Fetal Trigonocephaly (Strawberry Skull) in Early Pregnancy.

Trigonocephaly was previously described prenatally in association with severe abnormalities, mostly observed after 18 weeks of gestation. We describe our experience with this finding in early pregnancy, between 14 and 17 weeks of gestation. Our series includes 18 cases of trigonocephaly with several etiologies; trisomy 18, de novo translocation, thanatophoric dysplasia, and open spina bifida without hydrocephalus. Two fetuses had no other significant abnormalities and a spontaneous normalization of the skull shape was observed on follow-up. Both had normal genetic testing and postnatal outcome. These two cases represent a new phenomenon of an isolated transient form with normal outcome.

Early Prenatal Diagnosis of Double Aortic Arch: Prevalence, Associated Anomalies and Outcome.

PURPOSE: Our aims were to describe the feasibility of diagnosis of DAA in early pregnancy and to assess its prenatal prevalence, associated anomalies and outcome. MATERIALS AND METHODS: A retrospective cohort review of all DAA cases diagnosed by early prenatal transvaginal scans at 12-17 weeks of gestation between the years 2007-2018 was performed. Associated anomalies, genetic abnormalities and long-term postnatal outcome were evaluated. RESULTS: 12 cases of DAA were diagnosed by early prenatal transvaginal scans at a median of 15 (range: 12-17) weeks of gestation out of a total of 28 654 early scans preformed with a prevalence of at least 1:2378. Associated anomalies/genetic abnormalities were found in 5/12 (42 %) cases. The diagnosis was confirmed postnatally in all newborns. In two cases termination of pregnancy was performed. Four patients (40 %) were symptomatic. Six patients (60 %) underwent surgery due to symptoms or due to severe obstruction on imaging with resolution of symptoms in all except one patient. CONCLUSION: DAA can be readily diagnosed transvaginally even in the first trimester. Its prevalence is 1:2387. A search for associated anomalies and genetic abnormalities should be performed. If DAA is isolated, the prognosis with or without surgery is usually good.

Incidence of congenital thoracic malformations detected by prenatal ultrasound.

BACKGROUND: The increased and earlier use of prenatal ultrasound has facilitated the detection of congenital thoracic malformations (CTMs). Our Pediatric Pulmonology Institute follows an increasing number of patients with CTMs. Thus, we aimed to evaluate and describe prenatal sonographic findings of CTM, and to estimate changes in detection rates of CTMs over a period of 16 years. METHODS: A retrospective, cross-section analysis of prenatal ultrasound (US) screening tests carried out in a large community-based clinic, comparing two periods: 2001-2007 and 2007-2017. RESULTS: A total of 34 716 prenatal US were performed at a median gestational age of 15.4 weeks (range, 11.6-23.9) and 15.7 weeks (range, 12-33.6) in 2001-2007 and 2007-2017, respectively. In 2001-2007, 12 016 prenatal US tests detected 19 CTMs, compared to 30 CTMs in 22 700 tests in 2007-2017. Detection rates did not change (1.58/1,000 in 2001-2007 versus 1.32/1,000 in 2007-2017, P = 0.64). The most common abnormality was congenital pleural effusion (CPE) (17 cases, 34.7%), followed by congenital pulmonary airway malformation) and congenital diaphragmatic hernia; 13 cases each, 26.5%. Twenty CTMs, mainly congenital diaphragmatic hernia and CPE, were associated with other fetal lesions. CONCLUSIONS: Congenital diaphragmatic hernia and CPE tend to appear with multiple lesions and warrant further attention. The incidence rates stayed stable when comparing the last decade to previous years. Thus, the increased referral of CTM can be attributed to an increase in the number of prenatal screening studies performed, rather than a true higher incidence.

Early sonographic manifestation of fetal congenital lobar emphysema.

Advanced fetal sonographic equipment has contributed to the increase in prenatal diagnosis of congenital thoracic malformations. Among these anomalies is congenital lobar emphysema (CLE), a rare congenital anomaly characterized by over distention and overexpansion of the involved fetal pulmonary lobe. Several studies addressed the prenatal diagnosis of CLE in mid second or early third trimester. The early prenatal diagnosis and the outcome of a case of CLE are reported in this study.

