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Objective To assess the amniopatch procedure when premature rupture of membranes occurs after first-trimester chorionic villus sampling (CVS). Study Design From May 2001 to June 2004, the amniopatch procedure was offered in cases of premature rupture of membranes after CVS when severe oligohydramnios was present (largest vertical pocket < 2 cm) and persistent (more than 1 week). Results The amniopatch was placed in five pregnancies at 12–18 weeks of gestation, resulting in amniotic fluid restoration in all but one pregnancy. In three pregnancies, fetal demise was observed at 1, 2 and 36 days after the procedure. The last procedure resulted in a healthy newborn. Conclusion Although the amniopatch restored normal amniotic fluid levels in all cases, 4 of the 5 cases resulted in fetal demise. Copyright © 2007 John Wiley & Sons, Ltd.

Objective To describe the false-positive diagnoses of prenatal ultrasound screening of fetal structural anomalies. Methods Pregnancies with fetal structural anomalies either detected prenatally in our center or referred to us, were registered, evaluated, and followed-up prospectively by a multidisciplinary Congenital Defects Committee. After postnatal follow-up was completed, cases were assigned as true positives, false positives or false negatives and categorized by anatomical systems. Pregnancies referred with a nonconfirmed suspicion of anomaly were not included. The false-positive diagnoses were analyzed. Results From 1994 to 2004, 903 new registry entries of fetuses structurally abnormal at ultrasound with a complete follow-up were included in the Committee database. There were 76 false positives, accounting for 9.3% of all the prenatally established diagnoses. The urinary tract anomalies were the most frequent false-positive diagnoses found (n = 25; accounting for 8.7% of the urinary tract defects), but the genital anomalies showed the higher rate of no confirmation (n = 5; 15.2%). The specific anomalies most commonly not confirmed were renal pyelectasis (n = 9), cerebral ventriculomegaly (n = 9), abdominal cysts (n = 7) and short limbs (n = 7). Conclusion Several prenatally diagnosed anomalies would benefit from prudent counseling, because they may be normal variants or transient findings. Copyright © 2007 John Wiley & Sons, Ltd.

Resumen Objetivo Evaluar la efectividad del Test Combinado (bioquimica y ecografia en el primer trimestre) para la deteccion prenatal del syndrome de Down en la poblacion general. Material y metodos Se determinaron los marcadores bioquimicos de primer trimester (proteina plasmatica A asociada al embarazo y fraccion β libre de la gonadotropina corionica) en suero materno a las 7-12 semanas. La translucencia nucal fetal y la edad gestacional se determinaron mediante ecografia a las 10-14 semanas. Se estimo el riesgo combinado el mismo dia de la ecografia y se ofrecio el diagnostico citogenetico mediante biopsia de corion si el riesgo era de 1:250 o superior. Resultados La edad gestacional media en la determinacion bioquimica fue de 9,5 semanas y de 12,1 para la ecografia. En las 4.447 gestaciones estudiadas con seguimiento completo, los indices de deteccion fueron del 91% (10/11) para la trisomia 21 y del 83% (5/6) para la trisomia 18 o 13, con una tasa de falsos positivos del 3,8% (167/4.423). Conclusion El Test Combinado, al determinar los valores de marcadores bioquimicos y de translucencia nucal en intervalos gestacionales optimos durante el primer trimestre, mostro una tasa de deteccion del 91% para la trisomia 21 con una reduccion en la tasa de falsos positivos al 3,8%.

Resumen Objetivo Evaluar los resultados de la transfusion fetal intravascular en el tratamiento de la isoinmunizacion, durante el periodo 1990-2003. Sujetos y metodos Se ofrecio una cordocentesis para realizar un hemograma fetal a las gestantes isoinmunizadas con sospecha de anemia fetal significativa. Se practico transfusion intrauterina cuando el valor del hematocrito fetal fue inferior a –2 desviaciones estandar para la edad gestacional. Las transfusiones se repitieron aproximadamente cada 3 semanas hasta la semana 34-35. Resultados Se practico una cordocentesis en 32 gestaciones, en 11 (34%) de las cuales no se objetivo una anemia fetal significativa de acuerdo con los criterios establecidos. En 19 gestaciones se realizaron un total de 50 transfusiones entre las 21 y 35 semanas. No se observo ninguna perdida fetal espontanea. A los 0-13 anos de vida, todos los ninos presentan una evolucion correcta para su edad. Conclusion La transfusion intravascular fetal es una tecnica efectiva en el tratamiento prenatal de la anemia fetal con resultados favorables a largo plazo.

The different strategies applied for Down syndrome (DS) screening in a single center are presented and the results are analyzed taking into account the number of invasive procedures needed for the diagnosis of one affected pregnancy. The use of advanced maternal age as a single criterion, from 1980 to 1992 proved to be poorly effective since 102 amniocentesis are needed to diagnose one DS affected pregnancy (1:102) or 52 to diagnose any aneuploidy (1:52) With the use of second trimester screening with serum markers (AFP and hCG) at 14–18 weeks in 8711 women less than 38 years, from 1993 to 1999 the ratios were improved to 1:82 and 1:47 respectively. With the introduction of the combined test in 1999 using free hCG, PAPP-A (sampling at 9–10 weeks) and NT (measured at 12 weeks) in 3644 women under 38 years, and gestational weeks adjusted by US in 3644 singleton pregnancies with complete follow-up, the ratios were substantially improved to 1:16 procedures for DS or 1:8 for any aneuploidy. The detection rate ...

