Prenatal Identification of a Missense Mutation of the L1CAM Gene Associated With Hydrocephalus Using Next-Generation Sequencing.

We present the case of a 35-year-old pregnant woman who visited our department for a routine ultrasonography screening scan for fetus anatomy during the 22nd week of gestation. Our report revealed a male fetus with marked hydrocephalus and severe intrauterine growth retardation. After extensive counseling, the couple decided to proceed with an invasive diagnosis via amniocentesis. The cytogenetic analysis showed findings related to clinical history and ultrasound findings related to the presence of a nucleotide change in c.578T>C with an amino acid change in p.Leu198Pro of the L1CAM gene. The result was reported as a hemizygote missense L1CAM gene variant of unknown significance. After extensive parental counseling, the couple decided on pregnancy termination. We report the present case of L1CAM mutation in p.Leu198Pro to add to the limited knowledge regarding the clinical presentation of mutations of the L1CAM gene with emphasis on prenatal diagnosis.

A de novo 2.9 Mb interstitial deletion at 13q12.11 in a child with developmental delay accompanied by mild dysmorphic characteristics.

BACKGROUND: Proximal deletions in the 13q12.11 region are very rare. Much larger deletions including this region have been described and are associated with complex phenotypes of mental retardation, developmental delay and various others anomalies. RESULTS: We report on a 3-year-old girl with a rare 2.9 Mb interstitial deletion at 13q12.11 due to a de novo unbalanced t(13;14) translocation. She had mild mental retardation and relatively mild dysmorphic features such as microcephaly, flat nasal bridge, moderate micrognathia and clinodactyly of 5(th) finger. Molecular karyotyping revealed a deletion on the long arm of chromosome 13 as involving sub-bands 13q12.11, a deletion of about 2.9 Mb. DISCUSSION: The clinical application of array-CGH has made it possible to detect submicroscopical genomic rearrangements that are associated with varying phenotypes.The description of more patients with deletions of the 13q12.11 region will allow a more precise genotype-phenotype correlation.

Dual testing with QF-PCR and karyotype analysis for prenatal diagnosis of chromosomal abnormalities. Evaluation of 13,500 cases with consideration of using QF-PCR as a stand-alone test according to referral indications.

OBJECTIVE: Evaluate the results obtained from Quantitative Fluorescent (QF)-PCR and conventional karyotype analysis to determine the advantages and disadvantages of dual testing in prenatal diagnosis. METHODS: From 1 June 2006 to 1 June 2010, dual testing by QF-PCR and karyotype analysis was performed in 13,500 prenatal samples. The rates of concordant results between the two methods were evaluated and the rates of clinically significant chromosomal abnormalities undetected by QF-PCR were assessed. RESULTS: Abnormal karyotype was found in 320 out of 13,500 cases (2.37%, 95% confidence interval (CI) 2.11-2.63%). From these, QF-PCR did not detect the abnormality in 70 cases (0.52%, 95% CI 0.4-0.64%), whereas 34 had a high/unknown risk of adverse outcome (0.25%, 95% CI 0.17-0.33%). By selectively applying dual testing only at cases with ultrasound findings and/or genetic history, 13 cases of high/unknown risk would have been missed (0.1%, 95% CI 0.05-0.15%). CONCLUSION: Selective dual testing is expected to achieve a serious beneficial economical outcome and reduce parental anxiety produced by ambiguous cytogenetic findings. However, the percentage of 0.1% undetected clinically significant abnormalities cannot be ignored. A suggestion would include the offering of a choice to the pregnant women, undergoing prenatal screening, by informing them about different approaches and various complications.

Assessment of nuchal translucency thickness and the fetal anatomy in the first trimester of pregnancy by two- and three-dimensional ultrasonography: a pilot study.

