Efficacy of three different antithrombotic regimens on pregnancy outcome in pregnant women affected by recurrent pregnancy loss.

INTRODUCTION: Recurrent pregnancy loss (RPL) is a common health problem affecting 1-5% of women at reproductive age. AIM OF THE STUDY: Evaluation of three different antithrombotic treatments in women with antecedent of RPL, comparing the results in negative and positive to thrombophilic screening pregnant women. MATERIALS AND METHODS: We recruited 361 women with an antecedent of two or more pregnancy losses. From this group, 167 women became pregnant and considered for the study. The evaluated pregnant women were divided as negative/positive to thrombofilic screening: (a) 80 (48%) with negative thrombophilic screening, (b) 87 (52%) positive to thrombophilic screening. Pregnant women included in the study and considered negative or positive for thrombophilic screening, were randomized into three different therapy groups: (a) group 1: Acetil salicylic acid (ASA) 100 mg daily until third month of pregnancy, (b) group 2: low molecular-weight heparin (LMWH) - enoxaparine 40 mg daily until third month of pregnancy, (c) group 3: ASA 100 mg plus LMWH 40 mg daily until third month of pregnancy. RESULTS: In 80 negative to thrombophilic screening pregnant women, the comparison of efficacy of the three treatments, shows that all three treatment regimens were significantly effective comparing live births against fetal losses. In 87 positive to thrombophilic screening pregnant women, the comparison of efficacy for the three regimens, shows that the therapy with LMWH or LMWH plus ASA are significantly protective against fetal losses with respect to ASA, which showed a high number of fetal losses (11 live births, 18 fetal losses). COMMENT: We suggest that thromboprophylaxis is indicated in women with RPL independently from positiveness to thrombophilic markers.

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.

Doppler velocimetry alterations related to platelet changes in third trimester pregnancies.

The aim of this study was to evaluate the correlations between the haematological parameter mean platelet volume and Doppler velocimetry parameters in order to improve clinical management in third trimester complicated pregnancies (pre-eclampsia, PE, and IUGR) affected by altered uterine resistances. Fifty-one patients were included in the abnormal uterine arteries Doppler velocimetry group (25 pregnancies were complicated by PE, 26 pregnancies were complicated by IUGR). Ninety-nine normotensive pregnant women taking no drugs for at least 2 weeks prior to testing and with no difference in gestational age at evaluation, with normal Doppler velocimetry profiles at routine screen, were used as controls. From all pregnant women, 20 mL of whole blood were obtained into citrate tubes after Doppler velocimetry evaluation and analysed for red blood cell counts (RBC), mean corpuscular volume (MCV), haemoglobin (HGB), haematocrit level (HCT), white blood cells count (WBC), platelet counts (PLT), mean platelets volume (MPV) and other biochemical parameters. From all blood parameters studied, MPV was significantly higher in women with altered uterine artery Doppler velocimetry compared with those with normal Doppler profiles (9.4 +/- 1.0 vs. 8.05 +/- 1.2 fL, P<0.001). In the group with altered uterine artery Doppler velocimetry, pregnancies complicated by PE showed a MPV value higher than pregnancies affected by IUGR (9.5 +/- 1.6 vs. 8.9 +/- 1.1, P<0.001). Finally, mean uterine arteries RI values were significantly related to MPV (fL) in both PE and IUGR groups (P<0.01, r=0.37 and P<0.01, r=0.38, respectively). Our study shows that a periodical monitoring of haematological parameters such as MPV can be associated to Doppler velocimetry in order to improve the management of pregnancies with uterine arteries Doppler velocimetry alterations.

Improvement of uterine artery Doppler velocimetry indices after metroplasty in arcuate uteri.

OBJECTIVE: Our study aimed to evaluate the effect of metroplasty performed in arcuate uteri on uterine artery Doppler velocimetry. STUDY DESIGN: We performed uterine artery Doppler velocimetry transvaginally before and after metroplasty in 36 women with arcuate uteri. Pulsatility indexes (PI) of uterine arteries were calculated and the presence or absence of a protodiastolic notch was evaluated. RESULTS: Comparing Doppler indexes before and after metroplasty, we found that uterine artery impedance improves as assessed by lower mean PI. We observed that PI after intervention was significantly lower compared with indexes before for mean Doppler index evaluations (mean uterine PI pre: 2.07+/-0.61 and post: 1.49+/-0.24 [p<0.03]). No differences were observed as regards bilateral protodiastolic notch absence or presence. A protodiastolic notch was present in 22 out of 36 women before metroplasty (61%), and a notch was observed in 19 out of 36 (52%) after metroplasty. CONCLUSIONS: Our results suggest that, metroplasty, as well as making the uterine cavity wider, leads to better uterine perfusion.

Prediction of persistent vaginal intraepithelial neoplasia in previously hysterectomized women by high-risk HPV DNA detection.

AIM: To estimate the incidence and latency of Vaginal Intraepithelial Neoplasia (VAIN) in women previously hysterectomized for benign/malign pathology and to evaluate the role of high risk HPVs in the prediction of persistent or recurrent disease. SUBJECTS AND METHODS: 830 women with prior hysterectomy for benign/malign pathologies followed by cytological scraping and vaginal colposcopy. Forty-four patients presented VAIN lesions confirmed by histopathological diagnosis. HPV DNA test was performed at the time of diagnosis. Patients were treated by Laser CO(2) vaporization and underwent follow-up by cytology, colposcopy for a mean period of 3 years. HPV DNA test was performed at 6 months after treatment and every years. Persistent or relapsed disease was confirmed by histopathology. RESULTS: Incidence of VAIN in women hysterectomized for benign pathologies did not differ significantly from the malign group. VAIN degree was more severe in the hysterectomized patients with cervical malignancy and subsequently radiated respect to non-radiated patients. The HPV DNA test at 6 months after VAIN treatment showed fifteen positive cases: twelve HPV 16 (80%) and three HPV 18 (20%). In five cases HPV DNA test was positive with a persistent negative cytological smear during the years. Positivity to high-risk HPV (either 16 or 18) was significantly higher in the patients with relapse to VAIN (10/44, p<0.002). CONCLUSIONS: We suggest to include HPV DNA test in addition to cytology in the follow-up of patients previously treated for VAIN, in order to predict VAIN persistence or progression in vaginal carcinoma before cytology becomes abnormal.

