Maternal Physiological Variations Induced by Chronic Gestational Hypoxia: 1H NMR-Based Metabolomics Study.

Metabolomics have been widely used in pregnancy-related diseases. However, physiological variations induced by chronic hypoxia during pregnancy are not well characterized. We aimed to investigate physiological variations induced by chronic hypoxia during pregnancy. A Sprague-Dawley (SD) pregnant rat model of chronic hypoxia was established. Plasma and urine metabolite profiles at different stages of the pregnancy were detected by 1H NMR (nuclear magnetic resonance). Multivariate statistical analysis was used to analyze changes in plasma and urine metabolic trajectories at different time-points. We identified hypoxia-induced changes in the levels of 30 metabolites in plasma and 29 metabolites in urine during different stages of pregnancy; the prominently affected metabolites included acetic acid, acetone, choline, citric acid, glutamine, isoleucine, lysine, and serine. Most significant hypoxia-induced changes in plasma and urine sample metabolites were observed on the 11th day of gestation. In summary, chronic hypoxia has a significant effect on pregnant rats, and may cause metabolic disorders involving glucose, lipids, amino acids, and tricarboxylic acid cycle. Metabolomics study of the effect of hypoxia during pregnancy may provide insights into the pathogenesis of obstetric disorders.

Predictive value of aberrant right subclavian artery for fetal chromosome aneuploidy in women of advanced maternal age.

BACKGROUND: In the entire population, an aberrant right subclavian artery (ARSA) is closely associated with chromosomal abnormalities. ARSA with additional ultrasonic findings would increase risk of chromosomal abnormalities. The risk of fetal chromosomal abnormalities increased exponentially with the maternal age. These risks in the advanced maternal age (AMA) group are uncertain. This study aimed to determine the incidence of ARSA in Chinese AMA and non-AMA women and the frequency of aneuploidy among AMA and non-AMA women with ARSA. METHODS: This retrospective study included 13,690 singleton pregnancies, were divided into AMA and non-AMA groups. Integrated obstetric ultrasonic screening, biochemical screening, noninvasive prenatal screening, and fetal karyotype analysis were analyzed. RESULTS: The overall incidence of ARSA was 0.69%, with no difference between age groups. The incidence of chromosomal abnormalities in the AMA group (37 / 2860) was much higher than that of the non-AMA group. The risk of chromosomal abnormalities significantly increased with both ARSA detected and additional ultrasound findings. With combined ARSA and AMA, the likelihood of the incidence of chromosomal abnormalities increased. Chimerism (45X / 46XX) was found with isolated ARSA in AMA pregnancies. CONCLUSION: There is a high prevalence of chromosomal abnormalities in fetuses of AMA women. ARSA increases the risk of chromosomal abnormalities in both age groups, especially combined with ARSA. When ARSA occurs in AMA women, it confers a high likelihood of chromosomal abnormalities.

Three-dimensional sonographic minute structure analysis of fetal cerebellar vermis development and malformations: utilizing volume contrast imaging.

PURPOSE: To obtain three-dimensional ultrasonic (3D US) structural details and biometrics of the fetal cerebellar vermis and evaluate the value of developmental and malformation identification. METHODS: The 3D US minute structure of the fetal cerebellar vermis in mid-sagittal view was detected in normal fetuses (n = 438; 16-41 weeks). Biometric sizes were measured to establish the stage-specific norms and reproducibility analysis. Additionally, 28 fetuses with suspected abnormal posterior fossa contents were assessed to analyze the clinical value. RESULTS: The minute structure of normal fetuses, including cerebellar vermis contours and the fastigial recess of the fourth ventricle, were visible around Week 19. The main lobules and fissures were apparent around Week 22, and all nine lobules, fissures, and the fourth ventricle were clearly displayed by Week 28. Cerebellar vermis biometric sizes (anterior-posterior length, cranio-caudal length, circumference, and surface area (SA)) grew in a linear fashion with high reliability, especially SA measurements (for intraclass, ICC 0.989, 95% CI (0.980-0.994); for interclass, ICC 0.992, 95% CI (0.984-0.996)). On the middle sagittal section of 3D US, the SA reduced at least 50% in the Dandy-Walker group with no recognizable cerebellar vermis structures showing. The SA in vermian hypoplasia malformation reduced during [Formula: see text] to 50% with the primary/secondary fissures absent or partly absent and arborization of the lobules reduced. That would be an important diagnosis and antidiastole clue. Combined with minute structural observation, sonographic diagnoses were accurate in 88% of cases. CONCLUSION: Minute structures obtained by 3D US were clinically useful in the evaluation of cerebellar vermis development and cerebellar vermis malformations.

