Role of late amniocentesis in the era of modern genomic technologies.

OBJECTIVE: Traditionally, amniocentesis is performed between 17 and 23 weeks of gestation. This enables decisions regarding the course of pregnancy to be made before viability. Less frequently, amniocentesis is performed in the third trimester. Advanced genomic technologies such as chromosomal microarray analysis (CMA) provide more detailed information about the fetus compared with traditional G-banded chromosomal analysis. The aim of this study was to assess the indications for and safety of late amniocentesis, genetic-test results (especially in the context of CMA technology) and outcome of pregnancies that underwent the procedure after 24 weeks. METHODS: Medical records were analyzed retrospectively of all women in whom amniocentesis was performed at a gestational age of 24 + 0 to 38 + 6 weeks, at Hadassah Medical Center, between June 2013 and March 2017. Parameters investigated included indications for late amniocentesis, complications, CMA results and pregnancy outcome. RESULTS: During the study period, 291 women (303 fetuses, 277 singleton and 14 twin pregnancies; in two twin pairs, one fetus was terminated before amniocentesis) underwent late amniocentesis. CMA was performed in all instances of amniocentesis. The most frequent indication was abnormal sonographic finding(s) (204/303 fetuses, 67%). Preterm delivery occurred in 1.7% and 5.1% of pregnancies within the first week and within 1 month following the procedure, respectively. Aneuploidy was detected in nine (3%) fetuses and nine (3%) others had a pathogenic/likely pathogenic copy number variant, suggesting that CMA doubled the diagnostic yield of traditional karyotyping. Maximal diagnostic yield (17.5%) was achieved for the subgroup of fetuses referred with abnormal sonographic findings in two or more fetal anatomical systems. Variants of uncertain significance or susceptibility loci were found in another nine (3%) fetuses. CONCLUSIONS: In pregnancies undergoing late amniocentesis, CMA increased detection rates of fetal abnormalities and had a shorter turnaround time compared with traditional chromosomal analysis; therefore, late amniocentesis may serve as a helpful tool for detecting fetal abnormalities or reassuring parents following late-appearing abnormal sonographic findings. However, CMA may expose findings of uncertain significance, about which the couple should be precounseled. The procedure appears to be safe. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Walking reduces the post-void residual volume in parturients with epidural analgesia for labor: a randomized-controlled study.

BACKGROUND: The post-void residual volume is higher among parturients who received epidural analgesia than those who received no or alternative analgesia. METHODS: This prospective, randomized, controlled, non-blinded study was performed in a tertiary referral center labor suite. The post-void residual volume was measured by a transabdominal ultrasound following a voiding attempt. Healthy parturients with low-dose epidural analgesia in active labor were randomized either to walk to the toilet or to use a bedpan for voiding. The primary outcome measure (post-void residual volume in labor) was compared between the study groups. RESULTS: The toilet group (n=34) and the bedpan group (n=28) demonstrated similar post-void residual volumes (212 +/- 100 vs. 168 +/- 93 ml, P=0.289). Twenty patients (59%) randomized to the toilet group were unable to walk and actually voided in a bedpan. A secondary analysis was performed analyzing the groups as treated. The post-void residual volume was significantly lower in the actual toilet group (n=14, 63 +/- 24 ml) vs. the bedpan group (n=48, 229 +/- 200 ml), P=0.0052. Thirteen (93%) women who walked to the toilet managed to void before the ultrasound measurement vs. 20/48 (42%) using the bedpan, P=0.001. Fewer women who managed to walk to the toilet required urinary bladder catheterization during the labor than women who used the bedpan (6/14, 43% vs. 36/48, 75%) P=0.028. CONCLUSION: Women who were randomized to walk to the bathroom with epidural analgesia and were able to do so during labor had a significantly reduced post-void residual volume and a reduced requirement for urinary catheterization.

Early diagnosis and treatment of atrioventricular block in the fetus exposed to maternal anti-SSA/Ro-SSB/La antibodies: a prospective, observational, fetal kinetocardiogram-based study.

