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Objectives:The novel coronavirus disease 2019 (COVID-19) pandemic has spread to over 213 countries and territories. We sought to describe the clinical features of fatalities in patients with severe COVID-19.Methods:We conducted an Internet-based retrospective cohort study through retrieving the clinical information of 100 COVID-19 deaths from nonduplicating incidental reports in Chinese provincial and other governmental websites between January 23 and March 10, 2020.Results:Approximately 6 of 10 COVID-19 deaths were males (64.0%). The average age was 70.7 ± 13.5 y, and 84% of patients were elderly (over age 60 y). The mean duration from admission to diagnosis was 2.2 ± 3.8 d (median: 1 d). The mean duration from diagnosis to death was 9.9 ± 7.0 d (median: 9 d). Approximately 3 of 4 cases (76.0%) were complicated by 1 or more chronic diseases, including hypertension (41.0%), diabetes (29.0%) and coronary heart disease (27.0%), respiratory disorders (23.0%), and cerebrovascular disease (12.0%). Fever (46.0%), cough (33.0%), and shortness of breath (9.0%) were the most common first symptoms. Multiple organ failure (67.9%), circulatory failure (20.2%), and respiratory failure (11.9%) are the top 3 direct causes of death.Conclusions:COVID-19 deaths are mainly elderly and patients with chronic diseases especially cardiovascular disorders and diabetes. Multiple organ failure is the most common direct cause of death.

To assess the effect of periodontal treatment during pregnancy on maternal, fetal and neonatal outcomes. This is a systematic review and meta-analysis of randomized controlled trials that evaluated the effect of treatment of periodontal diseases on pregnancy outcomes. Primary outcome was perinatal mortality. Secondary outcomes were maternal and neonatal morbidity. Outcomes were pooled using fix-effect or random effects models and presented as risk ratio (RR), or mean difference (MD), and 95% confidence interval (CI). Twenty randomized controlled trials involving 8171 participants were included in this study. Periodontal treatment during pregnancy was associated with significantly decreased risk of perinatal mortality [N = 5942; RR = 0.53 (0.30–0.93); p = .03; heterogeneity (I2) = 0%, Number needed to treat (NNT): 162]. Periodontal treatment during pregnancy reduced risks of preterm birth [N = 7335; RR = 0.78 (0.62–0.98); p = .03; I2 = 72%, NNT = 37]. Periodontal treatment during pregnancy significantly increased birthweight (gram) [N = 4708; MD = 200.79 (63.34–337.24); p = .004; I2 = 93%]. Periodontal treatment during pregnancy was not associated with preeclampsia, gestational diabetes, cesarean section, small for gestational age, or congenital malformations. Periodontal treatment during pregnancy reduces the risks of perinatal mortality and preterm birth, and improves birth weight.

Women who had delivered a macrosomic newborn will have a higher risk to deliver another macrosomia. We aimed to examine the recurrence risk of macrosomia in the subsequent pregnancy and the implications in long-term child health. Data from the Collaborative Perinatal Project, a longitudinal birth cohort with 54,371 singleton births, were used. 401 recurrent macrosomic infants (macro-macro) and 1327 normal weight babies with a macrosomia in the last pregnancy (macro-normal) were selected to explore risk factors for recurrent macrosomia. Furthermore, 768 newly onset macrosomia with normal birthweight infant in previous pregnancies (normal-macro) were identified to examine long-term health effects of recurrent macrosomia. The recurrent rate of macrosomia was 23.2% [95% confidence interval (CI) 21.2%, 25.2%]. White race, higher pre-pregnant body mass index (BMI), more gestational weight gain, male infant and more prior macrosomic infants were significant risk factors for recurrent macrosomia. At 4 years of age, recurrent macrosomic infants had a higher BMI (16.7 vs. 16.1 kg/m2, adjusted β: 0.36, 95% CI: 0.12, 0.60) and a higher risk of overweight and obesity (adjusted OR: 1.56, 95% CI: 1.10, 2.23) than infants with normal birthweight after a previous macrosomic sibling. There was no significant difference between recurrent macrosomia and newly onset macrosomia in child outcomes after adjustment for covariates. Fetal macrosomia has a high recurrence rate in the following pregnancy. Higher maternal pre-pregnant BMI and gestational weight gain are still important risk factors for recurrence of macrosomia, which in turn increases the risk for childhood obesity.

OBJECTIVE Fetal excessive exposure to glucocorticoids may program cardiometabolic risk. Placental 11 β-hydroxysteroid dehydrogenase 2 (11β-HSD2) serves as a barrier to prevent fetal overexposure to maternal glucocorticoids. It has not been explored whether placental 11β-HSD2 levels are associated with cardiometabolic health in postnatal life. RESEARCH DESIGN AND METHODS In a prospective birth cohort study of 246 mother-infant pairs, we measured placental 11β-HSD2 expression and maternal (32–35 weeks of gestation) and cord plasma cortisol concentrations. The primary outcomes were HOMA of insulin resistance (IR) and blood pressure (BP) in infants at age 1 year. Other outcomes included fasting insulin, HOMA β-cell function, carotid intima-media thickness, weight z score, and skinfold thickness (triceps and subscapular) at age 1 year. RESULTS Placental 11β-HSD2 expression was negatively correlated with HOMA-IR (r = −0.17, P = 0.021) and fasting insulin (r = −0.18, P = 0.017) and marginally negatively correlated with systolic BP (r = −0.16, P = 0.057) but was not correlated with HOMA of β-cell function, diastolic BP, carotid intima-media thickness, and skinfold thickness (all P > 0.1) in infants at age 1 year. Cord plasma cortisol was negatively correlated to skinfold thickness (r = −0.20, P = 0007) but was not correlated with other outcomes at age 1 year. Maternal plasma cortisol was positively correlated with maximal carotid intima-media thickness (r = 0.20, P = 0.03) but was not correlated with other outcomes. Adjusting for maternal and infant characteristics, the associations were similar. CONCLUSIONS The study is the first to show that higher placental 11β-HSD2 expression is associated with lower IR in infancy. Independent cohort studies are required to confirm this novel finding.

IntroductionChildhood overweight and obesity (OWO) is a primary global health challenge. Childhood OWO prevention is now a public health priority in China. The Sino-Canadian Healthy Life Trajectories Initiative (SCHeLTI), one of four trials being undertaken by the international HeLTI consortium, aims to evaluate the effectiveness of a multifaceted, community-family-mother-child intervention on childhood OWO and non-communicable diseases risk.Methods and analysisThis is a multicentre, cluster-randomised, controlled trial conducted in Shanghai, China. The unit of randomisation is the service area of Maternal Child Health Units (N=36). We will recruit 4500 women/partners/families in maternity and district level hospitals. Participants in the intervention group will receive a multifaceted, integrated package of health promotion interventions beginning in preconception or in the first trimester of pregnancy, continuing into infancy and early childhood. The intervention, which is centred on a modified motivational interviewing approach, will target early-life maternal and child risk factors for adiposity. Through the development of a biological specimen bank, we will study potential mechanisms underlying the effects of the intervention. The primary outcome for the trial is childhood OWO (body mass index for age ≥85th percentile) at 5 years of age, based on WHO sex-specific standards. The study has a power of 0.8 (α=0.05) to detect a 30% risk reduction in the proportion of children with OWO at 5 years of age, from 24.4% in the control group to 17% in the intervention group. Recruitment was launched on 30 August 2018 for the pilot study and 10 January 2019 for the formal study.Ethics and disseminationThe study has been approved by the Medical Research Ethics Committee of the International Peace Maternity and Child Health Hospital in Shanghai, China, and the Research Ethics Board of the Centre Intégré Universitaire de Santé et Services Sociaux de l’Estrie–CHUS in Sherbrooke, Canada. Data sharing policies are consistent with the governance policy of the HeLTI consortium and government legislation.Trial registration numberChiCTR1800017773.Protocol versionNovember 11, 2020 (Version #5).

