Objective: To characterize the relationship between the levels of plasma methyl donor and related metabolites (including choline, betaine, methionine, dimethylglycine and homocysteine) and fetal growth in twin pregnancies. Methods: A hospital-based cohort study was used to collect clinical data of 92 pregnant women with twin pregnancies and their fetuses who were admitted to Peking University Third Hospital from March 2017 to January 2018. Fasting blood was collected from the pregnant women with twin pregnancies (median gestational age: 18.9 weeks). The levels of methyl donors and related metabolites in plasma were quantitatively analyzed by high-performance liquid chromatography combined with mass spectrometry. The generalized estimation equation was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and neonatal outcomes of twins, and the generalized additive mixed model was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and fetal growth ultrasound indicators. Results: (1) General clinical data: of the 92 women with twin pregnancies, 66 cases (72%) were dichorionic diamniotic (DCDA) twin pregnancies, and 26 cases (28%) were monochorionic diamniotic (MCDA) twin pregnancies. The comparison of the levels of five plasma methyl donors and related metabolites in twin pregnancies with different basic characteristics showed that the median levels of plasma choline and betaine in pregnant women ≥35 years old were higher than those in pregnant women <35 years old, and the differences were statistically significant (all P<0.05). (2) Correlation between plasma methyl donor and related metabolites levels and neonatal growth indicators: after adjusting for confounding factors, plasma homocysteine level in pregnant women with twins was significantly negatively correlated with neonatal birth weight (β=-47.9, 95%CI:-94.3- -1.6; P=0.043). Elevated methionine level was significantly associated with decreased risks of small for gestational age infants (SGA; OR=0.5, 95%CI: 0.3-0.9; P=0.021) and low birth weight infants (OR=0.6, 95%CI: 0.4-0.9; P=0.020). Increased homocysteine level was associated with increased risks of SGA (OR=1.5, 95%CI: 1.0-2.2; P=0.029) and inconsistent growth in twin fetuses (OR=1.9, 95%CI: 1.0-3.7; P=0.049). (3) Correlation between the levels of plasma methyl donors and related metabolites and intrauterine growth indicators of twins pregnancies: for every 1 standard deviation increase in plasma choline level in pregnant women with twin pregnancies, fetal head circumference, abdominal circumference, femoral length and estimated fetal weight in the second trimester increased by 1.9 mm, 2.6 mm, 0.5 mm and 20.1 g, respectively, and biparietal diameter, abdominal circumference and estimated fetal weight increased by 0.7 mm, 3.0 mm and 38.4 g in the third trimester, respectively, and the differences were statistically significant (all P<0.05). (4) Relationship between plasma methyl donor and related metabolites levels in pregnant women with different chorionicity and neonatal birth weight and length: the negative correlation between plasma homocysteine level and neonatal birth weight was mainly found in DCDA twin pregnancy (β=-65.9, 95%CI:-110.6- -21.1; P=0.004). The levels of choline, betaine and dimethylglycine in plasma of MCDA twin pregnancy were significantly correlated with the birth weight and length of newborns (all P<0.05). Conclusion: Homocysteine level is associated with low birth weight in twins, methionine is associated with decreased risk of SGA, and choline is associated with fetal growth in the second and third trimesters of pregnancy.
Adult ; Female ; Humans ; Infant, Newborn ; Pregnancy/metabolism* ; Betaine/metabolism* ; Birth Weight/physiology* ; Choline/metabolism* ; Cohort Studies ; Fetal Development/physiology* ; Fetal Weight/physiology* ; Homocysteine/metabolism* ; Methionine/metabolism* ; Pregnancy, Twin/physiology* ; Biomarkers/metabolism* ; Pregnancy Trimesters/physiology* ; Pregnancy Outcome

