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Objective: To determine the detection rate of chromosomal abnormalities and pregnancy outcomes in fetuses with intrauterine growth restriction. Study design A total of 151 fetal samples with intrauterine growth restriction were divided into the isolated fetal growth restriction (FGR) group, FGR group with structural malformation, and FGR group with non-structural malformation, according to ultrasound abnormalities. The enrolled patients were divided into an early onset FGR group (<32 weeks) and a late-onset FGR group (≥32 weeks). Chromosomal karyotype and microarray analyses were performed and pregnancy outcomes were monitored. Results The karyotypes of 122 patients were analyzed. Four patients exhibited abnormal chromosome numbers or structures. Variations in copy number were detected in 151 cases; 19 cases were found to have chromosomal abnormalities, with a positivity rate of 12.6 %. There was one trisomy in 18 cases, one trisomy in 21 cases, eight pathogenic copy number variations (CNVs), and nine CNVs of unknown clinical significance. The detection rate of FGR combined with structural malformation was significantly higher than that of isolated FGR group. The detection rate of FGR with structural malformations was significantly higher than that with non-structural malformations. The positive detection rate in the FGR group was similar to that in the FGR group with non-structural malformations, with no statistical significance. Chromosomal abnormalities were detected in 17 patients with early onset FGR, with a positivity rate of 13.8 %. Two cases of chromosomal abnormalities were detected in the late-onset FGR group, with a positive rate of 7.1 %, with no statistical significance. A total of 151 fetuses with FGR were followed up for pregnancy outcomes, resulting in 36 cases of pregnancy termination and 13 cases of loss to follow-up. Among the 102 delivered fetuses, six exhibited delayed growth and development, one presented with hypospadias, and another failed the hearing screening. The remaining 94 fetuses demonstrated normal growth and development. Conclusions This study confirms the value of CNV detection in fetuses and dynamic ultrasound monitoring for fetuses with intrauterine growth restriction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the association of the maternal serum albumin (MAlb) level with fetal growth and fetal growth restriction (FGR) risk in term-born singletons.Design: Prospective cohort study.Setting: Four hospital maternity units of the Tongji Maternal and Child Health Cohort study initiated from September 2013 to April 2016 at Wuhan City, in central China.Patient(s): A total of 3,065 mother-offspring pairs.Intervention(s): None.Main Outcome Measure(s): Fetal growth was evaluated by birth weight (BW) and birth length. Fetal growth restriction was defined as BW below the 10th percentile.Result(s): All MAlb levels were within the upper limit of normal. After adjustment for liver function parameters, inflammatory indicators, and others, a reverse U-shaped relationship between MAlb and fetal growth was observed. Specifically, BW increased significantly with an increasing MAlb level when the MAlb level was <36.1 g/L (per g/L: β = 36.8; 95% CI, 0.8, 72.7) but decreased with increasing the MAlb level when the MAlb level was >36.1 g/L (per g/L: β = -15.1; 95% CI, -21.2, -8.9). There was a similar association between MAlb and birth length. Furthermore, the adjusted odd ratios of FGR across increasing tertiles of the MAlb levels were 1.0 (reference), 1.1 (0.7, 1.8), and 1.7 (1.0, 2.6).Conclusion(s): There was a reverse U-shaped association between MAlb and fetal growth. A higher MAlb level was associated with an increased risk of FGR.Clinical Trial Registration Number: NCT03099837. [ABSTRACT FROM AUTHOR]