Diagnosing extraspinal sciatica and pudendal neuralgia remains a clinical challenge. MRI and MR Neurography (MRN) are currently the standard techniques used to support the diagnosis of extraspinal lumbosacral plexus entrapments; however, for the intrapelvic portions of the lumbosacral plexus their accuracy is still limited. MR Tractography (MRT) feasibility to image the lumbosacral plexus has been demosntrated, but its clinical applications have yet to be determined.To correlate MRT with intraoperative findings in patients undergoing laparoscopic treatment of intrapelvic entrapments of the lumbosacral plexus and compare its accuracy with Neuropelveological clinical assessment and MRN.This is a retrospective analysis of MRT reconstructions of diffusion tensor imaging (DTI) sequences acquired for the MRN collected from a cohort of 13 patients undergoing laparoscopic detrapment of the lumbosacral plexus. The primary outcome of this study was the correlation of MRT reconstruction with intraoperative findings. Secondary outcomes included the correlation of MRN, preoperative Neuropelveological clinical diagnoses and the diffusion-weighted imaging (DWI) fractional anisotropy (FA) and Apparent Diffusion Coefficient (ADC) in patients undergoing pelvic MRI and MRN for the investigation of intrapelvic nerve entrapments.MRT correlated with intraoperative findings in 11 of 13 patients (85%). Neuropelveological clinical assessment was able to accurately diagnose a pelvic nerve entrapment in 12/13 patients (92%) and MRN agreed with surgical findings in only 2/13 (15%) patients. MRT was significantly superior to MRN (p 0.001). FA and ADC did not correlate with the identification of a nerve entrapment, likely due to limitations regarding the placement of the seedpoints.This initial, retrospective analysis, suggests that MRT is superior to MRN at diagnosing intrapelvic entrapments of the lumbosacral plexus. A prospective, double-blinded study is underway to validate this data, but these initial findings show great potential for MRT as a diagnostic tool for extraspinal sciatica and pudendal neuralgia. Clinical Trials Registry: U1111-1261-4910 (REBEC - Brazilian Registry for Clinical Trials).

Background Humans are widely exposed to environmental perfluoroalkyl substances (PFAS), which may affect glucose homeostasis. However, research linking PFAS exposure to glucose homeostasis during pregnancy is limited and the results were inconsistent. We aimed to investigate the association between PFAS exposure and glucose homeostasis in pregnancy in a large prospective cohort. Methods A total of 2747 pregnant women who participated in the Shanghai Birth Cohort, had blood samples in early pregnancy and completed a 75 g oral glucose tolerance test (OGTT) at 24–28 gestational weeks were included. 10 PFAS were determined by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS-MS) in the plasma samples in early pregnancy. Logistic regression was used to explore the associations between PFAS concentrations and gestational diabetes mellitus (GDM), while multiple linear regression was used to model the associations between PFAS and OGTT fasting, 1-h and 2-h glucose levels. Potential confounders were adjusted. Bayesian kernel machine regression (BKMR) and a quantile-based g-computation approach (qgcomp) were employed to explore the joint and independent effects of PFAS on glucose homeostasis. Results The incidence of GDM was 11.8%. One log-unit increment in plasma concentrations in early pregnancy was associated with an increased risk of GDM for perfluorobutane sulfonate (PFBS) (adjusted odd ratio (aOR) = 1.23, 95% confidence interval (95% CI): 1.05, 1.44) and perfluoroheptanoic acid (PFHpA) (aOR = 1.25, 95% CI: 1.07, 1.46). Perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorohexanesulfonate (PFHxS) and PFHpA were positively correlated with 1-h and 2-h glucose levels. Results of the mixed exposure model showed that the joint effects of PFAS were significantly associated with abnormal glucose homeostasis; In the BKMR model, PFAS mixture exposure was positively associated with the GDM incidence, 1-h and 2-h glucose levels and negatively correlated with FBG level. A similar trend could be observed in qgcomp and the positive correlation between PFAS and 2-h glucose level was significant (β = 0.12, 95% CI: 0.04, 0.20). PFOS, PFNA and PFHpA may be the main contributors after controlling for other PFAS congeners. PFOS was significantly correlated with GDM incidence and 2-h glucose level, and PFHpA was significantly associated with FBG and 2-h glucose levels. The above associations were more prominent among women with a normal prepregnant BMI. Conclusions Environmental exposure to PFAS may affect glucose homeostasis in pregnancy and increase the risk of GDM, especially in normal weight women.

Objective: Early life is a critical period for gut microbial development. It is still controversial whether there is placental microbiota during a healthy pregnancy. Gestational diabetes mellitus (GDM) is associated with increased risk of metabolic syndrome in the offspring, and the mechanisms are unclear. We sought to explore whether microbiota in placenta and cord blood may be altered in GDM. Methods: Placenta and cord blood samples were collected from eight GDM and seven euglycemic (control) term pregnancies in cesarean deliveries without evidence of clinical infections. The Illumina MiSeq Sequencing System was used to detect the microbiota based on the V3-V4 hypervariable regions of the 16S ribosomal RNA gene. Results: The microbiota were detectable in all placental samples. Comparing GDM vs. controls, there were more operational taxonomic units (OTUs) (mean ± SE = 373.63 ± 14.61 vs. 332.43 ± 9.92, P = 0.024) and higher ACE index (395.15 ± 10.56 vs. 356.27 ± 8.47, P = 0.029) and Chao index (397.67 ± 10.24 vs. 361.32 ± 8.87, P = 0.04). The placental microbiota was mainly composed of four phyla: Bacteroidetes, Firmicutes, Actinobacteria, and Proteobacteria at the phylum level and 10 dominant genera at the genus level in both GDM and controls. Despite the dominant similarity in microbiota composition, at the OTU level, the abundance of Ruminococcus, Coprococcus, Paraprevotella, and Lactobacillus were higher, whereas Veillonella was lower in the placentas of GDM vs. controls. The microbiota was detected in one of the 15 cord blood samples, and its components were similar as to the corresponding placental microbiota at both phylum and genus levels suggesting placental microbiota as the potential source. Conclusions: The most abundant phyla and genus of placental microbiota were similar in GDM and euglycemic pregnancies, but GDM was associated with higher diversity of placental microbiota. Further study is needed to confirm the existence of microbiota in cord blood in pregnancies without clinical infection.

