Prenatal diagnosis and in utero treatment of congenital adrenal hyperplasia: An up-to-date comprehensive review.

Congenital adrenal hyperplasia (CAH) is a term that encompasses a wide range of conditions that affect the adrenals. Diagnosis and treatment before birth are important as irreparable birth defects can be avoided, decreasing the need for surgical intervention later in life, especially regarding genitalia anomalies. Although early implementation of dexamethasone in the prenatal treatment of CAH has been controversial, there is recent evidence that this treatment can reduce long-term complications.

Fetoscopic Release of Amniotic Bands Based on the Evidence-A Systematic Review.

The purpose of this review is to provide an overview of the perinatal outcomes of fetuses who underwent fetal surgery for the management of Amniotic Band Syndrome (ABS). A systematic review of studies reporting on the perinatal outcome of fetuses undergoing fetoscopic release of amniotic bands according to the (PRISMA) guidelines was performed. The MEDLINE, Embase, Scopus, and Cochrane Library databases were systematically searched. In total, 17 studies reporting 37 cases of ABS that underwent amniotic band release by fetoscopy were included. The median gestational age at which fetal surgery was performed was 22 weeks (range 18-29 weeks). PPROM occurred in 51.3%, while fetal survival reached 89.2%. The success of fetal surgery was 75.7% in preserving and maintaining the functionality of the affected limb. Fetoscopic release of amniotic bands can preserve the affected limb and its function in cases of ABS and prevent fetal death in cases of ABS involving the umbilical cord. Further studies are needed to determine the optimal criteria for selecting patients who can benefit from fetal surgery, considering that it is an intervention that is not free of perinatal complications.

Prenatal Diagnosis of Umbilical Cord Angiomyxoma: Case Studies and Literature Review of 45 Cases.

We describe two cases of umbilical cord (UC) angiomyxoma diagnosed prenatally by sonography in the second trimester of pregnancy. In both cases, a complex mass was detected at the placental insertion site, characterized by an echoic nodule surrounding the umbilical vessels and distal edematous Wharton's jelly. Follow-up scans showed that the mass grew mainly at the expense of its edematous component, with normal uteroplacental Dopplers throughout the remaining of the pregnancy. However, late-onset fetal growth restriction complicated the progress of pregnancy, requiring delivery by Cesarean section at 37 weeks' gestation in both cases. Neonatal courses were unremarkable. An extensive review of the English literature was also performed, collecting 45 similar cases including ours. Our experience as well as the review of the literature confirms that UC angiomyxoma is an uncommon, sporadic condition that is usually detected incidentally during prenatal sonography and presents as an isolated finding. Nevertheless, it represents a high-risk condition for pregnancy complications including prematurity, fetal growth restriction, and fetal demise.

Impact of overweight and obesity in the fetal cardiac function parameters in the second and third trimesters of pregnancy.

OBJECTIVE: To assess the impact of overweight and obesity in the second and third trimesters of pregnancy on fetal cardiac function parameters. METHODS: We performed a prospective cohort study of 374 singleton pregnant women between 20w0d and 36w6d divided into three groups: 154 controls (body mass index - BMI < 25 kg/m2), 140 overweight (BMI 25-30 kg/m2) and 80 obese (BMI ≥ 30 kg/m2). Fetal left ventricular (LV) modified myocardial performance index (Mod-MPI) was calculated according to the following formula: (isovolumetric contraction time + isovolumetric relaxation time)/ejection time. Spectral tissue Doppler was used to determine LV and right ventricular (RV) myocardial performance index (MPI'), peak myocardial velocity during systole (S'), early diastole (E'), and late diastole (A'). RESULTS: We found significant differences between the groups in maternal age (p < 0.001), maternal weight (p < 0.001), BMI (p < 0.001), number of pregnancies (p < 0.001), parity (p < 0.001), gestational age (p = 0.013), and estimated fetal weight (p = 0.003). Overweight pregnant women had higher LV Mod-MPI (0.046 versus 0.044 seconds, p = 0.009) and LV MPI' (0.50 versus 0.47 seconds, p < 0.001) than the control group. Obese pregnant women had higher RV E' than control (6.82 versus 6.33 cm/sec, p = 0.008) and overweight (6.82 versus 6.46 cm/sec, p = 0.047) groups. There were no differences in 5-min APGAR score < 7, neonatal intensive care unit admission, hypoglycemia and hyperglobulinemia between the groups. CONCLUSIONS: We observed fetal myocardial dysfunction in overweight and obese pregnant women with higher LV Mod-MPI, LV MPI' and RV E' compared to fetuses from normal weight pregnant women.