Unilateral Renal Agenesis Diagnosed on Early Prenatal Trans-Vaginal Scans.

BACKGROUND: Unilateral renal agenesis is a rare finding. There are no large-scale studies reporting this finding in early pregnancy. OBJECTIVES: To evaluate the incidence of unilateral renal agenesis (URA) and of associated anomalies diagnosed by early prenatal trans-vaginal sonography. METHODS: We performed a retrospective chart review of all 59,382 trans-vaginal scans performed at 14-16 weeks gestation by a single operator at different clinics during the period 1994-2013. RESULTS: The incidence of URA was 1:1212 (49/59382 cases). Associated anomalies were diagnosed in 22 cases (45%). Renal anomalies were diagnosed in 22.4%. Extra-renal anomalies (with exclusion of a single umbilical artery or nuchal edema as isolated findings) were diagnosed in 24.5%. Ambiguous genitalia were diagnosed in 8.2%. CONCLUSIONS: URA is a rare finding in early trans-vaginal sonography. Associated anomalies are very common and should be sought.

Early Transient Prenatal Ultrasound Features of Choanal Atresia.

We present a case series of early second-trimester prenatal ultrasound (US) features in 4 fetuses with a confirmed diagnosis of choanal atresia. The clinical characteristics and outcomes evaluated included prenatal US findings, genetic analyses, postmortem autopsies (2 cases), and computed tomographic findings. A transient large nasal cavity was detected by US in all 4 fetuses. This finding disappeared a few weeks later. Three cases were unilateral choanal atresia, and 1 was bilateral. Transient enlargement of the nasal cavity in early pregnancy appears to be a US sign of choanal atresia.

Characteristics and Outcomes of Ptyalism Gravidarum.

BACKGROUND: Ptyalism gravidarum (PG) is a condition of hypersalivation that affects pregnant women early in gestation. Symptoms include massive saliva volumes (up to 2 liters per day), swollen salivary glands, sleep deprivation, significant emotional distress, and social difficulties. OBJECTIVES: To examine maternal and fetal characteristics and pregnancy outcomes of patients with PG. METHODS: Patients diagnosed with PG in our clinic during the years 2001-2016 were identified and contacted. Demographic data were extracted from patient charts and clinical and outcome data was collected via telephone interviews. RESULTS: The incidence of PG was 1/963 (0.09%) in our sample. Eleven out of 22 women (40%) with PG were also diagnosed with hyperemesis gravidarum. Fetal gender did not increase the risk. Of the mothers presenting with PG, 37% had a positive family history for this condition. There was no associated increase in the rate of fetal or maternal complications. Two women reported a resolution of the symptoms immediately following hypnosis with acupuncture treatment. CONCLUSIONS: Although PG represents an unpleasant mental and physical condition, it does not pose any specific risk to the health of the mother or increase adverse perinatal outcomes for the fetus. Alternative medicine could play a role in the treatment of PG.

The recurrence of sonographic 'soft markers': ominous sign or 'just' genetics?

OBJECTIVES: 'Soft markers' (SMs) are nonspecific findings that might convey a higher risk for Down syndrome. We sought to determine the recurrence rate of the most common SM in subsequent pregnancies. METHODS: This is a retrospective study of all women who underwent early or late fetal sonographic anatomical screening in our ultrasound unit. The examined SMs were pyelectasis, thickened nuchal fold (TNF) and echogenic intracardiac foci (EIF). Data on recurrence and pregnancy outcome were retrieved retrospectively. RESULTS: The database included 20 672 singleton pregnancies; SMs were detected in 2347 (11.1%) of the fetuses and were isolated in 1739 (74%). Rates of solitary findings in the pregnancies were 6.5% (1360/20 672) EIF, 3% (624/18 850) TNF and 1.7% (363/20 672) pyelectasis. The recurrence rate of EIF, TNF and pyelectasis in subsequent consecutive pregnancies was 21%, 27% and 16%, respectively. Overall, 62 cases of Down syndrome were diagnosed in (1 : 333 pregnancies). No cases were diagnosed in patients with recurrent SMs. CONCLUSION: The high recurrence rate of solitary SM implies for genetic predisposition. These results might improve our counseling for pregnant women affected by the reappearance of solitary SM. Further studies are needed to assess the likelihood ratio for SM if recurrence occurs. © 2017 John Wiley & Sons, Ltd.