OBJECTIVE: To investigate the association of isolated thyroid peroxidase antibody (TPOAb) positive in the first trimester with fetal growth. METHODS: A total of 16 446 pregnant women were included in the birth cohort study, whose last menstrual period was between May 2016 and April 2019 and with singleton pregnancy. Maternal serum samples were collected when they firstly came for prenatal care in the first trimester. The pregnant women were consecutively seen and followed in the hospital and the information of pregnant women was extracted from the electronic medical information system. The pregnant women were divided into isolated TPOAb positive group (n=1 654) and euthyroid group (n=14 792). Three fetal ultrasound examinations were scheduled during the routine prenatal visits at the hospital and were performed by trained sonographers. All fetal growth indicators were quantified as gestational age- and gender- adjusted standard deviation score (Z-score) using the generalized additive models for location, scale and shape (GAMLSS). Fetal growth indicators included estimated fetal weight (EFW), abdominal circumference (AC), biparietal diameter (BPD), femur length (FL) and head circumference (HC). Fetal growth restriction (FGR) was defined as AC or EFW Z-score＜3rd centile based on clinical consensus. Generalized estimating equation (GEE) analysis was applied to assess the association of maternal isolated TPOAb positive with fetal growth. The generalized linear model was further used to analyze the association between isolated TPOAb positive and fetal growth indicator at different gestational ages when the fetal growth indicator was significantly associated with isolated TPOAb positive in the GEE mo-del. RESULTS: The median gestational age at three ultrasound measurements was 23.6 (23.3, 24.1), 30.3 (29.7, 30.9), 37.3 (37.0, 37.7) weeks, respectively. The BPD Z-score was higher in isolated TPOAb positive women, compared with the euthyroid pregnant women after adjustment (β=0.057, 95%CI: 0.014-0.100, P=0.009). The generalized linear model showed the BPD Z-score was higher in the isolated TPOAb positive women at the end of 21-25 weeks (β=0.052, 95%CI: 0.001-0.103, P=0.044), 29-32 weeks (β=0.055, 95%CI: 0.004-0.107, P=0.035) and 36-40 weeks (β=0.068, 95%CI: 0.011-0.125, P=0.020), compared with the euthyroid pregnant women. There was no difference in other fetal growth indicators (EFW, AC, FL and HC) and FGR between the isolated TPOAb positive and euthyroid pregnant women. CONCLUSION The BPD Z-score was slightly increased in the isolated TPOAb positive pregnant women in the first trimester, while other fetal growth indicators were not changed. The reproducibility and practical significance of this result need to be confirmed.
Pregnancy ; Female ; Humans ; Pregnancy Trimester, First ; Iodide Peroxidase ; Cohort Studies ; Reproducibility of Results ; Fetal Development ; Fetal Weight ; Fetal Growth Retardation ; Ultrasonography, Prenatal

BACKGROUND: The fetal growth charts in widest use in China were published by Hadlock >35 years ago and were established on data from several hundred of American pregnant women. After that, >100 fetal growth charts were published around the world. We attempted to assess the impact of applying the long-standing Hadlock charts and other charts in a Chinese population and to compare their ability to predict newborn small for gestational age (SGA). METHODS: For this retrospective observational study, we reviewed all pregnant women ( n  = 106,455) who booked prenatal care with ultrasound measurements for fetal biometry at the Shenzhen Maternity and Child Healthcare Hospital between 2012 and 2019. A fractional polynomial regression model was applied to generate Shenzhen fetal growth chart ranges for head circumference (HC), biparietal diameter (BPD), abdominal circumference (AC), and femur length (FL). The differences between Shenzhen charts and published charts were quantified by calculating the Z -score. The impact of applying these published charts was quantified by calculating the proportions of fetuses with biometric measurements below the 3rd centile of these charts. The sensitivity and area under the receiver operating characteristic curves of published charts to predict neonatal SGA (birthweight <10th centile) were assessed. RESULTS: Following selection, 169,980 scans of fetal biometry contributed by 41,032 pregnancies with reliable gestational age were analyzed. When using Hadlock references (<3rd centile), the proportions of small heads and short femurs were as high as 8.9% and 6.6% in late gestation, respectively. The INTERGROWTH-21st standards matched those of our observed curves better than other charts, in particular for fat-free biometry (HC and FL). When using AC<10th centile, all of these references were poor at predicting neonatal SGA. CONCLUSIONS Applying long-standing Hadlock references could misclassify a large proportion of fetuses as SGA. INTERGROWTH-21st standard appears to be a safe option in China. For fat-based biometry, AC, a reference based on the Chinese population is needed. In addition, when applying published charts, particular care should be taken due to the discrepancy of measurement methods.
Infant, Newborn ; Child ; Female ; Pregnancy ; Humans ; Growth Charts ; Prenatal Care ; Ultrasonography, Prenatal/methods* ; Fetal Development ; Fetal Growth Retardation ; Gestational Age ; Fetus ; China ; Infant, Newborn, Diseases ; Observational Studies as Topic

