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Background: Fetal acidemia at birth is defined as a newborn condition wherein the cord blood pH value is less than 7.0. It could represent an association with newborn brain damage; therefore, it is important to investigate which conditions precipitate its occurrence. No extensive placental analysis has been performed in cases of acidotic newborns delivered from low-risk pregnancies. Aims: To study placental characteristics in cases with severe fetal acidemia. Study design: Retrospective case-control study. Subject: 34 cases, 102 controls. Outcome measures: Umbilical artery pH was measured at delivery from a doubly clamped portion of the cord. Placental characteristics were compared between cases with severe fetal acidemia (cord pH at birth

To assess the combined use of cervical length and cervical phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) in the prediction of preterm delivery in symptomatic women.Cervical length was prospectively measured in 102 consecutive singleton pregnancies with intact membranes and regular contractions at 24-32 weeks, and phIGFBP-1 was assessed in those with a cervix ≤30 mm.Among women with a cervix30 mm (n = 42), none delivered34 weeks or within 7 days. Among women with a cervical length ≤30 mm (n = 60), eight delivered34 weeks, four of which within 7 days. A positive phIGFBP-1 conferred a significantly increased risk of delivery before 34 weeks in women with a cervix ≤30 mm (likelihood ratio 2.32, 95% confidence interval 1.15-4.67), and a significantly increased risk of delivering within 7 days in the subgroup of women with a cervical length of 20-30 mm (likelihood ratio 3.64, 95% confidence interval 2.20-6.01).In symptomatic women with a cervical length30 mm the risk of preterm delivery is very low. In women with a cervix ≤30 mm, adding phIGFBP-1 assessment may improve the risk assessment for preterm delivery, and help to plan subsequent pregnancy management.

An increased fetal DNA concentration in maternal plasma has been observed in placental pathological conditions associated with hypertension and preeclampsia. To confirm these data, we performed real-time quantitative PCR on the SRY gene in a group of physiological and pathological male-bearing pregnancies. In 78 physiological pregnancies, fetal DNA concentration in maternal plasma was 20.7, 13.4, 23.6, and 74.8 genome-equivalents (g.e.)/mL during the first, second, and third trimesters and at term, respectively. In 10 preeclamptic women, fetal DNA concentration ranged from 59.3 to 615.2 g.e./mL (median: 332.9). In 7 women with preeclampsia and IUGR (intrauterine growth retardation), fetal DNA ranged from 96.5 to 859 g.e./mL (median: 146.8). In 4 women with IUGR and hypertension, fetal DNA ranged from 34 to 473.5 g.e./mL (median: 142.4). In 3 patients with IUGR, fetal DNA ranged from 168.6 to 519.7 g.e./mL (median: 308.1). In 2 patients with IUGR and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, fetal DNA concentration ranged from 105 to 394.1 g.e./mL (median: 249.7). Four women who developed preeclampsia some weeks later showed fetal DNA levels within the physiological range. These data suggest that increased fetal DNA concentrations might represent a valuable marker of placental abnormalities and suggest that this rise may precede clinical manifestation of preeclampsia by only a few weeks.