Objective To examine the associations between risk of pre-eclampsia and pregnancy levels of maternal 25-hydroxyvitamin D (25[OH]D) and oxidative stress biomarkers. Methods A nested case-control study (n = 99; 34 cases; 65 controls) within a prospective pregnancy cohort. Maternal 25(OH)D and oxidative stress markers (six isomers of F2 -isoprostanes; F2 -isoPs) were measured in plasma at 12-18 and 24-26 gestational weeks. Vitamin D deficiency was defined as 25[OH]D less than 50 nmol/L. Results Maternal vitamin D deficiency was associated with increased 8-iso-PGF2α (P = 0.037), 15(R)-PGF2α (P = 0.004), (±)5-iPF2α -VI (P = 0.026) at 12-18 weeks. Vitamin D deficiency was inversely associated with 8-iso-PGF2α (P = 0.019) and (±)5-iPF2α -VI isomer (P = 0.010) at 24-26 weeks. Both maternal vitamin D deficiency (adjusted odds ratio [aOR], 4.79; 95% confidence interval [CI], 1.67-13.75) and increased (±)5-iPF2α -VI (aOR, 2.46; 95% CI, 1.16-5.22) at 24-26 weeks were associated with risk of pre-eclampsia. However, the interaction test between 25(OH)D and (±)5-iPF2α -VI was not significant (P = 0.143). Conclusion Plasma 25(OH)D below 50 nmol/L was associated with increased oxidative stress levels during pregnancy as measured by two F2 -isoP isomers, including the well-studied marker 8-iso-PGF2α . Whether vitamin D-induced oxidative stress mediates the risk of pre-eclampsia warrants future study.

Background Ambient air pollution has been linked to the development of gestational diabetes mellitus (GDM). However, previous studies provided inconsistent findings and no study has examined the effects of complex chemical constituents of the particular matter on GDM, especially in developing countries. Therefore, we aim to investigate the associations of exposure to PM2.5 (particular matter ≤ 2.5 μm) and its constituents with GDM, and to identify susceptible exposure window in a large survey in China. Methods The China Labor and Delivery Survey was a cross-sectional investigation conducted in 24 provinces in China between 2015 and 2016. A random sample of all deliveries in each participating hospital was selected and detailed obstetric and newborn information was extracted from medical records. Average concentrations of PM2.5 and six constituents (organic matter, black carbon, sulfate, nitrate, ammonium and soil dust) were estimated (1 km × 1 km) using a combined geoscience-statistical model. GDM was diagnosed based on an oral glucose tolerance test (OGTT) between 24 to 28 weeks of gestation and according to IADPSG criteria. Generalized linear mixed models were used to adjust for potential confounders. Results A total of 54,517 subjects from 55 hospitals were included. The incidence of GDM was 10.8%. An interquartile range (IQR) increase in PM2.5 exposure in the 2nd trimester of pregnancy was associated with an increased GDM risk in the single pollutant model, [adjusted odds ratio (aOR) = 1.11 and 95% confidence interval (CI): 1.01–1.22]. Exposure to organic matter (aOR = 1.14; 95%CI: 1.05–1.23), black carbon (aOR = 1.15; 95%CI: 1.07–1.25) and nitrate (aOR = 1.13; 95%CI: 1.02–1.24) during 2nd trimester were associated with increased risks of GDM. Associations between constituents and GDM were robust after controlling for total PM2.5 mass and accounting for multi-collinearity. Conclusions Exposure to PM2.5 in 2nd trimester of pregnancy was associated with an increased risk of GDM. Organic matter, black carbon and nitrate may be the main culprits for the association.

Background:Considering the potential inappropriateness of the 2009 Institute-of-Medicine criteria to Chinese women, we investigated the associations between pre-pregnancy body-mass-index (BMI), gestational-weight-gain (GWG) and breastfeeding-duration among Chinese women.Methods:This birth-cohort study included 225 mother-child pairs in Shanghai from 2010 to 2012. Mothers were interviewed during mid-to-late pregnancy and at 24-36 months postpartum. Information on pre-pregnancy BMI/GWG and breastfeeding-duration was collected during pregnancy and at 24-36 months postpartum, respectively. Using a data-driven approach based on spline-smoothing-fitting of the data, two-piecewise linear regression models were used to assess the relations between pre-pregnancy BMI, GWG and breastfeeding-duration. Results:Mothers being younger, longer daily working hours, and less time living with children per week were associated with shorter duration (P2 were associated with an increase (P=0.044) and a marginal decrease (P=0.077) in breastfeeding-duration, respectively. One-kilogram increase in GWG was associated with 0.4-month decrease (95% CI: -0.7, -0.1) in breastfeeding-duration when GWG ≥ 17.5 kilograms, however, with nonsignificant changes when GWG Conclusion:Appropriate pre-pregnancy BMI (around 22.5 kg/m2) and GWG (< 17.5 kilograms) were favorable to sustained breastfeeding.

Objective This study aims to determine the impact of assisted hatching (AH) on pregnancy outcomes in vitrified-warmed blastocyst transfers, and evaluate if embryo expansion or morphology influences outcomes. Methods A retrospective cohort study was performed including vitrified-warmed blastocyst transfers at our clinic between 2013 and 2017. Of the 2165 embryo transfers, 1986 underwent laser AH and 179 were non-assisted hatched (NAH). The primary outcome was live birth. Secondary outcomes included conception, implantation, clinical pregnancy, clinical pregnancy loss, and monozygotic twinning (MZT). Results AH and NAH groups had similar rates of conception (38.7% vs 42.1%), implantation (26.2% vs 27.3%), clinical pregnancy (29.1% vs 30.3%), clinical pregnancy loss (24.0% vs 17.8%), live birth (19.9% vs 20.5%), and MZT (2.08% vs 2.86%). Five pairs of dichorionic/diamniotic twins resulted from single embryo transfers. AH of embryos with expansion grades ≤3 was associated with lower rates of conception (32.5% vs 44.3%%, p p Conclusion AH prior to transfer of vitrified-warmed blastocysts was not associated with improved pregnancy outcomes. The identification of dichorionic/diamniotic twins from single blastocyst transfers challenges the previously held notion that dichorionic/diamniotic MZTs can only occur from division prior to the blastocyst stage. Prospective studies are needed to validate the novel finding of lower rates of conception and clinical pregnancy after AH in embryos with lower expansion grade.

Context Small-for-gestational-age (SGA) is an indicator of poor fetal growth “programming” an elevated risk of type 2 diabetes in adulthood. Little is known about early-life endocrine characteristics in SGA subtypes. Stunting (short) and wasting (skinny) are considered distinct SGA phenotypes in neonatal prognosis. Objectives This work aimed to assess whether SGA infants with stunting or wasting have similar alterations in neonatal endocrine metabolic health biomarkers. Methods This was a nested case-control study based on the 3D (Design, Develop, and Discover) birth cohort in Canada. The study subjects were 146 SGA (birth weight Results Comparing to OGA infants adjusted for maternal and neonatal characteristics, SGA infants with either stunting only or wasting only had lower cord plasma IGF-I and leptin concentrations. HMW adiponectin concentrations were lower in SGA infants with wasting only (P = .004), but similar in SGA infants with stunting only (P = .816). Only SGA infants with both stunting and wasting had substantially lower proinsulin (P Conclusion This study is the first to demonstrate that SGA infants with wasting only are characterized by low HMW adiponectin concentrations, whereas those with stunting only are not. SGA with both stunting and wasting are characterized by low proinsulin and high ghrelin concentrations.