Objective: To predict fetal growth restriction (FGR) by whole-genome promoter profiling of maternal plasma.Design: Nested case-control study.Setting: Hospital-based.Population or Sample: 810 pregnancies: 162 FGR cases and 648 controls.Methods: We identified gene promoters with a nucleosome footprint that differed between FGR cases and controls based on maternal plasma cell-free DNA (cfDNA) nucleosome profiling. Optimal classifiers were developed using support vector machine (SVM) and logistic regression (LR) models.Main Outcome Measures: Genes with differential coverages in promoter regions through the low-coverage whole-genome sequencing data analysis among FGR cases and controls. Receiver operating characteristic (ROC) analysis (area under the curve [AUC], accuracy, sensitivity and specificity) was used to evaluate the performance of classifiers.Results: Through the low-coverage whole-genome sequencing data analysis of FGR cases and controls, genes with significantly differential DNA coverage at promoter regions (-1000 to +1000 bp of transcription start sites) were identified. The non-invasive 'FGR classifier 1' (CFGR 1) had the highest classification performance (AUC, 0.803; 95% CI 0.767-0.839; accuracy, 83.2%) was developed based on 14 genes with differential promoter coverage using a support vector machine.Conclusions: A promising FGR prediction method was successfully developed for assessing the risk of FGR at an early gestational age based on maternal plasma cfDNA nucleosome profiling.Tweetable Abstract: A promising FGR prediction method was successfully developed, based on maternal plasma cfDNA nucleosome profiling. [ABSTRACT FROM AUTHOR]

Early-onset preeclampsia (PE) is a severe condition with highest risk of perinatal complications. In current study, we compared PE severity, laboratory results and placental pathological lesions between early-onset PE with fetal growth restriction (PE + FGR) and appropriate gestational age (PE + AGA) neonates, with the aim to identify potential maternal risk factors associated with FGR. A retrospective case study was conducted in 304 PE women, and 31 cases with mild PE were excluded. 276 patients with severe PE were divided into PE + FGR (163, 59.1%) and PE + AGA (113, 40.9%) groups and underwent clinical analysis. 244 cases were further submitted for pathologic examinations to compare the differences of placental lesions between these two groups. As compared to PE + AGA, the maternal pre-pregnancy BMI (P = 0.003) and the rate of anemia (P = 0.004) were lower in PE + FGR; while the rate of severe low serum albumin (P = 0.020) was higher. Moreover, severe low serum albumin level (aOR = 2.43, P = 0.046) and abnormal uric acid (aOR = 2.19, P = 0.033) were positively correlated to the incidence of FGR, while pre-pregnancy BMI (aOR = 0.39, P = 0.001) and anemia (aOR = 0.33, P = 0.001) showed negative correlation. The placental examinations further showed positively correlation between chronic villitis (aOR = 4.32, P = 0.028) and FGR. Surprisingly, general measures of maternal illness severity failed to present any significant correlation to FGR, except for blood pressure, which showed negative correlation. For the first time, we studied a relatively large case series of Chinses early-onset PE women, and identified multiple factors associated with FGR incidence. Our study provided some opinions on clinal diagnosis and treatment for early-onset PE with FGR. [ABSTRACT FROM AUTHOR]

Previous studies have shown conflicting findings regarding the relationship between maternal vitamin D deficiency (VDD) and fetal growth restriction (FGR). We hypothesised that parathyroid hormone (PTH) may be an underlying factor relevant to this potential association. In a prospective birth cohort study, descriptive statistics were evaluated for the demographic characteristics of 3407 pregnancies in the second trimester from three antenatal clinics in Hefei, China. The association of the combined status of vitamin D and PTH with birth weight and the risk of small for gestational age (SGA) was assessed by a multivariate linear and binary logistic regression. We found that declined status of 25-hydroxyvitamin D is associated with lower birth weight (for moderate VDD: adjusted β = −49·4 g, 95 % CI −91·1, −7·8, P < 0·05; for severe VDD: adjusted β = −79·8 g, 95 % CI −127·2, −32·5, P < 0·01), as well as ascended levels of PTH (for elevated PTH: adjusted β = −44·5 g, 95 % CI −82·6, −6·4, P < 0·05). Compared with the non-VDD group with non-elevated PTH, pregnancies with severe VDD and elevated PTH had the lowest neonatal birth weight (adjusted β = −124·7 g, 95 % CI −194·6, −54·8, P < 0·001) and the highest risk of SGA (adjusted risk ratio (RR) = 3·36, 95 % CI 1·41, 8·03, P < 0·01). Notably, the highest risk of less Ca supplementation was founded in severe VDD group with elevated PTH (adjusted RR = 4·67, 95 % CI 2·78, 7·85, P < 0·001). In conclusion, elevated PTH induced by less Ca supplementation would further aggravate the risk of FGR in pregnancies with severe VDD through impaired maternal Ca metabolism homoeostasis. [ABSTRACT FROM AUTHOR]

