First-trimester septated cystic hygroma, marked non-immune fetal hydrops, 45,X and coarctation of the aorta with neonatal survival.

Marked first-trimester nonimmue hydrops fetalis and 45,X with neonatal survival.

Incidental sonographic finding of a concealed placental abruption leading to delivery at 37 weeks' gestation.

Placental abruption occurs clinically in approximately 1% of births although placental pathology assessment suggests a higher incidence. Ultrasound rarely plays a role in the diagnosis or clinical management of patients with suspected placental abruption. A patient with an incidental sonographic finding of a large concealed abruption at 36 weeks' gestation, led to induction of labor. This case and the established association of increased stillbirth with placental abruption among patients of advanced maternal age, suggest that at term, following sonographic findings of abruption, consideration should be given to elective delivery of these patients even in the absence of clinical symptomatology.

Mid-trimester absent nasal bone and transient unilateral hydronephrosis associated with 16p13.3 microduplication.

Characteristic phenotypic features of 16p13.3 microduplication include impaired mental development, arthrogryposis-like musculoskeletal anomalies (club-feet, congenital hip dislocation, and camptodactyly of fingers and toes), facial dysmorphology, and at times congenital cardiac disease. Most of the described affected individuals have microduplications involving the CREBBP gene. Findings indicate this gene to be dosage-sensitive and likely involved in the phenotypes of 16p13.3 microduplication syndrome. We describe the incidental finding of 16p13.3 microduplication in a fetus with mid-trimester sonographic examination showing absent nasal bone and transient unilateral hydronephrosis.

Prenatal sonography of extracorporeal ductus venosus in association with large fetal gastroschisis.

Liver herniation commonly associated with omphalocele occurs in only approximately 2.3% to 16% of fetuses with gastroschisis. Liver herniation in such cases is associated with considerably decreased survival rates (43% vs 97% with or without liver herniation, respectively). Rarely, abnormally positioned fetal hepatic vasculature has been reported mainly in association with congenital diaphragmatic hernia. In these rare cases, intrathoracic depiction of hepatic venous vasculature has assisted in confirming intrathoracic displacement of the fetal liver. We present a case of a large gastroschisis with complete herniation of the fetal liver in which prenatal sonography depicted an extracorporeal ductus venosus.

Mid-trimester fetal facial dysmorphology associated with 2p25.3 microdeletion.

We describe unusual mid-trimester sonography of subtle fetal facial dysmorphic features including; flattened nasofrontal angle with an almost vertically positioned nasal bone, acute nasolabial angle, and convexity of the maxillary areas in a fetus with otherwise normal anatomy. Microarray identified a 64.5 KB interstitial deletion of 2q25.3, which includes one exon of MYT1L. Mutations and deletions in MTY1L have been associated with autosomal dominant intellectual disability, autistic features, and obesity. Association of these features and 2p25.3 microdeletion has not been reported previously. This case emphasizes the importance of detailed microarray analysis following the sonographic recognition of subtle fetal dysmorphic features.

Hyperemesis Gravidarum: A Review of Recent Literature.

BACKGROUND: In the United States, hyperemesis gravidarum is the most common cause of hospitalization during the first half of pregnancy and is second only to preterm labor for hospitalizations in pregnancy overall. In approximately 0.3-3% of pregnancies, hyperemesis gravidarum is prevalent and this percentage varies on account of different diagnostic criteria and ethnic variation in study populations. Despite extensive research in this field, the mechanism of the disease is largely unknown. Although cases of mortality are rare, hyperemesis gravidarum has been associated with both maternal and fetal morbidity. The current mainstay of treatment relies heavily on supportive measures until improvement of symptoms as part of the natural course of hyperemesis gravidarum, which occurs with progression of gestational age. However, studies have reported that severe, refractory disease manifestations have led to serious adverse outcomes and to termination of pregnancies. SUMMARY: Despite extensive research in the field, the pathogenesis of hyperemesis gravidarum remains unknown. Recent literature points to a genetic predisposition in addition to previously studied factors such as infectious, psychiatric, and hormonal contributions. Maternal morbidity is common and includes psychological effects, financial burden, clinical complications from nutritional deficiencies, gastrointestinal trauma, and in rare cases, neurological damage. The effect of hyperemesis gravidarum on neonatal health is still debated in literature with conflicting results regarding outcomes of birth weight and prematurity. Available therapy options remain largely unchanged in the past several decades and focus on parenteral antiemetic medications, electrolyte repletion, and nutritional support. Most studies of therapeutic options do not consist of randomized control studies and cross-study analysis is difficult due to considerable variation of diagnostic criteria. Key Messages: Hyperemesis gravidarum carries a significant burden on maternal health and US health care. Most published research on pathogenesis is observational and suggests multifactorial associations with hyperemesis gravidarum. Precise, strictly defined criteria for clinical diagnosis are likely to benefit meta-analyses of further research studies regarding pathogenesis as well as therapeutic options.