Placental and umbilical cord anomalies detected by ultrasound as clinical risk factors of adverse perinatal outcome: Case series review of selected conditions. Part 1: Placental abnormalities.

BACKGROUND: The aim of this extended review of multicenter case series is to describe the prenatal ultrasound features and pathogenetic mechanisms underlying placental and umbilical cord anomalies and their relationship with adverse perinatal outcome. From an educational point of view, the case series has been divided in three parts; Part 1 is dedicated to placental abnormalities. METHODS: Multicenter case series of women undergoing routine and extended prenatal ultrasound and perinatal obstetric care. RESULTS: Prenatal ultrasound findings, perinatal care, and pathology documentation in cases of placental pathology are presented. CONCLUSIONS: Our case series review and that of the medical literature confirms the ethiopathogenetic role and involvement of placenta abnormalities in a wide variety of obstetrics diseases that may jeopardize the fetal well-being. Some of these specific pathologies are strongly associated with a high risk of poor perinatal outcome.

Asymptomatic acute massive abruptio placenta at 30 weeks' gestation in a primigravida with no risk factors - clinical presentation and management.

Abruptio placenta can be a catastrophic event with a high association with adverse maternal and fetal outcomes. We present a case of massive abruptio placenta occurring in a young asymptomatic mother at 30 weeks' gestation. Although electronic fetal monitoring and ultrasound allowed a prompt diagnosis of an 8 × 5 cm retroplacental hematoma, the fetus died at the time of emergency cesarean section. The fetus was intubated, but could not be resuscitated. Histologic examination of the placenta documented thinning and stacked hypercapillarized villi, with syncytial buds and foci of fibrinoid necrosis in the presence of hyaline streaks on both the maternal and fetal sides.

Occult invasive cervical cancer, FIGO stage III, with a negative Pap smear test - clinical presentation and brief review of the literature.

Occult cervical cancer is rare and is diagnosed incidentally after a simple hysterectomy. The staging upon histological examination is usually International Federation of Gynecology and Obstetrics (FIGO) stage I, rarely higher with negative preoperative diagnostic tests such as a Pap smear. The clinical case in question is a rare case of cervical carcinoma diagnosed at the time of hysterectomy with a negative exo-endocervical Pap smear, diagnostic tests including transvaginal ultrasound, abdominal magnetic resonance imaging and abdominal computed tomography with a diagnosis of degenerating myoma or suspected sarcoma. In the operating theatre, the surgical radicality was modified and the operation was completed with removal of the parameters, vaginal collar and bilateral pelvic lymphadenectomy. The final histological examination indicated FIGO stage III, for which the patient underwent radiotherapy and chemotherapy.

Cesarean section incision along the posterior uterine wall - an obstetric and surgical complication of an obstructed pelvis due to previous endometriosis.

Pelvic endometriosis is a well-known clinical risk factor for pelvic inflammation and adhesions. We present a complex case of a woman undergoing a cesarean section where the traditional incision on the anterior lower uterine segment was not possible due to a congested pelvis. The newborn was delivered using a posterior uterine wall incision with rotation of the round ligament.

