Omphalocele—What should we tell the prospective parents?

An omphalocele is a congenital defect in the abdominal wall characterized by absent abdominal muscles, fascia, and skin. The characteristic ultrasound appearance includes a midline defect with herniation of abdominal contents into the base of the umbilical cord. Other anatomic abnormalities are seen in approximately 50% of cases, most notably cardiac defects (19%–32%). Approximately, 50% of cases are associated with genetic and multiple malformation syndromes including trisomy 13/18, pentalogy of Cantrell and Beckwith–Wiedemann syndrome. Therefore, a thorough evaluation is recommended, including detailed anatomic survey, fetal echocardiogram, genetic counseling, and prenatal diagnostic testing. Overall prognosis depends on the size of the omphalocele, genetic studies, and associated anomalies. Early prenatal diagnosis remains important in order to provide parental counseling and assist in pregnancy management. Delivery should occur at a tertiary care center. Timing and mode of delivery should be based on standard obstetric indications with cesarean delivery reserved for large omphalocele (>5 cm) or those that involve the fetal liver. Neonatal management involves either primary or staged reduction, both of which can be associated with a prolonged neonatal hospitalization.     

Prenatal diagnosis and management of anterior abdominal wall defects in the West of Scotland

An attempt was made to identify all the cases of abdominal wall defects occurring in the West of Scotland over a 7-year period to determine the current incidence, prenatal diagnosis, management, and prognosis for fetuses and neonates with abdominal wall defects. Cases were identified because they presented either for prenatal diagnosis, or to the Department of Pathology following termination or spontaneous pregnancy loss, or as neonates to the Neonatal Surgical Department. The incidence of abdominal wall defects was found to be 1 in 2500 births. Exomphalos was diagnosed before birth in 66 per cent of cases, and in 30 per cent of cases it was associated with another major abnormality. There was a 20 per cent intact survival in the cases diagnosed prenatally who had no fetal anomaly and who opted to continue with the pregnancy. Gastroschisis was diagnosed before delivery in 70 per cent of cases, and in the group who continued with the pregnancy there was an intact survival of 77 per cent. Body stalk anomalies were all diagnosed prenatally and terminated. Maternal serum alpha-fetoprotein was elevated in 89 per cent of the cases with exomphalos and in 100 per cent of the cases with gastroschisis and body stalk anomalies in which it was tested.     

Early prenatal sonographic appearance of rare thoraco-abdominal eventration

Fetal ventral wall malformations may be diagnosed prenatally with ultrasound. These include omphalocele, gastroschisis, or even thoracic defects with or without ectopia cordis. It is important whenever such a defect is found to carefully define the full extent of the lesion prior to parental counselling. Described and illustrated here is the prenatal diagnosis with real-time ultrasound at 17 weeks gestation of a rare thoraco-abdominal ventral wall defect including omphalocele, bifid sternum, diaphragmatic aplasia, and pericardial aplasia with incomplete ectopia cordis. The technique is described and the importance of the complete, accurate delineation of anatomic malformations is emphasized.     

Is there a role for fetal interventions in gastroschisis management? – An updated comprehensive review

We conducted a comprehensive evidence-based review on the epidemiology and current standard of care of gastroschisis management as well as the pathophysiology, rationale and feasibility of fetal therapy as a viable alternative. Gastroschisis is a periumbilical abdominal wall defect characterized by abdominal viscera herniation in utero. It affects 4 in 10 000 live births, but the prevalence has steadily increased in recent years. Gastroschisis is typically diagnosed on routine second-trimester ultrasound. The overall prognosis is favorable, but complex gastroschisis, which accounts for about 10% to 15% of cases, is associated with a higher mortality, significant disease burden and higher healthcare costs due to long- and short-term complications. The current standard of care has yet to be established but generally involves continued fetal surveillance and multidisciplinary perinatal care. Postnatal surgical repair is achieved with primary closure, staged silo closure or sutureless repair. Experimental animal studies have demonstrated the feasibility of in utero closure, antiinflammatory therapy and prenatal regenerative therapy. However, reports of early preterm delivery and amnioinfusion trials have failed to show any benefit in humans. Further experimental studies and human trials are necessary to demonstrate the potential benefit of fetal therapy in gastroschisis.     

Prenatal diagnosis of omphalocele and gastroschisis by ultrasonography

As the use of ultrasonography has become a routine procedure in the care of pregnant women, fetal congenital malformations have been frequently diagnosed prenatally. During a 4-year period abdominal wall defects (AWD) were diagnosed in 14 cases, five were gastroschises and nine were omphaloceles, seven females and seven males. Concomitant malformations were present in one case of gastroschisis and in five cases of omphalocele. Eleven AWD's were diagnosed in the second trimester and six pregnancies were interrupted. Eight children with AWD were born; two boys with omphalocele and one girl and one boy with gastroschisis are still alive. Alpha-fetoprotein was determined in amniotic fluid in 11 cases and also in maternal serum prior to the amniocentesis in eight cases. Chromosomal investigations were performed in 13 cases, 11 on amniotic fluid cells and two on lymphocytes from a blood sample made postnatally. Two abnormal karyotypes, 47,XX + 18 were found.     

