Fetal overgrowth and weight trajectories during infancy and adiposity in early childhood.

BACKGROUND: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood. Little is known about how infancy growth trajectories affect adiposity in early childhood in LGA. METHODS: In the Shanghai Birth Cohort, we followed up 259 LGA (birth weight >90th percentile) and 1673 appropriate-for-gestational age (AGA, 10th-90th percentiles) children on body composition (by InBody 770) at age 4 years. Adiposity outcomes include body fat mass (BFM), percent body fat (PBF), body mass index (BMI), overweight/obesity, and high adiposity (PBF >85th percentile). RESULTS: Three weight growth trajectories (low, mid, and high) during infancy (0-2 years) were identified in AGA and LGA subjects separately. BFM, PBF and BMI were progressively higher from low- to mid-to high-growth trajectories in both AGA and LGA children. Compared to the mid-growth trajectory, the high-growth trajectory was associated with greater increases in BFM and the odds of overweight/obesity or high adiposity in LGA than in AGA children (tests for interactions, all P < 0.05). CONCLUSIONS: Weight trajectories during infancy affect adiposity in early childhood regardless of LGA or not. The study is the first to demonstrate that high-growth weight trajectory during infancy has a greater impact on adiposity in early childhood in LGA than in AGA subjects. IMPACT: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood, but little is known about how weight trajectories during infancy affect adiposity during early childhood in LGA subjects. The study is the first to demonstrate a greater impact of high-growth weight trajectory during infancy (0-2 years) on adiposity in early childhood (at age 4 years) in subjects with fetal overgrowth (LGA) than in those with normal birth size (appropriate-for-gestational age). Weight trajectory monitoring may be a valuable tool in identifying high-risk LGA children for close follow-ups and interventions to decrease the risk of obesity.

Environmental antibiotics exposure and childhood obesity: A cross-sectional case-control study.

Children's exposures to environmental antibiotics are a major public health concern. However, limited data are available on the effects of environmental antibiotic exposures on childhood obesity. Our study aimed to explore this relationship. We conducted a cross-sectional case-control study nested in a population-based survey of primary school students, including 1855 obese and 1875 random selected control children. A total of 10 antibiotics in urine samples were measured by liquid chromatography-tandem mass spectrometry. Multivariable survey logistic regression was used to assess the associations between environmental antibiotics exposures and childhood obesity. After adjusting for potential confounders, increased odds of obesity were observed in children exposed to tetracycline (OR = 1.31, 95% CI: 1.09-1.57) and sulfamonomethoxine (OR = 1.43, 95% CI: 1-2.05). Comparing none (

Etiological subgroups of term small-for-gestational-age and childhood health outcomes.

BACKGROUND: Small-for-gestational-age (SGA) has a heterogeneous etiology. Our study aimed to examine the childhood health outcomes of etiology-distinct term SGA subgroups. METHODS: Data from the Collaborative Perinatal Project were used. The etiological factors of SGA were categorized into five groups: maternal, fetal, placental, environmental and physiological factors. Primary child outcomes included low IQ and growth restriction. A total of 8417 term infants were eligible. RESULTS: Compared with AGA, SGA children due to fetal factors had the highest risk of low IQ (aOR = 1.94, 95% CI: 1.45-2.59). SGA infants due to physiological factors had the highest risk of growth restriction (aOR = 6.04, 95% CI: 3.93-9.27). SGA children had a higher risk of growth restriction with the aOR ranging from 3.05 (95% CI: 2.36-3.96) to 5.77 (95% CI: 4.29-7.75) for the number of risk factors that the SGA infants had from 1 to 5. SGA children with any risk factor were associated with a higher risk of lower IQ with the aOR ranging from 1.59 (95% CI: 1.31-1.94) to 1.96 (95% CI: 1.50-2.55). SGA without the five types of etiologies was not associated with adverse child outcomes except for growth restriction (aOR = 3.82, 95% CI: 2.62-5.55). CONCLUSION: Term SGA of different etiologies may lead to different child health outcomes. IMPACT: Our study found that SGA of different etiologies may lead to different child health outcomes. Compared with AGA, SGA children due to fetal factors had the highest risk of low IQ. SGA infants due to physiological factors had the highest risk of growth restriction. SGA babies should not be treated the same. In the era of precision medicine, our findings may help pediatricians and parents better manage SGA babies according to different etiologies and the number of risk factors.

