Intervillous circulation in intra-uterine growth restriction. Correlation to fetal well being.

Magnetic resonance imaging requested for a potentially serious indication, provided a unique opportunity to explore the intervillous circulation of placentas from pregnancies complicated by Intra Uterine Growth Restriction (IUGR) and to compare them to normal cases. This allowed an innovative characterization of in vivo utero-placental blood flow, correlating a compromised intervillous circulation in IUGR to the deterioration of fetal condition. MR imaging was requested to rule out suspected posterior placental adhesive disorders in 26 patients. Twelve patients had fetuses appropriate for gestational age, while in 14 patients fetuses were affected by severe IUGR. Multiphasic dynamic contrast-enhanced sagittal sequences were acquired and a quantitative analysis of signal intensity and enhancement kinetics was performed for both the entire placenta and for selected regions. Images disclosed a homogeneous perfusion overall the placenta in normal cases, while IUGR placentas displayed a slow intervillous blood flow, along with many patchy unperfused areas. Intermittent stops worsen the perfusion dynamics of the intervillous mostly in IUGR cases with an elevated ductus venosus pulsatility index. In conclusion, we proved that in IUGR placenta maternal placental blood flow is extremely compromised and that superimposed dynamic phenomena concur to worsen the intervillous circulation leading to an end-stage fetal decompensation.

Mean platelet volume: association with adverse neonatal outcome.

The aim of the study was to investigate on a possible association between maternal mean platelet volume (MPV) and oxygen-metabolic changes in pregnancies affected by altered maternal-fetal Doppler velocimetry. We considered the altered maternal-fetal Doppler velocimetry group (n = 57) pregnant women admitted to our Institution for a pregnancy complication associated to the event Pre-eclampsia (PE) and intrauterine growth retardation (IUGR), with altered Doppler velocimetry in the umbilical artery ( UA) (high pulsatility index, absence or reverse end diastolic flow (ARED), blood flow cephalisation) and/or bilateral increased resistance in uterine arteries. Out of these cases, 25 pregnancies were complicated by PE and 32 pregnancies were complicated by IUGR. We included 145 normotensive third trimester pregnant women as a normal maternal-fetal Doppler velocimetry control group. From all women, 20 ml of whole venous blood was obtained from the antecubital vein soon after Doppler velocimetry evaluation. MPV was significantly higher in women with abnormal Doppler velocimetry compared to those with normal Doppler velocimetry (8.0 fl [7.0-8.7] vs. 9.1 fl [8.0-10.6], <0.001. Values are median [interquartiles]). We performed a ROC curve in order to find an MPV cut-off able to predict an uneventful event in Doppler velocimetry compromised fetuses (neonatal O(2) support > 48 hrs or intubation and/or pH < 7.2 at umbilical blood gas analysis (UBGA)). An MPV > or = 10 fl was significantly related to the former diagnostic endpoints compared to that of non-compromised fetuses (sensitivity: 45%, specificity: 89.7%, 95 CI: 18.8-66, p < 0.01). Our study suggests that pregnancies affected by Doppler velocimetry alterations, an MPV value > or = 10 fl may be associated with severe oxygen support and/or low UA ph at birth.

Nuchal translucency as a predictor of adverse pregnancy outcome.

BACKGROUND: Thickened nuchal translucency (NT) has been related to fetal genetic syndromes, structural abnormalities, and other diseases. The aim of this research was to evaluate the association of NT with adverse pregnancy outcomes. STUDY DESIGN: In the period 2002-2004 in 2104 pregnant women between 10+6 and 13+5 weeks' gestation, NT was evaluated as a parameter for aneuploidy screening: out of these, 734 singleton pregnant women that underwent 2nd trimester amniocentesis and whose pregnancy outcome were known were selected. NT was statistically correlated to pregnancy and neonatal outcome. RESULTS: Median gestational age (GA) at NT evaluation was 11+2 weeks' gestation. NT median was 1.1 mm (0.9-1.4 mm, 25th-75th centile, range 0.5-4.0 mm). After multiple logistic regressions, the variables significantly associated to NT values were: threatened preterm labor (p<0.008) and preterm labor (p<0.02). The best diagnostic accuracy point was NT>95th centile and >1.5 MoM for the prediction of threatened preterm labor. CONCLUSION: In this series, increased NT values were associated to threatened preterm labor and preterm labor in euploid fetuses: this finding may have clinical consequences in the management of such pregnancies.