IntroductionGestational diabetes (GD) is associated with impaired insulin sensitivity in newborns. Adiponectin and retinol-binding protein 4 (RBP-4) are involved in regulating insulin sensitivity. Females are more likely to develop diabetes at young ages than males. We tested the hypothesis that GD may affect RBP-4 and adiponectin levels in early life, and there may be sex-dimorphic associations.Research design and methodsIn a nested case–control study of 153 matched pairs of neonates of mothers with GD and euglycemic pregnancies in the Shanghai Birth Cohort, we evaluated cord plasma leptin, high molecular weight (HMW) and total adiponectin and RBP-4 concentrations.ResultsComparing GD versus euglycemic pregnancies adjusted for maternal and neonatal characteristics in female newborns, cord plasma total adiponectin (mean±SD: 30.8±14.3 vs 37.1±16.1 µg/mL, p=0.048) and HMW adiponectin (14.6±7.7 vs 19.3±8.3 µg/mL, p=0.004) concentrations were lower, while RBP-4 concentrations were higher (21.7±5.4 vs 20.0±4.8 µg/mL, p=0.007). In contrast, there were no differences in male newborns (all p>0.2). RBP-4 concentrations were higher in female versus male newborns (21.7±5.4 vs 18.8±4.5 µg/mL, pConclusionsGD was associated with lower cord plasma HMW adiponectin and higher RBP-4 concentrations in female newborns only. The study is the first to reveal a sex-dimorphic early life impact of GD on metabolic health biomarkers in the offspring. GD may alter the normal presence (HMW adiponectin) or absence (RBP-4) of sex dimorphism in some insulin sensitivity regulation-relevant adipokines in early life.

ObjectiveFetuin-A is a glycoprotein produced by hepatocytes and has been associated with insulin resistance and bone growth in postnatal life. Gestational diabetes mellitus (GDM) is a condition characterized by insulin resistance. It is unclear whether GDM may affect cord blood fetuin-A levels and whether fetuin-A is associated with fetal growth.Research design and methodsIn a nested case–control study of 153 matched pairs of neonates of mothers with GDM and euglycemic pregnancies in the Shanghai Birth Cohort, we evaluated cord blood fetuin-A in association with GDM and fetal growth.ResultsComparing the newborns of GDM versus euglycemic mothers, cord blood fetuin-A concentrations were similar (mean±SD: 783.6±320.0 vs 754.8±281.9 µg/mL, p=0.53), while insulin-like growth factor (IGF)-I (76.6±27.8 ng/mL vs 68.1±25.1 ng/mL, p=0.008) and IGF-II (195.3±32.5 ng/mL vs 187.5±30.8 ng/mL, p=0.042) concentrations were higher. Cord blood fetuin-A was not correlated with insulin, IGF-I or IGF-II. Cord blood fetuin-A was negatively correlated with birth weight (r=−0.19, p=0.025) and birth length (r=−0.24, p=0.005) z scores in GDM pregnancies, while there were no significant correlations in euglycemic pregnancies (tests for interaction: p=0.014 for birth length, p=0.013 for birth length). Adjusting for maternal and neonatal characteristics, the differential associations remained.ConclusionsGDM was not associated with cord blood fetuin-A levels. Fetuin-A was negatively associated with fetal growth in GDM but not in euglycemic pregnancies. This novel observation suggests a GDM-conditional negative correlation of fetuin-A with fetal growth.

Objective: Thyroid hormones are essential for fetal growth and neurodevelopment, however, data on cord blood thyroid hormones are sparse in China where maternal age at childbearing is increasing in recent decades. We aimed to assess cord blood levels of free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) in full-term Chinese newborns, and examine potential related perinatal factors.Methods: This study included 922 mother-newborn pairs from a prospective birth cohort enrolled in 2012–2013, Shanghai, China. Cord serum concentrations of FT3, FT4, TSH, and TPOAb were measured in newborns.Results: Newborns born via cesarean section had higher cord serum FT3 (mean ± SD: 1.90 ± 1.16 pmol/L) and lower cord serum TSH (5.15 ± 2.60 mIU/L) than those born via vaginal delivery (FT3: 1.62 ± 0.93 pmol/L; TSH: 9.27 ± 6.76 mIU/L). In cesarean section deliveries, the concentration of cord serum FT3 was 0.15 (95%CI: −0.03, 0.33; p = 0.10) pmol/L lower in infants of mothers aged 30–34 years, and 0.57 (95%CI: 0.22, 0.92; p = 0.002) pmol/L lower in infants of mothers ≥35 years compared to infants of mothers 90th percentile) was associated with higher TSH (p = 0.02). Similar results were also found in vaginal deliveries.Conclusions: In this Chinese term birth cohort, newborns born via cesarean section had higher cord serum FT3 and lower TSH than those born via vaginal delivery. Advanced maternal age was associated with lower fetal FT3. Further research is needed to understand whether this association may mediate the adverse impact of advanced maternal age on neurodevelopment in early life.

OBJECTIVE To determine whether pre-eclampsia is associated with polymorphisms in superoxide dismutase (SOD) genes among mother-father-infant triads. METHODS We did this follow-up cohort study at 17 urban hospitals in Canada between October 1, 2008, and September 30, 2010. We recruited Canadian participants who had participated in the International Trial of Antioxidant Supplementation for the Prevention of Pre-eclampsia. Saliva specimens were collected for DNA extraction. The SOD1 +35A/C (rs2234694) and SOD2 Ala16Val C/T (rs4880) single-nucleotide polymorphisms (SNPs) were genotyped. RESULTS Dual presence of the SOD2 Ala16Val TT variant among mother-father pairs (n=657) was associated with an increased risk of pre-eclampsia when compared with the absence of the TT variant among the mother-father pairs (7/48 [14.6%] vs 11/339 [3.2%]; adjusted odds ratio 6.80, 95% confidence interval 2.32-19.95; P

Dietary ω-3 polyunsaturated fatty acids (ω-3 PUFAs) may affect infants' executive function (EF), although it remains unclear whether this may be the effect of total ω-3 PUFAs or any specific ω-3 PUFA. We assessed the associations between ω-3 PUFAs in breast milk and EF in infants at 8 mo of age.Milk samples from the mothers of 120 breast-fed infants were collected at 42 d and 8 mo postpartum in Beijing, China. Infant's EF was evaluated by planning tasks and A-not-B tasks, including working memory, distractibility, and inhibition of prepotent response at age 8 mo.Eicosapentaenoic acid (EPA) concentrations in breast milk were significantly higher at 42 d than 8 mo postpartum. Breast milk EPA levels at both 42 d (P = 0.037) and 8 mo (P = 0.005) postpartum were negatively associated with infant distractibility when EPA levels were low (0.05%). No significant association was observed for other ω-3 PUFAs with infant EF scores.Our results suggest a beneficial effect of higher EPA in breast milk (improving infant's attention) when its levels are below a certain threshold.

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.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.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.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.

Maternal psychological stress during pregnancy has essentially been conceptualized as a teratogen. However, little is known about the effect of temperature on maternal stress during pregnancy. The aim of this study is to investigate the relationship between temperature and maternal stress during pregnancy.In 2010, a total of 1931 eligible pregnant women were enrolled across Shanghai from four prenatal-care clinics during their mid-to-late pregnancy. Maternal life-event stress and emotional stress levels during pregnancy were assessed by the "Life Event Scale for Pregnant Women" (LESPW) and "Symptom Checklist-90-Revised Scale" (SCL-90-R), respectively. Exposure to ambient temperature was evaluated based on daily regional average in different moving average and lag days. The generalized estimating equations were used to evaluate the relationship between daily average temperature/temperature difference and maternal stress.After adjusting for relevant confounders, an U-shaped relationship was observed between daily average temperature and maternal Global-Severity-Index (GSI) of the SCL-90-R. Cumulative exposures to extremely low temperatures (P5, 1.4-10.5℃, lag 0-1 days, 0-2 days and 0-5 days) and extremely high temperatures (≥ P95, 31.2-34.1℃, lag 0-1 days and 0-2 days), and acute exposures to extremely low (lag day 0, 1, 2 and 3) and high (lag day 0, 1) temperatures, all induced higher risks of high GSI (the highest tertile), compared to the risk induced by exposed to an optimal temperature range (20-25℃) (P0.05). Increased temperature difference was associated with high maternal GSI (P0.05). However, non-significant associations were observed between daily average temperatures/temperature differences and maternal log-transferred LESPW scores.Cumulative and acute exposures to extremely low/high temperatures may both induce emotional stress during pregnancy.