Small-for-gestational-age and predictors of HOMA indices, leptin and adiponectin in infancy.

AIM: To assess whether small-for-gestational-age (SGA) - an indicator of poor fetal growth, may affect metabolic health biomarkers in infancy and explore the predictors. METHODS: This was a nested matched (1:2) prospective observational study of 65 SGA (birth weight < 10th percentile) and 130 optimal-for-gestational-age (OGA, birth weight 25th-75th percentiles, control) infants in the 3D birth cohort with subjects recruited in Canada from 1 May 2010 to 31 August 2012. The outcomes included homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-ß), circulating leptin and adiponectin concentrations at age 2 years. RESULTS: HOMA-IR, HOMA-ß, leptin and adiponectin concentrations were similar in SGA versus OGA infants. Female sex and accelerated growth in length during mid-infancy (3-12 months) were associated with higher HOMA-IR. Caucasian ethnicity and decelerated growth in weight during late infancy (12-24 months) were associated with lower HOMA-IR. Current BMI was positively associated with circulating adiponectin in SGA infants only (+13.4% [4.0%-23.7%] per BMI z score increment). CONCLUSION: Insulin resistance and secretion, circulating leptin and adiponectin levels were normal in SGA subjects in infancy at age 2 years. The novel observation in SGA-specific positive association between current BMI and circulating adiponectin suggests dysfunctional adiposity-adiponectin negative feedback loop development during infancy in SGA subjects.

The association between maternal urinary Bisphenol A levels and neurodevelopment at age 2 years in Chinese boys and girls: A prospective cohort study.

The impact of maternal exposure to Bisphenol A on child cognitive development as well as its sex dimorphism remains uncertain. This study used data of 215 mothers and their children from a birth cohort in Shanghai. Urinary BPA were measured in spot urine samples of mothers at late pregnancy and children at age 2 years. Cognitive development was evaluated by Ages & Stages Questionnaires, Third Edition (ASQ-3) at age 2 years. Urinary BPA was detectable in 98.9% of mothers (geometric mean, GM: 2.6 µg/g. creatinine) and 99.8% children (GM: 3.4 µg/g. creatinine). Relative to the low and medium BPA tertiles, high tertile of maternal urinary BPA concentrations were associated with 4.8 points lower (95% CI: -8.3, -1.2) in gross motor and 3.7 points lower (95% CI: -7.4, -0.1) in problem-solving domain in girls only, with adjustment for maternal age, maternal education, pre-pregnancy BMI, passive smoking during pregnancy, parity, delivery mode, birth-weight for gestational age, child age at ASQ-3 test. This negative association remained with additional adjustment for child urinary BPA concentrations at age 2 years. No association was observed in boys. These results suggested the sex-dimorphism on the associations of maternal BPA exposure with gross motor and problem-solving domains in children at age 2 years. This study also indicated that optimal early child development should start with a healthy BPA-free "in utero" environment.

Urinary antibiotics concentrations, their related affecting factors and infant growth in the first 6 months of life: A prospective cohort study.