Prognostic value of umbilical-middle cerebral artery pulsatility index ratio in fetuses with growth restriction.

OBJECTIVE: To study the utility of Doppler velocimetry and computerized cardiotocography in the management of intrauterine growth restriction and prediction of neonatal outcome. PATIENTS AND METHODS: Seventy-two pregnant women with fetuses showing growth restriction and delivered within 48 h of their last Doppler velocimetry evaluation. The last computerized cardiotocographic trace from these fetuses was used for statistical analysis, and the last trace from the healthy fetuses of 93 consecutive women undergoing cesarean section was used as control. Umbilical artery pulsatility index (UA PI), middle cerebral artery pulsatility index (MCA PI), UA PI/MCA PI ratio, and uterine artery resistance index (Ut RI) were assessed. RESULTS: Among women with growth-restricted fetuses, all parameters were significantly higher in those who had hypertension; and in those who had diabetes, only the UA PI/MCA ratio was significantly higher. Umbilical artery PI values and the UA PI/MCA ratio were higher in those who had a nonreassuring result to computerized nonstress test immediately before delivery. A multiple logistic analysis showed that the UA PI/MCA ratio was the only Doppler velocimetry parameter predicting cardiotocographic nonreactivity; furthermore, the predictivity of extended newborn hospitalization (longer than 15 days) was verified, with a sensitivity of 56% and a specificity of 92% when the ratio was higher than 1.26. CONCLUSION: The MCA PI of fetuses with growth restriction should be assessed. The UA PI/MCA ratio is predictive of a nonreactive computerized cardiotocography trace and of prolonged neonatal hospitalization.

[Treatment strategies for neonatal pulmonary morbidity in Europe]. / Prise en charge de l'immaturité pulmonaire en néonatologie: enquête sur les pratiques européennes.

OBJECTIVES: To survey practices in 14 European countries and to describe strategies for the prevention and treatment of pulmonary morbidity in very preterm newborns. METHODS: Questionnaires covering the use of prenatal steroids, surfactant and postnatal steroids were sent in 1999-2000 to every neonatal unit taking very preterm newborns in charge in population-based areas covering at least 20,000 births annually. One questionnaire was sent by surveyed unit. RESULTS: Results are given concerning these three treatments and compared to evidence based recommendations. CONCLUSION: Antenatal steroids were given at recommended terms. Surfactant was prescribed with respect of best practices. Postnatal steroids utilisation was not well described.

The policy of antenatal corticosteroid administration in Italy vs. other European countries.

OBJECTIVE: To describe antenatal corticosteroid policies in Italy in comparison with other European countries, as inferred by the published data of the EURAIL Study Group (1999). METHODS: The results of a mail survey of departmental policies in Italy and Europe were compared. RESULTS: The survey response rate was similar in Italy and Europe (86% and 81%, respectively); 70.7% of the respondents in Italy and 84% in Europe started antenatal corticosteroids from 24 to 28 weeks' gestation; however, 5% of respondents in Italy started at a gestational age of >34 weeks. The use of multiple antenatal corticosteroid courses was observed in 81% of the units in Italy and 87% in Europe. Betamethasone was the more frequently used drug in Italy. CONCLUSIONS: Antenatal corticosteroids are used frequently in Italy and Europe in accordance with international recommendations, although many differences exist in the mode of administration. In 1999 almost all units used multiple courses, although this may not represent the rule 5 years later, following the publication of a prospective randomized trial that questioned the benefits of multiple courses of antenatal corticosteroids.

Antenatal corticosteroids policies in 14 European countries: factors associated with multiple courses. The EURAIL survey.