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 ( 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.

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.In the Shanghai Birth Cohort, we studied 125 pairs of larger-for-gestational-age (LGA, birth weight90th 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.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.RBP-4 was positively associated with fetal overgrowth. IGF-I (but not IGF-II) may mediate this association.

ObjectiveBoth pregestational and gestational diabetes mellitus (PGDM, GDM) occur more frequently in First Nations (North American Indians) pregnant women than their non-Indigenous counterparts in Canada. We assessed whether the impacts of PGDM and GDM on perinatal and postneonatal mortality may differ in First Nations versus non-Indigenous populations.DesignA population-based linked birth cohort study.Setting and participants17 090 First Nations and 217 760 non-Indigenous singleton births in 1996–2010, Quebec, Canada.Main outcome measuresRelative risks (RR) of perinatal and postneonatal death. Perinatal deaths included stillbirths and neonatal (0–27 days of postnatal life) deaths; postneonatal deaths included infant deaths during 28–364 days of life.ResultsPGDM and GDM occurred much more frequently in First Nations (3.9% and 10.7%, respectively) versus non-Indigenous (1.1% and 4.8%, respectively) pregnant women. PGDM was associated with an increased risk of perinatal death to a much greater extent in First Nations (RR=5.08[95% CI 2.99 to 8.62], pConclusionsThe study is the first to reveal that PGDM may increase the risk of perinatal death to a much greater extent in First Nations versus non-Indigenous populations, but may substantially increase the risk of postneonatal death in non-Indigenous infants only. The underlying causes are unclear and deserve further studies. We speculate that population differences in the quality of glycaemic control in diabetic pregnancies and/or genetic vulnerability to hyperglycaemia’s fetal toxicity may be contributing factors.

IntroductionOxidized low-density lipoprotein (OxLDL), a biomarker of oxidative stress, itself possesses proatherogenic and proinflammatory effects. Elevated circulating OxLDL levels have been consistently associated with insulin resistance and diabetes in adults. We sought to assess whether OxLDL may be associated with insulin sensitivity and beta-cell function in early life.Research design and methodsIn a birth cohort study, we assessed cord plasma OxLDL concentration and OxLDL to total LDL ratio in relation to glucose to insulin ratio (an indicator of fetal insulin sensitivity), proinsulin to insulin ratio (an indicator of fetal beta-cell function), and leptin and adiponectin concentrations in 248 singleton newborns.ResultsCord plasma OxLDL concentration was positively correlated with glucose to insulin ratio (r=0.24, pConclusionsHigher OxLDL levels were associated with lower fetal beta-cell function (higher proinsulin to insulin ratio) but higher insulin sensitivity (higher glucose to insulin ratio). The study is the first to demonstrate that OxLDL may affect glucose metabolic health in early life in humans.

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.

Objective High prepregnancy body mass index (BMI), excessive gestational weight gain (GWG), and gestational diabetes mellitus (GDM) are associated with the risk of childhood obesity. This study aims to examine the extent to which these effects may be mediated through the placenta. Methods Data included 33,893 mothers and their singleton infants from birth to 7 years old (total 154,590 visits) in the Collaborative Perinatal Project, a U.S. multicenter prospective cohort study from 1959 to 1976. The placentas were weighed after removing cord and membranes. We performed sequential generalized estimating equation-linear models excluding and including placental weight to evaluate its mediation effect. Results In this population, 21.7% of mothers had overweight or obesity, 17.3% had excessive GWG, and 350 (1%) had diagnosed GDM; in addition, 7.2% children had obesity. After adjustment for prepregnancy BMI and other covariates, childhood BMI was 0.23 (95% CI: 0.05, 0.40) kg/m2 higher for children born to mothers with GDM versus those without GDM. Inclusion of placental weight in the model attenuated the association by 52% to 0.11 (95% CI: −0.06, 0.28) and similarly attenuated the associations with childhood BMI for GWG by 25% and maternal prepregnancy BMI by 17%. Conclusions Placental weight partly mediates the effects of prepregnancy BMI, excessive GWG, and GDM on childhood BMI.

Aim Vulnerability to insulin resistance and Type 2 diabetes may originate in early life, but little is known about whether any perinatal biomarkers are predictive of later metabolic health. We sought to assess whether cord blood insulin, insulin-like growth factor (IGF)-I, IGF-II, leptin, adiponectin and ghrelin are associated with metabolic health indicators in infancy. Methods In a prospective singleton birth cohort, we assessed cord blood insulin, IGF-I, IGF-II, leptin, adiponectin and ghrelin concentrations in relation to the homeostasis model assessment of insulin resistance (HOMA-IR), β-cell function (HOMA-β), fasting proinsulin-to-insulin ratio, BMIz-score, and the sum of triceps and subscapular skinfold thickness (an indicator of adiposity) in infants at age 1 year (n = 185). Results Adjusting for maternal and infant characteristics, one standard deviation (sd) increase in cord blood adiponectin was associated with an 11.1% (95% confidence interval 1.8-19.5%) decrease in HOMA-β (P = 0.02) and a 13.6% (1.8-26.8%) increase in proinsulin-to-insulin ratio (P = 0.02), indicating worse β-cell function in infants at age 1 year. One sd increase in cord blood insulin was associated with a 0.5 (0.1-1.0) mm increase in skinfold thickness (P = 0.01). One sd increase in cord blood ghrelin was associated with a 0.2 (0.02-0.3) decrease in BMIz-score (P = 0.02) and a 0.5 (0.1-0.9) mm decrease (P = 0.02) in skinfold thickness. Cord blood IGF-I and IGF-II were not associated with the observed metabolic health indicators at age 1 year. Conclusion The study is the first to show that cord blood adiponectin may be negatively predictive of β-cell function, whereas cord blood ghrelin may be negatively predictive of adiposity in infancy.

ContextFetal overgrowth is associated with increased risk for type 2 diabetes in adulthood. It is unclear whether there are alterations in insulin sensitivity and β-cell function in early life.ObjectiveTo determine whether large-for-gestational-age (LGA) (birth weight > 90th percentile), an indicator of fetal overgrowth, is associated with altered fetal insulin sensitivity and β-cell function.Study Design, Population, and OutcomesIn the Design, Development, and Discover birth cohort in Canada, we studied 106 pairs of LGA and optimal-for-gestational-age (OGA; birth weight, 25th to 75th percentiles) infants matched by maternal ethnicity, smoking status, and gestational age. Cord plasma glucose-to-insulin ratio was used as an indicator of fetal insulin sensitivity, and proinsulin-to-insulin ratio was used as an indicator of β-cell function. Cord plasma leptin and high-molecular-weight (HMW) adiponectin concentrations were measured.ResultsComparisons of infants who were born LGA vs OGA, adjusted for maternal and newborn characteristics, showed that cord blood insulin, proinsulin, and leptin concentrations were significantly higher, whereas HWM adiponectin concentrations were similar. Glucose-to-insulin ratios were significantly lower (15.4 ± 28.1 vs 22.0 ± 24.9; P = 0.004), and proinsulin-to-insulin ratios significantly higher (0.73 ± 0.82 vs 0.60 ± 0.78; P = 0.005) in LGA vs OGA newborns, indicating lower insulin sensitivity and β-cell function in LGA newborns. These significant differences were almost unchanged after further adjustment for cord blood adiponectin levels but disappeared upon additional adjustment for cord blood leptin levels.ConclusionsThis study demonstrates that LGA may be associated with decreases in both fetal insulin sensitivity and β-cell function. The alterations appear to be linked to elevated leptin levels.