Antibiotic exposure even in low-dose could have potential adverse health effects, especially during early life. There is a lack of data on antibiotic burdens in early infancy. We aim to assess antibiotic exposure in infants from birth to 6 months of age, their related affecting factors and the association between antibiotic exposure and infancy growth. Urine samples were collected at ages of 3 days, 42 days, 3 months and 6 months from 197 term-born Chinese infants. A total of 33 representative antibiotics were measured by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Urinary antibiotics were detectable in 69.4%, 63.2%, 75.0% and 84.3% of infants at ages of 3 days, 42 days, 3 and 6 months, respectively. The dominant antibiotic categories detected were: Preferred as Veterinary Antibiotics (PVAs), Human Antibiotics (HAs), and Veterinary Antibiotics (VAs). The detectable rates were 30.6%, 45.8%, 58.9%, and 81.4% for PVAs, 34.1%, 20.8%, 28.6%, and 45.1% for HAs, and 36.5%, 12.5%, 6.3%, and 5.9% for VAs, at age 3 days, 42 days, 3 and 6 months, respectively. Urinary concentrations of HAs and preferred as human antibiotics (PHAs) in newborns at age 3 days were not associated with maternal intrapartum antibiotic prophylaxis. Similarly, no associations were observed between urinary antibiotics concentration and antibiotics use in infants at age 42 days or 6 months. The numbers and concentrations of urine detectable antibiotics were similar between infants with exclusive breastfeeding and infants fed with formula or mixed-feeding at all ages of 42 days, 3 and 6 months. At age of 42 days, infants in the low tertile of total antibiotics concentration or with one antibiotic detected had higher weight-for-length Z score and greater head circumference, compared to infants with no antibiotics detected. No associations were found between urinary antibiotics and any of the infant anthropometric measures at age 6 months. In conclusion, urinary antibiotics were detectable in most infants during the first 6 months of life, and PVAs, HAs and VAs were the most commonly detected antibiotics. This suggested the possibility of a foods-originated antibiotics exposure in children. No strong nor consistent associations were found between urinary antibiotic concentration and infant growth at the first six months of life. Still, attention is needed on the adverse health effect of early life exposure to antibiotics in future studies.

Maternal blood concentrations of toxic metal(loid)s and trace elements from preconception to pregnancy and transplacental passage to fetuses.

Intrauterine exposure to heavy metals may adversely affect the developing fetus and health later in life, while certain trace elements may be protective. There is limited data on their dynamic fluctuation in circulating concentration of women from preconception to pregnancy and the degree of transplacental passage to fetus. Such information is critically needed for an optimal design of research studies and intervention strategies. In the present study, we profiled the longitudinal patterns and trajectories of metal(loid)s and trace elements from preconception to late pregnancy and in newborns. We measured whole blood metal(loid)s in women at preconception, 16, 24 and 32 weeks of gestation and in cord blood in 100 mother-newborn pairs. Our data showed that the mean concentrations of mercury (Hg), lead (Pb), rubidium (Rb), manganese (Mn), and iron (Fe) were lower during early-, mid-, and late-pregnancy than at preconception. Copper (Cu), and calcium (Ca) concentrations increased after pregnancy (Cu 798 versus 1353, 1488, and 1464 µg/L). Concentrations at preconception were correlated with those during pregnancy for all examined metal(loid)s. Maternal Hg, Pb, and Se concentrations at late-pregnancy were correlated with those in newborn cord blood in various degrees (correlation coefficients: Hg 0.66, Pb 0.29, Se 0.39). The estimated placental transfer ratio for toxic metal(loid)s ranging from 1.68 (Hg) to 0.18 (Cd). Two trajectory groups were identified for Hg, Pb, Cd, Se concentrations. Hg concentrations may be correlated with maternal education levels. The study is the first to present longitudinal circulating concentration trajectories of toxic metal(loid)s and trace elements from preconception to pregnancy stages. A high degree of transplacental passage was observed in toxic metals Pb and Hg which may pose hazards to the developing fetus.

Breast-Milk Rubidium and Other Trace Elements are Associated with Neurocognitive Development in Infants at Age of 8 Months.

