Department of Obstetrics and Gynaecology

Objectives: The finding of fetal ventriculomegaly is variably associated with other fetal abnormalities and, even when isolated, is thought to be linked to abnormal neurodevelopmental outcome. The aim of this study was to undertake a systematic review and meta-analysis of the
current literature to assess the prevalence of neurodevelopmental
delay in cases of isolated mild fetal ventriculomegaly, as well as the false-negative rate of prenatal imaging for the diagnosis of associated abnormalities in patients referred for isolated mild ventriculomegaly.
Methods: Studies that assessed neurodevelopmental outcome in isolated ventriculomegaly were identified from a search of scientific databases. Studies that did not check for karyotype or that excluded cases of bilateral ventriculomegaly were not included in the analysis. Ventriculomegaly was defined as mild when the width of the ventricular
atrium was between 10 and 15 mm. Cases in which an associated abnormality (abnormal karyotype, structural abnormality or fetal infection) was observed either before or after birth were not considered as part of the isolated group.Neurodevelopmental delaywas defined as an abnormal quotient score, according to the test used.
Results: The search yielded 961 possible citations; of these, 904 were excluded by review of the title or abstract as they did not meet the selection criteria. Full manuscripts were retrieved for 57 studies, and 20 were included in the review with a total of 699 cases of isolated mild ventriculomegaly. The overall prevalence of neurodevelopmental
delay was 7.9% (95% CI, 4.7–11.1%). Of the 20 studies included in the systematic review, nine reported data on postnatal imaging, showing a prevalence of previously undiagnosed findings of 7.4% (95% CI, 3.1–11.8%).
Conclusions: The false-negative rate of prenatal imaging is 7.4% in apparently isolated fetal ventriculomegaly of≤15 mm. The incidence of neurodevelopmental delay in truly isolated ventriculomegaly of ≤15mm is 7.9%. As the latter rate is similar to that noted in the general
population, large prospective cohort studies assessing the prevalence of childhood disability, rather than subtle neurodevelopmental delay, are required.

Background: Ultrasonographic features of the underlying hemodynamic changes in twin-twin transfusion syndrome (TTTS) may be present at the first trimester scan. Aims: To investigate the value of intertwin discordance in nuchal translucency (NT) thickness and crown rump length (CRL) to predict TTTS and other adverse outcomes. Study design: Cohort study. Subjects: One hundred and thirty-five unselected consecutive monochorionic diamniotic twin pregnancies. Outcome measures: NT and CRL discordance were assessed at 11 to 13 + 6 weeks' gestation. Receiver-operating characteristics (ROC) curves were used to determine their predictive ability for the subsequent development of TTTS. Results: TTTS complicated 16/135 (12%) pregnancies. Four other pregnancies were complicated by selective intrauterine growth restriction (sIUGR) and 3 by miscarriage b 24 weeks gestation. The median NT discordance was 15% (range 0-37%) in TTTS pregnancies, 13% (12-19%) in those with miscarriage b 24 weeks' gestation, 47% (30-50%) in those with sIUGR, and 14% (0-86%) in those without complications. Prediction for subsequent development of TTTS provided by the discordance in CRL, expressed as the area under ROC curve, was 0.52 (95% confidence interval 0.38-0.67), while it was 0.50 for NT discordance (95% confidence interval 0.35-0.64). NT discordance was significantly higher in sIUGR compared to both uncomplicated and TTTS pregnancies (p = 0.004 and p = 0.003, respectively). Conclusion: In an unselected population of monochorionic twin pregnancies, discordance in CRL and NT measured during first trimester scan is not a clinically useful predictor of the subsequent development of TTTS. Therefore, strict ultrasound follow up is recommended for the timely diagnosis of TTTS.

Objective: The purpose of this study was to assess the role of fetal nasal bones evaluation in firsttrimester screening for trisomy 21 in selected and unselected pregnancies. Study design: Visualization of the nasal bones was attempted in women attending for routine nuchal translucency screening (unselected population, n = 7116, 12 cases of trisomy 21), as well as in high-risk pregnancies referred to our tertiary care center (selected population, n = 510, 23 cases of trisomy 21). Results: The sensitivity, specificity, positive and negative predictive value of absent nasal bones for trisomy 21 were 16.7%, 97.3%, 1.1%, 99.8% and 47.6%, 95.3%, 33.3%, 97.4% in the unselected and selected population, respectively. At logistic regression analysis including nuchal translucency and nasal bones findings, the latter resulted to be an independent predictor of trisomy 21 in the selected but not in the unselected population. Conclusion: First-trimester nasal bones assessment for trisomy 21 screening has a very different performance in selected and unselected pregnancies.

The finding of fetal ventriculomegaly is variably associated with other fetal abnormalities and, even when isolated, is thought to be linked to abnormal neurodevelopmental outcome. The aim of this study was to undertake a systematic review and meta-analysis of the current literature to assess the prevalence of neurodevelopmental delay in cases of isolated mild fetal ventriculomegaly, as well as the false-negative rate of prenatal imaging for the diagnosis of associated abnormalities in patients referred for isolated mild ventriculomegaly.