Use of amniotic fluid for determining pregnancies at risk of preterm birth and for studying diseases of potential environmental etiology.

Amniotic fluid (AF) is a biological medium uniquely suited for the study of early exposure of the human fetus to environmental contaminants acquired by the mother before and during pregnancy. Traditional diagnostic applications of AF have focused almost exclusively on the diagnosis of genetic aberrations such as Trisomy-21 and on heritable diseases in high-risk pregnancies. Since more than 50 anthropogenic compounds have been detected in AF, there is considerable potential in utilizing fetal protein biomarkers as indicators of health effects related to prenatal toxic exposure. Here, we focus on preterm birth (PTB) to illustrate opportunities and limitations of using AF as a diagnostic matrix. Representing a pervasive public health challenge worldwide, PTB cannot be managed simply by improving hygiene and broadening access to healthcare. This is illustrated by 15-year increases of PTB in the U.S. from 1989 to 2004. AF is uniquely suited as a matrix for early detection of the association between fetal exposures and PTB due to its fetal origin and the fact that it is sampled from women who are at higher risk of PTB. This critical review shows the occurrence in AF of a number of xenobiotics, including endocrine-disrupting compounds (EDCs), which are known or may reasonably be expected to shorten fetal gestation. It is not yet known whether EDCs, including bisphenol A, phytoestrogens, and polychlorinated biphenyls (PCBs), can affect the expression of proteins considered viable or potential biomarkers for the onset of PTB. As such, the diagnostic value of AF is broad and has not yet been fully explored for prenatal diagnosis of pregnancies at risk from toxic, environmental exposures and for the elucidation of mechanisms underlying important public health challenges including PTB.

Sonographic findings of complete tubal abortion.

Ectopic pregnancies, implantation of a fertilized ovum in any location other than within the endometrial cavity, occur in 1-2% of all pregnancies. Despite current enhanced early diagnosis enabled by serum beta-human choriogonadotropin (hCG) levels and high-resolution ultrasound, this clinical entity continues to account for between 2.7 and 6% of all maternal deaths. The most common site of ectopic implantation is the Fallopian tube (>90% of cases), and less commonly in previous Cesarean scar, ovary, cervix, or the abdomen. Complete tubal abortion refers to a tubal pregnancy having been expelled from the distal portion of the Fallopian tube into the peritoneal cavity and may be associated with either considerable hemorrhage, spontaneous resolution, or rarely serve as an initial nidus for an abdominal pregnancy. We present unusual sonographic findings of a complete tubal abortion in a patient with minimal symptomology.

Prenatal sonographic findings of prominent fetal tricuspid annulus: A case report.

The tricuspid valve positioned between the right atrium and right ventricle is composed of 3 leaflets (anterior, posterior, and septal) anchored by a collagenous fibrous annulus, a saddle-shaped, oval structure, providing a firm yet dynamic structural support for the tricuspid valve. The annulus is considered to separate between the right atrium and right ventricle. Structural anomalies of the fetal tricuspid valve are rare and include Ebstein's anomaly, tricuspid atresia, partial absence, unguarded tricuspid orifice (absent leaflets) cleft, double orifice, bicuspid valve and Uhl anomaly (absence of the right ventricular myocardium with an apposing endocardium and epicardium). We present an unusual case in which a prominent peripheral circular structure was noted above the periphery of the fetal tricuspid valve at 31 weeks' gestation. Inflow across the tricuspid valve was unimpaired, with no tricuspid regurgitation. The right atrium appeared normal with a normal functioning foramen ovale, and the entire fetal cardiac anatomy and function were normal with no signs of congestive cardiac failure or fetal hydrops. The prominent non-obstructing circular structure in immediate proximity to the tricuspid valve leaflets was considered to represent a prominent tricuspid annulus. An appropriate for gestational age fetus was delivered at term and neonatal echocardiography was normal. This case emphasizes that normal variations in fetal anatomical structures should always be considered and specifically that unimpaired inflow across the tricuspid valve in diastole is key upon encountering an unusually prominent fetal tricuspid annulus, which may be noted at a considerable distance above the tricuspid leaflets within the right atrium.

