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 study the dose-response relationship between maternal thyroid hormone levels in the first twenty weeks of pregnancy and the infant physical and neuropsychological development. Methods: In this prospective cohort study, a total of 945 women and their children were included. Maternal serum samples during first half of the pregnancy were collected and analyzed for levels of thyroid hormones by using the electro-chemiluminescence immunoassay. Maternal social demographic information was collected by using the a self-administered questionnaire. Physical measurements of newborns and neuropsychological evaluation of infants were performed by doctors of maternal and child health care. Results: The differences in newborns' birth length and head circumference were significant among the newborns of mothers with different percentiles of maternal serum (thyroid-stimulating hormone, TSH) levels (P<0.05). Newborns with maternal TSH level ≥P(95) or <P(5) had significantly lower birth length and birth head circumference, compared with the newborns with maternal TSH level between P(25)-P(75) (P<0.05). Newborns' birth head circumferences showed an inverted U-shaped association with maternal serum TSH level (Y=33.940+0.003X-0.109X(2), F=4.685, P=0.009). The difference in mental development index (MDI) of the infants at 18-30 months were significant among the infants of mothers with different percentiles of maternal serum TSH level (P<0.05). Infants with maternal TSH level ≥P(90) showed lower MDI (6.39, 95%CI: 2.29-10.49, P=0.002) compared with the infants with maternal TSH level between P(25)-P(75). Infant's MDI at 18- 30 months also showed an inverted U-shaped association with maternal serum TSH level (Y=103.249-1.524X-0.939X(2), F=6.616, P=0.001). Conclusions: Maternal TSH level was associated with newborn's birth length, birth head circumference and infant's MDI at 18-30 months. Newborn's birth head circumference and infant's MDI at 18-30 months showed an inverted U-shaped association with maternal serum TSH-Z score.
Birth Weight/physiology* ; Child ; Child Development/physiology* ; China ; Female ; Fetal Blood/metabolism* ; Humans ; Infant ; Infant, Newborn/blood* ; Pregnancy ; Prenatal Exposure Delayed Effects/blood* ; Prospective Studies ; Thyroid Gland/physiology* ; Thyroid Hormones/metabolism* ; Thyrotropin/blood*

Adult ; Birth Weight ; Body Mass Index ; Female ; Gestational Weight Gain ; physiology ; Humans ; Labor, Obstetric ; physiology ; Pregnancy

INTRODUCTIONWe studied the effects of ethnicity on early infant growth patterns in exclusively breast-fed (EBF) infants from a Singaporean multiethnic population. This was a prospective cohort study conducted in National University Hospital, Singapore.

MATERIALS AND METHODSHealthy, EBF infants born at-term completing 37 weeks and above, and whose birthweight was appropriate for gestational age (>10 centile, <90 centile) were recruited. Infants were required to be EBF at least until the minimum age of weaning. All infants who were preterm and premature, formula-fed, required Intensive/High Dependency care, or born with major congenital anomalies were excluded. A multivariable linear regression analysis was conducted at 5 predetermined time-points (birth; 4-8 weeks; 3-4, 5-8, 12 months) to study the effects of antenatal/parental factors on infant growth.

RESULTSA total of 213 infants were recruited. Maternal age, height and body mass index positively influenced birthweights while maternal hypertension and paternal smoking negatively influenced birthweights. Mean duration of breastfeeding was 8.9 months. Chinese ethnicity did not influence birth anthropometry, but was the single consistent factor that significantly increased weight and length Z-scores from 4-8 weeks until 8 months of life. Chinese ethnicity did not influence head growth throughout the first year of life.

CONCLUSIONEBF Chinese infants have increased weights and lengths compared to non-Chinese infants until 8 months' age, despite similar birth anthropometry. This period of discrepant growth coincides with the average duration of breastfeeding. We hypothesise that ethnic variations in breast milk macronutrient composition influence early somatic growth in infants.

Anthropometry ; methods ; Asian Continental Ancestry Group ; statistics & numerical data ; Birth Weight ; Body Mass Index ; Breast Feeding ; ethnology ; Child Development ; physiology ; Ethnic Groups ; Female ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Male ; Singapore ; epidemiology