BACKGROUND: A fetus exposed to maternal anti-SSA/Ro or anti-SSB/La antibodies (or both) may develop complete atrioventricular block (AVB), which results in high prenatal and postnatal morbidity and mortality. Until recently, only high-grade AVB could be diagnosed in utero. The tissue velocity-based fetal kinetocardiogram (FKCG) enables accurate measurement of AV conduction time and diagnosis of low-grade AVB. In the present multicenter observational study, we used FKCG to detect first-degree AVB in fetuses at risk. METHODS AND RESULTS: FKCG was performed in 70 fetuses of 56 mothers who were positive for anti-SSA/Ro and/or anti-SSB/La. Fetuses were monitored with weekly FKCG from 13 to 24 weeks' gestation, followed by monthly assessments until delivery in unaffected fetuses and weekly assessments in affected fetuses. AV conduction in 70 at-risk and 109 normal fetuses was compared. FKCG was obtained readily in all fetuses; 6 showed first-degree AVB (AV conduction time >2 z scores above normal mean) at 21 to 34 gestational weeks. Immediate maternal treatment with dexamethasone resulted in normalization of AV conduction in all affected fetuses within 3 to 14 days. AV conduction time in the remaining 64 untreated fetuses remained normal throughout gestation. The ECG PR interval immediately after birth was normal in all affected newborns. No child developed AVB or cardiomyopathy in the subsequent 1- to 6-year (median 4-year) follow-up. CONCLUSIONS: The present findings suggest that an FKCG can detect first-degree AVB in the fetus exposed to maternal anti-SSA/Ro or anti-SSB/La antibodies (or both). Dexamethasone given on detection was associated with normalized AV conduction in fetuses with first-degree AVB. No fetus in the present study developed complete prenatal or postnatal AVB.

Antepartum continuous epidural ropivacaine therapy reduces uterine artery vascular resistance in pre-eclampsia: a randomized, dose-ranging, placebo-controlled study.

BACKGROUND: No therapy is currently available to improve the reduced uteroplacental blood flow (UPBF) that characterizes pre-eclampsia. We hypothesized that sympathectomy induced by epidural local anaesthesia reduces uterine vascular resistance (which is inversely correlated with UPBF) in pre-eclampsia. METHODS: Ten pregnant women between 24 and 32 weeks of gestation with pre-eclampsia and uterine artery flow abnormalities were randomized to antepartum continuous epidural therapy (ACET) or control. ACET was initiated by a 5 day dose-ranging trial (ACET-1) of 0.04, 0.06, 0.08, and 0.1% ropivacaine and saline placebo, each at 10 ml h(-1) for 24 h. Doses were randomized and double-blind. Doppler ultrasound indices of vascular resistance were assessed at baseline and after each 24 h dosing period in both uterine arteries. Subsequently, these ACET patients were administered 0.1% ropivacaine until delivery (ACET-2), with one additional randomized double-blind placebo day. RESULTS: Five patients were randomized to ACET. In each patient, one uterine artery exhibited a dose-dependent reduction in vascular resistance (P=0.035), a response that returned to baseline following placebo (P<0.001). The contralateral uterine artery exhibited either increased vascular resistance or no change. In all cases, the uterine artery that responded to ACET had higher baseline resistance than its pair (P=0.043). Baseline right-left difference in resistance between paired uterine arteries was greatly diminished following ACET. Although ACET patients had a mean (sd) duration to delivery of 19 (9) days compared with control 2 (1) days (P=0.008), this should be interpreted with caution because of demographic differences between groups. CONCLUSIONS: ACET reduces uterine artery resistance in pre-eclampsia <32 weeks. Uteroplacental re-distribution is a novel observation and warrants further investigation.

Post-void residual volume in labor: a prospective study comparing parturients with and without epidural analgesia.

BACKGROUND: This prospective, non-randomized study compared post-void residual volume in laboring and postpartum women with or without epidural analgesia. METHODS: The study was conducted over 1 year with institutional review board approval. Parturients were recruited in early labor and self-selected to either the study (with epidural) or control (without epidural) group. Post-void residual volume was compared between groups, using transabdominal ultrasound during labor, and on postpartum day 1 and 2. Main outcome measure was intrapartum residual bladder volume. RESULTS: Thirty patients were recruited to each group. During labor, residual bladder volume was significantly larger in the epidural group compared with the non-epidural group [median (range)] 240 (12-640), ml vs. 45 (13-250) ml, respectively, P < 0.001], but was similar on postpartum day 1 and 2. Twenty-five (83%) women with epidural analgesia required bladder catheterization during labor vs. one (3.3%) without (P < 0.0001). CONCLUSION: The greater post-void residual volume and increased inability to void in parturients with epidurals suggests that epidural analgesia plays a role in intrapartum urinary retention.

