The mediation of the placenta on the association between maternal ambient temperature exposure and birth weight.

Studies have indicated that exposure to low and high temperatures during pregnancy negatively affects fetal development. The placenta plays vital functions in fetal development and could also be impacted by suboptimal temperatures. However, whether the placenta mediates the association between suboptimal temperature and birth weight is unknown. Our study aims to evaluate the association between ambient temperature and birth weight as well as the mediation effect of the placenta. A prospective birth cohort study was conducted during 2017-2020 in Guangzhou, China (n = 3349 participants). We defined extreme temperature exposure during the whole pregnancy by using different thresholds, including low temperatures (< 25th, < 15th, < 10th, < 5th percentiles), and high temperatures (> 75th, > 85th, > 90th, > 95th percentiles). Three different approaches (generalized linear model, inverse probability weighting, and doubly robust model) were applied to estimate the effects of low/high temperatures on birth weight and placental indicators, including placental weight, placental volume, and placental-to-birth weight ratio (PFR), respectively. We observed that both low and high ambient temperatures during the whole pregnancy were associated with lower birth weight and negative changes in placental indicators. The estimated lower mean birth weight ranged from -158 g (95 % CI: -192 g, -123 g) to -363 g (95 % CI: -424 g, -301 g) for low temperatures and from -97 g (95 % CI: -135 g, -59 g) to -664 g (95 % CI: -742 g, -585 g) for high temperatures. In mediation analyses, placental weight mediated 28.79 % to 40.47 % and 48.22 % to 54.38 % of the association of low and high temperatures with birth weight, respectively. The findings suggest that placental weight may mediate the association between ambient temperature exposure and birth weight.

Potential occupational exposure of parents to endocrine disrupting chemicals, adverse birth outcomes, and the modification effects of multi-vitamins supplement and infant sex.

BACKGROUND: Maternal occupational exposure to endocrine disrupting chemicals (EDCs) may have adverse effect on birth outcomes. However, little is known about paternal EDCs exposure and the combined effect of parental exposure on birth outcomes. OBJECTIVES: To assess the effects of both maternal and paternal occupational EDCs exposure on adverse birth outcomes, and further explore if multi-vitamins supplement and infant sex modify the association. METHODS: We conducted a prospective cohort study of 5421 mother-father-newborn groups in Guangzhou, China. A questionnaire informed by a job exposure matrix (JEM) was applied to collect parental occupational EDCs exposure based on the type of work performed. We used logistic regression to estimate association between parental EDCs exposure and birth outcomes (including preterm birth (PTB), low birth weight (LBW), birth defects and congenital heart defects (CHD)). Stratified analyses and Cochran Q tests were performed to assess the modifying effect of maternal multi-vitamins supplement use and infant sex. RESULTS: Compared with mothers unexposed, we found that mothers those exposed to EDCs were associated with increased odds of birth defects (aOR=1.70, 95% confidence interval (CI): 1.10-2.62), especially for those exposed for > 1.5 years (aOR= 3.00, 95% CIs: 1.78-5.03), or those with directly occupational exposed to EDCs (aOR= 2.94, 95% CIs: 1.72-5.04). Maternal exposure for > 1.5 years and direct exposure increased the risk of CHD, with aORs of 2.47 (1.21-5.02) and 2.79 (1.37-5.69), respectively. Stronger adverse effects were also observed when mothers and fathers were both exposed to EDCs. Paternal occupational EDCs exposure and exposure ≤ 1.5 years was associated with increased odds of LBW, with aORs of 2.14 (1.63-2.79) and 1.54 (1.10-2.15), respectively. When stratified by multi-vitamins supplement and infant sex, we observed slightly stronger effects for maternal exposure on birth defects/CHD as well as paternal EDCs exposure on PTB and LBW, among those without multi-vitamins supplement and among male babies, although the modification effects were not significant. CONCLUSION: Maternal exposure to EDCs was associated with greater odds of birth defects and CHD, while paternal exposure was mainly associated with greater odds of LBW. These effects tend to be stronger among mothers without multi-vitamins supplement and among male babies.

Assessing the effects of non-optimal temperature on risk of gestational diabetes mellitus in a cohort of pregnant women in Guangzhou, China.