BACKGROUND: Trace elements may affect neurodevelopment. There is a lack of data on breast-milk rubidium (Rb) in relation to neurodevelopment in infants. The associations of copper (Cu), zinc (Zn) and strontium (Sr) with neurodevelopment in infants remain uncertain. OBJECTIVES: We sought to evaluate the associations of breast-milk Rb (primary exposure), Cu, Zn, and Sr with neurodevelopment in infants at age 8 months. METHODS: The study cohort included 117 breastfed infants. Breast-milk samples were collected at 42 days and 8 months postpartum. Breast-milk Rb, Zn, Cu, and Sr were measured by inductively coupled plasma mass spectrometer. Neurodevelopment was assessed at age 8 months. The primary outcomes were attention and working memory scores, as evaluated by the A-not-B task. Other outcomes included the Mental Development Index (MDI) and Psychomotor Development Index (PDI) as evaluated by the Bayley Scale of Infant Development III. Generalized linear models and restricted cubic spline regression were used to assess the associations between trace elements and neurodevelopment indices. Bonferroni correction was conducted on all data presented. RESULTS: A nonlinear association was observed between breast-milk Rb at 42 days and infant's attention at age 8 months (nonlinearity P = 0.037). Positive associations were observed with infant MDI scores and breast-milk Rb at 42 days (ß = 4.46; P = 0.06) and 8 months (ß = 3.79; P = 0.009) postpartum. Breast-milk Zn at 42 days was positively associated with infant's attention (ß = 0.31; P = 0.039). Sr at 42 days was positively correlated with attention (ß = 0.18; P = 0.043) and MDI scores (ß = 2.18; P = 0.015) at 8 months. Inverted U-shape associations were observed for breast-milk Cu at 42 days with infant attention and PDI scores. All associations were not significant after correction for multiple tests. CONCLUSIONS: Our data suggest that Rb, Zn, Cu, and Sr in breast milk at certain concentrations are associated with neurodevelopment in breastfed infants. Further studies are warranted to validate the findings.

Breast-feeding, rapid growth in the first year of life and excess weight at the age of 2 years: the 3D Cohort Study.

OBJECTIVE: To assess relationships between breast-feeding, rapid growth in the first year of life and overweight/obesity status at the age of 2 years. DESIGN: As part of an observational, longitudinal study beginning in early pregnancy, multivariable logistic regressions were used to assess associations between breast-feeding duration (total and exclusive) and rapid weight gain (RWG) between birth and 1 year of age, and to determine predictors of overweight/obesity status at the age of 2 years. SETTING: Nine hospitals located in the province of Quebec, Canada. PARTICIPANTS: A sample of 1599 term infants who participated in the 3D Cohort Study. RESULTS: Children having RWG in the first year and those having excess weight at the age of 2 years accounted for 28 % and < 10 %, respectively. In multivariable models, children breastfed < 6 months and from 6 months to < 1 year were, respectively, 2·5 times (OR 2·45; 95 % CI 1·76, 3·41) and 1·8 times (OR 1·78; 95 % CI 1·29, 2·45) more likely to show RWG up to 1 year of age compared to children breastfed ≥ 1 year. Children exclusively breastfed < 3 months had significantly greater odds of RWG in the first year (OR 1·94; 95 % CI 1·25, 3·04) compared to children exclusively breastfed for ≥ 6 months. Associations between breast-feeding duration (total or exclusive) and excess weight at the age of 2 years were not detected. RWG in the first year was found to be the main predictor of excess weight at the age of 2 years (OR 6·98; 95 % CI 4·35, 11·47). CONCLUSIONS: The potential beneficial effects of breast-feeding on rate of growth in the first year of life suggest that interventions promoting breast-feeding are relevant for obesity prevention early in life.

Comparative epidemiology of gestational diabetes in ethnic Chinese from Shanghai birth cohort and growing up in Singapore towards healthy outcomes cohort.

BACKGROUND: Gestational diabetes mellitus (GDM) has been associated with adverse health outcomes for mothers and offspring. Prevalence of GDM differs by country/region due to ethnicity, lifestyle and diagnostic criteria. We compared GDM rates and risk factors in two Asian cohorts using the 1999 WHO and the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. METHODS: The Shanghai Birth Cohort (SBC) and the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort are prospective birth cohorts. Information on sociodemographic characteristics and medical history were collected from interviewer-administered questionnaires. Participants underwent a 2-h 75-g oral glucose tolerance test at 24-28 weeks gestation. Logistic regressions were performed. RESULTS: Using the 1999 WHO criteria, the prevalence of GDM was higher in GUSTO (20.8%) compared to SBC (16.6%) (p = 0.046). Family history of hypertension and alcohol consumption were associated with higher odds of GDM in SBC than in GUSTO cohort while obesity was associated with higher odds of GDM in GUSTO. Using the IADPSG criteria, the prevalence of GDM was 14.3% in SBC versus 12.0% in GUSTO. A history of GDM was associated with higher odds of GDM in GUSTO than in SBC, while being overweight, alcohol consumption and family history of diabetes were associated with higher odds of GDM in SBC. CONCLUSIONS: We observed several differential risk factors of GDM among ethnic Chinese women living in Shanghai and Singapore. These findings might be due to heterogeneity of GDM reflected in diagnostic criteria as well as in unmeasured genetic, lifestyle and environmental factors.