The agreement between predicted risks of Down syndrome and observed prevalence was investigated in a population of 11 847 singleton pregnancies screened by first trimester nuchal translucency at a single institution. Twenty-seven cases of Down syndrome were observed; 20 were detected prenatally by nuchal translucency and maternal age screening, three by other means and four postnatally. The screened women were grouped according to their predicted risk of having an affected pregnancy, and this was compared with the observed prevalence. A significant correlation between predicted and observed prevalences was noted, thus demonstrating that risk estimates for Down syndrome based on first trimester nuchal translucency screening are accurate. Copyright © 2002 John Wiley & Sons, Ltd.

We report on a case of fetal toxicity due to maternal treatment with olmesartan medoxomil. At 29 weeks’ gestation, oligohydramnios was found, although the fetus had normal kidneys on ultrasound evaluation. Withdrawal of olmesartan medoxomil, maternal rehydration, and a single dose of furosemide reversed the renal impairment. After term delivery, the neonate was confirmed to have normal renal function. The case suggested that fetal renal impairment due to olmesartan medoxomil may be reversible.

BACKGROUND: Defective trophoblastic invasion in early pregnancy is involved in the pathogenesis of preeclampsia. This study investigates the relationship between Doppler assessment of uterine artery resistance and endovascular trophoblastic invasion in the ®rst trimester of pregnancy. METHODS: Patients undergoing termination of pregnancy for non-medical reasons were categorized as having a low-or high-resistance uterine artery blood¯ow pattern by transabdominal Doppler ultrasound. Products of conception were examined histologically with regard to the extent of decidual endovascular trophoblast invasion. RESULTS: There were 14 low-resistance and 17 high-resistance uterine artery blood¯ow pregnancies identi®ed at 10±14 weeks of gestation. Normal intradecidual endovascular trophoblast invasion was identi®ed with a similar frequency in both groups (P = 0.79). However, the proportion of decidual vessels with endovascular trophoblast invasion was signi®cantly higher in the low-resistance pregnancies (49%) compared with the high-resistance ones (34%, P = 0.02). CONCLUSIONS: The ®ndings of this study support the use of uterine artery Doppler investigation for the non-invasive assessment of trophoblast invasion in early pregnancy. Further studies are necessary to clarify the biological signi®cance of these observations and their potential clinical applications.

Objective: To compare the rate and type of congenital anomalies in twin pregnancies in relation to chorionicity. Methods: This was a retrospective study from 06/2002 to 10/2008 including 360 monochorionic (MC) and 770 dichorionic (DC) twin pairs with targeted ultrasound examination between 11 and 32 weeks' gestation in a tertiary level setting. Results: The rate of malformations was 8.9% (64/720) in monochorionic and 6.1% (94/1540) in dichorionic twins (p < 0.05). Malformations were isolated in 5.3% (38/720) and 4.7% (72/1540) and complex in 3.6% (26/720) and 1.4% (22/1540) of MC and DC twins (p < 0.005), respectively. The most common anomalies in both twins were cardiovascular anomalies (MC 2.1%, DC 1.5%) and anomalies of the central nervous system (CNS) (MC 1.0%, DC 1.4%). There was an equal prevalence of anomalies of the genitourinary system (MC 1.1%, DC 0.9%), thoraco-abdominal system (MC 0.6%, DC 0.5%), and the extremities (MC 0.6%, DC 0.4%). Conclusion: There was a 1.5 times higher risk for fetal malformations in MC pregnancies. The excess risk was mainly attributed to the higher rate of complex anomalies. While the rate of cardiac abnormalities was higher in MC twins, the rate of CNS abnormalities was lower compared to DC twins.

Objectives: In first trimester risk assessment, crown-rump length has been utilized as the gold standard for dating pregnancies and interpreting screening results. Other fetal biometric measurements have been employed to confirm gestational age, but not to interpret screening results. The purpose of this study is the compare the accuracy and precision of crown-rump length and other fetal biometric measurements in the interpretation of first trimester nuchal translucency. The goal is to determine which measurement leads to the least variability when an observed nuchal translucency measurement is related to the expected level for the observed biometry value (MoMs). Methods: Women presenting to an academic fetal diagnostic center between 11+0 and 13+6 weeks were examined by one sonographer followed by one physician. Each examiner obtained 3 independent measurements of fetal biometric parameters, and NT. Patients were excluded for fetal malformations or demise. Biometry-specific expected NT values were calculated using regression models, and the results were converted into MoMs. The standard deviation of log MoM was compared, and the smallest value was regarded as reflecting the biometric measure with the greatest accuracy and precision. Results: Measurements were obtained on 135 fetuses. Abdominal circumference yielded MoMs with the smallest standard deviation, significantly lower than for CRL, the next smallest (P < 0.0001). The standard deviation of AC remained the smallest when results from sonographers and physicians were considered separately, and when the mean of the three exams was used rather than the individual exam results. Conclusions: Abdominal circumference is the most accurate and precise biometric measurement for the interpretation of nuchal translucency screening results. Since crown rump length is currently utilized to calculate NT MoMs in order to place fetuses in categories of risk for aneuploidy, consideration should be given to an alternative model for calculation of NT MoMs using other fetal biometric measurements.