Sonographic findings of transient marked proximal bowel dilatation in a growth-restricted fetus at 35 weeks' gestation.

Etiologies underlying the relatively infrequent third-trimester sonographic depiction of dilated fetal bowel include (functional or mechanical) bowel obstruction, intestinal atresia, volvulus, annular pancreas, intestinal malrotation, intussusception, gastrointestinal duplications, cystic fibrosis-associated meconium ileus, congenital chloride diarrhea, microvillus inclusion disease, intestinal neuronal dysplasia, and meconium plug syndrome. Fetal bowel obstruction may be associated with aneuploidy (mostly Trisomy 21 in association with esophageal or duodenal atresia), and rarely select microduplications or deletions. We present unusual sonographic findings associated with transient marked proximal fetal bowel dilatation in association with concurrent development of oligohydramnios, in a growth-restricted fetus at 35 weeks' gestation. This case supports that upon observation of dilated loops of fetal bowel, while not negating the potential need for delivery secondary to potential bowel compromise, consideration should be given for observation in anticipation of potential spontaneous resolution of this condition, especially among growth-restricted fetuses with decreased amniotic fluid volume in prematurity.

Extensive fundal placenta accreta spectrum (PAS) in a nulliparous patient with an unscarred uterus and systemic lupus erythematosus (SLE) necessitating cesarean hysterectomy at delivery.

Placenta accreta spectrum (PAS) defined by various degrees of abnormally invasive placentation is strongly associated with severe maternal morbidity and maternal mortality, mainly reflecting maternal hemorrhage. Predisposing factors for this condition include: multiparity, placenta previa, previous uterine surgeries (previous curettage, cesarean delivery, and myomectomy), smoking and previous PAS. Prenatal sonographic findings associated with PAS include the presence of placenta previa, loss of the hypoechoic retroplacental sonolucency, myometrial thinning, interruption of the irregularity of the bladder wall, excessive vascularity of the uterovesical plane, placental lacunae, increased placental vascularity, bridging vessels with vascularity extending from the placental bed across the uterine wall into the bladder or other pelvic organs. PAS is very rare among nulliparous patients, especially those without previous uterine surgery. We describe an unusual case of PAS in a nulliparous patient with an unscarred uterus and systemic lupus erythematosus in whom a fundal placenta with PAS and thinned and areas of absent myometrium suspected at midtrimester sonography, sustained uterine atony and severe hemorrhage at delivery, necessitated massive blood transfusion and subtotal hysterectomy. Both mother and infant did well. Pathology confirmed PAS and marked uterine thinning. Although PAS most commonly is associated with placenta previa and the presence of previous cesarean delivery, this case emphasizes the need for alertness of at times subtle prenatal sonographic findings of PAS irrespective of placental location even among nulliparous patients, especially those with systemic lupus erythematosus.

Reverse diastolic flow of the fetal middle cerebral artery associated with placental chorangiomatosis and asymptomatic concealed placental abruption.

Reverse diastolic flow of the fetal middle cerebral artery is a rare, yet ominous finding which has been associated with adverse perinatal outcomes including: intracranial hemorrhage, growth restriction, fetal-maternal hemorrhage, severe anemia, hydrops, hepatic anomaly, subsequent stillbirth, and early neonatal death. We report a case in which following notation of a nonreassuring fetal heart rate at 32 weeks' gestation, sonographic documentation of persistent reverse diastolic flow of the fetal middle cerebral artery was noted in association with sonographic findings of vascular placental dysmorphology and an asymptomatic concealed placental abruption. Subsequent fetal heart rate tracing consistent with uteroplacental insufficiency led to immediate Cesarean birth of an anemic yet nonacidotic, nonhypoxic neonate, who did well following management of respiratory distress syndrome and partial exchange transfusion. Placental abruption was confirmed at delivery. Histopathology of the placenta confirmed the presence of localized chorangiomatosis ("wandering" chorangioma). The association of reverse diastolic flow of the fetal middle cerebral artery, placental chorangiomatosis and placental abruption has not been reported previously. We conclude that in the presence of prenatal sonographic findings of placental dysmorphology and or placental abruption, insonation of the fetal middle cerebral artery should be performed to assess the possibility of increased peak systolic velocity and possible reverse diastolic flow, both associated with fetal anemia and increased likelihood of an adverse perinatal outcome.

Mid-trimester isolated bilateral rocker bottom feet leading to prenatal diagnosis of 7q11.23 microdeletion: Williams syndrome.