Gestational diabetes mellitus (GDM) is common during pregnancy, with the prevalence reaching as high as 31.0% in some European regions (McIntyre et al., 2019). Dysfunction of the glucose metabolism in pregnancy can influence fetal growth via alteration of the intrauterine environment, resulting in an increased risk of abnormal offspring birth weight (McIntyre et al., 2019). Infants with abnormal birth weight will be faced with increased risks of neonatal complications in the perinatal period and chronic non-communicable diseases in childhood and adulthood (Mitanchez et al., 2015; McIntyre et al., 2019). Therefore, accurate estimation of birth weight for neonates from women with GDM is crucial for more sensible perinatal decision-making and improvement of perinatal outcomes. Timely antenatal intervention, with reference to accurately estimated fetal weight, may also decrease the risks of adverse long-term diseases.
Adult ; Birth Weight ; Diabetes, Gestational ; Female ; Fetal Development ; Humans ; Infant ; Infant, Newborn ; Neural Networks, Computer ; Pregnancy

Animals ; Caffeine/adverse effects* ; Central Nervous System Stimulants/adverse effects* ; Dose-Response Relationship, Drug ; Female ; Fetal Growth Retardation/chemically induced* ; Immune System Diseases/chemically induced* ; Male ; Organ Size/drug effects* ; Pregnancy ; Pregnancy Complications/immunology* ; Rats ; Spleen/growth & development*

BACKGROUND: There are only limited numbers of reviews on the association of maternal-child genetic polymorphisms and environmental and lifestyle-related chemical exposure during pregnancy with adverse fetal growth. Thus, this article aims to review: (1) the effect of associations between the above highlighted factors on adverse fetal growth and (2) recent birth cohort studies regarding environmental health risks. METHODS: Based on a search of the PubMed database through August 2021, 68 epidemiological studies on gene-environment interactions, focusing on the association between environmental and lifestyle-related chemical exposure and adverse fetal growth was identified. Moreover, we also reviewed recent worldwide birth cohort studies regarding environmental health risks. RESULTS: Thirty studies examined gene-smoking associations with adverse fetal growth. Sixteen maternal genes significantly modified the association between maternal smoking and adverse fetal growth. Two genes significantly related with this association were detected in infants. Moreover, the maternal genes that significantly interacted with maternal smoking during pregnancy were cytochrome P450 1A1 (CYP1A1), X-ray repair cross-complementing protein 3 (XRCC3), interleukin 6 (IL6), interleukin 1 beta (IL1B), human leukocyte antigen (HLA) DQ alpha 1 (HLA-DQA1), HLA DQ beta 1 (HLA-DQB1), and nicotinic acetylcholine receptor. Fetal genes that had significant interactions with maternal smoking during pregnancy were glutathione S-transferase theta 1 (GSTT1) and fat mass and obesity-associated protein (FTO). Thirty-eight studies examined the association between chemical exposures and adverse fetal growth. In 62 of the 68 epidemiological studies (91.2%), a significant association was found with adverse fetal growth. Across the studies, there was a wide variation in the analytical methods used, especially with respect to the genetic polymorphisms of interest, environmental and lifestyle-related chemicals examined, and the study design used to estimate the gene-environment interactions. It was also found that a consistently increasing number of European and worldwide large-scale birth cohort studies on environmental health risks have been conducted since approximately 1996. CONCLUSION There is some evidence to suggest the importance of gene-environment interactions on adverse fetal growth. The current knowledge on gene-environment interactions will help guide future studies on the combined effects of maternal-child genetic polymorphisms and exposure to environmental and lifestyle-related chemicals during pregnancy.
Alpha-Ketoglutarate-Dependent Dioxygenase FTO ; Female ; Fetal Development ; Gene-Environment Interaction ; Humans ; Life Style ; Maternal Exposure/adverse effects* ; Polymorphism, Genetic ; Pregnancy