The relationship of lung cancer with menstrual and reproductive factors may be influenced by passive smoking, cooking oil fumes, and tea intake: A case-control study in Chinese women.

The aim of this study was to investigate the association of menstrual and reproductive factors with risk of lung cancer in women. Potential etiological clues related to lung cancer in women are identified to inform preventive strategies.Case-control study of 477 newly diagnosed women with lung cancer and 479 age-matched (±2 years) controls. Data on menstrual and reproductive factors and history of oral contraceptive use were obtained on personal interviews using a structured questionnaire. Risk factors were analyzed by unconditional logistic regression analysis.Maternal age ≥25 years at first birth appeared to protect against female lung cancer [odds ratios (ORs): 0.511, 95% confidence interval (CI), 0.376-0.693]. Age at menopause > 50 years and use of contraceptives was associated with an increased risk of lung cancer in women (OR: 1.471, 95% CI, 1.021-2.119 and OR: 1.844, 95% CI: 1.111-3.061, respectively). Age ≥13 years at menarche was associated with a decreased risk of lung adenocarcinoma (OR: 0.563, 95% CI, 0.317-0.997). There was significant heterogeneity in the levels of cooking oil fume (COF) exposure (Pheterogeneity = .015). Higher levels of exposure to passive smoking, COF, and lack of tea intake were associated with an increased risk of lung cancer.Menstrual and reproductive factors are considered to play a role in the development of lung cancer in women. Exposure to passive smoking, COF, and lack of tea intake appeared to significantly modify the relationship.

Maternal hypoxia increases the susceptibility of adult rat male offspring to high-fat diet-induced nonalcoholic fatty liver disease.

Exposure to an adverse intrauterine environment increases the risk for adult metabolic syndrome. However, the influence of prenatal hypoxia on the risk of fatty liver disease in offspring is unclear. The purpose of the present study was to evaluate the role of reduced fetal oxygen on the development and severity of high-fat (HF) diet-induced nonalcoholic fatty liver disease (NAFLD). Based on design implicating 2 factors, ie, maternal hypoxia (MH) and postnatal HF diet, blood lipid and insulin levels, hepatic histology, and potential molecular targets were evaluated in male Sprague Dawley rat offspring. MH associated with postnatal HF diet caused a significant increase in plasma concentration of triglycerides, free fatty acids, low-density lipoprotein cholesterol, and insulin. Histologically, a more severe form of NAFLD with hepatic inflammation, hepatic resident macrophage infiltration, and progression toward nonalcoholic steatohepatitis was observed. The lipid homeostasis changes and insulin resistance caused by MH plus HF were accompanied by a significant down-regulation of insulin receptor substrate 2 (IRS-2), phosphoinositide-3 kinase p110 catalytic subunit, and protein kinase B. In MH rats, insulin-stimulated IRS-2 and protein kinase B (AKT) phosphorylation were significantly blunted as well as insulin suppression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Meanwhile, a significant up-regulation of lipogenic pathways was noticed, including sterol-regulatory element-binding protein-1 and fatty acid synthase in liver. Our results indicate that maternal hypoxia enhances dysmetabolic liver injury in response to an HF diet. Therefore, the offspring born in the context of maternal hypoxia may require special attention and follow-up to prevent the early development of NAFLD.

The effect of fetal congenital heart disease on in utero urine production rate.

OBJECTIVES: To evaluate the influence of congenital heart disease (CHD) or congestive heart failure (CHF) on fetal urine production rate (UPR) and to establish normal reference intervals. METHODS: A cross-sectional study was performed on normal fetuses (n = 314) and on fetuses with CHD (n = 49). CHD cases were divided into groups on the basis of heart function as defined by Huhta score: with CHF (n = 11) and without CHF (n = 38). Fetal bladder volume was measured by two-dimensional as well as three-dimensional ultrasound with the Virtual Organ Computer-aided Analysis technique. RESULTS: In normal fetuses, UPR increased with gestational age from a mean value of 4.5 mL/h at 21 weeks to 66.5 mL/h at 40 weeks. There were no significant differences in UPR between CHD cases without CHF and controls (P = 0.581). However, fetuses with CHF had decreased UPR values (Controls vs. CHF, P = 0.007) compared with the controls. The interobserver and intraobserver variability for assessment of UPR was better using three-dimensional rather than two-dimensional US. CONCLUSIONS: Fetal UPR can be reproducibly measured by the Virtual Organ Computer-aided Analysis technique. It appears that heart function, rather than CHD, affects fetal UPR. Fetal UPR may therefore be an additional indicator of CHF.

[A correlation analysis between the rate of vertical transmission of HBV and HBsAg-positive father to infant and the rate of neonatal cord blood HBV-DNA].