Nuchal translucency (NT) is defined as the accumulation of subcutaneous fluid in the nuchal region of the fetus at 11–14 weeks. Its measurement in order to modify the previous background risk has been proved to be able to detect around 70% of trisomy 21 pregnancies (for a 5% fixed positive rate). When affected fetuses dying before 20 weeks are excluded, detection rate may decrease to 60%. Given that appropriate training of sonographers and adherence to a standard technique for the measurement of NT is of paramount importance to reduce variability, the Fetal Medicine Foundation has established a certification process. Fetal nuchal edema displayed at 15–20 weeks was described as enlarged nuchal skinfold, and is a less sensitive but more specific marker than nuchal translucency. Webbing of the neck in infants with trisomy 21 may be envisaged as the remainder of nuchal distension.

Objective To evaluate the effectiveness of the addition of first-trimester biochemistry to fetal nuchal translucency (NT) measurement in the Combined Test when screening for trisomy 21 in twin pregnancies. Methods Maternal serum free β-hCG and PAPP-A were determined at 8 to 12 weeks and fetal NT was measured at 11 to 14 weeks. The individual risks were estimated for each of the fetuses using both NT screening alone and the Combined Test. An invasive diagnostic procedure was offered when the risk was 1:250 or over in either one of the fetuses. In the first period, only the results of NT screening were clinically applied. After previous analysis, the Combined Test was introduced into clinical practice. Results In the two-and-a-half-year study period, a complete follow-up was obtained in 100 twin pregnancies. Three fetuses (two pregnancies) with trisomy 21 were detected by both methods. The false-positive rate achieved by NT screening (14.3% of pregnancies and 8.6% of fetuses) was substantially reduced when first-trimester biochemistry was added in the Combined Test (5.1% of pregnancies and 3.6% of fetuses). Conclusion The Combined Test appears to maintain the detection rate achieved by NT screening for trisomy 21 in twin pregnancies, but false-positive rates and invasive diagnostic procedures are reduced. Copyright © 2005 John Wiley & Sons, Ltd.

Objective To assess the effectiveness of the Combined Test in the prenatal detection of trisomy 21 in the general pregnant population using a new timing for the screening approach. Methods First-trimester maternal serum biochemical markers (pregnancy-associated plasma protein-A and free-β hCG) were determined in maternal serum at 7 to 12 weeks. Fetal nuchal translucency and gestational age were assessed at the 10- to 14-week ultrasound scan. A combined risk was estimated and delivered to the women the same day. When the risk was 1:250 or above, chorionic villus sampling was offered. Results Mean gestational age at biochemistry was 9.4 weeks, being 12.3 at ultrasound. In the 2780 studied pregnancies with a complete follow-up, observed detection rates were 88% (7/8) for trisomy 21 and 75% (3/4) for trisomy 18, with a 3.3% (92/2765) false-positive rate. Conclusion The Combined Test, assessing biochemistry and ultrasound at individually optimal ages in the first trimester, showed an 88% detection rate for trisomy 21 with a remarkably reduced false-positive rate (3.3%). Copyright © 2004 John Wiley & Sons, Ltd.

Resumen Objetivo Estudio de la efectividad del cribado bioquimico y ecografico en el segundo trimestre de la gestacion para la deteccion prenatal de trisomia 21 en poblacion de bajo riesgo de aneuploidia. Metodo Estudio prospectivo de intervencion de 8.894 gestaciones unicas de bajo riesgo de aneuploidia. Se realizo ecografia y extraccion simultanea de sangre materna para determinacion de alfafetoproteina (AFP) y fraccion β de la gonadotropina corionica (β-hCG) entre las 14 y 18 semanas. Se considero como criterio de riesgo para ofrecer amniocentesis una estimacion de riesgo superior a 1/270 combinando la edad materna y los valores de marcadores bioquimicos, valores sericos de AFP ≤ 0,4 multiplos de la mediana (MoM), de β-hCG ≤ 0,2 MoM (riesgo de trisomia 18), o pliegue nucal superior al percentil 95 para la edad gestacional. Resultados Las tasas de deteccion para la trisomia 21 fueron las siguientes: 65% para la bioquimica y edad materna (con un 11% de falsos positivos) y 45% para el pliegue nucal (con 5,3% de falsos positivos). Los resultados obtenidos con la aplicacion de los criterios de riesgo proporcionados indistintamente por cualquiera de ambos parametros, bioquimica o pliegue nucal, mostraron una tasa de deteccion del 75% con una tasa del 14,9% de falsos positivos. Conclusion La aplicacion simultanea e independiente de los marcadores bioquimicos (AFP y β-hCG) y del pliegue nucal para la estimacion del riesgo de trisomia 21 en el segundo trimestre permitio detectar el 75% de fetos afectados, con una tasa de falsos positivos del 14,9%.

Objective The aim of our study was to obtain measurements of the jugular vein and carotid artery pulsatility index (PI) at 10–14 weeks' gestation in chromosomally normal and abnormal fetuses with or without increased nuchal translucency (NT), in order to explore whether a relationship exists between increased NT and overperfusion of the head. Methods This was a prospective study involving 179 pregnant women at high risk for chromosomal anomalies or structural malformations who were referred for chorionic villus sampling or first-trimester ultrasound examination at 10–14 weeks' gestation, respectively. Color and pulsed Doppler ultrasound were used to obtain jugular vein and carotid artery blood flow velocity waveforms at the level of the mid-neck. All Doppler measurements were obtained by a single investigator. The PIs of the jugular vein and carotid artery were correlated with NT measurement and fetal karyotype. Results Doppler measurements of the jugular vein and carotid artery were successfully obtained in 90.5% of the fetuses. The fetal karyotype was abnormal in 13 cases, including three trisomies 21 and two trisomies 18, and normal in 149 cases. In the group with normal karyotype the NT was above the 95th percentile in 22 cases (15%). No correlation between the jugular vein or the carotid artery PI and the thickness of the NT was found. There were no significant differences when comparing the values of the jugular vein and carotid artery PI between the group with normal NT and the group with increased NT, or between the group with a normal karyotype and an abnormal karyotype. Conclusion Our results suggest that NT is not related to blood flow impedance in either the carotid artery or the jugular vein. Overperfusion and venous congestion of the head do not appear to be a causative pathophysiological mechanism involved in increased NT. Copyright © 2003 ISUOG. Published by John Wiley & Sons, Ltd.