Placenta is the only link between the pregnant woman and fetus, and the basis for maintaining the normal pregnancy process and fetal development. Maternal stress is the maternal physiological and psychological changes caused by various factors, characterized by the increased level of glucocorticoid, which affects the hypothalamic-pituitary-target gland axis and regulates the expression of target genes. Maternal stress also changes the weight, metabolism and nutrient transportation of the placenta, which will substantially influence the development of fetus. This paper will firstly summarize the characteristics of maternal stress and its influence on offspring. Then, the changes in the body under maternal stress will be described. Finally, we will clarify the proven mechanisms underlying maternal stress and raise some important problems that have not been clarified in this area. The study of maternal stress on fetus and its underlying mechanisms will serve as theoretical basis for the diagnosis and treatment of the stress-related pregnant diseases and disorders.
Female ; Fetal Development ; Fetus ; Humans ; Placenta ; Pregnancy

BACKGROUND: Twin pregnancies continue to increase worldwide; however, the current clinical prenatal evaluation for the intrauterine growth of twins still relies on the growth standards of singletons. We attempted to establish a set of fetal biometric references for Chinese twin pregnancies, stratified by chorionicity and conception mode as spontaneously conceived monochorionic diamniotic (SC-MCDA), spontaneously conceived dichorionic diamniotic (SC-DCDA), and assisted reproductive technology dichorionic diamniotic (ART-DCDA) twins. METHODS: From 2016 to 2019, the ultrasonographic fetal biometric measurements were longitudinally collected in pregnant women, including fetal weight, biparietal diameter, head circumference, abdominal circumference, femur length, and humerus length. The linear mixed models were used to test the difference of growth patterns between groups, and the growth curve of each biometric parameter was modeled by a generalized additive model for location scale and shape. RESULTS: A total of 929 twin pregnant women and 2019 singleton pregnant women, met the inclusion criteria. Among twin pregnancies, 148 were SC-MCDA, 215 were SC-DCDA, and 566 were ART-DCDA twins. Overall, SC-DCDA twins grew faster than SC-MCDA twins, while slower than ART-DCDA twins (all P < 0.05), and all of the three groups showed significant differences comparing with singletons, especially during the third trimester. Hence, the customized fetal growth charts of each fetal biometric parameter were, respectively, constructed for SC-MCDA, SC-DCDA, and ART-DCDA twins. CONCLUSIONS The fetal biometric trajectories demonstrated characteristic patterns according to chorionicity and conception mode. To fill the gap, we modeled fetal biometric parameters for Chinese SC-MCDA, SC-DCDA, and ART-DCDA twin pregnancies, hoping to provide a reference for the further establishment of fetal growth reference values for Chinese twin fetuses.
China ; Female ; Fetal Development ; Growth Charts ; Humans ; Pregnancy ; Pregnancy, Twin ; Retrospective Studies ; Ultrasonography, Prenatal

Objective: To verify the health advisory for short-term exposure to phenol. Methods: The method of this validation experiment was the same as the US Environmental Protection Agency (EPA) methodology for toxicology experiments used to determine phenol drinking water equivalent level (DWEL). Pregnant female Sprague-Dawley rats were administered phenol in distilled water by gavage at daily doses of 15, 30, 60, 120, and 240 mg/kg body weight (b.w.) from implantation (the 6th day post-mating) to the day prior to the scheduled caesarean section (the 20th day of pregnancy). The following information was recorded: general behavior; body weight; number of corpus luteum, live birth, fetus, stillbirth, and implantation; fetal gender; body weight; body length; tail length; and abnormalities and pathomorphological changes in the dams. Results: In the 60 mg/kg b.w. dose group, the mortality of pregnant rats increased with increasing doses, suggesting maternal toxicity. Fetal and placental weights decreased as phenol dose increased from 30 mg/kg b.w., and were significantly different compared those in the vehicle control group, which suggested developmental toxicity in the fetuses. However, the phenol-exposed groups showed no significant change in other parameters compared with the vehicle control group ( > 0.05). Conclusion Despite using the same method as the US EPA, a different NOEAL of 15 mg/(kg·d) was obtained in this study.
Animals ; Dose-Response Relationship, Drug ; Environmental Pollutants ; toxicity ; Female ; Fetal Development ; drug effects ; Phenol ; toxicity ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Toxicity Tests, Acute

fetal growth.Trial RegistrationClinical Research Information Service Identifier: KCT0000776]]>
Blood Glucose ; Diabetes, Gestational ; Diagnosis ; Female ; Fetal Development ; Gestational Age ; Glucose ; Glucose Tolerance Test ; Humans ; Information Services ; Odds Ratio ; Pregnancy ; Pregnant Women