Gad Barkai

Randomized management of the second nonvertex twin: Vaginal delivery or cesarean section

Sixty twin deliveries after the thirty-fifth gestational week with vertex-breech and vertex-transverse presentations were managed according to a randomization protocol. Thirty-three parturient women (21 vertex-breech and 12 vertex-transverse presentations) were allocated for vaginal delivery and 27 for cesarean section (18 vertex-breech and nine vertex-transverse). Six pairs of twins in the vaginal delivery group were delivered in a different mode than requested by the protocol (two women underwent cesarean section; in four cases the second twin spontaneously changed to vertex presentation). There were no significant differences between 1- and 5-minute Apgar scores and incidence of neonatal morbidity between the second-born twins in both study groups. Firstborn twins had higher 1-minute Apgar scores than the second-born infants irrespective of route of delivery (p less than 0.05). No case of birth trauma or neonatal death was recorded. Maternal febrile morbidity was significantly higher in the cesarean section group than in the vaginal delivery group (40.7% versus 11.1%, p less than 0.05). These results suggest that in twins with vertex-breech or vertex-transverse presentations after the thirty-fifth week of gestational age the neonatal outcome of the second twin was not significantly influenced by the route of delivery.

Frequency of Down's syndrome and neural-tube defects in the same family

BACKGROUNDnThere is evidence that some mothers of infants with Downs syndrome have abnormal metabolism of folate and methyl, as well as mutations in folate genes, which are features that are also seen in neural-tube defects (NTD). We therefore investigated whether Downs syndrome and NTD arise more often in the same family than would be expected from the incidence of each disorder considered separately.nnnMETHODSnWe studied two series of families using information obtained from medical records about maternal age, pregnancy outcome, congenital malformations, and karyotype: the first, 493 families from Israel who were at high risk of NTD (445 with a history of NTD and 48 with isolated hydrocephalus); and the second, 516 families from the Ukraine at high risk of Downs syndrome.nnnFINDINGSnIn the families at risk of NTD, there were a total of 11 pregnancies affected by Downs syndrome in 1492 at-risk pregnancies (compared with 1.87 expected on the basis of maternal age), which was a significant increase (p<0.00001). In the families at risk of Downs syndrome, there were seven NTD pregnancies in 1847 at risk, compared with 1.37 expected (p<0.001).nnnINTERPRETATIONnIn this study, we provide direct evidence of a link between Downs syndrome and NTD. Folate supplementation before conception has the potential to reduce the frequency of Downs syndrome.

Congenital diaphragmatic hernia in a family segregating a reciprocal translocation t(5;15)(p15.3;q24)

Congenital diaphragmatic hernia (CDH) is a relatively common malformation of unknown cause with high mortality due to hypoplasia of the lungs and pulmonary hypertension. We studied a family in which two fetuses had CDH, and two pregnancies resulted in first trimester missed abortions. Both fetuses with CDH had an apparently normal karyotype. In a subsequent pregnancy, fluorescent in situ hybridization analysis of amniocytes showed a balanced translocation 46,XY, t(5;15) (p15.3;q24) also present in the mother and in a normal child, suggesting that the diaphragmatic hernia in the first two fetuses was caused by a cryptic unbalanced translocation. This hypothesis is supported by a previous observation of CDH in a distal deletion of 15q as part of a multiple congenital anomalies syndrome. It is suggested that a gene distal to 15q21 is important for the normal development of the diaphragm.

Studies on sperm chromosomes in patients with severe male factor infertility undergoing assisted reproductive technology treatment

The aim of the study was to determine the rate of chromosome abnormalities in testicular sperm after intracytoplasmic sperm injection due to severe male factor infertility. The study groups included patient with non-obstructive azoospermia (n=9), obstructive azoospermia (n=10), Klinefelters syndrome (n=5) and normal controls (n=6, groups I-VI, respectively). The mean serum levels of FSH 17.5+/-8.2 (P<0.05), 3.5+/-2.6, 29.8+/-13.0 (P<0.05) and 3.1+/-0.4 mIU/ml, respectively. The rates of chromosome abnormalities were 19.6% (P<0.001), 8.2% (P<0.001), 6.3 and 1.6%, respectively. Chromosomes X and Y were significantly more involved in the aneuploidy than chromosome 18 in groups I and II. The present findings demonstrate a linkage between gonadal failure (high serum FSH levels) and sperm chromosome abnormalities. Our findings may explain the increased incidence of perinatal sex chromosome abnormalities found in severe male factor patients. Patients with non-mosaic Klinefelters syndrome have comparable risk for sex chromosomes aneuploidy as the rest of the patients with azoospermia. Therefore, genetic screening during pregnancy or before embryo replacement should be carefully considered in severe male factor patient following in vitro fertilization (IVF).