AIM: To describe antenatal corticosteroids (ANCs) policies in European obstetric units and to determine factors that influence the use of multiple courses. METHODS: 641 obstetricians from obstetric departments covering a geographical area in 14 European countries responded to a questionnaire on ANCs policies. Logistic regression was used to identify factors that were related to the use of multiple ANCs courses. RESULTS: The survey response rate was 76% (inter-country range 33-94%): 11% (0-50%) of the respondents started ANCs from 23 to 24 wk gestation, 82% from 24 to 28 wk (50-100%) and 7% from 28 to 36 wk (0-32%). Eighty-five percent of the units (63-100%) used multiple ANCs courses. After adjustment for country, number of infants delivered at 24-32 wk annually in the unit, NICU and maternal hypertension, maternal hypertension tended to be an explicative factor (OR 1.97; 95% CI: 0.75-5.17). CONCLUSIONS: The high proportion of departments that initiated ANCs between 24 and 28 wk of gestation is consistent with the high incidence of neonatal morbidity and mortality in that age range. Multiple courses are overwhelmingly prescribed in Europe, although their risk/benefit ratio compared with a single dose is not yet known. The likelihood of using repeated courses of ANCs may be related to the presence of maternal hypertension, and this highlights the importance of closely monitoring women at risk of premature delivery.

Computerized cardiotocography in the management of intrauterine growth restriction associated with Doppler velocimetry alterations.

OBJECTIVE: To verify the reliability of computerized cardiotocography (cCTG) in the prediction of the oxygen metabolism status of fetuses with growth restriction and Doppler velocimetry alterations. METHODS: From 24 third-trimester cesarean section performed because of intrauterine growth restriction (IUGR) and Doppler velocimetry alterations, there were 11 cases of fetal heart rate alterations (Dawes-Redman criteria were not satisfied) and 13 cases of reactive cCTG. Fetal lung maturity was detected by amniocentesis and blood samples for umbilical blood gas analysis (UBGA) were collected before the first neonatal breath from the umbilical artery in a double-clamped segment of the cord. RESULTS: Umbilical cord gas analysis showed arterial cord blood pH to be 7.20 or less in 11 newborns (45.8%), 7.10 or less in 6 (25%), and 7.00 or less in 3 (12.5%). Linear regression analysis showed short-term variation (STV) in the fetal heart rate to be significantly correlated with umbilical artery pH (r = 0.49; P = 0.01) and pCO2 (r = -0.50; P = 0.01). There were no significant correlations between cCTG and the other UBGA parameters considered. Receiver operator curves permitted to calculate the STV values at which pathological neonatal UBGA values can be expected (pH < 7.00 and pCO2 > 80 mmHg). A short-term variation less than 4.5 ms was found to predict acidemia with a sensitivity of 100% and a specificity of 70% (positive predictive value, 33%; negative predictive value, 100%), and hypercarbia with a sensitivity of 100% and a specificity of 77.8% (positive predictive value, 55.6%; negative predictive value, 100%). CONCLUSION: In view of the results of this study, 4.5 ms for STV may be a threshold below which timing of delivery should be decided in cases of fetal growth restriction.

Foscarnet therapy for congenital cytomegalovirus liver fibrosis following prenatal ascites.

We report on an infant with multi-system disease including liver fibrosis, right microphthalmia with cataract, interstitial pneumonitis, and hyperechoic lesions in the basal ganglia and in the periventricular and thalamic regions. Prenatal ascites with hepatomegaly concomitantly with detection of cytomegalovirus (CMV) DNA in the amniotic fluid, following recurrent maternal CMV infection, had been shown. Although CMV culture and DNA detection were negative in the urine, the infant was given foscarnet because CMV infection was demonstrated in the liver by DNA detection and immunohistochemical staining. Favorable clinical outcome and absence of CMV in the liver were subsequently shown. Our case suggests that congenital CMV disease following maternal recurrence may not be associated with disseminated infection but only with intracellular infection. The diagnosis should therefore be based on CMV detection in the involved organs. Moreover, this is the first report on the possible efficacy and safety of foscarnet for therapy of immunocompetent infants with congenital CMV disease.

[Controlled release vaginal dinoprostone for the induction of labour]. / Induzione del travaglio di parto con dinoprostone vaginale a rilascio controllato.