Objective To assess the potential value of ductus venosus Doppler studies in the detection of fetal aneuploidy on measurement of nuchal translucency. Methods The pulsatility index for veins (PIV) and the lowest velocity during atrial contraction (A-wave) were determined in the fetal ductus venosus in 3382 consecutive pregnancies at 10 to 14 weeks and studied from December 1996 to December 2001. Nuchal translucency was also measured. The population studied included 1664 pregnancies at high risk and 1718 at low risk for fetal aneuploidy. Results In relation to the prenatal detection of trisomy 21, the ductus venosus PIV was increased in 75% (36/48), the A-wave was decreased in 58% (28/48), and nuchal translucency was enlarged in 81% (39/48) of the trisomy 21 fetuses [71% (22/31) when nuchal translucency referrals were excluded]. The corresponding figures for trisomies 18 and 13 were 71, 58 and 83%, respectively, being 33, 33 and 33% for other unbalanced anomalies. Conclusion There is a high proportion of fetuses with trisomies 21, 18 and 13 (around 75%) in which the ductus venosus PIV is increased (above the 95th percentile) at 10 to 14 weeks, this proportion being similar to that observed for increased nuchal translucency measurement. Copyright © 2003 John Wiley & Sons, Ltd.

We describe a case of early prenatal diagnosis of a major congenital heart anomaly and trisomy 18 in a low-risk pregnant woman. Nuchal translucency (NT) measurement at 13 weeks' gestation was 1.2 mm and Doppler evaluation of the ductus venosus detected a persistent reversed flow during atrial contraction. This finding prompted us to perform fetal echocardiography which showed hypoplastic left heart syndrome. Karyotyping following chorionic villus sampling diagnosed trisomy 18. Review of the recent literature suggests that the finding of an abnormal ductus venosus Doppler pattern in the late first trimester of pregnancy may be an early sign of either congenital cardiac or chromosomal abnormality, even in the presence of normal NT screening.

Objective The aim of this study was to assess the effectiveness and safety of chorionic villus sampling (CVS) performed in multiple pregnancies by means of a transcervical biopsy forceps. Methods The study included CVS performed from January 1990 to March 2000 in our Unit. The results were analysed in two consecutive periods, period A (1990–1994) and period B (1995–2000), in an attempt to assess the effect of increasing experience. Results Seventy-five samplings were performed in 39 multiple pregnancies, 38 twin sets and one triplet. A cytogenetic report was obtained in 73% of cases in period A and in 98% in period B. An abnormal karyotype was observed in 11 samples. The need for subsequent amniocentesis decreased from 38% in period A to 10% in period B. The spontaneous fetal loss rate in chromosomally and structurally normal fetuses before the 20th week decreased from 8.7% in period A to 3.3% in period B. The fetal loss rate after the 20th week was 3.3% in period B and none in period A. It must be noted that in three out of the four cases of fetal loss an amniocentesis was needed after CVS. Conclusion Our results suggest that effectiveness and safety improved with increasing experience. Transcervical chorionic villus sampling allows an earlier prenatal genetic diagnosis in multiple pregnancies and this may be particularly relevant for a safer selective termination when chosen by parents if one of the fetuses has an abnormal karyotype. Copyright © 2002 John Wiley & Sons, Ltd.

During the past decade, an increasing number of reports concerning the diagnosis of most major congenital heart defects (CHDs) using early fetal echocardiography (before the 18th week of gestation) have been reported in both low- and high-risk populations for CHD. The finding of increased nuchal translucency seems to be the strongest predictor of CHD during the first trimester. Although some malformations are detected as early as 11 weeks' gestation, the optimal gestational age to perform the early scan is at least 13 weeks' gestation. Transvaginal ultrasound is the preferred approach, although most authors agree that results can be improved if transabdominal ultrasound is also incorporated. The further application of color Doppler enhances visualization. The sensitivity and specificity for the detection of CHD are of an acceptable level, compared with mid-gestational echocardiography. CHDs diagnosed early in pregnancy tend to be more complex than those detected later, with a higher incidence of a...

Objective: The purpose of this study was to assess the fetal outcome of first-trimester pregnancies with reversed end-diastolic flow in the umbilical artery. Study Design: Doppler studies in the umbilical artery were carried out in 2970 consecutive pregnancies scanned at 10 to 14 weeks. Results: We observed 11 (0.4%) cases of reversed end-diastolic flow. Of these, an autosomal trisomy was shown in 7 and a congenital heart defect in 2 additional fetuses. Fetal demise was observed in 5 pregnancies, neonatal death was observed in 1, and termination of pregnancy was carried out in 4. Only 1 fetus survived. Conclusions: Reversed end-diastolic flow in first-trimester umbilical artery signals an ominous prognosis even with normal karyotype. (Am J Obstet Gynecol 2001;185:204-7.)