Previous observational studies have shown that exposure to ambient temperature and air pollution were associated with the incidence of gestational diabetes mellitus (GDM). However, the susceptible time window of non-optimal temperature on GDM is still unknown, and the interaction with air pollution has not been examined. We conducted a prospective cohort study in Guangzhou, China to investigate the windows of susceptibility of temperature extremes and variability on the risk of GDM and to explore any interaction effect with air pollution. Daily maximum (Tmax), minimum temperature (Tmin) and diurnal temperature range (DTR) were obtained from Guangdong Meteorological Service. Distributed lag non-linear models with a logistic regression were applied to assess the effect of temperature extremes and DTR in different weeks of gestation on GDM. To examine the interaction effect, relative excess risk due to interaction index, attributable proportion and synergy index were calculated. There were 5,165 pregnant women enrolled, of which 604 were diagnosed with GDM (11.7%). Compared with a reference temperature (50th percentile of Tmax), we found that extreme high temperature (99th percentile of Tmax) exposure during 21st and 22nd gestational weeks was associated with an increased risk of GDM. Extreme low temperature (1st percentile of Tmax) exposure during 14th to 17th weeks increased the risk of GDM. We observed that per 1 °C increment of DTR during 21st to 24th weeks was associated with an elevated GDM risk. No interaction effect of temperature extremes or variability with air pollution on GDM were observed. Our results suggested that non-optimal temperature is an independent risk factor of GDM. The time window of susceptibility for extreme temperatures and DTR exposure on the risk of GDM generally occurred in second trimester of pregnancy. In the context of climate change, our study has important implications for reproductive health and justifies more research in different climate zones.

Ensembled deep learning model outperforms human experts in diagnosing biliary atresia from sonographic gallbladder images.

It is still challenging to make accurate diagnosis of biliary atresia (BA) with sonographic gallbladder images particularly in rural area without relevant expertise. To help diagnose BA based on sonographic gallbladder images, an ensembled deep learning model is developed. The model yields a patient-level sensitivity 93.1% and specificity 93.9% [with areas under the receiver operating characteristic curve of 0.956 (95% confidence interval: 0.928-0.977)] on the multi-center external validation dataset, superior to that of human experts. With the help of the model, the performances of human experts with various levels are improved. Moreover, the diagnosis based on smartphone photos of sonographic gallbladder images through a smartphone app and based on video sequences by the model still yields expert-level performances. The ensembled deep learning model in this study provides a solution to help radiologists improve the diagnosis of BA in various clinical application scenarios, particularly in rural and undeveloped regions with limited expertise.

Evaluation of interactive effects between paternal alcohol consumption and paternal socioeconomic status and environmental exposures on congenital heart defects.

BACKGROUND: While the maternal risk factors on congenital heart defects (CHDs) have often been assessed, paternal contribution to CHDs, especially the joint effects of paternal risk factors on CHDs remain unknown. This study examined the major impacts of paternal alcohol consumption and its interaction (on multiplicative and additive scales) with paternal socioeconomic status (SES) and environmental exposures on CHDs in China. METHODS: A population-based case-control study involving 4,726 singleton CHDs cases and 4,726 controls (without any malformation and matched on hospital, gender, and gestational age) was conducted in Guangdong, China, 2004-2014. Information on parental demographics, behavioral patterns, disease/medication, and environmental exposures (3 months before pregnancy) was collected through face-to-face interviews. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) while controlling for all parental factors. RESULTS: Paternal alcohol consumption was associated with an increased OR of CHDs (adjusted OR = 2.87, 95% CI: 2.25-3.65). Additionally, paternal smoking, industry occupation, organic solvent contact, virus infection and antibiotic use, living in rural areas, low household income, and migrant status were significantly associated with CHDs (ORs ranged: 1.42-4.44). Significant additive or multiplicative interactions were observed between paternal alcohol consumption and paternal smoking, industrial occupation, and low income on any CHDs (interaction contrast ratio [ICR] = 4.72, 95% CI: 0.96-8.47] and septal defects (ICRs ranged from 2.04 to 2.79, p < .05). CONCLUSIONS: Paternal alcohol consumption and multiple paternal factors were significantly associated with CHDs in China. Paternal smoking and low SES factors modified paternal alcohol consumption-CHDs relationships. Further studies are needed to confirm these findings.

Ambient air pollution exposure and gestational diabetes mellitus in Guangzhou, China: A prospective cohort study.

