Fetal Presentation of Walker-Warburg Syndrome with Compound Heterozygous POMT2 Missense Mutations.

Background: Walker-Warburg syndrome (WWS) (OMIM #236670) is an autosomal recessive disorder characterized by congenital muscular dystrophy, hydrocephalus, cobblestone lissencephaly, and retinal dysplasia. The main genes involved are: POMT1, POMT2, POMGNT1, FKTN, LARGE1, and FKRP. Case report: We present a fetus with WWS showing at ultrasound severe triventricular hydrocephalus. Pregnancy was legally terminated at 21 weeks +2 days of gestation. In vivo and postmortem magnetic resonance revealed corpus callosum agenesis and cerebellar hypoplasia. Cobblestone lissencephaly was observed at post-mortem. Next generation sequencing (NGS) of 193 genes, performed on fetal DNA extracted from amniocytes, detected two heterozygous mutations in the POMT2 gene. The c.1238G > C p.(Arg413Pro) mutation was paternally inherited and is known to be pathogenic. The c.553G > A p.(Gly185Arg) mutation was maternally inherited and has not been previously described. Conclusion: Compound heterozygous mutations in the POMT2 gene caused a severe cerebral fetal phenotype diagnosed prenatally at midgestation allowing therapeutic pregnancy termination.

The impact of assisted reproductive technology and chorionicity in twin pregnancies complicated by obstetric cholestasis.

OBJECTIVE: To assess in a cohort of twin pregnancies the prevalence of obstetric cholestasis (OC) and its correlation with the type of conception and chorionicity. METHODS: A retrospective cohort study including all the twin pregnancies delivered between 2005 and 2013 at our University Hospital was carried out. In the study population, the prevalence of OC was investigated in relationship to the impact of assisted reproductive technology (ART) and of chorionicity. RESULTS: Overall, 569 twin pregnancies were included in the study population. Among those complicated by OC, the rate of ART was 3-fold higher (OR 3.4, 95% CI 1.2-9.5, p = 0.02), whereas the rate of dichorionicity did not differ significantly (OR 1.6, 95% CI 0.3-7.9, p = 0.53). CONCLUSION: The risk of developing OC seems to be significantly higher among twin pregnancies obtained after ART in comparison with those conceived spontaneously.

Prenatal diagnosis versus first-trimester screening of trisomy 21 among pregnant women aged 35 or more.

OBJECTIVE: To compare the policy of prenatal diagnosis versus first trimester screening of trisomy 21 among pregnant women of advanced age. METHODS: A retrospective study was conducted on patients aged ≥35 divided in two groups: patients who requested first trimester combined test and only in case of screen-positive result underwent invasive testing (group A); patients undergoing chorionic villous sampling or amniocentesis as first investigation (group B). The following outcome variables were compared: antenatal detection of trisomy 21, occurrence of trisomy 21 at birth, miscarriage rate, hospitals' costs. RESULTS: 4527 women were included. Of these, 534 (11.80%) underwent T21 screening whereas 3993 (88.20%) requested primary invasive testing. In group A, 64 combined test were positive (11.99%) and 8 trisomy 21 cases were diagnosed (1.50%); the loss of euploid fetuses after invasive procedure was 4.55% (2/44). No false-negative case was observed. In group B 57 cases of trisomy 21 were diagnosed (1.43%), and pregnancy loss rate of chromosomally normal fetuses was 0.45% (17/3806). The estimated cost was, respectively, 67.720€ for the primary screening versus 1.996.500€ for direct prenatal diagnosis. CONCLUSION: First trimester screening of trisomy 21 is highly accurate and cost saving among women ≥35.

The descent of the fetal head is not modified by mobile epidural analgesia: a controlled sonographic study.

The aim of our study was to assess the sonographic indices of fetal head progression obtained by three-dimensional ultrasound during the second stage of labor in women with and without mobile epidural analgesia. Sonographic volume data sets were obtained with a transperineal approach every 20 min from the beginning of the active second stage until delivery. The ultrasound parameters were calculated off-line from each volume and compared between women with and without epidural analgesia. All the sonographic measurements of the fetal head descent were comparable at each time interval between the two groups. This observation suggests that mobile epidural analgesia is not likely to affect the dynamics of the second stage of labor.