To evaluate the circulating levels of antibodies to oxidized low-density lipoprotein (LDL) and their correlation with the lipid peroxide/vitamin E ratio in pregnant women with preeclampsia and chronic hypertension.Antibodies to oxidized LDL were measured by enzyme-linked immunoassay, lipid peroxides (malondialdehyde), and vitamin E were measured by high-pressure liquid chromatography. Patients were 25 healthy pregnant women, 20 previously nonhypertensive women diagnosed with preeclampsia, and 20 women with uncomplicated chronic hypertension.Serum levels of antibodies to LDL in preeclamptic patients were similar to controls, whereas women with chronic hypertension showed a trend for increased mean levels. Lipid peroxides in serum were significantly increased and vitamin E levels were significantly decreased in preeclampsia with respect to nonhypertensive pregnancy, but no differences were observed for chronic hypertensive women.Our results suggest that preeclampsia is not accompanied by increased levels of antibodies to oxidized LDL. By contrast, and according to previous studies in nonpregnant patients, chronic hypertensive patients showed a trend for elevated levels.

Resumen Objetivo Evaluar la aplicacion de la flujometria Doppler de las arterias uterinas realizada a las 19- 25 semanas de gestacion en la prediccion de resultados obstetricos desfavorables Material Y Metodo Estudio prospectivo de 313 gestantes mediante Doppler color y pulsado de ambas arterias uterinas. La primera evaluacion se realiza entre las semanas 19 y 21 de gestacion. En las pacientes que presentan la presencia de notch en una o ambas arterias uterinas se repite el estudio entre las semanas 22 y 25 de gestacion. Se analiza la relacion entre la presencia de la alteracion hemodinamica de la arteria uterina y la aparicion de preeclampsia, restriccion de crecimiento intrauterino (RCIU) o muerte perinatal Resultados Se observo la presencia de notch protodiastolico entre las semanas 19 y 21 en 92 gestantes. En 57 (18%) fue unilateral y en 35 (11%), bilateral. En 4 (27%) de las 15 gestantescon resultados obstetricos desfavorables se observo notch bilateral En las semanas 22-25 persistia el notch bilateral en 13 (37%) de los 35 casos, observandose un resultado obstetrico desfavorable solo en 2 de estas gestaciones. Se observo un resultado desfavorable en dos de los casos con notch unilateral (muerte fetal intrauterina y preeclampsia) El riesgo de resultado desfavorable en presencia de notch bilateral a las 20 semanas de gestacion es del 14%, y si este persiste hasta las 22 semanas el riesgo se incrementa hasta el 22% Conclusion El estudio Doppler de las arterias uterinas tiene un valor limitado en la prediccion de resultados perinatales adversos

To evaluate the serum levels of inhibin A in pregnant women with different types of hypertension.A case-control study, including 60 cases (20 women with preeclampsia, 20 with mild gestational hypertension, and 20 with chronic hypertension), and 60 gestational-age- and parity-matched controls. Inhibin A was measured in duplicate by enzyme-linked immunosorbent assay in serum samples frozen at -80 degrees C.As compared to controls, inhibin A levels were significantly elevated in women with preeclampsia ¿2.32 standard deviation (SD) 1.4¿ versus 0.50 (0.29) ng/mL, p0.001) and gestational hypertension [1.09 (0.73) versus 0.55 (0.29) ng/mL, p0.05], but not in the group of chronic hypertension [0.88 (0.69) versus 0.54 (0.39) ng/mL, p = 0.08]. Overlap in inhibin A values between cases and controls was observed in 20% (4/20) of women with preeclampsia and 55% (11/20) with gestational hypertension.Increased serum inhibin A may indicate that a proportion of mild nonproteinuric hypertension cases are associated with placental involvement.

Up to now, no data are available comparing amniocentesis and chorionic villus sampling (CVS) using biopsy forceps. A series of 1313 consecutive women referred to our unit before 12 weeks of pregnancy for fetal cytogenetic analysis because of advanced maternal age, were randomized into CVS with the use of transcervical biopsy forceps or mid-trimester amniocentesis. The diagnostic success rates of the two groups were 98 per cent and 100 per cent, and a second procedure was needed in 4.1 per cent (13/314) and in 0.3 per cent (1/358), respectively. Follow-up was achieved in 98.7 per cent of the pregnancies. Postprocedure spontaneous fetal losses, until the first week after birth, in the 672 pregnancies that completed the trial accounted for 2.2 per cent (7/314) in the CVS group and 2.8 per cent (10/358) in the amniocentesis group. Although the trial was prematurely discontinued, and therefore the sample size was smaller than initially planned, the results indicate that transcervical CVS was as safe as mid-trimester amniocentesis. Copyright © 1999 John Wiley & Sons, Ltd.

Objective: Our purpose was to assess the ductus venosus blood flow in trisomy 21 fetuses in the first half of pregnancy and the relation of this blood flow to nuchal thickness. Study Design: The ductus venosus blood flow has been studied in 534 consecutive fetuses between 10 and 18 weeks of gestation who were undergoing prenatal invasive diagnostic procedures. Before the sampling, the velocity during atrial contraction, the pulsatility index for veins, and the ratio of systole–end-systole to diastole were established in the Doppler waveforms and eventually correlated with the fetal karyotype. Results: Ductus venosus waveforms were successfully obtained in 82% of the pregnancies. Eleven fetuses were found to have trisomy 21; the pulsatility index was abnormally increased (>95th percentile) in 73% (8/11), the ratio of systole–end-systole to diastole was abnormally increased in 45% (5/11), and the velocity during atrial contraction was decreased ( Conclusions: An abnormally increased ductus venosus pulsatility index was found in a substantial proportion of early trisomy 21 fetuses, and this was apparently independent of nuchal thickening. (Am J Obstet Gynecol 1998;179:1612-7.)