Wave-shaped ribs were detected at prenatal ultrasound in a 20 þ1 week female fetus. At birth, skeletal radiographs showed marked hypomineralization and suggested hypophosphatasia. However, elevated blood calcium and alkaline phosphatase excluded hypophosphatasia and raised the possibility of Jansen metaphyseal dysplasia. Molecular analysis of the PTH/PTHrP receptor gene (PTH1R) showed heterozygosity for a previously undescribed transversion variant (c.1373T>A), which predicts p.Ile458Lys. In vitro evaluation of wild type and mutant PTH/PTHrP receptors supported the pathogenic role of the p.Ile458Lys substitution, and confirmed the diagnosis of Jansen metaphyseal dysplasia. This disorder may present prenatally with wavy ribs and in the newborn with hypomineralization, and may therefore be confused with hypophosphatasia. The mottled metaphyseal lesions typically associated with this disease appear only in childhood.

Doppler velocimetry is a non-invasive method to monitor pregnancies complicated by pre-eclampsia. We aimed to assess the predictive value of adverse perinatal or maternal outcome of three ratios, i.e. middle cerebral to umbilical arteries pulsatility indices (PI), middle cerebral to uterine arteries PI and uterine to umbilical arteries PI, compared with that of uterine and umbilical arteries PI in pre-eclamptic patients. This is a cohort study on 168 singleton pregnancies between January 2010 and June 2013. Doppler velocimetry was performed at the diagnosis of pre-eclampsia. Logistic regression analysis was performed and receiver-operating characteristics (ROC) curves were calculated to determine the predictive ability of each Doppler index. Multivariate analysis was run to adjust results for confounding parameters. Seventy-eight cases were complicated by adverse perinatal outcome, 79 by maternal one, 49 by both. Considering perinatal outcome, area under ROC curve was 0.730 for uterine arteries PI, 0.691 for umbilical artery PI and 0.834 for middle cerebral to uterine arteries PI ratio, while for maternal one 0.720 for uterine arteries PI, 0.686 for umbilical artery PI and 0.817 for middle cerebral to uterine arteries PI ratio. At multivariate analysis, only middle cerebral to uterine arteries PI ratio remain statistically significant for both outcomes (p ¼ 0.001). The cited ratio appeared more accurate than all other considered indices in predicting perinatal and maternal outcomes in patients affected by pre-eclampsia.

Study Objective: To assess the relationship between first-trimester maternal serum PAPP-A and free b-hCG and birth weight. Design: Observational study. Setting: Teaching hospital. Patient(s): Singleton pregnancies (n ¼ 1,630) at 10-14 weeks of gestation. Intervention(s): Fluorimetric immunoassays for maternal serum pregnancy-associated plasma protein A (PAPP-A) and free b-hCG. Main Outcome Measure(s): Customized birth weight percentiles, calculated taking into account maternal height, weight, ethnic origin, parity, smoking status, and fetal gender. Result(s): There was a significant positive correlation between birth weight and PAPP-A, but not free b-hCG levels. Maternal serum levels of PAPP-A were significantly lower in small-for-gestation (SGA) newborns than in control subjects and were significantly higher in large-for-gestation (LGA) newborns than in control subjects. Maternal serum free b-hCG levels were lower in pregnancies complicated by pre-eclampsia than in normotensive ones. Multivariable analysis found PAPP-A to be an independent predictor of absolute birth weight, SGA, and

Gualco M, Bonin S, Foglia G, Fulchieri E, Odicino F, Prefumo F, Stanta G, Ragni N. Morphologic and biologic studies on ten cases of verrucous carcinoma of the vulva supporting the theory of a discrete clinicopathologic entity. Int J Gynecol Cancer 2003;13:317-324.

Background. To compare the efficacy and side-effects of intravaginal gemeprost with those of oral misoprostol for cervical ripening prior to first-trimester pregnancy termination in nulliparous women. Methods. Retrospective analysis of surgical terminations of pregnancy performed before 90 days of gestation. Intravaginal gemeprost 1 mg or oral misoprostol 800 mg was administered 2 h before the procedure. Results. In total, 746 women were enrolled into the study, 84 received intravaginal gemeprost and 662 oral misoprostol. Median baseline cervical dilatation was significantly greater in women who received misoprostol before the operation than in those who received gemeprost (7 mm vs. 3 mm; p < 0.0001). The incidence of fever, vomiting and diarrhea was not different between the two groups. The incidence of abdominal pain with request for pain medication, emergency admission to operating room due to vaginal bleeding, hospital stay longer than 24 h and surgical repair of cervical injury due to Hegar dilatation was significantly higher among the gemeprost group than the misoprostol group. Conclusions. In cervical priming prior to first-trimester pregnancy termination in nulliparous women, oral misoprostol is more effective and is associated with fewer side-effects and complications than intravaginal gemeprost.