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.

Aim Gestational diabetes mellitus is a common complication of pregnancy. Long-chain polyunsaturated fatty acids (LCPUFA) are essential for fetal neurodevelopment. Docosahexaenoic acid (DHA) is the predominant n–3 LCPUFA in the brain and retina. Circulating absolute concentrations of total n–3 and n–6 LCPUFAs rise during normal pregnancy. It remains unclear whether gestational diabetes may affect the normal rise in circulating concentrations of LCPUFAs in the third trimester of pregnancy – a period of rapid fetal neurodevelopment. This study aimed to address this question. Methods In a prospective singleton pregnancy cohort, fatty acids in fasting plasma total lipids were measured at 24–28 and 32–35 weeks of gestation in women with (n = 24) and without gestational diabetes mellitus (n = 116). Fatty acid desaturase activity indices were estimated by relevant product-to-precursor fatty acid ratios. Dietary nutrient intakes were estimated by a food frequency questionnaire. Results Plasma absolute concentrations of total n–6 LCPUFAs rose significantly between 24–28 and 32–35 weeks of gestation in women with or without gestational diabetes, whereas total n–3 LCPUFAs and DHA concentrations rose significantly only in women without gestational diabetes (all P < 0.01). Delta–5 desaturase indices (20:4n–6/20:3n–6) were similar, but delta–6 desaturase indices (18:3n–6/18:2n–6) were significantly lower in women with gestational diabetes at 32–35 weeks of gestation. Dietary intakes of all fatty acids were comparable. Conclusion The normal rise in circulating absolute concentrations of DHA and total n–3 LCPUFAs in the third trimester of pregnancy may be compromised in gestational diabetes, probably due to impaired synthesis or mobilization rather than dietary intake difference.

The metabolic health effects of vitamin A and E nutritional status in early life are largely unknown. We assessed whether vitamin A and vitamin E nutritional status may affect circulating leptin, adiponectin, insulin-like growth factor (IGF)-I and IGF-II levels in early life in humans. In a singleton birth cohort (n = 248), vitamin A and E nutritional status in fetuses/newborns were assessed by cord plasma concentrations of retinol, β-carotene, α- and γ-tocopherols. The primary outcomes were cord plasma leptin, adiponectin, IGF-I and IGF-II concentrations. Cord plasma retinol was significantly positively correlated to IGF-I in girls (r = 0.42, P P = 0.11). Adjusting for maternal and newborn’s characteristics, one log unit increase in cord plasma retinol was associated with a 28.0% (95% CI: 11.1–47.5%) increase in IGF-I in girls (P P = 0.75). One log unit increment in cord plasma α-tocopherol was associated with a 6.6% (0.4–12.3%) decrease in adiponectin (P = 0.04), while one log unit increment in cord plasma γ-tocopherol was associated with a 21.2% (4.7–34.8%) decrease in leptin (P = 0.01). There may be a sex-specific association between retinol and IGF-I, a negative association between α-tocopherol and adiponectin, and a negative association between γ-tocopherol and leptin in early life in humans.

Objectives To compare third-trimester ultrasound screening methods to predict small-for-gestational age (SGA), and to evaluate the impact of the ultrasound–delivery interval on screening performance. Methods In this prospective study, data were collected from a multicenter singleton cohort study investigating the links between various exposures during pregnancy with birth outcome and later health in children. We included women, recruited in the first trimester, who had complete outcome data and had undergone third-trimester ultrasound examination. Demographic, clinical and biological variables were also collected from both parents. We compared prediction of delivery of a SGA neonate (birth weight < 10th percentile) by the following methods: abdominal circumference (AC) Z-score based on Hadlock curves (Hadlock AC), on INTERGROWTH-21st Project curves (Intergrowth AC) and on Salomon curves (Salomon AC); estimated fetal weight (EFW) Z-score based on Hadlock curves (Hadlock EFW) and on customized curves from Gardosi (Gardosi EFW); and fetal growth velocity based on change in AC between second and third trimesters (FGVAC). We also assessed the following ultrasound–delivery intervals: ≤ 4 weeks, ≤ 6 weeks and ≤ 10 weeks. Results Third-trimester ultrasound was performed in 1805 patients with complete outcome data, of whom 158 (8.8%) delivered a SGA neonate. Ultrasound examination was at a median gestational age of 32 (interquartile range, 31–33) weeks. The ultrasound–delivery interval was ≤ 4 weeks in 17.2% of cases, ≤ 6 weeks in 48.1% of cases and ≤ 10 weeks in 97.3% of cases. Areas under the receiver–operating characteristics curve (AUC) were 0.772 for Salomon AC, 0.768 for Hadlock EFW, 0.766 for Hadlock AC, 0.765 for Intergrowth AC, 0.708 for Gardosi EFW and 0.674 for FGVAC (all P < 0.0001). The screening method with the highest AUC for an ultrasound–delivery interval ≤ 4 weeks was Salomon AC (AUC, 0.856), ≤ 6 weeks was Hadlock AC (AUC, 0.824) and ≤ 10 weeks was Salomon AC (AUC, 0.780). At a fixed 10% false-positive rate, the best detection rates were 60.0%, 54.1% and 42.1% for intervals ≤ 4, ≤ 6 and ≤ 10 weeks, respectively. Conclusion Third-trimester ultrasound measurements provide poor to moderate prediction of SGA. A shorter ultrasound–delivery interval provides better prediction than does a longer interval. Further studies are needed to test the effect of including maternal or biological characteristics in SGA screening. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

To investigate the association of air pollution with maternal stress during pregnancy, we enrolled 1,931 women during mid-to-late pregnancy in Shanghai in 2010. The “Life-Event Scale for Pregnant Women” and “Symptom-Checklist-90-Revised Scale” (SCL-90-R) were used to evaluate life event stress and emotional stress, respectively. Air pollution data were collected for each district where pregnant women lived during pregnancy. We associated ambient air pollution with stress scores using multivariable logistic regression models. After adjusting for relevant covariates, an interquartile-range (IQR) increase in sulphur-dioxide (SO2) (OR = 1.30, 95% CI: 1.11–1.52) and particulate-matter with an aerodynamic-diameter 10) (OR = 1.16, 95% CI: 1.02–1.34) concentrations on the recruitment day, and in the 5-day moving average concentrations of nitrogen-dioxide (NO2) (OR = 1.34, 95% CI: 1.05–1.70) were associated with high Global-Severity-Indices (P75-P100) of the SCL-90-R. These associations were stronger among women bearing high levels (P25-P100) of air pollutants than among women experiencing low levels (P1-P25) of pollutants. The stronger associations and higher levels of pollutants were observed in the cool season than in the warm season. SO2 increases on the recruitment day were also associated with an increased risk of high depression scores (P75-P100). Our findings supported a dose-dependent association between air pollution and emotional stress during pregnancy.