Retinol-binding protein 4, fetal overgrowth and fetal growth factors.

BACKGROUND: Retinol-binding protein 4 (RBP-4) is an adipokine involved in regulating insulin sensitivity which would affect fetal growth. It is unclear whether RBP-4 is associated with fetal overgrowth, and unexplored which fetal growth factor(s) may mediate the association. METHODS: In the Shanghai Birth Cohort, we studied 125 pairs of larger-for-gestational-age (LGA, birth weight >90th percentile, an indicator of fetal overgrowth) and optimal-for-gestational-age (OGA, 25-75th percentiles) control infants matched by sex and gestational age. We measured cord blood concentrations of RBP-4, insulin, proinsulin, insulin-like growth factor-I (IGF-I), and IGF-II. RESULTS: Cord blood RBP-4 concentrations were elevated in LGA vs. OGA infants (21.9 ± 6.2 vs. 20.2 ± 5.1 µg/ml, P = 0.011), and positively correlated with birth weight z score (r = 0.19, P = 0.003), cord blood proinsulin (r = 0.21, P < 0.001), IGF-I (r = 0.24, P < 0.001), and IGF-II (r = 0.15, P = 0.016). Adjusting for maternal and neonatal characteristics, each SD increment in cord blood RBP-4 was associated with a 0.28 (0.12-0.45) increase in birth weight z score (P < 0.001). Mediation analyses showed that IGF-I could account for 31.7% of the variation in birth weight z score in association with RBP-4 (P = 0.01), while IGF-II was not an effect mediator. CONCLUSIONS: RBP-4 was positively associated with fetal overgrowth. IGF-I (but not IGF-II) may mediate this association.

Prenatal vitamin D status and offspring's growth, adiposity and metabolic health: a systematic review and meta-analysis.

In this systematic review and meta-analysis of observational studies, we aimed to estimate the associations between prenatal vitamin D status and offspring growth, adiposity and metabolic health. We searched the literature in human studies on prenatal vitamin D status and offspring growth in PubMed, up to July 2017. Studies were selected according to their methodological quality and outcomes of interest (anthropometry, fat mass and diabetes in offspring). The inverse variance method was used to calculate the pooled mean difference (MD) with 95 % CI for continuous outcomes, and the Mantel-Haenszel method was used to calculate the pooled OR with 95 % CI for dichotomous outcomes. In all, thirty observational studies involving 35 032 mother-offspring pairs were included. Vitamin D status was evaluated by circulating 25-hydroxyvitamin D (25(OH)D) level. Low vitamin D status was based on each study's cut-off for low 25(OH)D levels. Low prenatal vitamin D levels were associated with lower birth weight (g) (MD -100·69; 95 % CI -162·25, -39·13), increased risk of small-for-gestational-age (OR 1·55; 95 % CI 1·16, 2·07) and an elevated weight (g) in infant at the age of 9 months (g) (MD 119·75; 95 % CI 32·97, 206·52). No associations were observed between prenatal vitamin D status and other growth parameters at birth, age 1 year, 4-6 years or 9 years, nor with diabetes type 1. Prenatal vitamin D may play a role in infant adiposity and accelerated postnatal growth. The effects of prenatal vitamin D on long-term metabolic health outcomes in children warrant future studies.