BACKGROUND: Evidence concerning the effect of ambient air pollution exposure on gestational diabetes mellitus (GDM) is limited. No published studies have examined maternal weekly air pollution exposure and GDM, and the possible effect modification by folic acid supplementation has not been assessed. OBJECTIVES: To evaluate the association between air pollution exposure and GDM at trimester and weekly levels, and to explore the potential effect modification by folic acid supplementation. METHODS: A total of 5421 pregnant women were recruited during 2011-2014 in Guangzhou, China. Daily PM2.5, PM10, SO2 and NO2 levels were collected from 10 monitoring stations. Individual's exposure during pregnancy was estimated using inverse-distance weighting approach. Binary logistic regression was used to examine the trimester-specific association between air pollution exposure and GDM. Distributed lag models (DLMs) were applied to estimate maternal weekly air pollution exposure and GDM. Stratified analyses by folic acid supplementation and interaction test were performed. RESULTS: The GDM incidence was 11.69%. An interquartile range (IQR) increase in first trimester SO2 was associated with increased GDM risk in the single pollutant model, the adjusted odds ratio (aOR) and 95% confidence interval (CI) was 1.22 (1.02-1.47). In DLMs, an IQR increase in SO2 during 4th to 10th gestational weeks was associated with increased GDM risk, with the strongest effect in the 7th gestational week. When stratified by maternal folic acid supplementation, first trimester exposure to SO2 was associated with increased GDM risk among women taking folic acid supplements (aOR = 1.25, 95% CI: 1.03-1.53) and P value for interaction was 0.13. No significant effects were observed for PM2.5, PM10 and NO2. CONCLUSION: First trimester exposure to SO2 was associated with increased GDM risk, especially during the 4th to 10th gestational weeks. The effect might be stronger among women taking folic acid supplements.

Interaction of Air Pollutants and Meteorological Factors on Birth Weight in Shenzhen, China.

BACKGROUND: This study aimed to assess if air pollutants and meteorological factors synergistically affect birth outcomes in Shenzhen, China. METHODS: A total of 1,206,158 singleton live births between 2005 and 2012 were identified from a birth registry database. Daily average measurements of particulate matter ≤10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ambient air temperature (T), and dew point temperature (Td), a marker of humidity, were collected. Multivariable logistic regression models were used to evaluate associations between air pollution and small for gestational age (SGA), and full-term low birth weight (TLBW). We classified births into those conceived in the warm (May-October) and cold seasons (November-April) and then estimated interactions between air pollutants and meteorological factors. RESULTS: An interquartile range (IQR) increase in PM10 exposure during the first trimester (23.1 µg/m) and NO2 during both the first and second trimesters (15.1 and 13.4 µg/m) was associated with SGA and TLBW risk; odds ratios ranged from 1.01 (95% confidence interval [CI] = 1.00, 1.02) to 1.09 (1.07, 1.12). We observed interactive effects of both air temperature and humidity on PM10 and SGA for newborns conceived in the warm season. Each IQR increase in PM10 (11.1 µg/m) increased SGA risk by 90% (95% CI = 19%, 205%), 29% (23, 34%), 61% (10, 38%), and 26% (21, 32%) when T < 5th percentile, 5th < T < 95th percentile, Td < 5th percentile, and 5th < Td < 95th percentile, respectively. CONCLUSIONS: Our study found evidence of an interactive effect of air temperature and humidity on the relationship between PM10 exposure and SGA among newborns conceived in the warm season (May-October). Relatively low air temperature or humidity exacerbated the effects of PM10.

Two successive cases of fetal harlequin ichthyosis: A case report.

Harlequin ichthyosis (HI) is a genetic skin disorder characterized by thickening and splitting of the skin. In fetuses presenting with the disorder, the mortality rate is markedly high. A number of fetal HI cases have been documented. The present study reports a case of a pregnant woman who underwent two successive pregnancies at the ages of 35 and 36, respectively, with both fetuses presenting with HI. The first fetus was delivered alive though succumbed shortly after birth, while the second fetus was stillborn and birthed by induced labor. The fetuses exhibited typical features of fetal HI, including thick, platelike scaling and fissuring, which act as a nidus for infection. The present study is the first to report two cases of fetal HI from successive pregnancies in the same woman. Improved understanding of the genetic basis of HI indicates that genetic screening for candidate gene mutations related to HI, particularly mutations in the adenosine triphosphate binding-cassette transporter ABCA12, may prove beneficial in prenatal diagnosis. Establishing methods for early diagnosis of fetal HI may reduce the physical and mental distress to parents and relatives.