To correlate umbilical artery Doppler velocimetry with perinatal outcome in a group of growth-restricted fetuses.The study was a retrospective analysis of 578 singleton pregnancies with diagnosis of intrauterine growth restriction (IUGR), delivered in a single obstetric unit, at the Spedali Civili, Brescia, Italy, a university and teaching hospital with 3500 deliveries a year and neonatal intensive care unit (NICU).During 1991-99 we studied 578 pregnancies with a diagnosis of IUGR referred for Doppler velocimetry. From this population, four subsets were formed: normal umbilical artery pulsatility index (NUAPI; 334 fetuses); increased pulsatility index but with telediastolic flow (abnormal umbilical artery pulsatility index AUAPI; 137 fetuses); absent end-diastolic flow (AEDF; 70 fetuses); reverse telediastolic flow (RF; 37 fetuses). Fetal biometry, amniotic fluid and fetal-maternal Doppler velocimetry were evaluated in all patients, with biophysical profile and routine non-stress test, when indicated. The following outcomes were examined: mean gestational age at delivery, number of preterm deliveries (34 weeks), mean neonatal weight, Apgar score at 5 min7, prenatal and neonatal deaths (within the first 28 days of life), admission to the NICU and number of days spent after birth in hospital. Neonatal morbidity was analyzed, including respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH, grade 2-3), necrotizing enterocolitis (NEC) and retinopathy of prematurity. Long-term neurological follow-up is still ongoing and will not be presented in this paper.Out of 578 fetuses with IUGR, 547 were born alive. There were 26 neonatal deaths. The mean gestational age at delivery was 35.6 +/- 4 weeks and mean birth weight 1844 +/- 612 g. There were 28 intrauterine deaths and three elective terminations of pregnancy. A total of 60 cases (11%) were complicated by RDS, 13 cases (2.4%) by retinopathy of prematurity, IVH was present in nine cases (1.6%) and NEC in seven cases (1.3%). Total perinatal mortality was 9.8%; in the 26 cases of neonatal death, the mean week at delivery was 29.6 +/- 4 with a mean weight of 840 +/- 425 g. Patients with NUAPI had a mean week at delivery of 37 +/- 3, those with AUAPI delivered at 34 +/- 3.2, those with AEDF delivered at 31 +/- 3 and those with RF delivered at 29 +/- 2 weeks. In progressively worsening umbilical velocimetry, we observed an increase of incidence of low Apgar score. Days of admission to the NICU and incidence of perinatal mortality increased with the worsening of Doppler velocimetry.Our study underlines the existence of a strict correlation between umbilical Doppler velocimetry and an increased incidence of perinatal complications in IUGR fetuses.

Objective : To test whether late normalisation of abnormal uterine velocimetry is a favourable prognostic factor in high risk pregnancies. Study Design : Uterine artery colour Doppler velocimetry was performed at 24, 28–30 and 32–34 weeks in 282 high risk pregnancies treated with low dose aspirin. Results : 88 patients had abnormal waveforms at 24 weeks and 77 delivered after the second assessment at 28 weeks. Of these, 38 (49%) had a normalisation of Doppler indices by 34 weeks. Compared with the persistently abnormal Doppler group, these patients delivered fewer small for gestational age babies (5/38 versus 26/39; p =0.0001) and had less gestational hypertension without proteinuria (3/38 versus 15/39; p =0.004). No patients with preeclampsia or other severe complications of pregnancy were observed in the normalised group. Conclusions : Although abnormal uterine artery velocimetry at 24 weeks is predictive of adverse pregnancy outcome, nearly half have late normalisation of the Doppler indices and a better perinatal outcome. Persistently abnormal waveforms are related to the worst pregnancy outcome.

Objective: To compare the efficacy of transdermal glyceryl trinitrate and intravenous (IV) ritodrine as tocolytics. Methods: Two hundred forty-five women with preterm labor and intact membranes between 24 and 36 weeks' gestation were randomized to transdermal glyceryl trinitrate or intravenous ritodrine. Treatment was continued until contractions stopped or a maximum of 7 days. Glyceryl trinitrate was administered as a 10- or 20-mg transdermal patch. Intravenous ritodrine was administered according to nationally available guidelines. The primary outcome was prolongation of gestation expressed as a percentage of the time from entry to 37 weeks. Secondary outcomes were proportion of women who delivered the same day, next day, or within 7 and 14 days of entry, and by 32, 34, and 37 weeks. Analysis was by intention to treat. Results: Twelve women (5%) were lost to follow-up. Glyceryl trinitrate and ritodrine prolonged gestation by 74% of time to 37 weeks (difference glyceryl trinitrate-ritodrine 0%; 95% confidence interval (CI) −10%, +10%). There was no significant difference in the proportion of women receiving glyceryl trinitrate or ritodrine who delivered within the specified days from study entry or weeks of gestation; however, 42 women who received glyceryl trinitrate and 58 women who received ritodrine delivered by 37 weeks (difference −11%; 95% CI −24%, +2%). No serious maternal side effects were reported for ritodrine or glyceryl trinitrate. Conclusion: We found no overall difference between glyceryl trinitrate and ritodrine in the acute tocolysis of preterm labor but a suggested advantage of glyceryl trinitrate over ritodrine in reducing preterm delivery rate. The maternal side effect profile and treatment discontinuation rates were fewer for glyceryl trinitrate, suggesting it was a safer alternative to ritodrine.

