Update in the prenatal management of sacrococcygeal teratomas and the outcome of the newborn – case report

Sacrococcygeal teratomas complicate approximatively 1 in 27,000 pregnancies, being the most common congenital germ cell tumors in infants. The diagnosis is suspected using ultrasonographic examination and confirmed after a pathology report is performed. The main issue complicating fetuses with sacrococcygeal teratomas is represented by the rapid growth and the great need of blood supply captured by the tumor that interferes with the fetal growth and fetal wellbeing, generating heart failure and, unfortunately, increasing neonatal mortality. Thus, ultrasonographic monitoring is fundamental, to diagnose, closely monitor the growth and vascularization of the tumor and to ameliorate the neonatal prognosis by establishing the proper time of birth. There are specialized healthcare centers that could perform in utero surgery with the aim to aid the normal growth and development of the fetus until term, when a curative surgery is performed to the newborn. In cases complicated with heart failure leading to fetal hydrops, pregnancy termination could be a valuable option for the mothers, as soon as the etiology and the stage of heart decompensation are known. We present a case of a fetal sacrococcygeal teratoma in a 36-year-old pregnant woman, an uninvestigated pregnancy that had a dreadful outcome with neonatal death.

The fetus in the age of the genome

Due to a number of recent achievements, the field of prenatal medicine is now on the verge of a profound transformation into prenatal genomic medicine. This transformation is expected to not only substantially expand the spectrum of prenatal diagnostic and screening possibilities, but finally also to advance fetal care and the prenatal management of certain fetal diseases and malformations. It will come along with new and profound challenges for the normative framework and clinical care pathways in prenatal (and reproductive) medicine. To adequately address the potential ethically challenging aspects without discarding the obvious benefits, several agents are required to engage in different debates. The permissibility of the sequencing of the whole fetal exome or genome will have to be examined from a philosophical and legal point of view, in particular with regard to conflicts with potential rights of future children. A second requirement is a societal debate on the question of priority setting and justice in relation to prenatal genomic testing. Third, a professional-ethical debate and positioning on the goal of prenatal genomic testing and a consequential re-structuring of clinical care pathways seems to be important. In all these efforts, it might be helpful to envisage the unborn rather not as a fetus, not as a separate moral subject and a second “patient”, but in its unique physical connection with the pregnant woman, and to accept the moral quandaries implicitly given in this situation.

Prenatal Management Strategy for Immune-Associated Congenital Heart Block in Fetuses

Fetal congenital heart block (CHB) is the most commonly observed type of fetal bradycardia, and is potentially life-threatening. More than 50% of cases of bradycardia are associated with maternal autoimmunity, and these are collectively termed immune-associated bradycardia. Several methods have been used to achieve reliable prenatal diagnoses of CHB. Emerging data and opinions on pathogenesis, prenatal diagnosis, fetal intervention, and the prognosis of fetal immune-associated CHB provide clues for generating a practical protocol for clinical management. The prognosis of fetal immune-associated bradycardia is based on the severity of heart blocks. Morbidity and mortality can occur in severe cases, thus hieratical management is essential in such cases. In this review, we mainly focus on optimal strategies pertaining to autoimmune antibodies related to CHB, although the approaches for managing autoimmune-mediated CHB are still controversial, particularly with regard to whether fetuses benefit from transplacental medication administration. To date there is still no accessible clinical strategy for autoimmune-mediated CHB. This review first discusses integrated prenatal management strategies for the condition. It then provides some advice for clinicians involved in management of fetal cardiovascular disorder.

Value of Exome Sequencing in Diagnosis and Management of Recurrent Non-immune Hydrops Fetalis: A Retrospective Analysis

The purpose of the study was to use exome sequencing (ES) to study the contribution of single-gene disorders to recurrent non-immune hydrops fetalis (NIHF) and retrospectively evaluate the value of genetic diagnosis on prenatal management and pregnancy outcome. From January 2012 to October 2018, a cohort of 28 fetuses with recurrent NIHF was analyzed by trio ES. Fetuses with immune hydrops, non-genetic factors (including infection, etc.), karyotype, or CNV abnormalities were excluded. Variants were interpreted based on ACMG/AMP guidelines. Fetal therapy was performed on seven fetuses. Of the 28 fetuses, 10 (36%) were found to carry causal genetic variants (pathogenic or likely pathogenic) in eight genes (GBA, GUSB, GBE1, RAPSN, FOXC2, PIEZO1, LZTR1, and FOXP3). Five (18%) fetuses had variant(s) of uncertain significance (VUS). Of the 10 fetuses with definitive molecular diagnosis, five (50%) were diagnosed with inborn errors of metabolism. Among the seven fetuses who received fetal therapy, two had definitive molecular diagnosis and resulted in neonatal death. Among the remaining five fetuses with negative results, four had newborn survival and one had intrauterine fetal death. Trio ES could facilitate genetic diagnosis of recurrent NIHF and improve the prenatal management and pregnancy outcome.

A Broader Perspective on the Prenatal Diagnosis of Cornelia de Lange Syndrome: Review of the Literature and Case Presentation

Cornelia de Lange syndrome (CDLS) is caused by pathogenic variants in genes which are structural or regulatory components of the cohesin complex. The classical Cornelia de Lange (CDLS) phenotype is characterized by distinctive facial features, growth retardation, upper limb reduction defects, hirsutism, and developmental delay. Non-classical phenotypes make this condition heterogeneous. Although CDLS is a heterogeneous clinical and genetic condition, clear diagnostic criteria have been described by specialist consensus. Many of these criteria refer to features that can be seen on prenatal ultrasound. The aim of this paper is twofold: to present the ultrasound findings in fetuses affected by CDLS syndrome; to discuss the recent advances and the limitations in the ultrasound and genetic prenatal diagnosis of CDLS. Our review aims to offer, apart from the data needed to understand the genetics and the prenatal presentation of the disease, a joint perspective of the two specialists involved in the prenatal management of this pathology: the fetal medicine specialist and the geneticist. To better illustrate the data presented, we also include a representative clinical case.

Prenatal diagnosis of fetal right ventricular diverticulum with massive pericardial effusion in one of monochorionic diamniotic twins: a case report with a favorable outcome following in utero pericardiocentesis

Background Congenital ventricular diverticulum is a rare abnormality that may occur as an isolated malformation. Most cases are accompanied by pericardial effusion. Prenatal counseling can be difficult because the prognosis is uncertain and there is no consensus approach to prenatal management. Case presentation: We describe a case of congenital cardiac diverticulum complicated by large pericardial effusion in one of monochorionic diamniotic twins. The case was diagnosed by ultrasonography at 21 weeks of gestation. Therapeutic pericardiocentesis at 22 weeks resulted in complete resolution of the effusion and led to a favorable fetal outcome. We summarize the interventions and pregnancy outcomes in cases of cardiac diverticula reported in the literature. Conclusions Better awareness of clinical features, in utero therapies, and pregnancy outcomes could help define and improve prenatal management of congenital ventricular diverticula.