Walter Ventura

Placental expression of microRNA-17 and -19b is down-regulated in early pregnancy loss.

OBJECTIVE First, to determine if microRNA-17 and -19b are expressed in villous samples at early stages of pregnancy. Second, to determine whether placental expressions of these microRNAs along with their main targets (PTEN, CREB-1, TGFβ-1 and TGFβ-RII) are altered in early pregnancy loss. STUDY DESIGN Expression levels of microRNAs and mRNA targets in villous samples from early pregnancy loss (n=11) and matched normal cases (n=20) by gestational age were determined by RT-PCR. RESULTS Both microRNA-17 and -19b were expressed in all cases of normal pregnancy. They were significantly down-regulated (relative ratios: 0.35 and 0.34 respectively) in early pregnancy loss. Their main target, PTEN mRNA, was significantly up-regulated in early pregnancy loss (relative ratio: 2.6, 95%CI: 0.2-29.8). TGF-β1, CREB-1 and TGFβ-RII were not significantly different between the two groups. CONCLUSION microRNA-17 and -19b are expressed in early stages of pregnancy. They are down-regulated in villous samples from early pregnancy loss. We suggest that these main members of the microRNA-17-92 cluster might be involved in placental invasion and its dysregulation might also be related to other conditions characterized by defective placentation.

Effects of Maternal Smoking on the Placental Expression of Genes Related to Angiogenesis and Apoptosis during the First Trimester

Objective Maternal cigarette smoking is reportedly associated with miscarriage, fetal growth restriction and placental abruption, and is paradoxically associated with a decreased risk of developing preeclampsia. In the present study, we investigated the gene expression levels of villous tissues in early gestation. We compared the expression levels of the genes related to angiogenesis and apoptosis in the villous tissues obtained from smoking and non-smoking pregnant women. Materials and Methods We collected villous tissue samples from 57 women requesting surgical termination due to non-medical reasons at 6–8 weeks of gestation. The maternal cigarette smoking status was evaluated by the level of serum cotinine and patients were divided into active smokers and non-smokers by the serum cotinine level. The placental levels of VEGFA, PGF, FLT1, HIF1A, TP53, BAX and BCL2 mRNA were quantified by real time PCR. Results The gene expression level of PGF and HIF1A in the active smoker group was significantly higher than that in the non-smoker group. We did not observe any significant differences in the VEGFA or FLT1 expression between the groups. In active smoker group, the gene expression levels of TP53 and BAX were significantly higher than those in the non-smoker group. The ratio of BAX/BCL2 mRNA in the active smoker group was significantly higher than that in the non-smoker group. Conclusions Our findings revealed that smoking might affect the placenta during early pregnancy. Maternal cigarette smoking in early pregnancy may be associated with villus hypoxia, which may influence angiogenesis and apoptosis.

Perinatal outcomes after sonographic detection of isolated short femur in the second trimester

To determine the association of fetal isolated short femur in the second‐trimester ultrasound (US) examination with perinatal outcomes such as small‐for‐gestational age (SGA) and low‐birth weight (LBW) neonates.

Physiological changes in the pattern of placental gene expression early in the first trimester.

Objective: To assess the physiological changes in the placental expression pattern of a panel of genes related to angiogenesis and oxidative stress during the early part of the first trimester of pregnancy. Methods and Results: The expression of a selected panel of genes was quantified by reverse transcriptase–polymerase chain reaction in samples of villous trophoblasts obtained from women between 6 and 11 weeks of gestation undergoing elective artificial abortion. We found that the levels of messenger RNA (mRNA) expression of placental growth factor (PlGF), heme oxygenase 1(HO-1), and superoxide dismutase (SOD) increased significantly with gestational age (r = .37, P = .001; r = .24, P =.04; and r = .52, P < .001, respectively). Conversely, the mRNA expression level of fms-like tyrosine kinase 1 (FLT-1) decreased significantly (r = −.30, P = .009). Conclusion: During the early part of the first trimester of pregnancy, the placental gene expression levels of PlGF, HO-1, and SOD increase with gestational age, whereas the expression of FLT-1 decreases. The alteration in this pattern of gene expression in early pregnancy may therefore play an important role in placenta-related disorders such as preeclampsia.

Maternal smoking and placental expression of a panel of genes related to angiogenesis and oxidative stress in early pregnancy.

Objective: Maternal cigarette smoking is paradoxically associated with a decreased risk of developing preeclampsia. Since preeclampsia is thought to be associated with altered mechanisms of angiogenesis and oxidative stress, we aim to investigate the influence of maternal smoking on the early placental expression of a panel of genes related to angiogenesis and oxidative stress. Material and Methods: We collected villous tissue samples at 6-7 and 10-11 weeks of gestation from 31 women requesting surgical termination. Placental expression of the following genes were quantified by real-time PCR: vascular endothelial growth factor A (VEGFA), fms-like tyrosine kinase (Flt-1), soluble endoglin (sEng), placental growth factor (PlGF), heme oxygenase-1 (HMOX-1) and superoxide dismutase (SOD). Maternal smoking status was assessed by levels of serum cotinine. Results: Placental expression of VEGFA was significantly higher in smoking women at 10-11 weeks of gestation compared with nonsmoking women at the same gestational age. There was no significant difference at 6-7 weeks of gestation. There was no variation in the expression of the other genes explored related to smoking status. Conclusions: Here we report that VEGFA placental expression was higher in smoking women at 10-11 weeks of gestation. Increased VEGFA expression in the early stages of pregnancy in smoking women might contribute to the decreased risk of developing preeclampsia.