To evaluate relationship of maternal hepatic vein Doppler flow parameters and cardiac output (CO) with neonatal birth weight in uncomplicated pregnancies (UP) and pregnancies complicated by fetal growth restriction (FGR) .
 Methods: Hepatic vein impedance index (HVI), venous pulse transit time (VPTT), and CO were measured in women with UP at the 14th-37th weeks and complicated by FGR at the 26th-37th weeks who underwent maternal hepatic hemodynamic and echocardiographic examination during the ultrasonography. After delivery, the birth weight and the birth weight percentile of each neonate in this study were recorded. Correlations among HVI, VPTT, and CO were analyzed.
 Results: In the UP group, HVI, VPTT, and CO changed with the increase of gestation. In the FGR group, HVI was higher, VPTT was shorter, CO and neonatal birth weight were obviously lower than those in the UP at the 26th-37th weeks (P<0.05).
 Conclusion: There is a series of adaptive changes in hepatic venous hemodynamics and CO in UP with the increase of gestation to meet the demand of fetal growth, while the maladaptive changes in hepatic venous hemodynamics and CO in pregnant woman may contribute to FGR.
Birth Weight ; Cardiac Output ; Female ; Fetal Development ; physiology ; Fetal Growth Retardation ; physiopathology ; Hemodynamics ; physiology ; Hepatic Veins ; physiopathology ; Humans ; Infant, Newborn ; Pregnancy ; Ultrasonography, Prenatal

PURPOSE: Removal of CO₂ is much efficient during high-frequency oscillatory ventilation (HFOV) for preterm infants. However, an optimal carbon dioxide diffusion coefficient (DCO₂) and tidal volume (VT) have not yet been established due to much individual variance. This study aimed to analyze DCO₂ values, VT, and minute volume in very-low-birth-weight (VLBW) infants using HFOV and correlates with plasma CO₂ (pCO₂). MATERIALS AND METHODS: Daily respiratory mechanics and ventilator settings from twenty VLBW infants and their two hundred seventeen results of blood gas analysis were collected. Patients were treated with the Dräger Babylog VN500 ventilator (Drägerwerk Ag & Co.) in HFOV mode. The normocapnia was indicated as pCO₂ ranging from 45 mm Hg to 55 mm Hg. RESULTS: The measured VT was 1.7 mL/kg, minute volume was 0.7 mL/kg, and DCO₂ was 43.5 mL²/s. Mean results of the blood gas test were as follows: pH, 7.31; pCO₂, 52.6 mm Hg; and SpO₂, 90.5%. In normocapnic state, the mean VT was significantly higher than in hypercapnic state (2.1±0.5 mL/kg vs. 1.6±0.3 mL/kg), and the mean DCO₂ showed significant difference (68.4±32.7 mL²/s vs. 32.4±15.7 mL²/s). The DCO₂ was significantly correlated with the pCO₂ (p=0.024). In the receiver operating curve analysis, the estimated optimal cut-off point to predict the remaining normocapnic status was a VT of 1.75 mL/kg (sensitivity 73%, specificity 80%). CONCLUSION: In VLBW infants treated with HFOV, VT of 1.75 mL/kg is recommended for maintaining proper ventilation.
Blood Gas Analysis ; Carbon Dioxide/analysis ; Female ; High-Frequency Ventilation ; Humans ; Hypercapnia/physiopathology ; Incidence ; Infant ; Infant, Newborn ; Infant, Very Low Birth Weight/physiology ; Male ; ROC Curve ; Tidal Volume

INTRODUCTION: Neonatal care advances have resulted in improved survival but have raised concerns of increase in neurodevelopmental impairment. This study looked at long-term neurodevelopmental outcomes at ages 5 and 8 years of very low birthweight infants born in the 2000s as compared to the 1990s. Neurodevelopmental assessment at 2 years old was compared to that at 5 and 8 years to determine if assessment at 2 years was predictive of later outcomes. MATERIALS AND METHODS: A retrospective cohort study of consecutive infants with birthweight less than 1250 grams admitted to a tertiary centre in Singapore between January 1994 to December 1995 (Epoch I) and January 2004 to December 2005 (Epoch II) were included. Neurodevelopmental impairment was defined as having intelligence quotient (IQ) of less than 70, cerebral palsy, legal blindness, or hearing impairment requiring hearing aids. RESULTS: Mean gestational age was lower for Epoch II compared to Epoch I (28.1 ± 2.5 vs 29.4 ± 2.7 weeks, = 0.004). Death or neurodevelopmental impairment rates did not differ (24.3% and 17.1% at 5 years old, = 0.398; 29.1% and 25.0% at 8 years old, = 0.709). There was improvement in visual impairment rate at 8 years in Epoch II (10.7% vs 34.0%, = 0.024). Mean IQ was better in Epoch II (109 and 107 vs 97 and 99 at 5 [ = 0.001] and 8 years [ = 0.047], respectively). All infants with no neurodevelopmental impairment at 2 years remained without impairment later on. CONCLUSION Over a decade, neurodevelopmental outcomes did not worsen despite lower mean gestational age. Long- term improvement in IQ scores and a reduction in visual impairment rates were seen. Our data suggests that children without neurodevelopmental impairment at 2 years are without impairment later on; therefore, they may need only developmental monitoring with targeted assessments instead of routine formal IQ assessments.
Child ; Child, Preschool ; Humans ; Infant, Newborn ; Infant, Premature ; physiology ; Infant, Very Low Birth Weight ; physiology ; Neurodevelopmental Disorders ; etiology ; Singapore