AIM: To evaluate the use of three-dimensional ultrasonography (3D) as an alternative for examining fetal anatomy and nuchal translucency (NT) in the 1(st) trimester of pregnancy. METHOD: Prospective study of 199 low risk pregnant women undergoing 1(st) trimester ultrasound scan for fetal anomalies. The NT and fetal anatomy were evaluated by three-dimensional (3D) ultrasonography after the standard two-dimensional (2D) examination. The gold standard in this study was the 2D ultrasonography. RESULTS: In some of the evaluated parameters the 3D method approaches the conventional 2D results. These parameters are the crown-rump length (CRL), the skull - brain anatomy (93.5%), the spine (85.4%), the upper (88.4%) and lower limbs (87.9%) and the examination of the fetal abdomen (98.5%). Some of the anatomic parameters under evaluation revealed a statistically significant difference in favor of the 2D examination. During the 3D examination the nasal bone was identified in 62.1% of the cases, the stomach in 85.9%, and the urinary bladder in 57.3% of the cases. The NT was assessed accurately in half of the cases compared to 2D examination. CONCLUSION: The 3D ultrasound is insufficient for the detailed fetal anatomy examination during the 1(st) trimester of pregnancy. Nevertheless, the method might be improved in order to be considered as a screening method.

First trimester 3D volumetry. Association of the gestational volumes with the birth weight.

OBJECTIVE: To evaluate the three dimensional ultrasound (3D) in the volume assessment of the gestational contents during the 1st trimester of pregnancy. Our aim was to correlate the embryo, gestational sac, and placenta volume with the birth weight. To monitor the increase of these volumes according to the gestational age. METHOD: Prospective study of 199 singleton low risk pregnant women undergoing the 1st trimester ultrasound for fetal anomalies. In these women, gestational volumetry was performed and it was compared with the crown-rump length (CRL). Regression models were computed in order to analyze the dependence of birth weight with the volumes. RESULTS: The embryo volume reveals the strongest association with the birth weight at delivery (ß = 0.24), followed by the CRL (ß = 0.20) and the gestational sac volume (ß = 0.20). The placenta volume appears the weakest association with fetal weight at delivery (ß = 0.16). All volumes increased significantly from 11(+0)-11(+6) to 13(+0)-13(+6) weeks of gestation (p < 0.001). Ten cubic millimeter increase in embryo volume corresponds to a mean birth weight increase of 75 g, while 1 mm increase in the CRL corresponds to a birth weight increase of 113 g. CONCLUSION: Our results provide evidence that the embryo volume during the first trimester of pregnancy correlates better with birth weight than the CRL. This might assist in the identification of the high risk pregnancies caring macrosomic and low birth weight fetuses.

Selective reduction in twins and multiple pregnancies.

The number of multiple pregnancies has increased, mainly due to the uncontrolled use of the assisted conception techniques. Multifetal pregnancy reduction (MFPR) has been used to reduce the risks associated with these high-risk pregnancies. It is performed in the first trimester of pregnancy by transabdominal injection of potassium chloride into the fetal heart. The risk of miscarriage seems to be associated with the final number of fetuses. A review of the literature suggests that MFPR results in better pregnancy outcome, regardless of the initial number of fetuses. The reduction to a lower number of fetuses reduces fetal losses, prematurity, infant mortality and morbidity.

Second trimester amniocentesis in assisted conception versus spontaneously conceived twins.

OBJECTIVE: To compare the outcome of amniocentesis in twins conceived with assisted reproduction technology (ART) versus spontaneously conceived twins. DESIGN: Retrospective analysis of case records between 1993 and 2006. SETTING: University-affiliated tertiary center for fetal medicine. PATIENT(S): 167 ART twin pregnancies and 275 spontaneous twin pregnancies. INTERVENTION(S): Genetic amniocentesis. MAIN OUTCOME MEASURE(S): Comparison of pregnancy loss rate and perinatal outcome between the ART and spontaneous twin-pregnancy groups. RESULT(S): The fetal loss rate was similar between the two groups (4.2% vs. 4.0% in the ART twins and spontaneous twins, respectively), although the interval between amniocentesis to miscarriage was statistically significantly shorter in the ART twins than the spontaneous twins (6.2 and 20.1 days, respectively). In all cases, fetal loss refers to the loss of the entire pregnancy. The preterm delivery rate before 37 weeks was statistically significantly higher in the ART group (64.1%) compared with controls (49.5%). CONCLUSION(S): Amniocentesis in ART twins carries a fetal loss rate similar to spontaneous twins. However, ART twins have a statistically significantly increased risk of preterm delivery especially before 32 weeks' gestation.