Risk of impending preterm delivery associated with the presence of amniotic fluid sludge in women in preterm labor with intact membranes.

Objective: To determine the association of amniotic fluid sludge with impending preterm delivery in women in preterm labor with intact membranes. Methods: This was a retrospective cohort study in women at 22–34 weeks’ gestation in preterm labor with intact fetal membranes between February 2008 and May 2009. 16 women with amniotic sludge were identified. Each case of amniotic sludge was matched with 3 randomly selected controls. The primary outcome was delivery within 48 h of examination. Results: Mean cervical length was shorter in women with sludge than women without sludge (20.5 ± 9.0 vs. 27.9 ± 6.9 mm, p = 0.0016). There was a significant difference in the mean ultrasound-to-delivery interval in women with and without sludge (21.7 vs. 49.4 days, p = 0.006). Logistic regression analyses demonstrated that amniotic fluid sludge is a strong independent predictor of impending preterm delivery within 48 h (OR 11.2, 95% CI 1.2–125.9), 7 days (OR 3.8, 95% CI 1.2–17.3) and 14 days (OR 7.5, 95% CI 1.8–30.4). Conclusions: Amniotic fluid sludge on ultrasound scan is associated with impending preterm delivery in women in preterm labor with intact membranes.

Increased Levels of Cell-Free Human Placental Lactogen mRNA at 28-32 Gestational Weeks in Plasma of Pregnant Women With Placenta Previa and Invasive Placenta:

We compared the levels of cell-free human placental lactogen (hPL) messenger RNA (mRNA) in maternal plasma at 28 to 32 weeks of gestation between women with diagnosis of placenta previa or invasive placenta and women with an uneventful pregnancy. Sensitivity and specificity of hPL mRNA for the prediction of invasive placenta were further explored. Plasma hPL mRNA were quantified by real-time reverse-transcriptase polymerase chain reaction in women with placenta previa (n = 13), invasive placenta (n = 5), and normal pregnancies (n = 92). Median (range) hPL mRNA was significantly higher in women with placenta previa, 782 (10-2301) copies/mL of plasma, and in those with invasive placenta, 615 (522-2102) copies/mL of plasma, when compared to normal pregnancies, 90 (4-4407) copies/mL of plasma, P < .01 and P < .05, respectively. We found a sensitivity of 100% and a specificity of 61.5% for the prediction of invasive placenta among women with placenta previa. In conclusion, expression of hPL mRNA is increased in plasma of women with placenta previa and invasive placenta at 28 to 32 weeks of gestation.

Reliability of examining the external iliac artery with Doppler ultrasound in the first trimester and its relationship with maternal blood pressure and uterine artery blood flow

OBJECTIVE To explore the reliability of examining the external iliac artery (EIA) at 11+0 to 13+6 weeks of gestation with Doppler ultrasound and its relationship with maternal characteristics and uterine artery blood flow. STUDY DESIGN Cross-sectional study of 451 pregnant women undergoing an ultrasound scan in the first trimester. Mean pulsatility index (PI) of both EIAs was correlated to maternal characteristics (maternal age, parity, body mass index and mean arterial blood pressure (MAP)) and ultrasound parameters (crown-rump length (CRL) and mean uterine artery PI). Mean EIA-PI was logarithmically transformed to perform multiple linear regression analysis. The intra- and inter-observer reproducibilities of EIA-PI were examined. RESULTS Satisfactory flow velocity waveforms were obtained from both EIA in all patients. There is a significant negative correlation between mean EIA pulsatility index and maternal blood pressure. Multiple linear regression analysis showed an independent contribution of MAP to log EIA-PI (mean) (standardized regression coefficient = -0.20, 95% CI: -0.005 to -0.002). The intra-class correlation coefficients (ICCs) for intraobserver and interobserver reproducibility were 0.94 (95% CI, 0.88-0.97) and 0.87 (0.76-0.94) respectively. CONCLUSIONS Examining blood flow in the external iliac artery using Doppler ultrasound in the first trimester is feasible and reproducible. There is a negative correlation between mean EIA-PI and maternal blood pressure.

Umbilical artery Doppler at 19 to 22 weeks of gestation in the prediction of adverse pregnancy outcomes.

The aim of this study was to determine the clinical utility of Doppler assessment of the umbilical artery in the second trimester scan for predicting adverse pregnancy outcomes.

Uterine and umbilical artery Doppler at 28 weeks for predicting adverse pregnancy outcomes in women with abnormal uterine artery Doppler findings in the early second trimester

The objective of this study was to determine the contribution of uterine (UtA) and umbilical arteries (UA) Doppler examination at 28 weeks to predict adverse pregnancy outcomes in women who had increased resistance in UtA in the early second trimester.