Objective To establish the efficacy of prophylactic nifedipine vs. placebo in reducing spontaneous preterm delivery in asymptomatic women at high risk for preterm delivery. Design Prospective multicentric randomized double-blind study. Setting Tertiary care centre, University Hospitals of Brescia and Torino, Italy. Population Eighty-seven singleton pregnancies without uterine contractions and ultrasonographic cervical length of ≤25 mm at 24–32 weeks, at risk for preterm delivery, with longitudinal follow up in our Preterm Prevention Clinic. Methods Selection was done on the basis of ultrasonographic cervical length; 43 women were randomized to receive placebo and 44 to receive nifedipine. Main outcome measures Primary end point: spontaneous preterm delivery

Autophagy is an inducible catabolic process activated during compromised conditions, such as hypoxia. Neonatal encephalopathy (NE) is a syndrome of disturbed neurological function. No absolute prognostic indicators are available at birth to identify neonates at high risk to develop NE. Immunohistochemical staining with LC3 antibody was performed on 40 placentas from uneventful term singleton pregnancies with umbilical artery pH ≤ 7.00 at birth; semi-quantitative analysis was carried-out to estimate autophagy level. 6/40 (15%) neonates developed NE. Placentas from newborns with NE exhibited a higher LC3 expression. Autophagy protein expression in placentas with severe acidosis is a potential marker for poor outcome.

Aim: This study examines the influence of selected sociodemographic and pregnancy specific factors on the risk of Late Preterm Births (LPB) analyzing separately induced and spontaneous. Methods: We conducted a case-control study of LPB observed in 5 Italian Centers. Cases are 305 women who delivered at 34, 35 and 36 weeks gestation. The controls were 269 women who gave birth at term (>37 weeks of gestation). Results: Considering the total series, the risk of LPB was above unity in hypertensive women, but the OR was 6.70 (95% CI 3.25-13.82) in women with induced LPB and 0.90 (95% CI 0.35-2.32) in women with spontaneous LPB. Positive culture of vaginal smear was associated with an increased risk of LPB. Conclusions: According to our results hypertension increases the risk of medically indicated LPB while a history of preterm birth or positive vaginal smear are associated with an increased risk of spontaneous and induces LPB.

OBJECTIVE: We conducted a cohort study in growth-retarded fetuses to establish if absent or reverse end-diastolic flow in the umbilical artery was associated with increased perinatal mortality and morbidity and neurologic damage at long-term follow-up. STUDY DESIGN: Thirty-one fetuses with intrauterine growth retardation and absent or reverse end-diastolic flow in the umbilical artery (study group) and 40 growth-retarded fetuses with detectable diastolic flow in the umbilical artery, divided into two control groups, were followed up with serial nonstress tests, Doppler flow studies, and biophysical profiles. Twenty newborns from the study group survived the perinatal period and were observed for a mean of 18 months (range 12 to 24 months). Their neurologic outcomes were compared with those of 26 neonates from the two control groups. RESULTS: Study group fetuses had a higher incidence of abnormal karyotype (9.7% vs 0%) and corrected perinatal mortality (26% vs 6% and 4%) and a greater risk of permanent neurologic sequelae (35% vs 0% and 12%) compared with the fetuses from the two control groups. CONCLUSIONS: Growth-retarded fetuses with absent or reverse end-diastolic flow in the umbilical artery not only have an increased fetal and neonatal mortality but also a higher incidence of long-term permanent neurologic damage when compared with growth-retarded fetuses with diastolic flow in the umbilical circulation. (AM J OBSTET GYNECOL 1994;170:796-801.)