Fetal growth restriction (FGR) is a major determinant of perinatal morbidity and mortality, with adverse long-term neurocognitive effects in childhood and adulthood. Prenatal exposure to environmental pollutants has been reported to be associated with FGR. Neonicotinoids (NEOs) are extensively used insecticides worldwide and are suggested to have embryonic and developmental neurotoxicity. However, the effects of NEOs exposure on FGR is unknown. We aimed to quantify the single and combined associations of maternal exposure to NEOs and FGR. We conducted a nested case-control study based on the Guangxi Zhuang Birth Cohort, China. A total of 387 with FGR cases and 1096 without- FGR controls were included between 2015 and 2018. Ten NEOs were measured by UPLC-MS from the maternal blood samples were pre-collected in the first trimester. After adjusting for potential confounders, multivariable logistic regressions, weighted quantile sum regression and quantile g-computation were performed for individual and NEOs mixtures. In the individual exposure models, each 1-standard deviation increment of the natural-log in dinotefuran and acetamiprid concentrations were significantly associated with odds ratios of 1.93 (95% CI: 1.69, 2.20) and 1.31 (95% CI: 1.07, 1.59) higher odds of FGR, respectively. However, the FGR risk was negatively associated with thiacloprid, sulfoxaflor, and nitenpyram (OR = 0.23, 95%CI: 0.15, 0.34; OR = 0.48, 95%CI: 0.41, 0.56; OR = 0.86, 95%CI: 0.80, 0.93; respectively). Similar findings were found in the combined exposure analysis. Dinotefuran was the most strongly attributable to increase FGR, while sulfoxaflor and thiacloprid contributed the highest negative weighted on FGR. Furthermore, each quintile increase in all ten NEOs exposures was associated with FGR (OR = 0.21, 95% CI: 0.08, 0.54). Our findings suggest that maternal single and combined exposures to NEOs were associated with varying FGR risks. They contribute to the mounting evidence on serum NEOs exposure impact on FGR. However, a replication of these associations in other populations is warranted. [Display omitted] • Maternal single and combined exposure to different neonicotinoids varied in association with fetal growth restriction risk. • Dinotefuran and acetamiprid exposure were associated with increased risk of fetal growth restriction. • Sulfoxaflor and thiacloprid were the main contributors in inversely correlation with fetal growth restriction. [ABSTRACT FROM AUTHOR]

The root of Scutellaria baicalensis Georgi, also called Huangqin, is frequently used in traditional Chinese medicine. In ancient China, S. baicalensis root was used to clear heat, protect the fetus, and avoid a miscarriage for thousands of years. In modern times, pregnancy-related diseases can seriously affect maternal and fetal health, but few systematic studies have explored the mechanisms and potential targets of S. baicalensis root in the treatment of pregnancy-related diseases. Flavonoids (baicalein, wogonin and oroxylin A) and flavonoid glycosides (baicalin and wogonoside) are the main chemical components in the root of S. baicalensis. This study presents the current understanding of the major chemical components in the root of S. baicalensis, focusing on their traditional uses, potential therapeutic effects and ethnopharmacological relevance to pregnancy-related disorders. The mechanisms, potential targets and experimental models of S. baicalensis root for ameliorating pregnancy-related diseases, such as recurrent spontaneous abortion, preeclampsia, preterm birth, fetal growth restriction and gestational diabetes mellitus, are highlighted., (Copyright © 2022 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.)