Prenatal sonographic depiction of congenital vertical talus (rocker bottom feet), describing a prominent calcaneus and rounded convex appearance of the ventral aspect of the foot, has been reported with fetal Trisomies 18, 13, 9 HOXD10 mutations and recently 2q13 microdeletion. We present a 24 year old in whom mid-trimester sonographic finding of isolated bilateral rocker bottom feet led to diagnosis of 7q11.23 microdeletion-Williams syndrome. This association has not been reported previously. This case emphasizes the critical assessment of detail microarray upon prenatal sonographic notation of abnormal structural fetal features.

Mid-trimester dilated fetal bowel leading to diagnosis of interstitial duplication 46,XX,dup(8)(q21.13q21.2) associated with extensive neonatal jejuno-ileal atresia.

Small bowel atresia constitutes congenital obstruction of the lumen of the duodenum, jejunum or ileum, and is one of the most common causes of neonatal bowel obstruction with a reported incidence of between 1.3 and 2.8 per 10,1000 live births. Complete absence of the small bowel, or near total jejuno-ileal atresia (in the absence of malrotation or gastroschisis), are extremely rare. Mid-trimester prenatal sonographic finding of dilated fetal bowel led to the finding of interstitial 8q21.13q21.2 duplication. Following delivery at 32 weeks' gestation, at laparotomy almost complete small bowel atresia was noted. Anastomosis between the existing small bowel and colon was performed. At 7 months of age, the infant continued to receive total parenteral nutrition supplemented by gastrostomy and oral-spoon formula feeding, and weighed 7 kg (50th centile). This is the first report of the association interstitial 8q21.13q21.2 duplication, which includes OMIM genes (RALYL, LRRCC1, and E2F5) and extensive small bowel atresia.

Current Perspectives of Prenatal Cell-free DNA Screening in Clinical Management of First-Trimester Septated Cystic Hygroma.

First-trimester septated cystic hygroma occurs in approximately 1 in 268 pregnancies and has long been associated with a markedly increased risk of fetal aneuploidy and, among euploid fetuses, an increased risk of structural anomalies primarily affecting the cardiac and skeletal systems. Invasive prenatal diagnosis - chorionic villus sampling and/or amniocentesis - encompasses the time-honored clinical tools for the next step in management following prenatal sonographic diagnosis of first-trimester septated cystic hygroma. Currently, prenatal cell-free DNA (cfDNA) screening for fetal aneuploidy with select microdeletions is gradually replacing the considerably less sensitive, and labor-intensive combined first-trimester screening. These new technologies have opened potential new venues in the clinical management of this ominous late first-trimester sonographic diagnosis. Advances in cfDNA technologies are now permitting detection of chromosomal copy number variants (CNV) larger than 7Mb across genome and select serious single-gene disorders (mainly impacting skeletal and neurological development), affecting quality of life and may benefit from medical and/or surgical management. This commentary will address the available non-invasive prenatal screening technologies, which clearly enhance immediate genetic analysis modalities applicable in the presence of the complex sonographic finding of first-trimester septated cystic hygroma.

Sonographic diagnosis of an interstitial pregnancy in an asymptomatic patient at 7 weeks' gestation.

An interstitial pregnancy is an ectopic pregnancy located within the proximal intramural segment of the Fallopian tube traversing the myometrium. This type of ectopic pregnancy is relatively rare, occurring in approximately 1%-3% of all ectopic pregnancies. Given the myometrial mantle surrounding the gestational sac, which is considerably thicker than in other tubal pregnancies, patients with interstitial pregnancies classically manifest symptoms later in gestation. Thus, there is an increased risk of life-threatening intraperitoneal hemorrhage upon rupture of the myometrium encompassing the pregnancy. We present an unusual case of early sonographic diagnosis of an interstitial pregnancy in an asymptomatic patient at 7 and 3/7 weeks' gestation, discuss predisposing factors, hallmarks of sonographic diagnosis, and review the literature regarding available clinical management modalities. With the increasing application of point of care ultrasound (POCUS) by emergency room physicians and other providers in outpatient facilities, our case emphasizes both the importance of correct sonographic identification of interstitial pregnancy and the clinical importance of uniform early first-trimester sonography, preferably no later than 7-8 weeks' gestation.

First-trimester septated cystic hygroma and cavum velum interpositum cyst.

First-trimester septated cystic hygroma, frequently noted during general obstetric first-trimester screening, is strongly associated with fetal aneuploidy and structural anomalies and is considered an ominous finding. We present the case of a fetus with a first-trimester septated cystic hygroma and cavum velum interpositum cyst.