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

OBJECTIVE: 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. METHODS: The in-utero presentation and postnatal neurodevelopmental outcome of sonographically detected subdural hematoma or fetal stroke presenting as intraventricular hemorrhage (IVH) or intraparenchymal brain hemorrhage were investigated. RESULTS: Of 33 fetuses diagnosed with hemorrhagic brain lesions, 17 were electively terminated and two suffered intrauterine fetal demise. Thirteen were liveborn, seven by Cesarean delivery and six by spontaneous vaginal delivery. One case was lost to follow-up. Eight neonates had moderate to severe neurological deficit by a mean age of 35 (range, 6-96) months. One died at 2 months of age. These nine were diagnosed with Grade III-IV IVH in utero. Four neonates had normal neurological outcome by a mean age of 41 (range, 30-48) months; these four were diagnosed with subdural hematoma (n = 1) or Grade I-II IVH (n = 3) in utero. Fourteen cases were followed up with MRI, which confirmed ultrasound findings in 10 (71%) cases. In three (21%) cases MRI diagnosis was more accurate and the severity of grading was greater than that obtained on ultrasound imaging. Unilateral left hemispheric lesions were much more common than right-sided lesions (13 vs. 1, respectively). CONCLUSIONS: An antenatal sonographic diagnosis of fetal stroke with IVH Grade III-IV or with brain parenchymal involvement appears to be associated with poor neurological outcome. MRI may contribute to the accuracy of diagnosis, particularly in Grade II and III lesions. Left-sided unilateral lesions are more common than right-sided ones.

Growing teratoma syndrome vs chemotherapeutic retroconversion: case report and review of the literature.

BACKGROUND: Immature ovarian teratoma is the third most common germ cell tumor (GCT) following dysgerminoma and endodermal sinus tumor. The treatment of choice during childbearing age for immature teratoma composes of unilateral oophorectomy and in case of metastatic disease postoperative chemotherapy (BEP). Finding a solid mass in the peritoneal or chest cavity during routine follow up raises the suspicion of distance recurrence. DiSaia was the first to describe the appearance of benign distant metastasis during routine follow up. He termed this phenomenon "chemotherapeutic retroconversion". Latter, Logothetis described what seems to be a similar phenomenon in testicular non-seminomatous germ cell tumor (NSGCT) that he called the "growing teratoma syndrome". CASE: We present a case of a 12-year-old girl treated for growing teratoma syndrome after primary ovarian GCT. CONCLUSION: Review of the literature shows that this syndrome and the "chemotherapeutic retroconversion" are probably the same phenomenon.

Antenatal presentation of carnitine palmitoyltransferase II deficiency.

Carnitine palmitoyl transferase (CPT) II deficiency is usually manifested around puberty by exercise induced myoglobinuria. Two Ashkenazi Jewish sibs with the rare antenatal form of CPTII deficiency are reported. On the 5th gestational month periventricular calcifications and markedly enlarged kidneys were found in both of them. The activity of CPTII in lymphocytes was undetectable and both sibs were homozygous for the 1237delAG mutation. Because of the serious consequences of homozygosity for this mutation, genotype determination of all Ashkenazi patients with the adolescent form of CPTII deficiency is warranted.

Rhabdomyoma in the fetus: illustration of tumor growth during the second half of gestation.

Rhabdomyomata are the most common cardiac tumors in childhood and are associated with tuberous sclerosis. These tumors tend to regress in the first years of life. Little is known about their intrauterine growth pattern. We describe three fetuses with cardiac rhabdomyomata and illustrate the tumor growth by serial echocardiographic views during the second half of gestation. Tumor growth is proportional to cardiac growth and tends to be somewhat slower toward the end of pregnancy.

The coronary sinus in the fetus.