Effects of prenatal exposure to air pollution on preeclampsia in Shenzhen, China.

The impact of ambient air pollution on pregnant women is a concern in China. However, little is known about the association between air pollution and preeclampsia and the potential modifying effects of meteorological conditions have not been assessed. This study aimed to assess the effects of prenatal exposure to air pollution on preeclampsia, and to explore whether temperature and humidity modify the effects. We performed a retrospective cohort study based on 1.21 million singleton births from the birth registration system in Shenzhen, China, between 2005 and 2012. Daily average measurements of particulate matter <10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), air temperature (T), and dew point (Td) were collected. Logistic regression models were performed to estimate associations between air pollution and preeclampsia during the first and second trimesters, and during the entire pregnancy. In each time window, we observed a positive gradient of increasing preeclampsia risk with increasing quartiles of PM10 and SO2 exposure. When stratified by T and Td in three categories (<5th, 5th -95th, and >95th percentile), we found a significant interaction between PM10 and Td on preeclampsia; the adverse effects of PM10 increased with Td. During the entire pregnancy, there was a null association between PM10 and preeclampsia under Td < 5th percentile. Preeclampsia risk increased by 23% (95% CI: 19-26%) when 5th < Td < 95th percentile, and by 34% (16-55%) when Td > 95th percentile. We also found that air pollution effects on preeclampsia in autumn/winter seasons were stronger than those in the spring/summer. This is the first study to address modifying effects of meteorological factors on the association between air pollution and preeclampsia. Findings indicate that prenatal exposure to PM10 and SO2 increase preeclampsia risk in Shenzhen, China, and the effects could be modified by humidity. Pregnant women should limit air pollution exposure, particularly during humid periods.

Congenital heart defects of fetus after maternal exposure to organic and inorganic environmental factors: a cohort study.

OBJECTIVE: Maternal exposure to various contaminants has been reported to be correlated with congetinal heart defects (CHDs). In this study, the effect of maternal exposure to organic and inorganic environmental factors upon the incidence of CHDs was investigated. We conducted a retrospective birth cohort study of infants born in the Maternal and Child Health Hospital of Panyu District in Guangzhou. MATERIALS AND METHODS: A total of 5381 cases with complete medical records, including mothers, fathers, and infants, were enrolled. The relationship between maternal occupational exposure to hazardous substances and strong noise during pregnancy and CHDs was analyzed. Occupational exposure to hazardous substances increased the incidence of CHDs. RESULTS: Forty-eight of 145 mothers (33.1%) in the CHDs group worked in hazardous and strong noise factories, while the corresponding percentage mothers in the control group was 22.8% (1193/5236). The percentage of mothers with a history of contact with organic solvents and exposure to strong noise in the CHDs group was significantly higher than the control group. There was no significant difference in the histories of contact with heavy metals, high temperatures, and other extreme environments between two groups. CONCLUSIONS: Hazardous substances in factories, especially organic solvents, were identified as potential risk factors for CHDs. Besides, exposure to high noise also increased the incidence of CHDs.

The influence of maternal exposure history to virus and medicine during pregnancy on congenital heart defects of fetus.

Congenital heart disease (CHD) is the most common birth defect. It is due to dysfunction of the heart and great vessels during embryo development stage, or the channel was not closed after birth. This study focuses on investigating the influence of virus infection and medicine history during pregnancy on the incidence rate of CHD of fetus. We conducted a retrospective birth cohort study of infant born in the maternal and child health hospital of Fanyu district in Guangzhou. Five thousand three hundred eighty one cases with complete medical records, including mothers, fathers, and infants, were enrolled. The exposure history of mothers to virus and medicine from 6 months before pregnancy to prenatal examination was investigated, including mflu, mumps, measles, rubella, chickenpox, and hepatitis and antibiotics, tocolytic agent, anticonvulsants, antipyretic and analgesic, antitumor drug, folic acid supplement, and contraceptive. The relationship between virus infection and medicine history during pregnancy and CHD was analyzed. There was statistical difference between a normal group and a defected group in influenza infection and tocolytic agent and contraceptive pill. The exposure history to influenza and medicines, such as tocolytic agent and contraceptive pill, during pregnancy influenced the incidence rate of CHD of fetus.