Nifedipine versus labetalol in the treatment of hypertensive disorders of pregnancy.

PURPOSE: To assess the maternal and fetal outcomes of pregnancies affected by hypertensive disorders treated with nifedipine versus labetalol. METHODS: A retrospective study in hypertensive patients treated during pregnancy with nifedipine or labetalol was conducted. After the charts review the patients were divided in the four groups: gestational hypertension (113 patients); mild preeclampsia (77 patients); severe preeclampsia (31 patients); HELLP syndrome (21 patients). The pregnancy and neonatal records were analyzed by paired and unpaired t test. RESULTS: We found that there was an higher rate of intrauterine growth restriction infants among women treated with labetalol compared with those treated with nifedipine (38.8 vs. 15.5 %; p < 0.05), but only in the subgroup of women affected by Gestational Hypertension and Mild Preeclampsia. In this group was also higher the rate of fetal worsening assessed by fetal heart rate tracing (33.3 vs. 14.2 %; p < 0.05). No neonatal malformations and no differences in the rate of adverse side effects were observed. CONCLUSIONS: Antihypertensive therapy in pregnancy with Labetalol may have the potential to impair fetal behavior in low degrees hypertensive diseases of pregnancy. Optimal care must balance the potentially conflicting risks and benefits to mother and fetus.

Doppler analysis and placental nitric oxide synthase expression during fetal growth restriction.

OBJECTIVE: To assess placental nitric oxide (NO) metabolism related to changes in the uteroplacental circulation during fetal growth restriction (FGR). METHODS: The resistance index (RI) from the uterine arteries and pulsatility index (PI) from the umbilical artery were determined by Doppler analysis in 15 patients with FGR and 12 healthy controls, before elective cesarean section. Inducible (iNOS) and endothelial (eNOS) NO synthase expression were measured in placental samples. Immunohistochemistry was performed for iNOS location in the placenta. RESULTS: During FGR, we observed a significant elevation of iNOS when compared with controls. Conversely, eNOS did not differ between the two groups. A negative correlation with eNOS (r = -0.85) and a positive correlation with iNOS (r = 0.91) was found correlating to umbilical PI. The iNOS proteins were reduced in syncytiotrophoblast cells and increased in endothelium in the FGR group compared to the controls. CONCLUSIONS: During FGR, placental iNOS expression is significantly increased; this increase possibly represents an adaptive physiological mechanism for overcoming a fetoplacental circulation deficiency.

Computerized analysis of the fetal heart rate in pregnancies complicated by preterm premature rupture of membranes (pPROM).

OBJECTIVE: We aimed to show that in pregnancies complicated by preterm premature rupture of membranes (pPROM), there are alterations to the fetal heart rate pattern that can be detected by computerized analysis. METHODS: The study population consisted of 27 pregnant women with pPROM at 29-34 weeks of gestation and 33 normal pregnancies matched according to age, parity and gestation. A 30-minute fetal heart rate (FHR) tracing was analyzed by computer and umbilical artery cord blood was collected at birth. RESULTS: The baseline heart rate, the number of decelerations exceeding 20 beats per minute and the duration of episodes of low variation were higher in the pPROM group versus the controls. The number of decelerations exceeding 20 beats per minute had an independent, statistically significant association with umbilical artery pH at birth. CONCLUSIONS: Even if our data require a prospective validation involving a larger number of pathological cases, a computerized FHR tracing analysis may improve the clinical care and the timing of delivery during pPROM by definition of the risk of acidemia and pre-acidemia.

Placental expression of nitric oxide synthase during HELLP syndrome: the correlation with maternal-fetal Doppler velocimetry.

BACKGROUND: To correlate Doppler waveform of the uterine and umbilical vessels to placental nitric oxide synthase (NOS) expression in pregnant women with HELLP (hemolysis, elevated liver enzymes, low platelets count) syndrome. METHODS: mRNA expression of inducible NOS (iNOS) and endothelial NOS (eNOS) was assessed, after cesarean section, in placental samples from 10 women affected by HELLP syndrome and 10 controls. Pulsatility indices on Doppler waveform analysis from uterine and umbilical arteries were measured. RESULTS: iNOS expression was significantly lower in placenta from women with HELLP syndrome than controls. When comparing the results with Doppler flow measurements, we found a negative correlation between umbilical pulsatility index and eNOS expression (r = -0.91) and a positive correlation with iNOS expression (r = 0.86). CONCLUSIONS: The reduced iNOS expression in women with HELLP syndrome may indicate the extreme placental dysfunction that is unable to compensate for the endothelial derangement and related hypertension in spite of trying to improve fetoplacental perfusion and the delivery of nutrients to the fetus.