AIM: To study the efficacy and safety of controlled release dinoprostone (PGE2) for the induction of labour. METHODS: From March 2001 to August 2002, a total of 173 patients hospitalized for postdate pregnancy, maternal hypertension, intrauterine delayed growth, reduction of amniotic fluid, were studied. In 33 of these patients, a hydrogel strip containing 10 mg dinoprostone, inserted into the posterior fornix of the vagina and release PGE2 at constant rate of 0.3-0.4 mg/h was used. RESULTS: Indications for induction, mode and time of delivery, maternal, fetal and neonatal parameters anomalies are evaluated. In 23 patients dinoprostone was used for postdate pregnancy, in 4 for maternal hypertension, in 4 for oligohydramnios and in 2 for intrauterine delayed growth. In 2 cases, the vaginal insert was removed for hyperstimulation in 1 case and for abnormal fetal heart rate in the other case. After vaginal delivery, Apgar scores and umbilical artery pH values were evaluated without anomalies. Vaginal delivery within 24 hours occurred in 51.6% of patients and medium time to delivery was 17.5 (nulliparous) and 12.3 (multiparous) hours. Only one case of uterine hyperstimulation to PGE2 was recorded, and the induction was suspended. The cesarean section rate was 12% and vaginal delivery after 24 hours was 38.7%. CONCLUSION: The continuous release of PGE2 from the vaginal insert permits a controlled and safe induction of labour, minimal risk of hyperstimulation, fast and easy removal of drugs in cases of fetal or maternal anomalies, easy accetability for patients, but high cost.

Treatment strategies for bronchopulmonary dysplasia with postnatal corticosteroids in Europe: the EURAIL survey.

AIM: To survey practices in 14 European countries and describe strategies for the prevention and treatment of bronchopulmonary dysplasia with postnatal steroids (PNS). METHODS: In 1999-2000 questionnaires covering the use of PNS were sent to every neonatal unit taking very preterm newborns in charge, in population-based areas covering at least 20000 births annually. One questionnaire was sent to surveyed unit. The participating areas were chosen by an expert from each country participating in the Europe Against Immature Lung (EURAIL) study group. RESULTS: Responses to 331 questionnaires were received; the mean response rate by countries was 84% (range 64-100%). Teaching hospitals accounted for 19% of the responding units. The number of extremely premature newborns (less than 28 wk of gestation) admitted yearly to these units was 0 in 16%, < 20 in 62%, 20-39 in 11% and > 39 in 11%. Overall, 67% of the centres used PNS: 48% initiated treatment in non-intubated infants and 53% at 7-14 d. Treatment duration was 4-15 d in 62% and > 15 d in 21%. PNS administration was limited to intubated infants less often in smaller units [odds ratio (OR) 0.2, 95% confidence interval (95% CI) 0.1-0.6] and more often in non-teaching hospitals (OR 2.5, 95% CI 2.5-5.0). CONCLUSIONS: Although PNS have important side effects, they were still widely used in 1999 to treat or prevent chronic lung disease. Surprisingly, steroids are still prescribed in non-ventilated infants. PNS use should be based on guidelines derived from the evidence from randomized controlled trials. This evidence should be regularly updated and disseminated.

Ultrasonographic patterns of fetal breathing movements in normal pregnancy.

OBJECTIVE: To assess through pregnancy fetal breathing movements (FBMs) patterns detected by M-mode and Doppler velocimetry technology. METHODS: In this cross-sectional study FBMs were investigated in 1882 uncomplicated pregnancies over a 4-year period. Abdominal and thoracic wall movements of fetuses between 14 and 40 weeks of gestation were studied by M-Mode scan, and color Doppler velocimetry with spectral imaging analysis was used to investigate the presence of FBMs associated with nasal fluid flow velocity waveforms (NFFVWs). RESULTS: Abdominal movements were observed in 19% of cases when gestation was less than 20 weeks and in 61% of cases when it was between 21 and 25 weeks; chest movements were significant after 21 weeks; and NFFVWs were detected at 22 weeks and increased progressively to 93% of cases at term. CONCLUSIONS: Fetal breathing movements are a complex phenomenon with a composite, progressive pattern of development during gestation.

The combination of computerized cardiotocography and amniotic fluid index for the prediction of neonatal acidemia at birth: a modified biophysical profile.