Significance of uteroplacental Doppler at midtrimester in patients with favourable obstetric history.

OBJECTIVE: To reassess the usefulness of midtrimester uterine Doppler in low-risk multiparous women. METHODS: We prospectively recruited low-risk pregnant women at 20-22 weeks attending our clinic. Among those, women with a favourable obstetric history (group A) were distinguished from nulliparous (group B) and of each group we measured uterine artery Doppler (pulsatility index (PI)). We evaluated the accuracy of uterine artery Doppler in the prediction of preeclampsia and small for gestational age (SGA) neonates. RESULTS: Between January 2009 and October 2010, 382 women were included in the study of which 147 in group A and 235 in group B. Overall, 26/382 (6.8%) women presented preeclampsia and SGA occurred in 59/382 (15.4%) cases. In our population, at a 10% false positive rate (FPR) uterine artery Doppler showed a detection rate (DR) of 19.2% for preeclampsia and of 37.3% for SGA, with a higher sensitivity for SGA neonates delivered ≤ vs. >34 weeks (87% vs. 29.4%). The univariable receiver operating characteristics (ROC) curve by uterine artery PI yielded a significant prediction only for SGA in nulliparous women (areas under the curve (AUC) of 0.70; 95% CI 0.60-0.79). CONCLUSIONS: Our data confirmed that midtrimester uterine artery Doppler is not an efficient strategy in anticipating the risk of pregnancy complications among low-risk multiparous women.

Three-dimensional ultrasound is an accurate and reproducible technique for fetal crown-rump length measurement.

OBJECTIVE: The aim of the study was to evaluate the accuracy and reproducibility of fetal crown-rump length (CRL) measurement using three-dimensional ultrasound (3DUS). METHODS: We included a series of women with singleton pregnancy at 6-13 + 6 weeks. Following CRL measurement by the two-dimensional ultrasound (2DUS), a 3DUS volume was acquired. On the reconstructed midsagittal plane, CRL was measured twice by an operator and once by another. The correlation between CRL measured by 3DUS and 2DUS, as well as the intraobserver and interobserver agreement, was then calculated. Furthermore, the agreement between 2DUS and 3DUS CRL measurements together with intraobserver and interobserver agreement was calculated separately for the groups with a midsagittal acquisition plane (MSAP) and non-midsagittal acquisition plane (NMSAP). RESULTS: Overall, 137 pregnancies were included in the analysis. CRL measurements performed using 3DUS showed excellent correlation with 2DUS [intraclass correlation coefficient (ICC) = 0.992]. In addition, the 3DUS showed a high intraobserver and interobserver agreement (ICC = 0.999 and 0.993, respectively). Finally, when we divided the acquired volumes according to the plane of acquisition, excellent 2DUS-3DUS, as well as intraobserver and interobserver agreement, was maintained for both MSAP and NMSAP. CONCLUSION: 3DUS is a highly accurate and reproducible tool for fetal CRL measurement regardless of the fetal position at the time of 3D volume acquisition.

Screening for pre-eclampsia by using changes in uterine artery Doppler indices with advancing gestation.

OBJECTIVE: The aim of the study was to assess the relationship of changes in uterine artery (UtA) Doppler pulsatility indices (PI) between first and second trimesters and the subsequent development of pre-eclampsia. METHODS: A retrospective study of singleton pregnancies undergoing both first and second trimesters UtA Doppler screening between 2002 and 2009 was conducted. Multiples of median of UtA Doppler PI were used for developing indices describing UtA changes between the two trimesters. Receiver-operating characteristics curves (ROC) were calculated for multiple comparisons. RESULTS: Three thousand five hundred sixty women had UtA Doppler screening in the first and second trimesters. Eleven women were excluded because of termination of pregnancy before 24 weeks. Out of the 3549 women recruited, 126 developed Pre-eclampsia (PE; 22 early PE delivered <34 weeks and 41 preterm PE delivered <37 weeks). The best index for predicting pre-eclampsia was the difference between the mean second trimester and mean first trimester UtA PI (areas under the ROC for early PE and preterm PE of 0.851 and 0.786, respectively). CONCLUSION: Changes of UtA resistance between the first and second trimesters can be calculated as the difference between UtA PI at these gestations. The data of this study demonstrate that the difference in mean PI is the best index in predicting early PE and preterm PE.