Transabdominal amnioinfusion in preterm premature rupture of membranes: a randomised controlled trial.

OBJECTIVE: To evaluate the role of transabdominal amnioinfusion in improving the perinatal outcomes of pregnancies complicated by preterm premature rupture of membranes (pPROM). DESIGN: A randomised controlled trial. SETTING: A teaching hospital in Italy, obstetric unit. Population Women with singleton pregnancies complicated by pPROM, between 24 + 0 and 32 + 6 weeks of gestation. METHODS: Patients were randomised 24 hours after admission to our referral hospital, to expectant management with transabdominal amnioinfusion or expectant management only. MAIN OUTCOME MEASURES: The effects of transabdominal amnioinfusion on pPROM-delivery interval and on perinatal outcomes. RESULTS: Of the 65 women with pPROM 34 met the inclusion criteria. Seventeen women were assigned to amnioinfusion (the amnioinfusion group) and the other 17 to expectant management. Compared with the control group (median: 8 days; range: 3-14), the pPROM-delivery period was significantly longer in women who underwent amnioinfusion (median: 21 days; range: 15-29) (P < 0.05). Women with amnioinfusion were less likely to deliver within seven days since pPROM (RR: 0.18; range: 0.04-0.69 95% CI) or within two weeks (RR: 0.46; range: 0.21-1.02 95% CI). In the amnioinfusion group the neonatal survival was significantly higher at each gestational age (P < 0.01, Yates's correction for Log Rank Test) with a reduction in pulmonary hypoplasia. CONCLUSIONS: We demonstrated that compared with standard expectant management the treatment with transabdominal amnioinfusion after pPROM resulted in significant prolongation of pregnancy and better neonatal outcomes.

Amniotic levels of nitric oxide and vascular endothelial growth factor in pregnancy with subsequent intrauterine fetal death.

OBJECTIVE: Nitric oxide (NO) and vascular endothelial growth factor (VEGF) regulate angiogenesis and seem involved in the early stages of placentation. If angiogenesis is reduced, this may lead to poor placentation and fetal death. This study was aimed to determine whether VEGF and NO are associated to subsequent fetal death. STUDY DESIGN: We retrospectively assessed NO and VEGF on midtrimetster amniotic fluid from seven women who had subsequently had intrauterine fetal death before 20 weeks, and compared the results with those of 14 controls matched for age and gestation. All women had undergone amniocentesis for maternal age. All were at 16 weeks of gestation. None had shown chromosomal abnormalities. Results (mean+/-S.D.) were tested for statistics with Student's t-test with significance at P<0.05. RESULTS: Women with subsequent fetal death had both amniotic NO and VEGF lower than women with normal pregnancy (NO 3.28+/-1.20 microg/mg creatinine versus 6.02+/-1.57 microg/mg creatinine, P<0.05; VEGF 210.10+/-69.55 pg/ml versus 255.05+/-88.66 pg/ml). CONCLUSIONS: An early reduction of both NO and VEGF may be responsible of an impaired placental vascular development and endothelial regulation that may lead to fetal death.

Amniotic vascular endothelial growth factor (VEGF) and nitric oxide (NO) in women with subsequent preeclampsia.

OBJECTIVE: To assess whether amniotic fluid concentrations of nitric oxide (NO) and vascular endothelial growth factor (VEGF) in early pregnancy correlate to subsequent preeclampsia. STUDY DESIGN: We performed a retrospective study to assess VEGF and NO on the second trimester amniotic fluid of 15 healthy women, and 15 women who subsequently developed preeclampsia. RESULTS: In women with subsequent preeclampsia, both VEGF (213.19+/-78.42 pg/ml) and NO concentrations (4.31+/-1.02 micromol/mg creatinine) were significantly lower than healthy controls (VEGF 255.05+/-88.66 pg/ml; NO 5.02+/-1.57 microg/mg creatinine; P<0.05). CONCLUSIONS: Our findings suggest that reduced VEGF may be responsible, at least in part, for the impaired vascular development which occurs in preeclampsia. Low concentrations of VEGF and NO in the second trimester may represent an impaired stimulus to vascular formation and endothelial regulation that induce placental disease and preeclampsia.