Cleft Lip and Cleft Palate: Time to Include Orofacial Ultrasound Markers Into the First-Trimester Anatomy Scan?

Orofacial clefts are one of the most common congenital malformations. The prenatal diagnosis is often made in the second trimester of pregnancy as result of ultrasound examination of the midface on coronal and axial planes. However, the diagnosis in the first trimester is elusive due to the small size of the facial structures and technical limitations present at this early gestational age. In this Commentary, we suggest the routine systematic ultrasound identification of easy-to-obtain landmarks to improve the detection of cleft lip and cleft palate in the first trimester. These include, but are not limited to, visualization of the primary palate using the coronal plane of the face looking for disruption at the base of the retronasal triangle, and visualization of the palate using the sagittal plane looking for the maxillary gap and loss of the superimposed line. Early prenatal detection of orofacial clefts would allow a more detailed search for associated chromosomal anomalies or genetic syndromes.

Simulator, machine learning, and artificial intelligence: Time has come to assist prenatal ultrasound diagnosis.

In this Commentary authors investigated and extended the role of simulator in assisting obstetric sonographers in training program. The interconnection of different digitalized technologies such as digital data, artificial neuronal and convolutional networks, machine and deep learning, telemedicine, and output are discussed and contribute to the generation of artificial intelligence.

3D ultrasound angioscan with MV-Flow™: Enhancing fetal brain low-flow microvascular neuroimaging.

MVFlow™ is a 3D algorithm that enhances the study of the microvasculature, useful in the study of tumoral lesions or in assessing the slow-flow of the placenta vessels and the developing fetal brain. It may improve the study of the corpus callosum in normal fetuses and be applied in the characterization of brain pathologies.

Basic sonographic examination of the fetal brain at 11-13 weeks' gestation: Rationale for a simple and reliable four-step technique.

The widespread incorporation of first-trimester scanning between 11 and 13 weeks' gestation has shifted from the screening of chromosomal abnormalities, mainly by measuring nuchal translucency thickness and visualization of the nasal bone, to a more detailed study of the fetal anatomy leading to early detection of several structural congenital anomalies. This goal can be improved by the routine and focused sonographic assessment of specific anatomic planes and the identification of distinctive landmarks that can help disclosing a particular, non-evident condition. In this article we present the basis for a basic, early examination of the fetal brain during screening using a four-step technique, which can be readily incorporated during the first-trimester scan. The technique includes the focused visualization of the cranial contour, choroid plexuses of the lateral ventricles and midline, aqueduct of Sylvius, brainstem, fourth ventricle, and the choroid plexus of the fourth ventricle. The rationale for this approach is presented and discussed.

Ultrasound and fetal magnetic resonance imaging: Clinical performance in the prenatal diagnosis of orofacial clefts and mandibular abnormalities.

Cleft lip, with or without cleft palate, is the most common congenital craniofacial anomaly and the second most common birth defect worldwide. Micrognathia is a rare facial malformation characterized by small, underdeveloped mandible and frequently associated with retrognathia. Second- and third-trimester prenatal ultrasound is the standard modality for screening and identification of fetal orofacial abnormalities, with a detection rate in the low-risk population ranging from 0% to 73% for all types of cleft. The prenatal ultrasonography detection can also be performed during the first trimester of pregnancy. Given the potential limitations of obstetric ultrasound for examining the fetal face, such as suboptimal fetal position, shadowing from the surrounding bones, reduce amniotic fluid around the face, interposition of fetal limbs, umbilical cord and placenta, and maternal habitus/abdominal scars, the use of adjunct imaging modalities can enhance prenatal diagnosis of craniofacial anomalies in at-risk pregnancies. Fetal magnetic resonance imaging (MRI) is a potentially useful second-line investigation for the prenatal diagnosis of orofacial malformations with a pooled sensitivity of 97%. In this review, we discuss the role of ultrasound and fetal MRI in the prenatal assessment of abnormalities of the upper lip, palate, and mandible.