Objective: To evaluate the serum levels of interleukin-4, interleukin-10, and granulocyte-macrophage colony–stimulating factor at the moment of diagnosis and in early second-trimester serum from women with preeclampsia and from gestational age-matched controls. Methods: Serum from 14 women with preeclampsia at the moment of diagnosis and 14 gestational age-matched controls was analyzed. In 10 cases and 10 controls, second-trimester serum also was studied. Cytokines were measured by specific enzyme-linked immunosorbent assay. Results: Serum levels of granulocyte-macrophage colony–stimulating factor at the moment of diagnosis were detected less frequently (21 compared with 71%, P < .01) and in lower concentrations (0 pg/mL [range 0–56] compared with 55.5 pg/mL [range 0–105], P = .01) in women with preeclampsia as compared with controls. In second-trimester serum, granulocyte-macrophage colony–stimulating factor detection rates (20 and 70% respectively, P = .06) and concentrations (0 pg/mL [range 0–32] and 2.5 pg/mL [range 0–37], respectively, P = .08) were lower in the group of preeclampsia, but the differences do not reach statistical significance. Measurements regarding interleukin-4 and interleukin-10 were similar between both study groups. Conclusion: Differences in granulocyte-macrophage colony–stimulating factor support the concept of the existence of an immunologic imbalance as part of the etiologic mechanisms leading to preeclampsia.

Objective: To evaluate whether the combined use of fetal heart rate (FHR) and nuchal translucency measurements would be useful in the prediction of fetal chromosomal abnormalities at 10–13 weeks’ gestation. Methods: In a prospective study, 1053 (553 reported previously) consecutive singleton pregnancies between 10 and 13 weeks’ gestation underwent chorionic villus sampling at our institution. Fetal heart rate and fetal nuchal translucency thickness were measured immediately before the invasive procedure. Results: Thirty-five abnormal karyotypes were diagnosed, including 17 trisomy 21, seven trisomy 18, one trisomy 13, one trisomy 9, four unbalanced translocation, two Klinefelter syndrome, one Turner syndrome, one deletion of chromosome 18, and one true mosaicism. Using 95% of normal ranges as the cutoff for both measurements, the detection rate for all chromosomal anomalies was 77.1%, with a false-positive rate (1-specificity) of 7.7%, a positive predictive value of 25.7%, and a negative predictive value of 99.2%. Fetal heart rate improved the sensitivity of nuchal thickness in trisomies 21 and 18 (from 62.5% to 75%) and was particularly useful to detect other chromosomal anomalies (from 27.2% to 81.8%). Conclusion: Our findings suggest that there is an added role of FHR in ultrasound screening of chromosomal abnormalities, specifically for those other than trisomy 21 and 18. The value of a single measurement of fetal heart rate for screening purposes needs to be confirmed by further investigation in a low-risk population.

OBJECTIVES: We sought to evaluate the circulating levels of lipid peroxides and vitamin E and the placental levels of lipid peroxides in pregnant women with different types of hypertension. STUDY DESIGN: Lipid peroxides were measured in serum and placental tissue by the thiobarbituric acid method and high-pressure liquid chromatography, and vitamin E was measured by high-pressure liquid chromatography. The patients studied were 36 healthy pregnant women and 92 women with hypertension classified as having mild gestational hypertension ( n = 28), severe gestational hypertension ( n = 10), preeclampsia ( n = 34), and chronic hypertension ( n = 20). RESULTS: Lipid peroxides in serum and placental tissue were significantly increased, and vitamin E levels in serum were significantly decreased in women with severe gestational hypertension and preeclampsia compared with controls. The groups of mild gestational hypertension or chronic hypertension had similar values of lipid peroxides or vitamin E as controls. CONCLUSIONS: Our results suggest that the category of gestational hypertension may be composed of at least two entities with different pathophysiology and support the concept of nonproteinuric preeclampsia. (Am J Obstet Gynecol 1998;178:1072-6.)

Objective To assess the natural evolution of nuchal thickness in trisomy-21 fetuses. Methods Serial measurements of nuchal thickness were performed over a 1- to 6-week period in 45 consecutive fetuses with trisomy 21, between the 10th and the 23rd weeks of pregnancy. To avoid a gestational age confounding effect, nuchal thickness also was expressed in standard deviations (SDs) for the corresponding gestational week. In addition, the changes were assessed in terms of the presence of clinical positive thickening, considered as such when the measurement was above 2.5 SD. Result A mean increase of 1.8 mm (95% confidence interval [CI] 1.3, 2.3) for nuchal thickness was observed for a mean period of 21 days. When corrected by gestational age, the mean increase of 0.3 SD (95% CI −0.2, 0.9) was found to be not significant. No clinically relevant nuchal thickening changes were recorded (51% versus 69%) at re-examination. Conclusion Nuchal thickening at re-examination is observed in a similar proportion of trisomy-21 fetuses as when first observed.

Bacterial vaginosis in pregnant women is an established risk factor for premature labor, rupture of membranes, and preterm delivery, but information on its natural history during pregnancy is limited.In this study, 635 pregnant women at less than 35 weeks' gestation were screened for bacterial vaginosis.The prevalence of bacterial vaginosis, as assessed by Gram stain examination of vaginal smears, was 19.7% (125/635). Ninety-two women were retested 4 to 8 weeks later, and bacterial vaginosis persisted in 51.1% (47/92). The incidence of preterm delivery was significantly increased in women with bacterial vaginosis at enrollment (RR 3.1, 95% CI: 1.8-5.4). However, the risk of prematurity was similar in women with or without a persistence of bacterial vaginosis.These results suggest that the diagnosis of bacterial vaginosis at any point during pregnancy is associated with an increased risk of perinatal complications in spite of spontaneous recovery in subsequent examinations.