To explore the hypothesis that female fetus is associated with greater maternal insulin resistance during pregnancy.In a singleton pregnancy cohort study (n = 299), we compared maternal insulin resistance according to fetal sex, based on plasma biomarkers from a 50-g 1-h oral glucose tolerance test at 24-28 weeks gestation. The primary outcome was plasma glucose-to-insulin ratio. Other outcomes included plasma proinsulin-to-insulin ratio, and insulin, proinsulin, leptin, adiponectin and insulin-like growth factor I and II concentrations.After adjusting for maternal race, age, parity, education, pre-pregnancy BMI, smoking and alcohol use, history of gestational diabetes, and gestational age at blood sampling, plasma insulin concentrations were significantly higher (mean ± sd: 66.4 ± 50.5 vs. 51.0 ± 46.1 mU/l; adjusted P = 0.001), and glucose-to-insulin ratios significantly lower (2.60 ± 2.03 vs. 3.77 ± 4.98 mg/dl/mU/l; adjusted P = 0.002) in women bearing a female vs those bearing a male fetus, despite similar glucose levels (116.4 ± 27.2 vs. 117.0 ± 31.9 mg/dl; adjusted P = 0.92).There were no significant differences in proinsulin-to-insulin ratios, or leptin, adiponectin, insulin-like growth factor I and insulin-like growth factor II concentrations by fetal sex.Female fetus may be associated with greater maternal insulin resistance during pregnancy.

Large-for-gestational-age (LGA) babies have a higher risk of metabolic disease later in life, and their postnatal growth in early childhood may be associated with long-term adverse outcomes. This study aimed to determine childhood health outcomes of term LGA babies with different growth patterns. Data were obtained from the US Collaborative Perinatal Project for the years between 1959 and 1976. The growth trajectories of 3,316 term LGA babies were identified and odds ratios of obesity, growth restriction, low intelligence quotient (IQ), and high blood pressure (HBP) were calculated by logistic regression. Compared with term appropriate-for-gestational-age infants, term LGA babies without catch-down growth had increased risks of obesity (adjusted odds ratio (aOR) = 6.37, 95% confidence interval (CI): 5.24, 7.73) and HBP (aOR = 1.67, 95% CI: 1.37, 2.03). Those with high catch-down growth had higher risks of growth restriction (aOR = 2.21, 95% CI: 1.66, 2.95) and low IQ (aOR = 1.61, 95% CI: 1.04, 2.49). Nevertheless, infants with small catch-down growth had lower risks of obesity (aOR = 0.78, 95% CI: 0.63, 0.95), growth restriction (aOR = 0.28, 95% CI: 0.17, 0.46), low IQ (aOR = 0.66, 95% CI: 0.41, 1.06), and HBP (aOR = 0.89, 95% CI: 0.77, 1.04). According to our data, term LGA infants with small catch-down growth had no increased risks of adverse outcomes.

Background: Inuit and First Nations populations have higher rates of stillbirth than non-Aboriginal populations in Canada do, but little is known about the timing and cause of stillbirth in Aboriginal populations. We compared gestational age– and cause-specific stillbirth rates in Inuit and First Nations populations with the rates in the non-Aboriginal population in Quebec. Methods: Data included singleton stillbirths and live births at 24 or more gestational weeks among Quebec residents from 1981 to 2009. We calculated odds ratios (ORs), rate differences and 95% confidence intervals (CIs) for the retrospective cohort of Inuit and First Nations births relative to non-Aboriginal births using fetuses at risk (i.e., ongoing pregnancies) as denominators and adjusting for maternal characteristics. The main outcomes were stillbirth by gestational age (24–27, 28–36, ≥ 37 wk) and cause of death. Results: Rates of stillbirth per 1000 births were greater among Inuit (6.8) and First Nations (5.7) than among non-Aboriginal (3.6) residents. Relative to the non-Aboriginal population, the risk of stillbirth was greater at term (≥ 37 wk) than before term for both Inuit (OR 3.1, 95% CI 1.9 to 4.8) and First Nations (OR 2.6, 95% CI 2.1 to 3.3) populations. Causes most strongly associated with stillbirth were poor fetal growth, placental disorders and congenital anomalies among the Inuit, and hypertension and diabetes among the First Nations residents. Interpretation: Stillbirth rates in Aboriginal populations were particularly high at term gestation. Poor fetal growth, placental disorders and congenital anomalies were important causes of stillbirth among the Inuit, and diabetic and hypertensive complications were important causes in the First Nations population. Prevention may require improvements in pregnancy and obstetric care.

To estimate the associations between maternal vitamin D status and adverse pregnancy outcomes.We searched electronic databases of the human literature in PubMed, EMBASE and the Cochrane Library up to October, 2012 using the following keywords: "vitamin D" and "status" or "deficiency" or "insufficiency" and "pregnancy". A systematic review and meta-analysis were conducted on observational studies that reported the association between maternal blood vitamin D levels and adverse pregnancy outcomes including preeclampsia, gestational diabetes mellitus (GDM), preterm birth or small-for-gestational age (SGA).Twenty-four studies met the inclusion criteria. Women with circulating 25-hydroxyvitamin D [25(OH)D] level less than 50 nmol/l in pregnancy experienced an increased risk of preeclampsia [odds ratio (OR) 2.09 (95% confidence intervals 1.50-2.90)], GDM [OR 1.38 (1.12-1.70)], preterm birth [OR 1.58 (1.08-2.31)] and SGA [OR 1.52 (1.08-2.15)].Low maternal vitamin D levels in pregnancy may be associated with an increased risk of preeclampsia, GDM, preterm birth and SGA.

Polymorphisms in endothelial nitric oxide synthase (eNOS) gene may affect the risk of preeclampsia. This systematic review aimed to provide an updated review of the literature to better understand the association between the eNOS gene polymorphisms and the risk of preeclampsia. We searched electronic databases of the human literature in PubMed, EMBASE, and the Cochrane Library up to July 2012. A meta-analysis was conducted on the association of eNOS G894T, T786C, and intron 4b/a polymorphisms with preeclampsia using (1) allele contrast, (2) recessive, (3) dominant, and (4) additive models. Thirty-three studies comprising 10,671 participants met the inclusion criteria. There was statistically significant association between the G894T variant and increased risk of preeclampsia (TT versus TG + GG: odds ratio 1.43, 95% confidence interval: 1.13 to 1.82). However, no significant risk of preeclampsia was observed either in the T786C or the intron 4b/a polymorphism. Homozygosity TT in eNOS G894T variant is significantly associated with an increased risk of preeclampsia.

Objective: It remains uncertain whether leptin and adiponectin levels are correlated in maternal vs. fetal circulations. Little is known about whether leptin and adiponectin affect insulin sensitivity during fetal life. Design and Methods: In a prospective singleton pregnancy cohort (n = 248), we investigated leptin and adiponectin concentrations in maternal (at 24-28 and 32-35 weeks of gestation) and fetal circulations, and their associations with fetal insulin sensitivity (glucose/insulin ratio, proinsulin level). Results: Comparing concentrations in cord vs. maternal blood, leptin levels were 50% lower, but adiponectin levels more than doubled. Adjusting for gestational age at blood sampling, consistent and similar positive correlations (correlation coefficients: 0.31-0.34, all P 0.4) levels). Similar associations were observed in nondiabetic full-term pregnancies (n = 211). Conclusions: The results consistently suggest a maternal impact on fetal leptin and adiponectin levels, which may be an early life pathway in maternal-fetal transmission of the propensity to obesity and insulin resistance.