Objective: The aims of this study were to investigate the time intervals of each component of cardiac flow velocity waveforms (FVWs) in fetuses with fetal growth restriction (FGR) and to compare these with those of normal fetuses using reference ranges.Methods: The durations of atrioventricular (AV) valve opening (AVVO), AV valve closure (AVVC), total E- (total-E) and A- (total-A) waves, total ejection time (total-ET), acceleration time (acc-E for E-wave, acc-A for A-wave, and acc-ET for ejection time), and deceleration time (dec-E for E-wave, dec-A for A-wave, and dec-ET for ejection time) were measured in fetuses with FGR. All variables were analyzed using z-scores.Results: Measurements of 17 growth-restricted fetuses were obtained. The time intervals between the last Doppler examination and delivery ranged from 0 to 6 days, with a median of 1 day. Significant increases were observed in AVVO, total-E, dec-E, and acc-A of the left heart. acc-E, acc-ET and AVVC of the left heart were significantly decreased. In the right heart, AVVO, total-E and dec-E were significantly increased.Conclusion: A prolonged time interval between early ventricular inflow and atrial contraction, as well as increased duration of AV valve opening, may reflect hemodynamic alterations in FGR fetuses. [ABSTRACT FROM AUTHOR]

Phthalates (PAEs) are common endocrine disrupting chemicals (EDCs) that disrupt fetal development. The present study aimed to evaluate the effects of single and coexposure to phthalates in early pregnancy on fetal growth restriction (FGR) by a nested case-control study based on the Guangxi Zhuang Birth Cohort (GZBC). Maternal serum concentrations of seven phthalates in 97 neonates with FGR and 291 matched controls were detected through gas chromatography-mass spectrometry (GC-MS). The associations between phthalates and FGR were analyzed using multiple logistic regression, weight quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models. We found that exposures to butyl-benzyl phthalate (BBP, OR adj  = 1.849, 95% CI: 1.080-3.177, P adj  = 0.025, P trend  = 0.046), di (2-ethyl-hexyl) phthalate (DEHP, OR adj  = 3.893, 95% CI: 1.305-11.910, P adj  = 0.015, P trend  = 0.098) and dimethyl phthalate (DMP, OR adj  = 1.722, 95% CI: 1.089-2.725, P adj  = 0.020, P trend  = 0.002) were significantly positively associated with the risk of FGR, while mono-butyl phthalate (MBP) showed a significant negative association with FGR (OR high  = 0.192, 95% CI: 0.036-0.795, P adj  = 0.033, P trend  = 0.035) only among girls. The WQS model identified that BBP, di(2-ethyl)phthalate (DEP), DMP, DEHP, di-n-butyl phthalate (DBP), and MBP were highly weighted in the association with FGR. The BKMR model supported the positive association between joint exposure to phthalates and the risk of FGR and identified no significant interaction between the seven phthalates. Overall, maternal exposure to BBP, DEHP, and DMP may cause adverse effects on FGR, especially with combined effects., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Since the effectiveness of low-dose aspirin (LDA) in twin pregnancies is uncertain, we aimed to preliminarily assess whether LDA is beneficial in preventing preeclampsia in twin pregnancies., Methods: This study is an observational study in two hospitals in China. Among 932 women, 277 in the First Affiliated Hospital of Chongqing Medical University were routinely treated with aspirin (100 mg daily) from 12 to 16 weeks to 35 weeks of gestational age, while 655 in Chongqing Health Center for Women and Children were not taking aspirin during pregnancy. We followed each subject and the individual details were recorded., Results: LDA significantly reduced the risk of preeclampsia (RR 0.48; 95% CI 0.24-0.95) and preterm birth 34 weeks (RR 0.50; 95% CI 0.29-0.86) and showed possible benefits to lower the rate of SGA babies (RR 0.74; 95% CI 0.55-1.00). Moreover, the risk of postpartum hemorrhage was not increased by LDA (RR 0.89; 95% CI 0.35-2.26)., Conclusions: Treatment with low-dose aspirin in twin pregnancies could offer some protection against adverse pregnancy outcomes in the absence of significantly increased risk of postpartum hemorrhage., Trial Registration: Chinese Clinical Trial Registry (ChiCTR); ChiCTR-OOC-16008203 , Retrospectively registered date: April 1st, 2016., (© 2021. The Author(s).)

Objective: Fetal growth restriction (FGR) refers to impaired and insufficient intrauterine growth potential caused by a variety of adverse factors and is a serious perinatal complication that leads to fetal or neonatal mortality and morbidity. FGR has numerous causes, and its pathogenesis has not been fully understood. Recently, increasing numbers of researchers have begun to focus on the placenta, the only link between the fetus and the mother. The placenta is a vital organ that plays key roles in fetal development. PLAC1 is a trophoblast-specific gene located on the X chromosome and is important for placental development. However, the biological role of PLAC1 in fetal growth restriction is not well understood. In this study, we investigated the changes in the expression of placental-specific protein 1(PLAC1) in the placentas of pregnant women with FGR and in the placentas of normal pregnancies. We also explored the regulation of PLAC1 in the growth of trophoblast cells., Methods: Western blotting was used to detect the expression of PLAC1 in FGR and in normal placenta tissues. Cell counting kit 8 (CCK-8), wound healing, and transwell assays were used to detect the effects of PLAC1 knockdown on trophoblast cell proliferation, migration, and invasion. Western blotting was used to detect the expression of PLAC1 under hypoxic conditions, and the cell viability and apoptosis of trophoblast cells in a low oxygen concentration after overexpression of PLAC1 were detected by CCK-8 and flow cytometry assay., Results: Compared with the placentas in the control group of normal pregnancies, the expression of PLAC1 in the placentas of the FGR group was significantly down-regulated ( p <0.05). Knocking down PLAC1 by siRNA significantly inhibited the proliferation, migration, and invasion of trophoblast cells. After treatment with alow oxygen concentration, the expression of PLAC1 protein was significantly reduced ( p <0.05). The overexpression of PLAC1 can reverse the cell viability of trophoblast cells ( p <0.05) and inhibit apoptosis of trophoblast cells ( p <0.05) in low oxygen concentration., Conclusion: The expression of PLAC1 was reduced in fetal growth restriction and did not protect trophoblast cells from hypoxic damage, suggesting that PLAC1 may be an important regulator in the occurrence of fetal growth restriction., (© 2021 by the Association of Clinical Scientists, Inc.)