Polybrominated Diphenyl Ether Concentrations in Human Breast Milk Specimens Worldwide.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are a class of flame retardants of ubiquitous presence in numerous consumer products. PBDEs may impair neurodevelopment in infants. There is a lack of meta-analysis on PBDE concentrations in human breast milk worldwide. We aimed to summarize global research data on PBDE concentrations in human breast milk specimens in recent years. METHODS: We conducted a systematic review through PubMed search of original studies on PBDE concentrations in human individual breast milk specimens collected in the general population over the recent 15-year period (2000-2015) worldwide. RESULTS: A total of 49 eligible studies (total number of study subjects = 7,502) were identified. The pooled means (95% CI) of total PBDE concentration in breast milk (ng/g lipid) were 66.8 (44.7, 88.9) in North America, 2.6 (2.2, 3.1) in Europe, and 2.8 (2.4, 3.3) in Asia, respectively. The pooled means (95% CI) of median total PBDEs concentration in breast milk (ng/g lipid) were 40.0 (30.8-49.1) in North America, 1.9 (1.4-2.4) in Europe, and 2.2 (1.3-3.2) in Asia. The high concentrations of total PBDEs in breast milk in North America were mainly due to high concentrations of brominated diphenyl ether-47 (BDE-47), BDE-99, BDE-100, and BDE-153. There were too few studies from other continents (Africa, South America, and Oceania) for meaningful meta-analysis. CONCLUSION: Total PBDE concentrations in breast milk in the recent 15-year period were over 20 times higher in North America versus Asia or Europe, and comparable in Europe versus Asia. There is a need for more research data from other continents.

Urinary Bisphenol A Concentration and Gestational Diabetes Mellitus in Chinese Women.

BACKGROUND: Bisphenol A (BPA) has been associated with variable metabolic effects in animal models. It is unknown whether BPA exposure affects glucose tolerance in pregnancy. We aimed to investigate whether maternal urinary BPA concentration is associated with gestational diabetes mellitus (GDM). METHODS: This study included 620 pregnant women from Shanghai, China 2012-2013. Maternal urinary BPA concentration was measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). GDM (n = 79) was diagnosed according to the criteria of the International Association of Diabetes and Pregnancy Study Groups (IADPSG). Multivariate regressions were used to explore the relationships of urinary BPA with GDM, plasma glucose levels in the 75-g 2-hour oral glucose tolerance test (OGTT), birth weight, and ponder index. RESULTS: The geometric mean of BPA was 1.32 µg/L. After adjustment for maternal age, education, husband smoking status, prepregnancy body mass index (BMI), and urinary creatinine concentration, plasma glucose at 2 hours in the 75-g OGTT was 0.36 mmol/L lower (95% confidence index [CI] = -0.73, 0.01) for women with urine BPA in the high versus the low tertile. For each unit increase in natural log-transformed BPA, the odds of GDM was reduced by 27% (odds ratio (OR) = 0.73; 95% CI = 0.56, 0.97), the birth weight decreased by 25.70 g (95% CI = -54.48, 3.07), and ponder index was decreased by 0.02 (100 g/cm) (95% CI = -0.03, 0.00). CONCLUSIONS: Higher maternal urinary BPA concentrations were associated with reduced risk of GDM and marginally lower birth weight and ponder index.

Disparities in infant hospitalizations in Indigenous and non-Indigenous populations in Quebec, Canada.

BACKGROUND: Infant mortality is higher in Indigenous than non-Indigenous populations, but comparable data on infant morbidity are lacking in Canada. We evaluated disparities in infant morbidities experienced by Indigenous populations in Canada. METHODS: We used linked population-based birth and health administrative data from Quebec, Canada, to compare hospitalization rates, an indicator of severe morbidity, in First Nations, Inuit and non-Indigenous singleton infants (< 1 year) born between 1996 and 2010. RESULTS: Our cohort included 19 770 First Nations, 3930 Inuit and 225 380 non-Indigenous infants. Compared with non-Indigenous infants, all-cause hospitalization rates were higher in First Nations infants (unadjusted risk ratio [RR] 2.05, 95% confidence interval [CI] 1.99-2.11; fully adjusted RR 1.43, 95% CI 1.37-1.50) and in Inuit infants (unadjusted RR 1.96, 95% CI 1.87-2.05; fully adjusted RR 1.37, 95% CI 1.24-1.52). Higher risks of hospitalization (accounting for multiple comparisons) were observed for First Nations infants in 12 of 16 disease categories and for Inuit infants in 7 of 16 disease categories. Maternal characteristics (age, education, marital status, parity, rural residence and Northern residence) partly explained the risk elevations, but maternal chronic illnesses and gestational complications had negligible influence overall. Acute bronchiolitis (risk difference v. non-Indigenous infants, First Nations 37.0 per 1000, Inuit 39.6 per 1000) and pneumonia (risk difference v. non-Indigenous infants, First Nations 41.2 per 1000, Inuit 61.3 per 1000) were the 2 leading causes of excess hospitalizations in Indigenous infants. INTERPRETATION: First Nations and Inuit infants had substantially elevated burdens of hospitalizations as a result of diseases of multiple systems. The findings identify substantial unmet needs in disease prevention and medical care for Indigenous infants.