Objective The aim of our study was to evaluate whether the combined use of umbilical artery pulsatility index (UAPI) and nuchal translucency (NT) measurements would be useful in the prediction of fetal chromosomal abnormalities at 10 to 13 weeks of gestation. Design A prospective study. Population and methods Five hundred and fifty-three consecutive women with singleton pregnancies between 10 and 13 weeks of gestation, who underwent chorionic villus sampling at our institution. UAPI and fetal NT thickness were measured immediately before the invasive procedure. Pregnancies in which structural malformations had been detected by ultrasound were excluded. Results Using the 95th centile and 3 mm as the cutoffs for UAPI and NT, respectively, the detection rate for all chromosomal anomalies was 84.2%, with a false positive rate (1-specificity) of 6.6%, a positive predictive value of 31.3%, and a negative predictive value of 99.4%. Out of the 553 tested pregnancies 502 had both parameters within the normal range and only three of them (0.6%) were chromosomally abnormal; in six of the eight cases (75%) in which both parameters were abnormal a chromosome anomaly was present. Of the 43 cases in which only one parameter was abnormal, 10 were chromosomally abnormal (23.2%). Conclusions Our results suggest that the presence of chromosomal anomalies may be strongly suspected when an increased NT thickness (NT 3 mm) is associated with an abnormally high UAPI at 10 to 13 weeks of gestation. The number of cases studied is small, however, and these conclusions are tentative and preliminary. The value of a single measurement of NT and UAPI for screening purposes needs to be substantiated by further investigation.

An attempt has been made to establish a more effective cut-off criterion for nuchal thickness (NT) and to assess the optimal gestational period for the prediction of trisomies 21 and 18. Reference intervals were established for NT from the tenth to the 18th week, using either gestation-specific centiles or the parametric method. The measurements in 47 consecutive trisomy 21 and 18 trisomy 18 cases were plotted against these intervals. Assaying different cut-off criteria for both the centile and the parametric methods, sensitivities and false-positive rates for each gestational week were calculated and then compared with the commonly applied ‘two-stepped’ cut-off method (3 mm early, 6 mm later). The parametric method, based on a progressive rise, with +2·5 SD for the corresponding gestational week as a cut-off value, showed the best performance (likelihood ratio 38) in the prediction for trisomy 21. The optimal gestational age was the 12–18 week period, with an overall sensitivity of 62 per cent (23/37) for an average false-positive rate of 0·7 per cent. For trisomy 18, the most effective cut-off was also +2·5 SD, and 10–13 gestational weeks as the optimal period, achieving 86 per cent (6/7) sensitivity for a 1·9 per cent false-positive rate. © 1997 by John Wiley & Sons, Ltd.

During 1988-1994 in Spain data on 113 primigravidae with pregnancy-induced hypertension were compared with data on 109 age- and parity-matched controls to examine the effect of exposure to spermatozoa on the risk of developing pregnancy-induced hypertension. Both cases and controls delivered at the Hospital Clinic of the University of Barcelona in Spain. Duration of unprotected sexual intercourse was about 50% shorter in cases than controls (2.3 vs. 4.7 months; p < 0.0001) regardless of previous contraceptive method used. In women having no previous exposure to spermatozoa women with pregnancy-induced hypertension had reduced exposure to spermatozoa (i.e. unprotected sexual intercourse) than the controls (2.8 vs. 4.7 months; p < 0.01). In women who had used oral contraceptives (OCs) cases had a significantly shorter duration of unprotected sexual intercourse than controls (2.1 vs. 4.7 months; p < 0.001). Duration of exposure to fathers spermatozoa with condoms had no effect on pregnancy-induced hypertension. Women with pregnancy-induced hypertension were more likely to conceive during the first month of unprotected sexual intercourse than the healthy women (48.6% vs. 25.6%; p < 0.001). They were also more likely to conceive during the first three months of unprotected sexual intercourse than controls (85.8% vs. 54.1%; p < 0.00001). This was especially true for women with preeclampsia (91.5% vs. 54.1%; p < 0.0001) and when compared to those with gestational hypertension (79.6% vs. 54.1%; p < 0.01). These findings do not support the belief that OCs protect against pregnancy-induced hypertension. They suggest that increased exposure to fathers spermatozoa reduces the risk of pregnancy-induced hypertension. In conclusion use of contraception to reduce the risk of pregnancy-induced hypertension is not a likely viable public health option.

The aim of this study was to evaluate the feasibility of transcervical chorionic villus sampling (CVS) after 12 completed weeks of pregnancy. The transcervical route for CVS, using thin biopsy forceps, was accomplished in 335 procedures in the study group, between 12 + 1 and 15 + 0 weeks. Cases were subdivided into two subgroups, the late (13 + 0 to 15 + 0 weeks) and intermediate (12 + 1 and 12 + 6 weeks) subgroups, and the results were compared with a previous series of 1202 early (8 + 0-12 + 0 weeks) transcervical CVS. A successful diagnosis was made in 97.3% of the cases. No differences were found in diagnostic success between the study subgroups, in comparison to the early transcervical CVS series. However, success rates in the study group increased from 90% in the first 60 procedures to 98.9% in the remaining cases (p < 0.001). Amniocentesis was eventually performed in nine cases (2.7%). All cases were rescanned 2 weeks after the procedure, and fetal demise was detected in five cases (1.5%). The spontaneous fetal loss rate up to 28 weeks was 3.1% (2.7% for intermediate and 4.0% for late subgroups). No cases of transverse limb reduction defects were observed. The results of our study suggest that the transcervical route for CVS beyond the 12th week of pregnancy has a satisfactory diagnostic success rate, and an acceptable pregnancy loss rate.