Prelabour rupture of membranes at term: early induction of labour versus expectant management

OBJECTIVESnTo compare expectant management with early induction of labour in pregnant patients with prelabour rupture of membranes at term and unfavourable cervix.nnnSTUDY DESIGNnA prospective, randomised study of 154 women with prelabour rupture of membranes at term of whom 80 had been managed expectantly, and 74 had undergone oxytocin induction at a rate of 2.5 mU/min. Digital examination was not performed before oxytocin infusion, and the first was delayed until 4 h (nulliparae), or 2 h (multiparae) of regular uterine contractions.nnnRESULTSnThe mean period from rupture of membranes to delivery was significantly shorter in the induction group. The mean duration of labour was significantly shorter in the expectant group. Operative vaginal deliveries were more common in the induction group, and fetal distress was the most common cause of operative vaginal deliveries. The caesarean rates were low and similar in both groups. Maternal and neonatal infectious morbidity was similar and no difference was found in the length of hospitalisation.nnnCONCLUSIONSnExpectant management in patients with ruptured membranes at term is safe and reduces the frequency of operative vaginal deliveries.

CAG repeat polymorphism within the KCNN3 gene is a significant contributor to susceptibility to anorexia nervosa: A case-control study of female patients and several ethnic groups in the Israeli Jewish population

The human small‐conductance Ca2+‐activated potassium channel gene KCNN3 has been involved in mechanisms underlying neuronal function and plasticity. A multiallelic CAG repeat polymorphism within the KCNN3 has been associated with schizophrenia and bipolar disorder. We have previously reported in a family‐based study that longer CAG repeats are preferentially transmitted to patients with anorexia nervosa (AN). The present study extends the analysis of KCNN3 allele distribution to a larger series of AN female patients and control groups, incorporating information on ethnicity and co‐morbidities associated with AN. The data analysis is presented while considering separately the two alleles of each individual, namely a minor (shorter) and a major (longer) allele. This study has found that the KCNN3 allele distribution in the general Israeli population does not differ significantly in at least four Jewish ethnic groups of Ashkenazi, North African, Iraqi, and Yemenite origin. These have been used as control groups in a matched case‐control analysis that has demonstrated a significant over‐representation of KCNN3 alleles with longer CAG repeats among AN patients (Pu2009<u20090.001 for the major allele and Pu2009=u20090.035 for allele sum). Under dichotomization, a significantly higher prevalence of the L allele (>19 repeats) has been observed among AN patients (Pu2009<u20090.001). While considering AN and co‐morbid phenotypes, a tendency towards longer (L) alleles has been observed in the subset of patients with obsessive‐compulsive disorder (OCD) co‐morbidity. These findings further implicate KCNN3 as a significant contributor to predisposition to AN.

No founder effect detected in Jewish Ashkenazi patients with fragile-X syndrome

Abstract Several studies on small homogenous populations suggested that fragile-X syndrome originated from a limited number of founder chromosomes. The Israeli Jewish population could serve as an adequate model for tracing a founder effect due to the unique ethnic makeup and traditional lifestyle. Furthermore, a common haplotype for Jewish Tunisian fragile X patients was recently reported. To test for a similar occurrence in the Jewish Ashkenazi population, we performed haplotype analysis of 23 fragile-X patients and 28 normal chromosomes, all Jewish Ashkenazi, using microsatellite markers within and flanking the FMR-1 gene: FRAXAC1, FRAXAC2, and DXS548. The combined triple-marker analysis identified a wide range of diverse haplotypes in patients and controls, with no distinct haplotype prevalent in the patient group. Our data suggest that no common ancestral X chromosome is associated with the fragile-X syndrome in the Israeli Jewish Ashkenazi patient population studied. These findings are in contrast to other reports on founder effect associated with fragile-X syndrome in distinct European as well as Jewish Tunisian populations. On this basis, a more complex mechanism for the development of fragile-X syndrome in the Jewish Ashkenazi population should be considered.

Fish based preimplantation genetic diagnosis to prevent DiGeorge syndrome

PurposeTo report the performance of fluorescence in-situ hybridization in the setting of preimplantation genetic diagnosis in order to diagnose embryos affected by DiGeorge syndrome.DesignCase report.SettingAcademic referral center.PatientA 32xa0year-old female affected by DiGeorge syndrome.Intervention(s)History and physical examination, karyotyping, amniocentesis, preimplantation genetic diagnosis, fluorescence in-situ hybridization.Main outcome measure(s)Avoidance of pregnancy with embryo affected by DiGeorge syndrome.Result(s)Termination of pregnancy with an affected embryo followed by fluorescence in-situ hybridization based preimplantation genetic diagnosis and delivery of healthy offspring.Conclusion(s)The combination of preimplantation genetic diagnosis with fluorescence in-situ hybridization is recommended to prevent pregnancies with DiGeorge syndrome affected embryos in properly selected patients.