Association between abnormal uterine artery Doppler flow velocimetry, risk of preeclampsia, and indices of arterial structure and function: a pilot study.

Preeclampsia increases the risk of future cardiovascular disease. The association between abnormal uterine artery Doppler flow velocimetry, risk of preeclampsia, and indices of arterial structure and function is investigated in this study. The carotid intima-media thickness of 34 pregnant women with normal uteroplacental flow was compared with 30 women with abnormal uterine artery Doppler analysis during the transvaginal assessment of the uterine arteries at the routine anomaly scan (20-23 weeks of gestation). Women with abnormal uterine artery Doppler results had a greater mean internal (but not common) carotid intima-media thickness (0.58 +/- 0.06 vs 0.53 +/- 0.08, respectively, P = .005) and risk of developing preeclampsia (6 of 30 vs 0 of 34 or 20% vs 0%, respectively, P = .0079) compared with those with normal uteroplacental flow. Women with abnormal uterine artery Doppler results may be at increased risk not only for developing subsequent preeclampsia but also for future cardiovascular disease.

Increasing the noninvasive management of rhesus isoimmunization.

OBJECTIVE: To determine the clinical outcome of isoimmunized pregnancies managed by middle cerebral artery peak systolic velocity (MCA-PSV) in an intention-to-treat study. METHOD: Rhesus isoimmunized pregnancies were managed with serial ultrasound and Doppler studies at 7-day intervals up to 34 weeks of gestation, between 2001 and 2005. Invasive diagnostic and therapeutic procedures were carried out when MCA-PSV was indicative of moderate or severe anemia. RESULTS: The overall sensitivity in detecting moderate to severe fetal anemia at less than 34 weeks was 100% (95% confidence interval, 54.1-100.0 L). Twenty-two cases were managed with MCA-PSV. Twelve cases needed fetal blood sampling and 6 cases needed intrauterine transfusion. Cordocentesis revealed a hematocrit of more than 26% in 6 fetuses. CONCLUSION: Management by MCA-PSV Doppler at weekly intervals is a highly sensitive method for detecting fetal anemia. It reduces the number of fetal blood samples needed and significantly lowers interventional procedures.

Maternity unit performance index. A novel approach for evaluation of the changing obstetric practice in a single maternity unit.

OBJECTIVE: To audit obstetric outcomes for primiparous laborers in order to provide accurate information to the population we serve. To establish a simple index by which a maternity unit's performance can be compared over time and to other units. This index is named, maternity unit performance index (MUPI). STUDY DESIGN: A retrospective analysis of the obstetric outcome of all nulliparous singleton gestations that have been admitted to labor ward for delivery, between 37 and prior to 41, gestational weeks. The chronical periods examined were: 1 January 2005 to 31 December 2005, 1 January 1995 to 31 December 1995 and 1 January 1985 to 31 December 1985. To these chronical periods we have utilized the MUPI formula. RESULTS: Retrospective implementation of the MUPI formula resulted in lower mean scores as time progressed. Mean MUPI values for the years 2005, 1995 and 1985 were respectively 0.8, 1.2 and 1.4. Significant differences of MUPI between the three time periods were found (P < 0.001). CONCLUSION: In our attempt to counsel our first time mothers, we have proposed a simple index of our unit's performance. This index overcomes the widely used cesarean birth rate. As years go by, MUPI scores decreased steadily. Interpretation of these results suggests a continuously evolving obstetric practice rather than a decrease in the quality of obstetric service provided.

Management of pregnancy in adolescence complicated by acute lymphoblastic leukemia.

The management of the common acute lymphoblastic leukemia in pregnancy has been controversial. We report a case of a 16-year-old primigravida with acute lymphoblastic leukemia, first presented in pregnancy, which was treated with aggressive chemotherapy protocols. Full remission of the disease was achieved. The neonate was born at 32 weeks following a cesarean section. The woman remains in complete remission, continuing maintenance chemotherapy, 18 months following diagnosis. The offspring did not show any abnormality in physical examinations or laboratory tests and keeps growing normally 18 months after birth.

