Michel Nadjari

Rudimentary horn pregnancy: First-trimester prerupture sonographic diagnosis and confirmation by magnetic resonance imaging

Two cases of rudimentary horn pregnancy diagnosed in the first trimester by sonography and confirmed by magnetic resonance imaging (MRI) are reported. We suggest criteria for early, prerupture sonographic diagnosis of this rare condition.

Fetal intracranial hemorrhage (fetal stroke): does grade matter?

To determine if the severity of antenatally diagnosed hemorrhagic fetal brain insults and fetal stroke detected by ultrasound and magnetic resonance imaging (MRI) predicts postnatal neurodevelopmental prognosis.

Early prenatal ventriculomegaly due to an AIFM1 mutation identified by linkage analysis and whole exome sequencing.

The identification of disease causing mutation in patients with neurodegenerative disorders originating from small, non-consanguineous families is challenging. Three siblings were found to have ventriculomegaly at early gestation; postnatally, there was no acquisition of developmental milestones, and the muscles of the children were dystrophic. Plasma and CSF lactate levels were normal, but the activities of mitochondrial complex I and IV were markedly decreased. Using linkage analysis in the family, followed by whole exome sequencing of a single patient, we identified a pathogenic mutation in the AIFM1 gene which segregated with the disease state and was absent in 86 anonymous controls. This is the second report of a mutation in the AIFM1 gene, extending the clinical spectrum to include prenatal ventriculomegaly and underscores the importance of AIF for complex I assembly. In summary, linkage analysis followed by exome sequencing of a single patient is a cost-effective approach for the identification of disease causing mutations in small non-consanguineous families.

The clinical spectrum of fetal Niemann-Pick type C.

Niemann–Pick type C (NPC) disease is a lysosomal neurovisceral storage disease. The spectrum of the clinical presentation as well as the severity of the disease and the age of presentation may be highly variable. Fetal presentation is rarely described in the literature. Here, we report on seven new cases of fetal onset NPC of whom two were diagnosed in utero and five postnatally. The fetal clinical presentation, included, in utero splenomegaly (6/7), in utero hepatomegaly (5/7), in utero ascites (4/7), intra uterine growth retardation (IUGR) (2/7), and oligohydramnios (2/7). Placentomegaly was present in two of the three pregnancies examined. Congenital thrombocytopenia (4/4), congenital anemia (2/4), and petechial rash (2/5) were diagnosed immediately after birth. Three patients were born preterm. Pregnancy and postnatal outcome were remarkably poor with one case of intrauterine fetal death, one elective termination of pregnancy, and four patients who died within the first months of life from a rapidly fatal neonatal cholestatic disease. NPC1 gene mutation analysis identified all of the mutant alleles including three novel mutations. Splenomegaly, hepatomegaly, and ascites were the most consistent prenatal ultrasonographic findings of the NPC fetuses. We suggest that once identified these findings, should raise the suspicion of fetal NPC. Our study further expands the antenatal clinical spectrum of NPC and provides clues to its prenatal diagnosis.

The Role of Magnetic Resonance Imaging in the Evaluation of Isolated Mild Ventriculomegaly

Objective. Isolated mild ventriculomegaly is defined as dilatation of the lateral ventricle from 10 to 15 mm, with no other structural abnormalities observed at the time of diagnosis. Its reported frequency is between 1 per 50 and 1 per 700 deliveries. There are no universal recommendations for evaluation of isolated mild ventriculomegaly. Targeted sonography, karyotype analysis, and viral antigen testing, particularly for cytomegalovirus, are most often used for further investigation of this finding. We studied the role of magnetic resonance imaging as part of the prenatal evaluation of isolated mild ventriculomegaly. Methods. Thirty‐six pregnant women were referred to 2 Hadassah hospitals between 1999 and 2002 for evaluation of isolated mild ventriculomegaly. They underwent targeted sonography to exclude other anomalies, genetic amniocentesis for fetal karyotype, and serologic cytomegalovirus tests. Mild ventriculomegaly was the only pathologic finding diagnosed. Fetal brain magnetic resonance imaging was performed to evaluate the correlation between sonographic and magnetic resonance imaging findings and the additional contribution of magnetic resonance imaging in evaluating isolated mild ventriculomegaly. Results. Thirty‐six magnetic resonance imaging studies were performed. All tests were adequate for evaluation. In 3 (8.3%) of 36 cases, magnetic resonance imaging showed additional findings: in a severely obese woman, ventricular dilatation up to 18 mm and periventricular cystic lesions with abnormal sulcation suggestive of diffuse parenchymal abnormality were diagnosed, and in 2 cases, bleeding in germinal centers was found. On subsequent sonographic examination, no other finding but isolated mild ventriculomegaly was diagnosed. In the remaining 33 women (91.7%), magnetic resonance imaging studies correlated well with sonographic findings. Further sonographic follow‐up in this subgroup failed to reveal any other pathologic findings. Conclusions. Our study supports the view that magnetic resonance imaging should be considered as part of the evaluation of isolated mild ventriculomegaly, especially when objective difficulties preclude detailed sonographic examination.

