Exposure During Pregnancy and Fetal Markers of Metabolic function: The MIREC Study.

Previous evidence suggests that exposure to outdoor air pollution during pregnancy could alter fetal metabolic function, which could increase the risk of obesity in childhood. However, to our knowledge, no epidemiologic study has investigated the association between prenatal exposure to air pollution and indicators of fetal metabolic function. We investigated the association between maternal exposure to nitrogen dioxide and fine particulate matter (aerodynamic diameter ≤2.5 µm) and umbilical cord blood leptin and adiponectin levels with mixed-effects linear regression models among 1,257 mother-infant pairs from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, conducted in Canada (2008-2011). We observed that an interquartile-range increase in average exposure to fine particulate matter (3.2 µg/m(3)) during pregnancy was associated with an 11% (95% confidence interval: 4, 17) increase in adiponectin levels. We also observed 13% (95% confidence interval: 6, 20) higher adiponectin levels per interquartile-range increase in average exposure to nitrogen dioxide (13.6 parts per billion) during pregnancy. Significant associations were seen between air pollution markers and cord blood leptin levels in models that adjusted for birth weight z score but not in models that did not adjust for birth weight z score. The roles of prenatal exposure to air pollution and fetal metabolic function in the potential development of childhood obesity should be further explored.

Vitamin D Status and Gestational Diabetes: Effect of Smoking Status during Pregnancy.

BACKGROUND: Vitamin D status, as measured by serum 25-hydroxyvitamin D (25(OH)D), has been shown in some studies to be inversely associated with gestational diabetes risk. Recently, it has been suggested that maternal smoking status may modify this relationship. We explored the association between 25(OH)D concentration and gestational diabetes and determined if there was an interaction between smoking and 25(OH)D. METHODS: A nested case-control study was conducted in Halifax, Nova Scotia and Quebec City, Quebec. Women were recruited before 20 weeks gestation and 25(OH)D was measured. Cases were women who developed gestational diabetes and controls were frequency matched to cases on study site, gestational age at blood draw, and season and year of blood draw. Logistic regression models estimated adjusted odds ratios (aOR) and 95% confidence intervals (CI). Models were tested for multiplicative and additive interaction, which was estimated by relative excess risk due to interaction (RERI). RESULTS: The study included 395 gestational diabetes cases and 1925 controls. Women who smoked during pregnancy and had 25(OH)D concentrations <30 nmol/L had an aOR = 3.73 [95% CI 1.95, 7.14] compared to non-smokers with 25(OH)D concentrations ≥50 nmol/L. Additive interaction was detected between smoking status and 25(OH)D [RERI = 2.44, 95% CI 0.03, 4.85]. CONCLUSION: Our study supports the inverse association of vitamin D status with gestational diabetes risk, particularly among women who smoke during pregnancy. More research is needed to confirm this finding and, if confirmed, to determine the mechanism by which the combined effect of smoking and low vitamin D status increases the risk of developing gestational diabetes.

Exposure to organophosphorus and organochlorine pesticides, perfluoroalkyl substances, and polychlorinated biphenyls in pregnancy and the association with impaired glucose tolerance and gestational diabetes mellitus: The MIREC Study.

BACKGROUND: Studies report increases in rates of gestational diabetes mellitus (GDM) over recent decades. Environmental chemicals may increase the risk of diabetes through impacts on glucose metabolism, mitochondrial dysfunction, and endocrine-disrupting mechanisms including effects on pancreatic ß-cell function and adiponectin release. OBJECTIVES: To determine the associations between pesticides, perfluoroalkyl substances (PFASs) and polychlorinated biphenyls (PCBs) measured in early pregnancy and impaired glucose tolerance (IGT) and GDM in a Canadian birth cohort. METHODS: Women enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study were included if they had a singleton delivery and did not have pre-existing diabetes. Exposure variables included three organophosphorus (OP) pesticide metabolites detected in first-trimester urine samples, as well as three organochlorine (OC) pesticides, three PFASs, and four PCBs in first-trimester blood samples. Gestational IGT and GDM were assessed by chart review in accordance with published guidelines. Adjusted logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CI) for the association between quartiles of environmental chemicals and both gestational IGT and GDM. RESULTS: Of the 2001 women recruited into the MIREC cohort, 1274 met the inclusion criteria and had outcome and biomonitoring data available. Significantly lower odds of GDM were observed in the third and fourth quartiles of dimethylphosphate (DMP) and in the fourth quartile of dimethylthiophosphate (DMTP) in adjusted analyses (DMP Q3: OR=0.2, 95% CI=0.1-0.7; DMP Q4: OR=0.3, 95% CI=0.1-0.8; DMTP: OR=0.3, 95% CI=0.1-0.9). Significantly elevated odds of gestational IGT was observed in the second quartile of perfluorohexane sulfonate (PFHxS) (OR=3.5, 95% CI=1.4-8.9). No evidence of associations with GDM or IGT during pregnancy was observed for PCBs or OC pesticides. CONCLUSIONS: We did not find consistent evidence for any positive associations between the chemicals we examined and GDM or IGT during pregnancy. We observed statistical evidence of inverse relationships between urine concentrations of DMP and DMTP with GDM. We cannot rule out the influence of residual confounding due to unmeasured protective factors, such as nutritional benefits from fruit and vegetable consumption, also associated with pesticide exposure, on the observed inverse associations between maternal OP pesticide metabolites and GDM. These findings require further investigation.