First trimester ultrasound diagnosis of congenital diaphragmatic hernia.

Congenital diaphragmatic hernia is a rare structural defect, usually diagnosed in the second or third trimester of pregnancy. We present here a case of left-sided diaphragmatic hernia diagnosed at 12 weeks of gestation and a short review of published reports on first trimester diagnosis of this defect. Ultrasound diagnosis of congenital diaphragmatic hernia cases, with early herniation of the viscera in the thorax, is feasible during the first trimester. The prerequisite is the systematic examination of the fetal anatomy. Hallmarks of the diagnosis, in the first trimester as well as later in pregnancy, are the presence of the stomach, bowel or liver in the chest, and the shift of the mediastinum. Early diagnosis of this defect is essential. This will allow timely intervention and appropriate management, following extensive parental counseling.

Uterine prolapse complicating pregnancy.

BACKGROUND: Uterine prolapse is extremely rare during pregnancy. However in some cases significant complications may develop. We report a case of uterine prolapse which developed during pregnancy. Our case was managed conservatively and there were no fetal or maternal complications. Postnatally the uterine prolapse recovered spontaneously. Early recognition and close follow-up during pregnancy is essential. Successful pregnancy outcome requires individualized treatment but bed rest should always be considered.

A case of heterotopic pregnancy in the absence of risk factors. A brief literature review.

OBJECTIVE: To reinforce the risk of heterotopic pregnancy in a natural cycle when intrauterine pregnancy and abdominal pain co-exist. METHOD: A single case report with a literature review. RESULTS: Our case was associated with significant haemorrhage, laparotomy and salpingectomy. The obstetric outcome was favourable in this case. The literature review demonstrates the diagnostic difficulties as well as treatment options. CONCLUSIONS: Sonographic diagnosis of a heterotopic pregnancy is not always possible. Patients with abdominal pain and intrauterine pregnancy should heighten the clinician's suspicion of a heterotopic pregnancy.

Emergency obstetric hysterectomy.

BACKGROUND: All cases of obstetric hysterectomies that were performed in our hospital during a seven-year study period were reviewed in order to evaluate the incidence, indications, risk factors, and complications associated with emergency obstetric hysterectomy. METHODS: Medical records of 45 patients who had undergone emergency hysterectomy were scrutinized and evaluated retrospectively. Maternal age, parity, gestational age, indication for hysterectomy, the type of operation performed, estimated blood loss, amount of blood transfused, complications, and hospitalization period were noted and evaluated. The main outcome measures were the factors associated with obstetric hysterectomy as well as the indications for the procedure. RESULTS: During the study period there were 32,338 deliveries and 9,601 of them (29.7%) were by cesarean section. In this period, 45 emergency hysterectomies were performed, with an incidence of 1 in 2,526 vaginal deliveries and 1 in 267 cesarean sections. All of them were due to massive postpartum hemorrhage. The most common underlying pathologies was placenta accreta (51.1%) and placenta previa (26.7%). There was no maternal mortality. CONCLUSIONS: Obstetric hysterectomy is a necessary life-saving procedure. Abnormal placentation is the leading cause of emergency hysterectomy when obstetric practice is characterized by a high cesarean section rate. Therefore, every attempt should be made to reduce the cesarean section rate by performing this procedure only for valid clinical indications.

Prenatal diagnosis and management of fetal pharyngeal teratoma: a case report and review of the literature.

We present a case of a fetal pharyngeal teratoma, which was diagnosed at 21 weeks' gestation. At the time of examination, a mass of mixed echogenicity was detected that protruded through the mouth. During a second examination 3 weeks later, the tumor had increased in size, and a severe polyhydramnios had developed. Intrauterine death of the fetus was detected at 27 weeks' gestation. Labor was induced with misoprostol, and a 1,015-g stillborn female neonate was delivered. Postmortem examination confirmed the diagnosis of a pharyngeal teratoma.