The study illustrate the inner correlation between global DNA methylation variation and different birth weights. Infant birth weight was used to identify cases and controls. Cord blood and placentas were collected. We performed DNA methylation profiling of bisulphite-converted DNA. We have identified many differentially methylated CpG sites in experimental groups; these sites involved in hundreds of signalings. Among these, more than ten pathways were referred to the glucose and lipid metabolism. Methylation changes in the insulin-signaling pathway (ISP), adipocytokine signaling pathway (ASP) and MAPK signaling pathway are involved in the fetal programming of diabetes..
Birth Weight ; DNA Methylation ; Female ; Gene Expression Regulation, Developmental ; physiology ; Genome-Wide Association Study ; Humans ; Infant, Newborn ; Male ; Organ Size ; Placenta ; anatomy & histology ; Pregnancy ; Signal Transduction

BACKGROUNDGestational diabetes mellitus (GDM) is associated with both short- and long-term adverse health consequences for both the mother and her offspring. The aim was to study the prevalence and risk factors for GDM in Beijing.

METHODSThe study population consisted of 15,194 pregnant women attending prenatal care in 15 hospitals in Beijing, who delivered between June 20, 2013, and November 30, 2013, after 28 weeks of gestation. The participants were selected by cluster sampling from the 15 hospitals identified through random systematic sampling based on the number of deliveries in 2012. A questionnaire was designed to collect information.

RESULTSA total of 2987 (19.7%) women were diagnosed with GDM and 208 (1.4%) had diabetes in pregnancy (DIP). Age (OR: 1.053, 95% CI: 1.033-1.074, P < 0.01), family history of diabetes mellitus (OR: 1.481, 95% CI: 1.254-1.748, P < 0.01), prepregnancy body mass index (BMI) (OR: 1.481, 95% CI: 1.254-1.748, P < 0.01), BMI gain before 24 weeks (OR: 1.126, 95% CI: 1.075-1.800, P < 0.01), maternal birth weight (P < 0.01), and fasting plasma glucose at the first prenatal visit (P < 0.01) were identified as risk factors for GDM. In women with birth weight <3000 g, GDM rate was significantly higher.

CONCLUSIONSOne out of every five pregnant women in Beijing either had GDM or DIP and this constitutes a huge health burden for health services. Prepregnancy BMI and weight gain before 24th week are important modifiable risk factors for GDM. Ensuring birth weight above 3000 g may help reduce risk for future GDM among female offsprings.

Birth Weight ; physiology ; Body Mass Index ; Diabetes, Gestational ; metabolism ; Female ; Glucose Tolerance Test ; Humans ; Pregnancy ; Prevalence ; Risk Factors ; Weight Gain ; physiology

BACKGROUNDHyperglycemia is associated with adverse pregnancy outcomes. However, the relationships between them remain ambiguous. This study aimed to analyze the effect of different oral glucose tolerance test (OGTT) results on adverse perinatal outcomes.

METHODSThis retrospective cohort study included data from 15 hospitals in Beijing from June 20, 2013 to November 30, 2013. Women with gestational diabetes mellitus (GDM) were categorized according to the number and distribution of abnormal OGTT values, and the characteristics of adverse pregnancy outcomes were evaluated. Chi-square test and logistic regression analysis were used to determine the associations.

RESULTSIn total, 14,741 pregnant women were included in the study population, 2927 (19.86%) of whom had GDM. As the number of hyperglycemic values in the OGTT increased, the risk of cesarean delivery, preterm births, large-for-gestational age (LGA), macrosomia, and neonatal complications significantly increased. Fasting hyperglycemia had clear associations with macrosomia (odds ratios [OR s]:1.84, 95% confidence intervals [CI s]: 1.39-2.42,P < 0.001), LGA (OR: 1.70, 95% CI: 1.29-2.25,P < 0.001), and cesarean delivery (OR: 1.33, 95% CI: 1.15-1.55,P < 0.001). The associations were stronger as fasting glucose increased. GDM diagnosed by hyperglycemia at OGTT-2 h was more likely to lead to preterm birth (OR: 1.50, 95% CI: 1.11-2.03,P < 0.01).

CONCLUSIONSVarious characteristics of OGTTs are associated with different adverse outcomes. A careful reconsideration of GDM with hierarchical and individualized management according to OGTT characteristics is needed.

Birth Weight ; physiology ; Blood Glucose ; metabolism ; Body Mass Index ; Cesarean Section ; Chi-Square Distribution ; Diabetes, Gestational ; blood ; physiopathology ; Female ; Fetal Macrosomia ; blood ; physiopathology ; Glucose Tolerance Test ; methods ; Humans ; Pregnancy ; Pregnancy Complications ; Pregnancy Outcome ; Premature Birth ; blood ; physiopathology ; Retrospective Studies