3D Cohort Study: The Integrated Research Network in Perinatology of Quebec and Eastern Ontario.

BACKGROUND: The 3D Cohort Study (Design, Develop, Discover) was established to help bridge knowledge gaps about the links between various adverse exposures during pregnancy with birth outcomes and later health outcomes in children. METHODS: Pregnant women and their partners were recruited during the first trimester from nine sites in Quebec and followed along with their children through to 2 years of age. Questionnaires were administered during pregnancy and post-delivery to collect information on demographics, mental health and life style, medical history, psychosocial measures, diet, infant growth, and neurodevelopment. Information on the delivery and newborn outcomes were abstracted from medical charts. Biological specimens were collected from mothers during each trimester, fathers (once during the pregnancy), and infants (at delivery and 2 years of age) for storage in a biological specimen bank. RESULTS: Of the 9864 women screened, 6348 met the eligibility criteria and 2366 women participated in the study (37% of eligible women). Among women in the 3D cohort, 1721 of their partners (1704 biological fathers) agreed to participate (73%). Two thousand two hundred and nineteen participants had a live singleton birth (94%). Prenatal blood and urine samples as well as vaginal secretions were collected for ≥98% of participants, cord blood for 81% of livebirths, and placental tissue for 89% of livebirths. CONCLUSIONS: The 3D Cohort Study combines a rich bank of multiple biological specimens with extensive clinical, life style, and psychosocial data. This data set is a valuable resource for studying the developmental etiology of birth and early childhood neurodevelopmental outcomes.

Three alternative methods to resolve paradoxical associations of exposures before term.

To propose three methods to estimate associations between pregnancy exposures and outcomes before term, including the association between preeclampsia and preterm fetal-infant mortality, while avoiding the selection bias found in conventional analytic designs. Population-level analysis of 1,099,839 women who delivered live or stillborn infants in Quebec hospitals from 1989 to 2012, covering nearly a quarter of Canadian births. The exposure of interest was preeclampsia at 20-29, 30-33, 34-36, and ≥37 weeks of gestation. We compared preeclamptic with non-preeclamptic pregnancies in parametric survival models with a Weibull distribution using three analytic designs: (1) fetuses-at-risk; (2) bias correction factors; and (3) analysis of pregnancies at high risk of preterm delivery. Main outcome measures were occurrence of fetal or postnatal infant death before discharge. In models affected by bias due to selection of preterm births, women with preeclampsia early in gestation had paradoxically lower risks of fetal and infant mortality than women without preeclampsia. All three analytic approaches reversed the associations, showing a harmful effect of preeclampsia before term. At 20-29 weeks, for example, preeclampsia was associated with 1.35 times the risk of infant mortality (95 % confidence interval 1.14-1.60) and 1.40 times the risk of stillbirth (95 % confidence interval 1.18-1.67) with the fetuses-at-risk approach. Paradoxically protective benefits of exposures such as preeclampsia before term are artifacts of inappropriate analytic design. Outcomes before term should be analyzed with care, using methods that address bias due to selection of preterm deliveries.

Prevalence and risk factors of posttraumatic stress disorder among survivors five years after the "Wenchuan" earthquake in China.