Prenatal and Postnatal Zika Intrauterine Infection: Diagnostic Imaging Techniques and Placental Pathology.

Introduction: Zika virus (ZIKV) is an arbovirus (arthropod-borne virus) in the genus Flavivirus and Flaviviridae family. In November 2015, several cases of microcephaly in Northeastern of Brazil suggested ZIKV involvement. Case Report: A 33-year-old primigravida developed fever and cutaneous rash at 7th week of gestation (WGA). The ultrasound and MRI examination showed head circumference < 5th centile and enlargement of lateral ventricles. The infant was delivered at 39th WGA with microcephaly. Microscopy of the placenta showed chronic villitis and intervillitis, nodular stromal fibrosis in the stem villi, and vascular thickening. Postnatal CT showed collapsed cranium due to growth impairment of the suprathalamic brain, multiple cerebral calcifications, parenchymal atrophy, and ventricular dilatation. Now, at 6 years old, the child suffers from severe neurologic symptoms, including seizures. Conclusion: This case gathers images of prenatal and postnatal period, and placental histopathology. The long-term follow-up highlights the dramatic neurological sequelae induced by ZIKV.

Clinical Presentations and Diagnostic Imaging of VACTERL Association.

Background: VACTERL association consists of Vertebral, Anorectal, Cardiac, Tracheo-Esophageal, Renal, and Limb defects. The diagnosis depends on the presence of at least three of these structural abnormalities. Methods: The clinical presentation and diagnostic prenatal imaging of VACTERL association are comprehensively reviewed. Results: The most common feature is a vertebral anomaly, found in 60-80% of cases. Tracheo-esophageal fistula is seen in 50-80% of cases and renal malformations in 30% of patients. Limb defects including thumb aplasia/hypoplasia, polydactyly, and radial agenesis/hypoplasia are present in 40-50% of cases. Anorectal defects, like imperforate anus/anal atresia, are challenging to detect prenatally. Conclusion: The diagnosis of VACTERL association mostly relies on imaging techniques such as ultrasound, computed tomography, and magnetic resonance. Differential diagnosis should exclude similar diseases such as CHARGE and Townes-Brocks syndromes and Fanconi anemia. New insights into genetic etiology have led to recommendations of chromosomal breakage investigation for optimal diagnosis and counseling.

Area of the Fetal Ascending and Descending Aorta by Spatiotemporal Image Correlation in the Rendering Mode: Reproducibility and Comparison with Pregestational Diabetic Mothers.

Background: The objective of this study was to assess the ascending and descending aorta area measurements by three-dimensional (3D) ultrasound using spatiotemporal image correlation (STIC) in the rendering mode comparing these measurements with pregestational diabetic mothers and assessing the reproducibility of the method. Methods: We carried out a retrospective cross-sectional study with 58 normal and nine fetuses from pregestational diabetic mothers between 20 and 33 + 6 weeks of gestation. Fetal heart volumes were acquired at the level of four-chamber view to obtain the reconstructed planes for the ascending and descending aorta areas in the rendering mode. Linear regression was performed to assess the correlation between the fetal aorta areas and gestational age (GA). To assess the intra- and interobserver reproducibility, we used the concordance correlation coefficient (CCC). Results: The mean ascending and descending aorta areas were 0.12 (0.02-0.48) and 0.11 (0.04-0.39) cm2 in normal fetuses, respectively. There was a moderate positive correlation between GA and ascending aorta area measurements (0.005676*GA - 0.01283; r = 0.53, P < 0.0001) and strong positive correlation between GA and descending aorta area (0.01095*GA - 0.1581; r = 0.68, P < 0.0001). We observed a weak intra- and interobserver reproducibility with CCC ranging from 0.05 to 0.91. The mean difference in the ascending and descending aorta area measurements of normal and fetuses of pregestational diabetic mothers was -0.03 cm2 (P = 0.276) and -0.03 cm2 (P = 0.231), respectively. Conclusion: The fetal ascending and descending aorta area measurements obtained by 3D ultrasound using STIC in the rendering mode increased with GA in normal fetuses. The method showed weak intra- and interobserver reproducibility.