Mode of delivery in the preterm gestation and maternal and neonatal outcome.

OBJECTIVE: To determine if the mode of delivery in preterm gestations is associated with changes in maternal and neonatal outcome. METHODS: A retrospective cohort study that included all singleton deliveries occurring after spontaneous onset of labour between 25+0 and 32+6 weeks of gestation. Cases of early preterm delivery were identified from clinical records and classified according to the mode of delivery. The following outcomes were derived for each case and compared between caesarean and vaginal deliveries: perinatal death, cranial findings compatible with haemorrhage or white matter disease in the neonate, new-onset of maternal severe anaemia or pyrexia. RESULT: From 1990 to 2007, 109 cases of spontaneous preterm labour were retrospectively selected, including 50 (45.8%) caesarean sections and 59 (54.2%) vaginal deliveries. Perinatal death occurred in 10 infants (9.1%), whereas among survivors abnormal cerebral findings were detected in 20, including 6 cases with haemorrhage, 12 with white matter findings and 2 with both. At multiple logistic regression, a birthweight lower than 1100 g was the only predictor of all adverse outcomes, whereas male sex increased the risk of white matter findings. Caesarean section compared to vaginal delivery conferred a higher risk of maternal complications (23/50 or 46% vs. 6/59 or 10.2%; OR: 11.9, CI 95%: 4.2-333; p<0.0005). CONCLUSIONS: In severely premature infants born after spontaneous onset of labour, the risk of adverse perinatal outcome does not seem to depend upon the mode of delivery, whereas the risk of maternal complications is significantly increased after Caesarean section.

Neonatal hypoxic-ischemic encephalopathy in apparently low risk pregnancies: retrospective analysis of the last five years at the University of Bologna.

OBJECTIVE: To provide recent figures on the occurrence of neonatal hypoxic-ischemic encephalopathy (NHIE) from a Teaching Hospital. STUDY DESIGN: A retrospective case-control study was conducted in a tertiary level university hospital with more than 3000 deliveries annually. Twenty-four cases of NHIE that occurred in apparently low-risk pregnancies were analysed and compared to a group of controls for the most common labor variables. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. RESULTS: Of 15,371 apparently low-risk deliveries, 24 cases of NHIE were observed (0.16%), with perinatal death or cerebral palsy occurring in nine of these cases (0.06%). The following intra-partum variables were significantly more common in cases than in controls: stained amniotic fluid (OR: 7.50; 95% CI:1.77-31.79), maternal fever (none in the control group), abnormal CTG (OR: 253.0; 95% CI: 26.70-2397), persistent occiput posterior (OR: 15.67; 95% CI: 2.25-104.53) and operative delivery (OR: 3.98; 95% CI: 1.39-11.33). CONCLUSION: The incidence of NHIE is considerably low in a Tertiary care Centre.

A second trial of clozapine in a case of granulocytopenia.

It is generally believed that agranulocytosis, a major problem with clozapine treatment, will tend to occur dose-dependently once it develops in an individual. Therefore, despite clinical progress obtained, the drug has to be discontinued and treatment shifts to another drug. We report on the case of a 29-year-old woman with DSM-IV undifferentiated schizophrenia who developed agranulocytosis after 5 years of 300 mg/day clozapine treatment. The drug was withdrawn and two trials with thioridazine and olanzapine were unsuccessful. Four months after clozapine suspension, we decided to make a further trial, reintroducing clozapine titrated up to 500 mg/day. The patient's symptoms improved and blood leukocytes remained within the normal range after eight months. Copyright 2000 John Wiley & Sons, Ltd.