Objective To determine the accuracy of placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and inhibin A in singleton and multiple-gestation pregnancies for predicting preeclampsia (PE) and small for gestational age (SGA). Study Design A prospective cohort nested in a randomized controlled trial of antioxidant supplementation for the prevention of PE. Plasma biomarkers were evaluated at 12 to 18 (visit 1) and 24 to 26 (visit 2) weeks' gestation and expressed as adjusted multiples of the median. Results Multiple-gestation pregnancy (74/772) had a significant impact on all biomarkers' levels. PlGF was the best predictor of PE and SGA. At a 10% false-positive rate, PlGF at visit 1 had 21% sensitivity for predicting PE in singleton versus 60% in multiple-gestation pregnancies. PlGF at visit 1 had a 31% sensitivity in singleton and 27% in multiple-gestation pregnancies for SGA prediction. Conclusion PlGF level was a good predictor of subsequent PE as early as 12 to 18 weeks in multiple-gestation pregnancies but was not clinically useful enough to be used as a single marker.

Background Cree births in Quebec are characterized by the highest reported prevalence of macrosomia (~35%) in the world. It is unclear whether Cree births are at greater elevated risk of perinatal and infant mortality than other First Nations relative to non-Aboriginal births in Quebec, and if macrosomia may be related. Methods This was a population-based retrospective birth cohort study using the linked birth-infant death database for singleton births to mothers from Cree (n = 5,340), other First Nations (n = 10,810) and non-Aboriginal (n = 229,960) communities in Quebec, 1996-2010. Community type was ascertained by residential postal code and municipality name. The primary outcomes were perinatal and infant mortality. Results Macrosomia (birth weight for gestational age >90th percentile) was substantially more frequent in Cree (38.0%) and other First Nations (21.9%) vs non-Aboriginal (9.4%) communities. Comparing Cree and other First Nations vs non-Aboriginal communities, perinatal mortality rates were 1.52 (95% confidence intervals 1.17, 1.98) and 1.34 (1.10, 1.64) times higher, and infant mortality rates 2.27 (1.71, 3.02) and 1.49 (1.16, 1.91) times higher, respectively. The risk elevations in perinatal and infant death in Cree communities attenuated after adjusting for maternal characteristics (age, education, marital status, parity), but became greater after further adjustment for birth weight (small, appropriate, or large for gestational age). Conclusions Cree communities had greater risk elevations in perinatal and infant mortality than other First Nations relative to non-Aboriginal communities in Quebec. High prevalence of macrosomia did not explain the elevated risk of perinatal and infant mortality in Cree communities.

Background The optimal mode of delivery in twin pregnancies remains controversial. A recent randomized trial did not find any benefit of planned cesarean vs. vaginal delivery at 32–38 weeks gestation, but the trial was not powered to detect a moderate effect. We aimed to evaluate the impact of cesarean delivery on perinatal mortality and severe neonatal morbidity in twin pregnancies at ≥32 weeks through a large database exploration approach with the power to detect moderate risk differences. Methods In a retrospective birth cohort study using the U.S. matched multiple births, 1995–2000 (the available largest multiple birth dataset), we compared perinatal outcomes in twins (n = 181,810 pregnancies) delivered at 32–41 weeks gestation without congenital anomalies. The primary outcome was a composite of perinatal death and severe neonatal morbidity. Cox regression was used to estimate the adjusted hazard ratio (aHR) controlling for the propensity to cesarean delivery, fetal characteristics (sex, birth weight, birth weight discordance, same-sex twin or not) and twin-cluster level dependence. Prospective risks were calculated using the fetuses-at-risk denominators. Results The overall rates of the primary outcome were slightly lower in intended cesarean (6.20%) vs. vaginal (6.45%) deliveries. The aHRs of the primary outcome were in favor of vaginal delivery at 32 (aHR = 1.06, p = 0.03) or 33 (aHR = 1.22, p

It remains uncertain whether maternal IGF-I is associated with fetal growth. Little is known about the role of maternal IGF-II in fetal growth and whether IGF-I or IGF-II is implicated in fetal hypertrophy in gestational diabetes.The objective of the study was to assess maternal and fetal IGF-I and IGF-II levels in association with fetal growth and gestational diabetes. STUDY DESIGN, POPULATION, AND OUTCOMES: A singleton pregnancy cohort study (n = 307). The primary outcome was birth weight.Maternal plasma concentrations increased by an average of 55.4% for IGF-I and 11.8% for IGF-II between 24-28 and 32-35 weeks of gestation. The maternal IGF-I but not IGF-II level was correlated with birth weight and placental weight. Adjusting for maternal and infant characteristics, each SD increase in maternal IGF-I level at 24-28 weeks was associated with a 75-g (95% confidence intervals 29-120) increase in birth weight, a 20-g (7-33) increase in placental weight, and a 1.91-fold (1.28-2.86) higher odds of macrosomia (birth weight90th percentile). Similar associations were observed for the maternal IGF-I level at 32-35 weeks. Maternal and fetal IGF-I (but not IGF-II) levels were significantly higher in gestational diabetic than in nondiabetic pregnancies. The significantly higher birth weight z scores in diabetic pregnancies disappeared after adjusting for maternal and fetal IGF-I levels alone.Higher maternal IGF-I (but not IGF-II) levels at mid- and late gestation may indicate greater placental and fetal growth. IGF-I (but not IGF-II) may be implicated in fetal hypertrophy in gestational diabetes.

Objective: Whether vitamin D deficiency in pregnancy is a cause of pre-eclampsia remains controversial. Most previous studies to date have assessed exposure at only one time-point in pregnancy. The authors assessed longitudinal vitamin D status during pregnancy and the risk of pre-eclampsia.

In vitro cell model studies have shown that oxidative stress may affect beta-cell function. It is unknown whether oxidative stress may affect metabolic health in human fetuses/newborns. In a singleton pregnancy cohort (n = 248), we studied maternal (24–28 weeks gestation) and cord plasma biomarkers of oxidative stress [malondialdehyde (MDA), F2-isoprostanes] in relation to fetal metabolic health biomarkers including cord plasma glucose-to-insulin ratio (an indicator of insulin sensitivity), proinsulin-to-insulin ratio (an indicator of beta-cell function), insulin, IGF-I, IGF-II, leptin, adiponectin and ghrelin concentrations. Strong positive correlations were observed between maternal and cord plasma biomarkers of oxidative stress (r = 0.33 for MDA, r = 0.74 for total F2-isoprostanes, all p

In order to overcome the disadvantages which existed in traditional control system of electro-excavator,such as backward technology,large noise,inconvenient operation,low dynamic efficiency,high cost and so on,the structure and the working principle of DC speed control system were firstly analyzed.Then core board UTU2440-F-V4.5 was adopted to design a digital controller, which can produce 12 triggering pulses to trigger 12 GTOs and monitor the work condition of electro-excavator.Furthermore,synchronous signal detection circuit,work parameter detection circuit and triggering pulse circuit were discussed in detail.Finally,good performance of speed,convenient maintenance and significant energy saving of DC speed control system were proved by experiments.

Diabet. Med. 28, 1068–1073 (2011) Abstract Aim We tested the hypothesis that diabetes in pregnancy may differentially affect neonatal outcomes in twin vs. singleton pregnancies. Methods In a retrospective cohort analysis of twins (n = 422 068) and singletons (n = 14 298 367) born in the USA from 1998 to 2001, we evaluated the adjusted odds ratios of adverse neonatal outcomes comparing diabetic vs. non-diabetic pregnancies, controlling for maternal characteristics. Primary outcomes include macrosomia (birthweight for gestational age > 90th percentile), congenital anomalies, low 5-min Apgar score (