Biochemical screening for Down syndrome (DS) is well established in the second trimester of pregnancy, but there is little information available on its value in the first trimester. This study describes our preliminary results with biochemical screening for DS in the first trimester of pregnancy in order to evaluate its efficacy at this time. Our study population, including 19 DS pregnancies, was evaluated using maternal serum levels of α-fetoprotein (AFP), β-human chorionic gonadotropin (β-hCG), and pregnancy-associated plasma protein A (PAPP-A). At a false positive rate (FPR) of 5 per cent, the detection rate (DR) for DS is 9 per cent for β-hCG, 18 per cent for AFP, and 66 per cent for PAPP-A when considering these parameters individually. With different combinations of the analytes, the best detection rates are obtained with the association of PAPP-A and AFP (85 and 82 per cent DR for a 10 and 5 per cent FPR, respectively). Our data support the value of first-trimester biochemical screening for DS and that of PAPP-A as a single marker.

Long permanent remissions in malignant hematopoietic disorders can often be achieved by autologous bone marrow transplantation (ABMT) or by allogenic bone marrow transplantation (BMT). Previous studies have shown that such therapies may induce osteoporosis due to iatrogenic ovarian failure. The administration of hormone replacement therapy (HRT) in these women could prevent the adverse effects of long-term ovarian failure without remarkable side effects. The aim of this study was to evaluate how the bone mass is affected by HRT in patients undergoing ABMT or BMT adjusting the results for age, weight, and height. Subjects and methods: Thirteen women with previous ABMT/BMT were treated with a standard dose (0.625 mg/day) of conjugated equine estrogen (CEE) or with 50 μg/day of 17-β-estradiol in transdermal therapeutic systems (TTS) plus 5 mg/day of medroxyprogesterone acetate sequentially added to the last 12 days of estrogen therapy. Bone mass was measured prior to and 12 months following HRT. Blood samples were collected before therapy and during the 6th and 12th treatment months. Results: The mean time elapsed between bone transplantation and HRT initiation was 13.0 months (range 3–26 months). Before treatment nine patients were osteopenic and after HRT bone mass increased in all cases. Following ABMT/BMT, hepatic hyperenzymemia was detected in three patients. After 6 and 12 months of treatment no significant changes were observed in hepatic enzymes. Conclusion: Although hepatic hyperenzymemia is commonly considered as a contraindication for HRT, our results suggest that HRT is safe for these patients and that such therapy should be initiated after transplantation in women to prevent adverse effects of long-term ovarian failure.

We evaluated modifications in the pituitary-ovarian-adrenal axis in severely hirsute women after administration of the gonadotropin-releasing hormone analog (GnRHa), D-Trp-6-luteinizing hormone-releasing hormone (LHRH) (Triptorelin) in a prospective study at a tertiary hospital. A total of 20 hirsute women aged 19 to 38 years were included. Hyperandrogenism of adrenal origin was excluded in all subjects. Patients received 3.75 mg D-Trp-6-LHRH intramuscularly (Decapeptyl 3.75; Lasa-Ipsen, Barcelona, Spain). Serum levels of follicle-stimulating hormone (FSH), LH, estradiol (E2), prolactin (PRL), testosterone (T), androstenedione (delta 4 An), dehydroepiandrosterone sulfate (DHEAS), 17-OH-progesterone (17-OHP), and sex hormone-binding globulin (SHBG) were determined before GnRHa administration, 24 and 48 hours after, and on days 7, 15, 30, and 45. GnRHa suppresses FSH, LH, and E2 in all women. Unexpectedly, adrenal steroids showed a flare-up phenomenon in the first days and subsequent decrease to lower values than before GnRHa administration. SHBG showed slight changes. After GnRHa, patients showed a significant decrease in T and delta 4 An: these hormones were reduced to half the basal levels. We conclude that GnRHa can potentially be used in the treatment of hyperandrogenism to reduce androgen levels in hirsute women.

Anticardiolipin antibodies were measured in 60 pregnant women with acute parvovirus B19 infection. Test results for eight (13.3 per cent) women were positive for anticardiolipin antibody. Six of these eight women became negative later, yielding a prevalence of anticardiolipin antibodies of 3.3 per cent (2/60) 6 months after acute parvovirus B19 infection. Anticardiolipin antibody positivity was not associated with an increased risk of abortion, fetal death, or maternal complications. This study suggests that there is an elevated frequency of anticardiolipin antibodies in pregnant women with acute parvovirus B19, probably representing an epiphenomenon. However, this is not associated with an adverse maternal or perinatal outcome.

A prospective study of parvovirus B19 infection during pregnancy was conducted at a large teaching hospital in Barcelona, Spain. Women (1610) who were < 28 weeks pregnant at enrollment were screened for parvovirus infection. The prevalence of IgG positivity was 35.03% (564/1610). The incidence of acute infection during pregnancy was 3.7% (60/1610). There were five abortions among the B19-infected women but only one was caused by parvovirus, as assessed by histologic examination and polymerase chain reaction assay. The incidence of fetal loss caused by parvovirus was, therefore, 1.66% (1/60). The remaining 55 pregnancies were uneventful, and at 1 year of age, none of the infants had serious abnormalities. The incidence of vertical transmission of infection was estimated at 25%. This study provides evidence that although acute parvovirus infection may occur relatively commonly during pregnancy, an adverse fetal outcome is a rare complication.