OBJECTIVE: The aim of this study was to investigate the prevalence of posttraumatic stress disorder (PTSD) and its risk factors among survivors in a heavily-hit area five years after the Wenchuan earthquake in 2008, China. METHODS: 684 survivors from Beichuan county, the center of the Wenchuan Earthquake in 2008, were evaluated using the PTSD Checklist-Civilian Version (PCL-C) questionnaire in 2013. RESULTS: The prevalence of PTSD among survivors was 9.2% in 2013. Significant risk factors of PTSD included gender (females 12.1%, males 5.2%), age (18-35 y 0.8%, 36-59 y 9.7%, ≥60 y 12.9%), occupation (farmers 12.2%, non-farmers 1.6%), education (less than high school 11.0%; > = high school 0.8%) and family member loss (yes: 12.4%, no: 7.3%). Multivariate logistic regression showed that females, older people, farmers and those with family member loss were significantly more likely to develop PTSD. CONCLUSIONS: Posttraumatic stress symptoms remained relatively common among survivors five years after the "5.12" Earthquake in Beichuan county, China. It is important to provide psychological aid and social support for survivors to decease health burden from PTSD, especially for females, farmers, old age survivors and those with family member loss.

Perinatal mortality in second- vs firstborn twins: a matter of birth size or birth order?

OBJECTIVE: Second-born twins on average weigh less than first-born twins and have been reported at an elevated risk of perinatal mortality. Whether the risk differences depend on their relative birth size is unknown. The present study aimed to evaluate the association of birth order with perinatal mortality by birth order-specific weight difference in twin pregnancies. STUDY DESIGN: In a retrospective cohort study of 258,800 twin pregnancies without reported congenital anomalies using the US matched multiple birth data 1995-2000 (the available largest multiple birth dataset), conditional logistic regression was applied to estimate the odds ratio (OR) of perinatal death adjusted for fetus-specific characteristics (sex, presentation, and birthweight for gestational age). RESULTS: Comparing second vs first twins, the risks of perinatal death were similar if they had similar birthweights (within 5%) and were increasingly higher if second twins weighed progressively less (adjusted ORs were 1.37, 1.90, and 3.94 if weighed 5.0-14.9%, 15.0-24.9%, and ≥25.0% less, respectively), and progressively lower if they weighed increasingly more (adjusted ORs were 0.67, 0.63, and 0.36 if weighed 5.0-14.9%, 15.0-24.9%, and ≥25.0% more, respectively) (all P < .001). The perinatal mortality rates were not significantly different in cesarean deliveries or preterm (<37 weeks) vaginal deliveries but were significantly higher in second twins in term vaginal deliveries (3.1 vs 1.8 per 1000; adjusted OR, 2.15; P < .001). CONCLUSION: Perinatal mortality risk differences in second vs first twins depend on their relative birth size. Vaginal delivery at term is associated with a substantially greater risk of perinatal mortality in second twins.

Plasma cotinine indicates an increased risk of preeclampsia in previous and passive smokers.

OBJECTIVE: Self-reported tobacco smoking in pregnancy has been consistently associated with a decreased risk of developing preeclampsia, but the evidence has been limited and inconsistent for previous and passive smokers. Misclassifications and inaccuracies of self-reported tobacco exposure may disguise the true relationship. This study aimed to assess the association of gestational hypertension and preeclampsia with maternal smoking status as ascertained by plasma cotinine. STUDY DESIGN: This was a prospective study of 605 pregnant women without chronic hypertension. Maternal smoking status at 24-26 weeks' gestation was defined by plasma cotinine: >3.0 ng/mL "current smokers," 0.20-3.00 ng/mL "previous and passive smokers," and <0.20 ng/mL "nonsmokers." RESULTS: Compared to nonsmokers, the risk of developing preeclampsia did not change significantly for current smokers, but increased significantly (adjusted odds ratio, 6.06; 95% confidence interval, 2.32-15.85; P < .001) for previous and passive smokers. There were no significant differences in the risk of developing gestational hypertension only. CONCLUSION: Previous and passive smoking may increase the risk of preeclampsia. Avoidance of exposure to environmental tobacco smoke in pregnancy may decrease the risk of preeclampsia.