OBJECTIVE: To study the combination of computerized cardiotocography (cCTG) and the amniotic fluid index (AFI) in the prediction of neonatal acidemia at birth. METHODS: A total of 89 singleton third-trimester high-risk pregnancies delivered by Cesarean section, with an AFI evaluated within 24 h from birth, and an antepartum cCTG performed within 6 h from delivery, were studied. The score was the sum of values for AFI (oligo/anhydramnios = 1, normal = 0) and cCTG (Dawes-Redman criteria, not met = 1, met = 0). The endpoint was to predict an abnormal neonatal outcome as defined by an umbilical artery pH of < or = 7.2. RESULTS: Fifteen neonates had an umbilical artery pH of < 7.2. The combination of cCTG + AFI score was able to predict pH values (< or = 7.20) with an OR = 2.83 (p < 0.02). The diagnostic accuracy of the combination of cCTG + AFI was as follows: sensitivity 80%, specificity 58%, positive predictive value 28%, negative predictive value 83%. COMMENT: We suggest that the cCTG + AFI score may be of value in the prediction of neonatal acidemia and help in the management of third-trimester high-risk pregnancies.

The prognostic significance of acetowhitening of the vulva and HPV-DNA test. A multicentre study.

Acetowhitening of the vulva has been related to a subclinical human papillomavirus (HPV) infection. No consense has been reached about undertaking -or not- any therapy for these acetowhite changes. We have observed from our clinical experience and in a 10 years observational follow-up, that acetowhitening of the vulva regarding high risk (16-18) and low risk (6-11) HPV groups (as assessed by PCR analysis) significantly decreased; and acetowhitening areas negative to polymerase chain reaction (PCR), significantly increased from 53% (202/382) to 85% (276/325) (P<0.001). Our findings suggest that independently from HPV type and in the absence of cofactors, there is a statistically significant spontaneous remission of these areas.

Lamellar body counts: a consensus on protocol.

Lamellar bodies, concentrically layered "packages" of phospholipid that represent the storage form of surfactant, can be counted in the platelet channel of most electronic cell counters. The lamellar body count has been used for more than a decade and performs as well as traditional phospholipid analysis as an assay for evaluating fetal lung maturity. It is preferable to phospholipid analysis because it is rapid, objective, and inexpensive and can be performed in any hospital laboratory. The current methodologies for specimen preparation vary widely among laboratories, most notably with respect to centrifugation, resulting in differences in maturity cutoffs used. Our goal was to establish a consensus regarding a standardized methodology for the lamellar body count. Institutions that previously had published their results with lamellar body counts were invited to contribute. The consensus of the four participating institutions includes the following: centrifugation is not a necessary step and should be abandoned, maturity is suggested by a count of 50,000/microL or greater, and immaturity is suggested by a count of 15,000/microL or lower. As the lamellar body count gains wider acceptance as a primary assay for assessing fetal lung maturity, the test must be performed uniformly and accurately, given the implications of acting on a falsely negative test resulting from improper methodology.

Effect of antenatal betamethasone therapy on maternal-fetal Doppler velocimetry.

BACKGROUND: The effect of antenatal betamethasone on fetal parameters includes a transient reduction of FHR variation and of fetal body movements. An effect on maternal-fetal blood flow has also been shown, with non-univocal results. AIMS: To evaluate the effect of antenatal betamethasone in third trimester singleton high-risk pregnancies by Doppler technology. SUBJECTS AND METHODS: Thirty-six pregnant women who received a full course of betamethasone (12 mg i.m. two times, 24 h apart) were studied. The Doppler examination included the assessment of the pulsatility index (PI) of the umbilical artery (UA PI), the middle cerebral artery (MCA PI) and of resistance index of uterine arteries (Ut RI) before treatment, and 48 and 96 h after second dose of betamethasone. RESULTS: No significant variation was noted in UA PI through betamethasone therapy. MCA PI decreased significantly 48 h from the last injection of betamethasone (P=0.002), and returned to basal values at 96 h. No difference was found for the other Doppler parameters examined. When serial Doppler studies were analyzed according to the gestational age, in the group <32 weeks' gestation, MCA PI decreased significantly after 48 h (P<0.006) and returned to pre-treatment values after 96 h from the last betamethasone dose. Conversely, no difference was found in Doppler serial measurements in any of the analyzed districts in the subgroup > or =32 weeks. CONCLUSION: Betamethasone treatment is associated with a significant, although transient, reduction of MCA PI, especially at gestational ages <32 weeks'.