Prenatal Sonographic Abnormal Appearances of the Fetal Hyaloid Artery: From Normal Variants to Pathology.

This is a case series on the abnormal sonographic appearance and outcome of the fetal hyaloid artery (HA) detected during between 1987 and 2015 at one medical center. Fifteen cases were detected during fetal anatomy scans, usually performed at 14 to 16 weeks' gestation. Three other cases were diagnosed following referral for a second opinion. In nine fetuses, the HA regressed normally throughout pregnancy. Of them, eight neonates had normal outcomes and one had cataract at the same eye. All nine other cases ended with adverse outcomes. Failure of the HA to regress in the third trimester appears to be an indicator of congenital blindness.

Transient Distention of Right Posterior Located Sigma, a New Sonographic Sign for the Prenatal Diagnosis of Anal Atresia.

We describe a new sonographic sign for the detection of anal atresia in the early midtrimester on transvaginal sonography. In six cases of fetal anal atresia, the finding of a transient, distended, and right-sided sigmoid colon was observed at 13-16 weeks' gestation. Three cases have undergone pregnancy termination due to multiple anomalies. In the other three, the colonic distension resolved by 19 weeks' gestation. In two of these, the finding was isolated, and no other anomalies were detected. In all six cases, anal atresia or cloaca was confirmed on postabortal autopsy or after delivery. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:160-162, 2017.

Congenital Absence of Salivary Glands in Fetuses with Trisomy 21.

BACKGROUND: The congenital absence of salivary glands has been reported in children but never in fetuses with trisomy 21. OBJECTIVES: To determine whether the congenital absence of salivary glands can be detected prenatally between 13 and 16 weeks of gestation in normal and trisomy 21 fetuses using transvaginal ultrasound. METHODS: We performed a retrospective analysis of recordings of normal and trisomy 21 fetuses. Inclusion criteria were a single viable fetus and good visualization of the anatomic area of the salivary glands on both sides of the fetal face. All videos were reviewed by one examiner who reported the presence or absence of one or more salivary glands and was blinded to the fetal karyotype. RESULTS: Of the 45 videos reviewed, 4 were excluded from the study: namely, a non-viable fetus, twin pregnancy, and in 2 there was unsatisfactory visualization of the anatomic area of the salivary glands. Of the remaining 41 fetuses, 24 had trisomy 21 and 17 were normal. In the trisomy 21 fetuses, 8 (33.3%) had congenital absence of one or more salivary glands compared to 1 of 17 normal fetuses (5.9%) (P < 0.05). CONCLUSIONS: Congenital absence of the salivary glands has a high specificity but low sensitivity for detecting trisomy 21 fetuses.

Detection Rate and Sonographic Signs of Trisomy 21 Fetuses at 14-17 Weeks of Gestation.