Objective: To assess the effect of regular third-trimester ultrasound on antenatal detection and perinatal outcomes of small for gestational age (SGA) infants., Methods: Data from SGA infants delivered at ≥28 weeks' gestation were retrospectively studied. Each pregnancy had undergone three regular third-trimester ultrasound examinations, and data were grouped according to with or without antenatal ultrasound suspicion of fetal growth restriction (FGR). Adjusted risk ratios (aRRs) of perinatal outcomes were analysed., Results: A total of 407 infants were included, comprising 268 (65.85%) with antenatal ultrasound suspicion of FGR. Antenatal suspicion of FGR was associated with increased risk of iatrogenic delivery (aRR 2.03, 95% confidence interval [CI] 1.31, 3.14) that included risk of preterm birth (aRR 10.61, 95% CI 1.35, 83.62) and elective caesarean section (aRR 1.306, 95% CI 1.051, 1.623). Differences in fetal death, 1-min Apgar score, and admission to neonatal intensive care unit were not statistically significant. Resuscitation risk was reduced (aRR 0.22, 95% CI 0.06, 0.79)., Conclusions: Regular use of third-trimester ultrasound in one teaching hospital in China showed satisfactory antenatal detection of FGR among SGA infants. Ultrasound suspicion of FGR was associated with higher incidence of iatrogenic deliveries, but not improved neonatal outcomes, except for reduced perinatal resuscitation.

Objective: To explore the effects of prenatal exposure to polybrominated diphenyl ethers (PBDEs) on placental size and birth outcomes., Methods: Based on the perspective Wenzhou Birth Cohort, this nested case-control study included 101 fetal growth restriction (FGR) and 101 healthy newborns. Maternal serum samples were collected during the third trimester and measured for PBDEs by gas chromatography tandem mass spectrometry. The basic information of mother-newborn pairs was collected from questionnaires, whereas the placental size and birth outcomes of newborns were obtained from hospital records., Results: A total of 19 brominated diphenyle ether (BDE) congeners were detected in maternal serum samples. Higher concentrations of BDE-207, -208, -209, and ∑ 19 PBDEs were detected in FGR cases than in controls. Increased BDE-207, -208, -209, and ∑ 19 PBDEs levels in maternal serum were related to decreased placental length, breadth, surface area, birth weight, birth length, gestational age, and Quetelet index of newborns. After adjusting for confounders, BDE-207 and ∑ 19 PBDE concentrations in maternal serum were significantly associated with an increased risk of FGR., Conclusion: A negative association was found between PBDE levels in maternal serum and placental size and birth outcomes. Prenatal PBDE exposure may be associated with elevated risk of the incidence of FGR birth., (Copyright © 2020 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Humans are exposed to polybrominated diphenyl ethers (PBDEs) via ingestion of food, dust inhalation, and dermal absorption. Exposure to PBDEs via the placenta and breast milk is a special and important pathway in infants. This nested case-control study aimed to investigate the levels of PBDEs in maternal serum and colostrum, and to assess the association between the occurrence of fetal growth restriction (FGR) and prenatal exposure to PBDEs. We recruited 293 mother-newborn pairs, including 98 FGR cases and 195 healthy controls in Wenzhou, China. Maternal serum and colostrum samples were collected during pregnancy and after delivery, respectively, and the levels of PBDEs were measured by gas chromatography-tandem mass spectrometry. The total levels of PBDEs in maternal serum and colostrum were found to be in equilibrium, but congener profiles of PBDEs in these matrices were different. Increased BDE-207, BDE-209, ∑BDE196-209 and ∑PBDEs levels in maternal serum and BDE-99, ∑BDE17-154 and ∑PBDEs levels in colostrum were correlated with decreased birth weight Z score. Increased concentrations of higher brominated BDEs in maternal serum (odds ratio (OR) = 1.010, 95%CI = 1.003-1.018) and low-to moderately brominated BDEs in colostrum (OR = 1.004, 95%CI = 1.000-1.009) were associated with increased risk of FGR, which showed an exposure-response relationship. In addition, infants with FGR were more exposed to PBDEs in colostrum after birth than healthy infants. Longitudinal