INTRODUCTION: The normal coronary sinus drains venous blood from the cardiac veins to the right atrium. In some instances, the coronary sinus may be dilated due to volume or more rarely pressure overload. AIMS: To assess the feasibility of detecting the coronary sinus in the fetus and to establish the normal values of the coronary sinus dimensions throughout gestation. SUBJECTS AND METHODS: Fetal echocardiography was performed in 78 normal fetuses from the 16th to the 40th week of gestation (median 25 week). The coronary sinus was measured in four-chamber view (87% of cases) or in parasternal short axis view equivalent (13%). A second group of nine fetuses with a dilated coronary sinus was compared to the normal group. RESULTS: Adequate imaging of coronary sinus was obtained in 97.4% of the normal fetuses. The diameter of the coronary sinus ranged from 1 to 3.2 mm (2 mm +/- 0.13 mm, mean +/- 5% confidence interval) and correlated well with the age of pregnancy (r = 0.86). The length-to-diameter ratio of 24% (+/- 6%) did not vary throughout pregnancy. All nine fetuses with a dilated coronary sinus had a persistent left superior vena cava which drained into it. The diameter of the coronary sinus was approximately three times larger in the abnormal group with a diameter-to-length ratio of approximately 83% (P < 0.0001). CONCLUSION: The coronary sinus is readily identified in the fetus. It gradually increases during pregnancy. An abnormal coronary sinus is easily diagnosed and should prompt the sonographer to look for a persistent left superior vena cava.

Ultrasonographic prenatal diagnosis of microcephalic osteodysplastic primordial dwarfism types I/III.

Microcephalic osteodysplastic primordial dwarfism is a rare disease characterized by unique clinical appearance and specific radiographic findings, and distinctive brain abnormalities. We describe the prenatal diagnosis of two siblings with microcephalic osteodysplastic primordial dwarfism types I/III at 23 and 26 weeks of gestation, respectively. Early detection by sequential antenatal sonographic evaluation is important for counselling families known to be at risk of this rare disease.

Sonographically thick placenta: a marker for increased perinatal risk--a prospective cross-sectional study.

The aim of this study was to determine placental thickness by ultrasound examination throughout pregnancy and establish the correlation of sonographically thick placenta with perinatal mortality and morbidity. Placental thickness was determined by routine sonographic examination throughout pregnancy in 561 normal singleton pregnancies. Thick placenta was determined as placenta that was above the 90th percentile. Gravidae between 20-22 weeks' gestation (n=193) and 32-34 weeks (n=73) were then divided into two groups according to placental thickness. The study group consisted of 44 gravidae with thick placenta. The control group included 151 gravidae with placental thickness between the 10th and 90th percentile. A comparison of perinatal mortality and morbidity rates as well as the incidence of small and large for gestational age neonates was conducted.A linear increase of placental thickness was found to correlate with gestational age throughout pregnancy. No statistical differences were observed between the two groups with regard to obstetrical variables such as maternal age, parity and gestational age at delivery. No correlation was found between placental thickness and maternal age or parity. The incidence of perinatal mortality was significantly higher among gravidae with thick placentae (6.82% versus 0.66 per cent, P=0.037, 95 per cent confidence interval 1.71-70.29). Birthweight at term was found to be above 4000 g in 20.45 per cent of the thick-placenta group as compared to 5.3 per cent in the control group (P=0.001, 95 per cent CI 2.08-13.85), and birthweight of less than 2500 g was found in 15. 9 per cent of the thick-placenta group as compared to 7.3 per cent in the control group (P=0.03, 95 per cent CI 1.11-8.14). The incidence of fetal anomalies was 9.1 per cent in the thick-placenta group and 3.97 per cent in the control group (not significant). Sonographically thick placenta is associated with increased perinatal risk with increased mortality related to fetal anomalies and higher rates of both small for gestational age and large for gestational age infants at term.

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

OBJECTIVE: To compare the efficacy of intravaginal and intrarectal 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.

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.

Detection of an obstructive membrane in the ductus arteriosus of a fetus using high frame rate echocardiography.

We examined a fetus at 38 weeks of gestation because of marked disproportion in size of the left and right ventricles. A membrane was detected at the distal end of the ductus arteriosus with significant flow gradient through it. New echocardiographic technologies such as high frame rate imaging and dynamic beam focusing increase spatial and temporal resolution and enhance more precise anatomical diagnosis in the fetus. This ductal membrane might have been related to the transient tachypnea from which the baby suffered after birth.

Gallbladder and pancreatic involvement in hepatitis A.

Gallbladder (GB) abnormalities are rarely reported in children, but involvement of the GB has been demonstrated in various inflammatory disorders. Thirty-nine children hospitalized with hepatitis A virus infection were evaluated by ultrasound. Pseudosurgical gallbladder wall of 10 mm or more with striation was found in 10. Pathological echographic findings were found in the pancreas of three patients, one with frank pancreatitis. Ascitic fluid was noted in eight. Pediatricians and pediatric surgeons alike should be familiar with this gallbladder and pancreatic involvement, which might avoid unnecessary procedures or surgery.