BACKGROUND: Early prenatal ultrasound is an important part of prenatal screening in Israel. No studies have described the rate of trisomy 21 [T21] identification at 14-17 weeks gestation. OBJECTIVES: To describe the rate of T21 identification by transvaginal sonograms (TVS) at 14-17 weeks gestation. METHODS: We conducted a historical prospective study. Since 1986, early TVS of 72,000 fetuses at 14-17 weeks gestation have been prospectively recorded together with prenatal screening data at a private ultrasound center (AL-KOL, Haifa). We calculated the fraction of T21 cases by dividing the total number of cases with abnormal sonographic findings by the total number of diagnosed T21 cases. We also examined the percentage of verified T21 cases that had completely normal prenatal screening tests prior to the early prenatal TVS, thus revealing the contribution of this examination to the existing prenatal screening. Fisher's exact test was used to calculate odds ratios for each sonographic marker. RESULTS: Of 137 T21 fetuses, 123 had sonographic markers on early TVS, yielding a prediction capability of at least 89.87%. Of all T21 cases, 14% had completely normal nuchal translucency/first-trimester screening prior to the abnormal 14-17 week TVS findings. Isolated abnormal sonographic findings, which were found to increase the risk for T21, were common atrioventricular septal canal (odds ratio 88.88), duodenal atresia (OR 88.23), nuchal edema (OR 39.14), and hydrocephalus (OR 15.78). Fetal hydronephrosis/pyelectasis was non-significant when isolated (OR 1), and cardiac echogenic focus was associated with a decreased risk (OR 0.13). CONCLUSIONS: Early prenatal TVS at 14-17 weeks may identify almost 90% of T21 and adds 14% to the identification rate at the first-trimester screening.

Prenatal sonographic features of triploidy at 12-16 weeks.

OBJECTIVE: The purpose of our study was to describe the sonographic appearance of triploidy in early pregnancy. METHODS: We report the sonographic characteristics of a cohort of fetal triploid cases detected at targeted ultrasonographic vaginal examinations between 12 and 16 weeks of gestation from 2008 to 2014. Indications for fetal karyotype following ultrasound were maternal request, advanced maternal age, increased nuchal translucency, and/or fetal abnormalities. RESULTS: Triploidy was detected in 25 cases during the 6 years of the study period with an estimated incidence of ~1 in 5000 pregnancies. Four cases had molar changes in the placenta. Among the remaining 21 cases, a consistent sonographic pattern was noted, which included the combination of asymmetric growth restriction with abdominal circumference lagging 2 weeks behind head circumference in 21/21, oligohydramnios in 20/21, abnormal posterior fossa or enlarged fourth ventricle in 20/21, and absent gall bladder in 17/21. Other findings present in more than 50% of cases included cardiac (70%) and renal (55%) abnormalities, clenched hands (55%), and hypoplastic lungs (67%). CONCLUSION: Fetal triploidy can manifest at 12-16 weeks with molar changes in the placenta or with a cluster of unusual sonographic findings whose presence should prompt appropriate testing for diagnosis in early pregnancy. © 2016 John Wiley & Sons, Ltd.

Fetal demise in the early second trimester: sonographic findings.

PURPOSE: To report the etiology and the sonographic findings of fetal demise at 14-17 weeks' gestation. METHODS: A prospective transvaginal sonographic search of fetal anomalies was performed in 61 early second-trimester cases of fetal demise. The findings were compared with the results of sonographic examinations of 22,500 viable fetuses between weeks 14 and 17. RESULTS: Of 61 cases of early fetal demise in 60 women (1:370), more than half of the fetuses (35/61, 57%) were associated with fetal edema, ranging from nuchal edema and cystic hygroma to fetal hydrops. In 9/61 (14.7%) fetuses, major anatomic anomalies were detected. There was no significant difference between the study group (nonviable fetuses) and the control group (viable fetuses) regarding maternal age and the prevalence of maternal fever, maternal thrombophilic mutations, vaginal bleeding, fertility treatments, maternal diseases, or use of medications. CONCLUSIONS: The incidence of early midtrimester fetal demise is 1:370 pregnancies. The sonographic findings in fetal demise in the early second trimester suggest that 57% of them are associated with fetal edema and 14.7% are associated with major fetal malformations. We did not identify any significant maternal risk factor for fetal demise in the study group.

Paternal deletion of the 11p15.5 centromeric-imprinting control region is associated with alteration of imprinted gene expression and recurrent severe intrauterine growth restriction.