Fluid from pleural effusion (n = 2) and cystic hygroma (n = 7) was obtained from eight fetuses, between 13 and 32 weeks of pregnancy at the time when a conventional prenatal diagnosis procedure was carried out. As these fluids contain lymphocytes, they were processed like peripheral blood. A karyotype was obtained in 4 days in both cases of pleural effusion and in four out of seven samples of cystic hygroma. An abnormal karyotype was detected in three of the four samples of cystic hygroma: two trisomies 21 and a monosomy X. Different parameters were evaluated in order to predict the feasibility of obtaining a cytogenetic diagnosis. Our data showed that if the amount of fluid obtained was > or = 4 ml and the initial lymphocyte count (ILC) was > 0.2 x 10(6) cells/ml, a cytogenetic diagnosis was possible from an initial concentration of cultured lymphocytes (ICCL) of > 0.06 x 10(6) cells/ml.

Targeted ultrasonographic screening for nuchal fluid accumulation during the first trimester (9–13 weeks) seems to be a recommendable method for the detection of Down's syndrome and other chromosomal anomalies in pregnant women. It compares favorably with current methods of maternal serum screening performed during the second trimester. Using a 4-mm cut-off value, the detection rate of aneuploidy among our population was found to be 57.1%, with a false-positive rate of 0.7% and a positive predictive value of 72.7%. Chromosomal analysis should be considered for fetuses with nuchal translucency equal to or greater than 4 mm in the first trimester. Copyright © 1995 International Society of Ultrasound in Obstetrics and Gynecology

Previous studies conducted at our clinic suggested that the administration of hormone replacement therapy (HRT) in postmenopausal women could result in the inhibition of oestrogen-induced prolactin (PRL) release. The aim of this study was to determine how the pituitary function is affected by the sequential addition of medroxyprogesterone acetate (MPA) to oestrogen replacement therapy. Twenty-one postmenopausal women receiving no other medication were treated with a standard dose (0.625 mg/day) of conjugated equine oestrogens (CEE) for a period of 24 days, plus 5 mg/day MPA added sequentially during the last 12 days of the oestrogen therapy. Blood samples were collected before treatment, during oestrogen and oestrogen-progestogen administration and after cessation of treatment. Folliclestimulating hormone (FSH), luteinizing hormone (LH), 17β-oestradiol (E2) and PRL levels were studied. During treatment gonadotrophin concentrations decreased significantly, while after cessation of HRT the levels of FSH and LH increased. These gonadotrophin fluctuations indicated a sharp rise in E2 levels during therapy and a significant decrease during the treatment-free period. PRL levels were found to be higher during CEE therapy, but they fell when patients received CEE in combination with MPA. These observations suggest that the role of progestogens in a variety of experimental and clinically relevant situations needs to be investigated not only as regards their direct action but also their modulation of the effect of oestrogen.

There is evidence that skin collagen content and bone mass are influenced by estrogen deficiency, both of them declining in the years following menopause. The aim of our study was to analyze the relationship between changes in skin collagen content and bone mass during aging. A total of 76 nulliparous women who had been admitted for surgery of non-malignant processes were studied. All subjects were arranged into five age-groups (from 20 to 60 years). Bone mineral density was measured by dual photon absorptiometry and expressed in g/cm2 as the mean of the second to fourth lumbar vertebrae. Additionally, in all patients skin biopsies were taken from a non-sun exposed site in the lower abdomen (4 cm above the pubic symphysis) and osteocalcin levels were determined. Collagen decreased significantly with age after the 40s (P < 0.001) and after menopause (P < 0.001). Changes in bone mass were closely related to those detected in collagen (r = 0.586; P < 0.0001). In conclusion, our data suggest that bone mass and skin collagen decline in parallel with aging and that the hypoestrogenism developing in postmenopausal years has a significant effect on skin collagen content. Nevertheless, the question of whether osteoporosis is an intrinsic collagen disorder remains to be demonstrated.

The purpose of this study was to determine how oophorectomy and different hormone replacement therapy (HRT) regimens using low doses of medroxyprogesterone acetate (MPA, 2.5 mg/day) influence the pituitary-gonadal axis function. Ninety (90) women, who had had regular menses prior to surgery, completed a 1-year follow-up period. Patients were assigned to 5 groups. The first (n = 16) received 0.625 mg/day conjugated equine oestrogens (CEE) cyclically, the second (n = 20) 50 micrograms day transdermal oestradiol (E2) cyclically and the third (n = 15) 0.625 mg/day CEE continuously. These 3 groups also received 2.5 mg MPA sequentially for the last 12 days of HRT administration. The fourth group (n = 20) received 0.625 mg/day CEE and 2.5 mg/day of MPA continuously, while the fifth (n = 19) constituted a control group. After oophorectomy all patients showed increases in follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, and decreases in those of E2, oestrone (E1), prolactin (PRL), sex-hormone-binding globulin (SHBG), androstenedione (delta A4) and testosterone (T). No changes were detected in dehydroepiandrosterone sulphate (DHEA-S) levels. After HRT, decreases in FSH, LH and PRL levels and increases in those of E2, E1 and SHBG were observed, but no changes were seen in T, delta A4 or DHEA-S plasma levels. As the differences that were found cannot be attributed to the presence of ovaries, it is reasonable to assume that they were perhaps due to the treatment. All these changes, with the exception of a decrease in PRL levels, are therefore to be expected after HRT.

The prenatal diagnosis of an 11q;22q translocation in a triplet pregnancy detected at the time of chorionic villus sampling (CVS) because of advanced maternal age is reported. Karyo-types obtained from two apparently different CV samples showed the balanced form of translocation, while the one obtained from a third empty sac showed the unbalanced form: 46, XX, −22, + der(22)t(11;22). Second-trimester amniocentesis confirmed the balanced translocation in one of the two viable fetuses and a normal karyotype in the other. The detected karyotypes derived from two different types of meiotic segregation, alternate and adjacent 1. To our knowledge, this is the first reported case of an unbalanced karyotype not due to a 3:1 meiotic segregation of this specific translocation.