Contraction of the fetal ductus arteriosus induced by diclofenac. Case report.

The ductus arteriosus in the fetus may contract after administration of nonsteroidal anti-inflammatory drugs such as indomethacin and aspirin. We report a similar effect observed after a 36-week pregnant women was given diclofenac against flank pains. The ductus of this fetus was vasoconstricted with evidence of right ventricular hypertension. It resolved after cessation of the drug. Diclofenac is a cyclo-oxygenase inhibitor and thus carries the pharmacodynamic properties of other nonsteroidal anti-inflammatory drugs with inhibition of prostaglandin synthesis, resulting in vasoconstriction of the ductus arteriosus. We suggest monitoring of the fetal ductus state and velocities by fetal echocardiography in women treated with diclofenac.

Indomethacin for preterm labor: a randomized comparison of vaginal and rectal-oral routes

Objective To compare the efficacy of intravaginal and intra-rectal plus oral indomethacin for the treatment of preterm labor. Methods Between December 1996 and November 1998, 46 eligible gravidas admitted with singleton pregnancies and idiopathic preterm labor before 33 gestational weeks were randomized to receive 200 mg of intravaginal or intrarectal plus oral indomethacin. Results Twenty-three subjects were allocated to each study group. The interval from initiation of treatment to delivery was significantly longer in the intravaginal indomethacin group (26.5 ± 5.7 versus 12.6 ± 3.7 days; P = .007). Delivery was delayed by more than 7 days in 18 of 23 subjects (78%) in the intravaginal indomethacin group compared with ten (43%) in the intrarectal plus oral indomethacin group (P = .03). Birth weights were significantly higher (2306 ± 436 versus 1862 ± 232 g; P = .002) and hospitalization in a neonatal intensive care unit (NICU) (3.1 ± 0.8 versus 9.3 ± 3.7 days; P = .001) and mechanical ventilation (1.4 ± 0.2 versus 5.3 ± 1.6 days; P = .001) were significantly shorter in the intravaginal indomethacin group. Conclusion Intravaginal indomethacin is more effective than intrarectal plus oral application in delaying preterm labor and is associated with higher birth weights, shorter NICU stays, and shorter intervals of mechanical ventilation.

Severe infantile carnitine palmitoyltransferase II deficiency in 19-week fetal sibs.

Antenatal presentation of carnitine palmitoyltransferase type II deficiency due to mutations in the CPT2 gene has been rarely reported. We report an Ashkenazi Jewish family with 3 terminated pregnancies for multicystic kidneys and/or hydrocephalus. Fetal autopsy after termination of the couples 4th pregnancy (sib 2) showed renal parenchyma replaced by cysts that appeared to increase in diameter toward the medulla. Fetopsy after termination of the 7th pregnancy (sib 3) revealed micrognathia; hypospadias; cystic renal dysplasia; hepatosteatosis; and lipid accumulation in the renal tubular epithelium, myocardium, and skeletal muscle. Microvascular proliferative changes and focal polymicrogyria were seen in the brain. A beta-oxidative enzyme deficiency was suspected. CPT2 gene analysis showed a homozygous complex haplotype for the F448L mutation associated with a c.del1238_1239AG (p.Q413fs) truncating mutation in exon 4. Carnitine palmitoyltransferase type II deficiency should be included in the differential diagnosis in fetuses of Ashkenazi origin with multicystic kidneys and unusual cerebral findings.

Castleman disease in pregnancy.

Background Castleman disease, a rare disorder characterized by benign proliferation of lymphoid tissues, generally presents as a solitary mediastinal mass. We report the first case of this disease during pregnancy. Case A 32-year-old woman presented with a large abdominal mass and vaginal bleeding during the second trimester of pregnancy. Abdominal ultrasound demonstrated a large, retroperitoneal solid mass of mixed echogenicity and increased vascularity. The patient underwent explorative laparotomy that revealed a mesenteric mass, histologically consistent with Castleman disease of the hyaline-vascular type. The mass was excised completely, and the immediate postoperative course was uneventful, although the patient went into spontaneous preterm labor during the 29th week of pregnancy. Conclusion Castleman disease should be considered one of the benign etiologies for an abdominal or retroperitoneal mass during pregnancy.

Prepartum sonographic demonstration of 'to-and-fro' motion in fetal intestinal obstruction : a novel sign for immediate postnatal surgery

G. Rizzo*†, A. Capponi‡, M. E. Pietrolucci† and D. Arduini† †Department of Obstetrics and Gynecology, Università di Roma ‘Tor Vergata’, Ospedale Fatebenefratelli S. Giovanni Calabita, Isola Tiberina 89, 00186, Rome and ‡Department of Obstetrics and Gynecology, Ospedale GB Grassi Roma, Rome, Italy *Correspondence. (e-mail: giuseppe.rizzo@uniroma2.it) DOI: 10.1002/uog.5387 Published online 6 June 2008