BACKGROUND: Heterogeneous molecular defects affecting the 11p15.5 imprinted gene cluster are associated with the opposite growth disorders Beckwith-Wiedemann Syndrome (BWS) and Silver Russell syndrome (SRS). Maternal deletions of the centromeric domain usually result in BWS, but paternal deletions have been so far associated with normal phenotype. Here we describe a case of recurrent severe Intra-Uterine Growth Restriction (IUGR) with paternal transmission of an 11p15.5 60 kb deletion. METHODS AND RESULTS: Chromosome microarray (CMA), PCR and DNA sequencing analyses showed that two fetuses conceived by a normal couple inherited from their father a 60 kb deletion encompassing the Imprinting Control Region of the 11p15.5 centromeric domain. The two fetuses died in utero with severe growth restriction. PCR amplification of parental DNAs indicated that the father carried the mutation in the mosaic state. DNA methylation and gene expression analyses showed that the deletion led to an imprinting alteration restricted to the centromeric domain and resulting in silencing of KCNQ1OT1 and activation of CDKN1C and PHLDA2. CONCLUSIONS: Our data demonstrate that the phenotype associated with 11p15.5 deletions is strongly influenced by the size of the region involved and indicate imprinting defects leading to CDKN1C and PHLDA2 activation as cause of severe IUGR.

[The advantages of early midtrimester targeted fetal systematic organ screening for the detection of fetal anomalies--will a global change start in Israel?].

INTRODUCTION: Despite more than three decades of universal popularity of fetal sonography as an integral part of pregnancy evaluation, there is still no unequivocal agreement regarding the optimal dating of fetal sonographic screening and the type of ultrasound (transvaginal vs abdominal). METHODS: TransvaginaL systematic sonography at 14-17 weeks for fetal organ screening. RESULTS: The evaluation of over 72.000 early (14-17 weeks) and late (18-24 weeks) fetal ultrasonographic systematic organ screenings revealed that 96% of the malformations are detectable in the early screening with an incidence of 1:50 gestations. Only 4% of the fetal anomalies are diagnosed later in pregnancy. Over 99% of the fetal cardiac anomalies are detectable in the early screening and most of them appear in low risk gestations. CONCLUSIONS: Therefore, we suggest a new platform of fetal sonographic evaluation and follow-up: The extensive systematic fetal organ screening should be performed by an expert sonographer who has been trained in the detection of fetal malformations, at 14-17 weeks gestation. This examination should also include fetal cardiac echography Three additional ultrasound examinations are suggested during pregnancy: the first, performed by the patient's obstetrician at 6-7 weeks for the exclusion of ectopic pregnancy, confirmation of fetal viability, dating, assessment of chorionicity in multiple gestations, and visualization of maternal adnexae. The other two, at 22-26 and 32-34 weeks, require less training and should be performed by an obstetrician who has been qualified in the sonographic detection of fetal anomalies. SUMMARY: The advantages of early midtrimester targeted fetal systematic organ screening for the detection of fetal anomalies may dictate a global change.

Fetal isolated prominent left brachiocepalic vein: in utero natural history and neonatal outcome.

The objectives of this series were to describe the prenatal sonographic findings of a fetal isolated prominent left brachiocephalic vein with its in utero natural history and neonatal outcome and to discuss the differential diagnosis, especially with a total or partial anomalous pulmonary venous return malformation. We reviewed all cases referred to 2 tertiary medical centers with the presenting finding of a prominent, upper thorax transverse vein entering the superior vena cava. The primary suspicion of a subjective dilated left brachiocephalic vein, as a part of a supracardiac anomalous pulmonary venous return malformation, was investigated by a systematic anatomic evaluation. After exclusion of other cardiac and structural anomalies, we followed the pregnancies and their outcomes. Eight cases were recruited during a 7 year period. The mean maternal age was 31 years, and the mean gestational age at the time of diagnosis was 17 weeks. In 7 cases, the dilatation was not evident during 6 weeks of follow up. In 1 case, the dilatation was evident until delivery at 39 weeks and was not apparent on postnatal echocardiography or spiral computed tomography. All neonates developed without any heart or other complications. We conclude that after exclusion other malformations, a prominent left brachiocephalic vein is a benign transient phenomenon that does not persist post-partum in the neonate.