birth cohort studies are needed to determine the prolonged effect of PBDEs exposure on the growth of FGR infants in the future., Competing Interests: Declaration of competing interest No competing interests exist., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Polybrominated diphenyl ethers (PBDEs) are environmental chemicals with harmful effects on pregnancy, but their effects on adverse developmental outcomes are not fully understood. The placental DNA methylation is strongly influenced by prenatal environmental factors and has been linked to fetal growth., Objective: To evaluate the association between in utero PBDEs exposure, placental DNA methylation changes (growth regulatory genes), and pathophysiology of fetal growth (birth outcomes, fetal growth retardation) in a population-based pregnancy cohort study., Methods: This was a nested case-control study within the prospective Wenzhou Birth Cohort including 130 fetal growth retardation (FGR) cases and 130 healthy controls and their mothers recruited from June 2016 to June 2017. FGR was diagnosed based on the comprehensive evaluation of ultrasound results at 24, 28, and 32 weeks of gestation. Neonatal birth measurements were obtained from medical records. Gestational exposure to 19 PBDEs, including 13 lower BDE congeners (BDE-17-190) and 6 higher brominated BDE congeners (BDE-196-209), were determined by gas chromatography tandem mass spectrometry in the umbilical cord blood. Placental DNA methylation changes of one repetitive element (LINE1) and two candidate genes (HSD11B2, IGF2) were characterized by quantitative polymerase chain reaction-pyrosequencing. Multiple linear regression and logistic regression models were used to examine the associations among PBDEs exposure, fetal growth indicators, and DMR (differential methylation region) methylation fractions. Sobel tests were conducted to assess DNA methylation as a mediator in multivariate models., Results: After excluding women who withdrew from the study or were lost to follow-up or failed to provide placenta or umbilical cord blood, 249 mother-newborn pairs (124 FGR cases, 125 controls) were included in the final analysis. Elevated BDE-206 (OR: 1.569, 95% CIs: 1.053-2.338), BDE-17-190 (OR: 2.860, 95% CIs: 1.233-6.634), BDE-196-209 (OR: 1.688, 95% CIs: 1.024-2.783) and ∑ 19 PBDEs (OR: 2.387, 95% CIs: 1.220-4.668) concentrations were associated with increased risk of FGR in newborns. FGR birth was also associated with increased DNA methylation of HSD11B2 (OR: 1.145, 95% CIs: 1.032-1.270) and decreased DNA methylation of IGF2 (OR: 0.892, 95% CIs: 0.845-0.941). In addition, BDE-17-190 showed significant associations with DNA methylation of HSD11B2 and IGF2 (β: 1.127, 95% CIs: 0.069-2.186; β: -3.452, 95% CIs: -5.512-1.392), indicating placental DNA methylation changes of HSD11B2 and IGF2 were related to both lower BDE congeners exposure and fetal growth. Further mediation analyses showed that IGF2 methylation mediated about 40% of the effects of BDE-17-190 in umbilical cord blood on neonatal FGR., Conclusion: We report an inverse association between in utero exposures to PBDEs and fetal growth and provide evidence supporting epigenetic gene plasticity in these associations. Changes in placental DNA methylation might be part of the underlying biological pathway between prenatal PBDEs exposure and adverse fetal growth., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: To investigate the changes of placental DNA methylome in preeclampsia (PE). Materials & methods: We performed an epigenome-wide association study in a Chinese cohort and six published datasets consisting of 335 samples in total. Results & conclusion: Numerous consistently hypomethylated probes were associated with early-onset PE in different populations, with 2125 reaching epigenome-wide significance. The validated probes were enriched for cytosine-phosphate-guanine dinucleotide (CpG) sites partially methylated and located in genes related to trophoblast fusion. The methylation levels of the validated probes were associated with clinical severity, while the intermediate samples showed antagonistic fetal/maternal outcomes. The DNA methylation patterns of PE and clinically relevant obstetrical syndromes suggested partially common pathophysiologies and complex maternal/fetal adaptive responses contributing to variable clinical outcomes.