Objective: To compare the effects of oxytocin and amniotomy or vaginal prostaglandin E 2 (PGE 2 ) for induction of labour. Study design: We conducted a randomized clinical trial. Eligible for the trial were women with normal pregnancy, parity 0–3, with intact membranes, >40 weeks of gestation documented by ultrasound examination before 20 weeks gestation, observed in a network of 13 general and teaching hospitals in Italy. Inclusion criteria were cervical Bishop's score 5–7, less than six uterine contractions per hour, single pregnancy, cephalic presentation, no history of cesarean section and uterine surgery. Eligible women were randomly assigned by phone to oxytocin plus amniotomy (163 women) or vaginal PGE 2 2 mg, two doses at 6-h intervals (157 women). Results: Overall, 50 women (15.6%) delivered by cesarean section, 22 (13.5%) randomized to oxytocin, and 28 (17.8%) randomized to PGE 2 (not significant). Twelve hours after randomization, induction had failed in 26 women of the 163 randomized to oxytocin plus amniotomy (21.6%) and 34 out of the 157 randomized to PGE 2 (15.9%): the difference was not significant. Neonatal outcome was similar in the two groups. Conclusions: This study did not find marked differences in labour and neonatal outcome between women randomized to oxytocin plus amniotomy or vaginal PGE 2 . A shorter induction delivery interval in the group receiving amniotomy and oxytocin after PGE 2 priming was observed.

To evaluate the role of uterine artery Doppler investigation in predicting perinatal outcome of patients with chronic hypertension.Uterine artery velocimetry was investigated at 24 weeks gestation in 78 chronic hypertensive pregnant women by means of color Doppler. The resistance index (RI) and the presence of a diastolic notch were recorded and related to the development of superimposed preeclampsia (SPE), pregnancy aggravated hypertension (PAH). and intrauterine growth retardation (IUGR).There were more pregnancy complications in the 25 patients with abnormal RI, compared with the 53 women with normal RI (SPE 12% vs. 0%, PAH 36% vs. 7% and IUGR 52% vs. 2%; P0.01), and more in women with a bilateral diastolic notch compared with those without (SPE 23% vs. 0, PAH 54% vs. 4%, IUGR 85% vs. 2%; P0.0001), while no differences were detected in those with only a unilateral notch, except for PAH (27% vs. 4%; P0.01).Uterine artery Doppler velocimetry identifies a subgroup of chronic hypertensive patients with a high frequency of pregnancy complications.

The aim of this study was to evaluate the role of uterine artery Doppler velocimetry performed at 20 and 24 weeks gestation in predicting gestational hypertension and small-for-gestational age babies in a population of nulliparous women. Four hundred and fifty-six patients without risk factors for pregnancy complications and with fetuses free from structural abnormalities at ultrasonographic examination at 20 weeks gestation were considered in the study. During the routine 20 weeks ultrasound a continuous-wave Doppler examination of the uterine arteries was performed. The patients with abnormal uterine Resistance Index (RI) repeated the Doppler evaluation at 24 weeks by means of Colour Doppler equipment. Among the 419 women who completed the study an abnormal Doppler uterine arteries velocimetry was found in 8.6% of the patients. Pregnancy complications (gestational hypertension and/or small-for-gestational age babies) were observed in 56% of the patients presenting high uteroplacental RI versus 10% of those with normal uterine artery velocimetry ( P =0.0001). In the group of patients with an abnormal RI value, the presence of a diastolic notch in one or both of the uterine arteries identified a population of pregnant women at higher risk for pregnancy complications when compared with patients without notch (78% vs. 33%, P =0.007). The knowledge of the uteroplacental resistance can help in identifying a subgroup of patients at higher risk of hypertensive disorders and small-for-gestational age babies that could benefit from prophylaxis with low dose aspirin.

Objectives: Preterm delivery is defined as a labor that occurs at less than 37 weeks’ gestation. There has been a recent interest in ultrasonographic and biochemical markers designed to differentiate the truly high-risk patient. We analyzed biochemical cervical–vaginal inflammatory markers like cytokines and insulinlike growth factor binding protein’s phosphorylated isoform (phIGFBP-1). Methods: We analyzed 214 symptomatic and 285 asymptomatic women. Transvaginal ultrasonography was performed at admission. We collected from cervical–vaginal secretions two samples of IL-6 and IL-8 and a sample of the decidual phIGFBP-1. Results: Characteristics of the two groups are shown in the Table.