Bronchopulmonary dysplasia: Can we provide a link between prenatal and postnatal lung ultrasound?

The role of lung ultrasound in the prediction of bronchopulmonary dysplasia.

Heterotaxy Syndrome with Increased Nuchal Translucency and Normal Karyotype Associated with Complex Systemic Venous Return. Ultrasound Diagnosis with Autopsy Correlation.

Background: Prenatal ultrasound (US) detection of heterotaxy syndrome can be challenging, especially in identifying cardiovascular and associated anomalies. We present a new case of heterotaxy syndrome with anomalous systemic venous return (ASVR) fully displayed at autopsy. Case report: Left heterotaxy syndrome was diagnosed in a 19 weeks' of gestation fetus with right-sided stomach. The heart showed both ventricles with left morphology, a large ventricular septal defect, persistent left superior vena cava draining into the coronary sinus, ASVR with interrupted inferior vena cava (IVC) and azygous continuation. Autopsy dissection further identified the azygous draining into the left lower pulmonary vein (LLPV). Prenatal a-CGH on villous sampling showed 22q13.1 microduplication inherited from the father, not contributory to the phenotype. Conclusion/discussion: Heterotaxy syndrome requires US accuracy for anomaly identification, as they allow legal termination of pregnancy. Our case is unusual as IVC drained into the azygous vein and then into the LLPV.

Mosaic Trisomy 12: Prenatal Diagnosis at Amniocentesis and Molecular Genetic Analysis on Fetal Tissues.

Background: Mosaic trisomy 12 is a genetic condition with few cases diagnosed prenatally and postnatally. Phenotypic variability is wide ranging from normal patients to severe congenital anomalies. Case report: A 35-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Prenatal ultrasound was negative. Cultured amniocytes revealed a karyotype of 47,XX,+12/46,XX. Parents opted for termination of pregnancy at 22 weeks. Postmortem revealed dysmorphic face; hands with broad thumbs and incomplete transverse palmar creases; partial anomalous pulmonary venous return, intestinal malrotation, and bicornuate uterus. Histologically, no anomalies were identified. Cytogenetic analyses on fetal tissues detected mosaic trisomy 12 in thymus, lung, brain, kidney, placenta, and cord blood. Discussion/Conclusion: We report a new case of mosaic trisomy 12 with non-lethal morphological findings not previously described. Although prenatal ultrasound may be negative, genetic counseling should consider minor abnormalities and widespread presence of trisomic cell lines in various internal organs.

Early Prenatal Ultrasound and Molecular Diagnosis of Apert Syndrome: Case Report with Postmortem CT-Scan and Chondral Plate Histology.

Background Apert syndrome is characterized by craniosynostosis, midface hypoplasia and symmetric syndactyly. Case report: A 36-year-old mother, G2P1 underwent an ultrasound scan at 19 week's gestation. There was craniosynostosis, brachi-turricephaly and bilateral hand syndactyly. Genomic DNA from amniocentesis revealed the mutation C758C>Gp. (Pro to Arg substitution) at 252 of the exon 8 of the FGFR2 encoding for Apert syndrome. The pregnancy was terminated. Femoral chondral plate histology showed an increased interstitial matrix between bony trabeculae. Compared with normal, the trabeculae were thinner, more irregular with numerous osteoclasts suggesting abnormal bone remodeling. Hands and feet had an abrupt transition between resting and proliferating cartilage. Conclusion: Apert syndrome has increased intertrabecular matrix, thin trabeculae, increased remodeling, and irregular transition between the maturing and mineralization zones in the femur, and abnormal abrupt transition between the resting and proliferating cartilage in the fingers and toes.