Background: Fetal growth restriction (FGR) is not only a major determinant of perinatal morbidity and mortality but also leads to adverse health effects in later life. Over the past decade, numerous studies have indicated that maternal exposure to ambient air pollution has been a risk factor for abnormal fetal growth in developed countries where PM 2.5 levels are relatively low. However, studies in highly polluted regions, such as China, and studies that rely on assessments in utero are scarce., Methods: A total of 7965 women were selected from 11,441 women from the Shanghai Maternity and Infant Living Environment (SMILE) cohort who were pregnant between January 1, 2014, and April 30, 2015. From January 1, 2014, to April 30, 2015, weekly average PM 2.5 values from 53 monitors were calculated and the inverse distance weighted (IDW) method was used to create a Shanghai pollution surface map according to the participants residential addresses. Individual exposure was the average PM 2.5 value of every gestational week between the first gestational week and one week before the ultrasound measurement date (the range of measurements per participant was 1 to 10). Repeated fetal ultrasound measurements during gestational weeks 14~40 were selected. The estimated fetal weight (EFW) was calculated by biparietal diameter (BPD), abdominal circumference (AC), and femur length (FL) formulas. In total, 29,926 ultrasound measurements were analysed. Demographic variables, other pollutants (SO 2 , NO 2 , PM 10 and O 3 ) and relative humidity and temperature were controlled for potential confounding through generalized estimating equations (GEE)., Results: The full model showed that with each 10 μg/m 3 increase in PM 2.5 exposure, the means (mm) of AC, BPD, FL decreased by 5.48 (- 9.06, - 1.91), 5.57 (- 6.66, - 4.47), and 5.47 (- 6.39, - 4.55), respectively; the mean EFW decreased by 14.49 (- 16.05, - 13.49) grams by Hadlock's third formula and 13.56 (- 14.71, - 12.50) grams by Shepard's formula with each 10 μg/m 3 increase in PM 2.5 exposure., Conclusions: A negative correlation existed between maternal PM 2.5 exposure during pregnancy and fetal growth indicators, which may increase the risk of fetal growth restriction.

Background: Trophoblast invasion into the maternal endometrium serves an important function in human pregnancy. Dysregulation of the finely controlled process of trophoblast invasion can result in a wide spectrum of pregnancy abnormalities., Aims: We aimed to elucidate the relationship between the expression of matrix metalloproteinases and pregnancy complication., Study Design: The study group consisted of placental bed biopsy tissues obtained from normal vaginal deliveries (N=15), normal cesarean deliveries (N=15), pre-eclampsia (N=24) and fetal growth restriction (FGR) (N=10). We evaluated the expressions of MMP-2, -8, -9, -11, -19, -15 (MT2-MMP), -16 (MT3-MMP), and -24 (MT5-MMP), as well as TIMP-1 and -3, by applying Western blot and immunohistochemistry methods., Subjects: Human placental tissues were used for this study., Outcome Measures: The expressions of MMP-2, -8, -9, -11, -19, -15 (MT2-MMP), -16 (MT3-MMP), and -24 (MT5-MMP), as well as TIMP-1 and -3 in human placenta tissues., Results: Compared with those in normal pregnancies, the expression of MMP-2, -8, -9 and -11 was downregulated in villous tissues of pre-eclampsia and FGR cases (p<0.05). TIMP-1 and -3 were increased in pre-eclampsia and FGR (p<0.05). No significant difference was found between normal vaginal deliveries and cesarean deliveries., Conclusions: We speculate that the change in invasion-associated proteinase expression will affect placental development and may thus contribute to the development of complicated pregnancies., (Copyright © 2014 Elsevier Ltd. All rights reserved.)