OBJECTIVE: To study the influence of HBV-DNA with different load levels of HBsAg-positive among fathers on the rate of neonatal cord blood HBV-DNA. METHODS: Using HBsAg and HBV-DNA as screening indicators for pregnant women and their husbands from an obstetric clinic. 161 pregnant women whose HBsAg and HBV-DNA were negative, but HBsAg was positive among their husbands and their newborns, were selected. Blood samples from those pregnant women, their husbands and their newborns were collected to detect the related indicators. Using ELISA to detect hepatitis B virus markers (HBVM), and FQ-PCR to detect the levels of HBV-DNA load. According to neonatal cord blood HBV-DNA detection guideline, newborns with cord blood HBV-DNA positive were selected as cases, others as controls. RESULTS: (1) Result of the study showed that there was a dose-response relationship between paternal serum HBV-DNA load levels and neonatal cord blood HBV-DNA positive rates in newborns (trend χ(2) = 64.117, P = 0.000). The rate of vertical transmission of HBV from HBsAg-positive father to infant in the paternal serum HBV-DNA ≥ 1.0 × 10(7) copies/ml group was significantly higher than HBV-DNA < 1.0 × 10(7) copies/ml group (χ(2) = 71.539, P = 0.000). (2) There was a positive rank correlation between semen positive HBeAg and vertical transmission of HBV from HBsAg-positive father to infant (χ(2) = 6.892, P = 0.009). CONCLUSION: There was a dose-response relationship between paternal serum HBV-DNA load levels and neonatal cord blood HBV-DNA positive in newborns. Paternal serum HBV-DNA ≥ 1.0 × 10(7) copies/ml and with HBeAg positive status were risk factors of vertical transmission of HBV from HBsAg-positive father to infant.

[Risk factors for paternal vertical transmission of hepatitis B virus.].

OBJECTIVE: To explore the risk factors of and the influence of different hepatitis B virus (HBV) DNA load on paternal vertical transmission of HBV. METHODS: Totally, 161 HBsAg negative women, whose husband was HBsAg positive, attended the antenatal clinics of the Provincial Maternity and Child Health Hospital of Fujian from September 2007 to December 2008 and their newborns were selected, and the epidemiologic information, the duration of being a HBV carrier, the first class HBV family history of the fathers, HBV markers, HBV DNA load, HBsAb of the gravidas, the outcomes of the newborns were all collected. Cord blood was sampled after delivery for HBV DNA quantification and those with HBV DNA load >/= 1.0 x 10(3) copy/ml were chosen as the case group and those < 1.0 x 10(3) copy/ml as control. RESULTS: (1) Among the 161 newborns, 36 HBV DNA positive cord blood samples were detected, giving a rate of 22.4% (36/161) for paternal vertical transmission of HBV. The HBV DNA positive rate in cord blood was 32.0% (23/72) in HBeAg-positive fathers and 14.6% (13/89) in HBeAg-negative fathers. (2) Univariate analysis showed that HBeAg-positive, HBV DNA positive, first class family history of HBV and the duration of being a HBV carrier of the fathers were risk factors of paternal HBV vertical transmission [chi(2) = 6.892, 29.916, 29.499 and 23.821, OR = 2.7, 5.2, 8.3 and 1.4 (P < 0.01)]. (3) Multivariate analysis found that paternal serum HBV DNA positive and the first class family history of HBV of the father side were risk factors of paternal vertical transmission of HBV (OR = 11.1, 95%CI: 4.6 - 27.1; OR = 17.1, 95%CI: 3.5 - 82.6). (4) According to the different serum HBV DNA load of the HBsAg-positive father, 7 groups were divided. A dose dependent effect was found that the HBV DNA positive rate of the cord blood increased with the rising of HBV DNA load. No HBV DNA positive cord blood was detected when paternal HBV DNA load was < 1.0 x 10(4) copy/ml, while 100% of the cord blood were positive when paternal HBV DNA load >/= 1.0 x 10(8) copy/ml. (5) The average birth weight of the newborns in the two groups was the same (3.3 +/- 0.4) kg. And the delivery mode, gestational age at delivery, height and Apgar score of the newborns at 1 minute, neonatal pathological jaundice and other complications had no significant difference between the two groups (P > 0.05). No relationship was found between the neonatal outcomes and the paternal HBV vertical transmission (P > 0.05). CONCLUSIONS: HBV DNA load in the serum of HBsAg-positive father, and the paternal first class family history of HBV are risk factors of paternal HBV vertical transmission. When the serum HBV DNA load in HBsAg-positive father is >/= 1.0 x 10(7) copy/ml, the possibility of paternal vertical transmission of HBV would increase.