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.

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.

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.

Successful diagnostic and surgical hysteroscopy for endometrial ossification.

PURPOSE OF INVESTIGATION: Diagnostic-operative hysteroscopy was successful in two cases of endometrial ossification, and fertility was restored. METHODS: A 30-year-old and a 32-year-old woman presented at our Department with a history of secondary infertility, complaining of pelvic pain, dysmenorrhea and polymenorrhea which lasted for about one year before admission. Previous ultrasound studies revealed the presence of two bright hyperechogenic bands with posterior shadowing. RESULTS: In both cases diagnostic-operative hysteroscopies were performed, displaying osseous fragments which were removed with resectoscopy, mainly mechanically. CONCLUSION: Hysteroscopic resection should be the elective treatment for endometrial ossification because it allows complete removal of osseous fragments and reduces the chance of residual synechia. The mean objective of hysteroscopy in endometrial ossification is the restitution of conceivement capability.

Lamellar body counts compared with traditional phospholipid analysis as an assay for evaluating fetal lung maturity.

OBJECTIVE: To compare lamellar body counts with the lecithin/sphingomyelin ratio and phosphatidylglycerol analysis in terms of assessment of risk of respiratory distress syndrome (RDS). METHODS: Lamellar body counts, lecithin-sphingomyelin ratios (L/Ss), and phosphatidylglycerol levels were assessed in 1611 amniotic fluid samples obtained at four clinical sites from pregnant women whose fetuses were at risk for RDS. Cases in which delivery occurred within 72 hours of sample collection (n = 833) were analyzed. Specific cutoffs for predicting the likelihood of RDS for both the lamellar body count and the L/S had been derived previously at each of the clinical sites based on receiver operating characteristic curves using unrelated samples, whereas phosphatidylglycerol was reported as either mature (present) or immature (absent). Standard clinical and radiographic criteria were used to diagnose RDS, and the diagnosis was confirmed by review of newborn records. RESULTS: One hundred (12.0%) of the 833 infants delivered within 72 hours of sample collection developed RDS. The negative predictive value of the lamellar body count (97.7%) was similar to that of the L/S (96.8%) and slightly better than that of phosphatidylglycerol analysis (94.7%) (P =.048). The lamellar body count performed as well as phospholipid analysis irrespective of gestational age or patient population. CONCLUSION: The lamellar body count compares favorably with traditional phospholipid analysis as an assay for assessment of fetal lung maturity. Lamellar body counts are preferable because they are faster, more objective, less labor intensive, less technique dependent, and less expensive and because they can be performed with equipment available in every hospital laboratory.

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'.

[Effects of betamethasone administration on maternal-fetal Doppler velocimetry]. / Effetti della somministrazione del betametasone sulla velocimetria Doppler materno fetale.

BACKGROUND: The effect of antenatal betamethasone on fetal parameters includes a transient reduction of fetal heart rate 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 hrs 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 hrs after second dose of betamethasone. RESULTS: No significant variation was noted in UA PI through betamethasone therapy. MCA PI decreased significantly 48 hours from the last injection of betamethasone (p = 0.004), and returned to basal values at 96 hours. 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 wks' gestation, MCA PI decreased significantly after 48 hours (p < 0.006) and returned to pre-treatment values after 96 hours 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 wks' gestation. CONCLUSION: Betamethasone treatment is associated with an increase in end diastolic flow of the middle cerebral artery, as reflected by a significant, although transient, reduction of MCA PI, especially at gestational ages < 32 weeks.

[Combination of the computerized analysis of fetal heart rate and amniotic fluid index in the prediction of neonatal acidemia: a modified biophysical profile]. / Combinazione dell'analisi computerizzata della frequenza cardiaca fetale (cCTG) e dell'indice del liquido amniotico nella predizione di acidemia neonatale: un profilo biofisico modificato.

OBJECTIVE: To study the use of a modification of the classical biophysical profile by the combination of computerized analysis of fetal heart rate (cCTG) and the amniotic fluid index (AFI) in the prediction of neonatal acidemia at birth. METHODS: We considered 89 singleton third trimester high risk pregnancies delivered by cesarean section, with an AFI evaluated within 24 hrs from birth, and an antepartum cCTG performed within 6 hrs from delivery. We assigned values for AFI (oligo/anhydramnios = 1, normal = 0) and cCTG (Dawes-Redman criteria, not satisfied = 1, satisfied = 0). The endpoint was to predict an abnormal neonatal outcome as defined by an umbilical artery (UA) pH < or = 7.2. RESULTS: Fifteen neonates presented an UA pH < or = 7.2. By performing a logistic regression, we found that cCTG + AFI score (abnormal value 1-2) was able to significantly predict a pH value (< or = 7.20) with an Odds Ratio = 2.83 (p < 0.02). The diagnostic accuracy of the combination of cCTG + AFI was as follows: sensitivity: 80%, specificity: 58%. COMMENT: We suggest that the combination of cCTG + AFI included in the simple score we propose, may be of value in the prediction of neonatal acidemia and help in the management of third trimester high risk pregnancies.