Cardiac and extra-cardiac anomalies as indicators for trisomies 13 and 18: A prenatal ultrasound study

The purpose of the present study was to establish sonographic markers for prenatal diagnosis of trisomies 13 and 18. Retrospective analysis of sonographic morphology was therefore carried out in seven fetuses with trisomy 13, and 16 fetuses with trisomy 18. Gestational age ranged between 17 and 39 weeks (median 28 weeks). Polyhydramnios and symmetrical growth retardation were present in 14 of 23 fetuses. A cardiac anomaly was diagnosed in all 23 fetuses, the majority representing a ventricular septal defect (n = 8) or double outlet right ventricle (n = 8). Extra-cardiac anomalies were characterized by a high incidence of limb deformities (polydactyly, clenched hands, club feet; n = 15) and omphalocele (n = 7). We conclude that the combined appearance of cardiac and extra-cardiac anomalies should prompt fetal karyotyping. Cardiac anomalies in combination with fetal limb deformities and omphalocele are suspicious for trisomies 13 and 18.     

Turner syndrome-omphalocele association: Incidence,karyotype, phenotype and fetal outcome

Objective

Omphalocele is known to be associated with genetic anomalies like trisomy 13, 18 and Beckwith–Wiedemann syndrome, but not with Turner syndrome (TS). Our aim was to assess the incidence of omphalocele in fetuses with TS, the phenotype of this association with other anomalies, their karyotype, and the fetal outcomes.

Method

Retrospective multicenter study of fetuses with confirmed diagnosis of TS. Data were extracted from a detailed questionnaire sent to specialists in prenatal ultrasound.

Results

680 fetuses with TS were included in this analysis. Incidence of small omphalocele in fetuses diagnosed ≥12 weeks was 3.1%. Including fetuses diagnosed before 12 weeks, it was 5.1%. 97.1% (34/35) of the affected fetuses had one or more associated anomalies including increased nuchal translucency (≥3 mm) and/or cystic hygroma (94.3%), hydrops/skin edema (71.1%), and cardiac anomalies (40%). The karyotype was 45,X in all fetuses. Fetal outcomes were poor with only 1 fetus born alive.

Conclusion

TS with 45,X karyotype but not with X chromosome variants is associated with small omphalocele. Most of these fetuses have associated anomalies and a poor prognosis. Our data suggest an association of TS with omphalocele, which is evident from the first trimester.     

New genetic and clinical evidence associated with fetal Beckwith–Wiedemann syndrome

Early detection of Beckwith–Wiedemann syndrome (BWS) is very important since it is very useful regarding counseling of parents concerning the risk of developing embryonic tumors, selection of the mode of delivery due to potential adrenal cysts that might bleed during labor, prevention of neonatal hypoglycemia and even options of pregnancy termination in non-viable fetuses. This report describes the prenatal classic sonographic triad of fetal BWS (omphalocele, macrosomia, macroglossia) and other supporting findings (hepatomegaly, adrenal enlargement) as well as additional postnatal evidence. Also, it demonstrates new molecular genetic evidence potentially associated with the disease (the presence of a novel heterozygous c.358G>T variant of the CDKN1C gene). Importantly, we provide new evidence indicating that elevated levels of the four serum biomarkers (alpha-fetoprotein, beta-human gonadotropin, unconjugated estriol, and inhibin-A) in late first or early second trimester might be strongly suggestive of BWS which may facilitate early detection especially in cases of no obvious anomaly. In conclusion, this study emphasizes on early detection of BWS as early as at 14 weeks of gestation, based on the abnormal rise of the four serum biomarkers together with omphalocele. To the best of our knowledge, this is the earliest prenatal detection of BWS ever reported. Finally, we provide new molecular genetic evidence that is, potentially associated with BWS.     

Fetal therapy: practical ethical considerations

Progress in prenatal diagnosis can lead to the diagnosis of severe fetal abnormalities for which natural history anticipates a fatal outcome or the development of severe disability despite optimal postnatal care. Intrauterine therapy can be offered in these selected cases. Prenatal diagnosis is the only field of medicine in which termination is an option in the management of severe diseases. Fetal therapy has therefore developed as an alternative to fatalist expectant prenatal management as well as to termination of pregnancy (TOP). There are few standards of fetal care that have gone beyond the stage of equipoise and even fewer have been established based on appropriate studies comparing pre- and postnatal care. Several ethical questions are being raised as fetal surgery develops, including basic Hippocratic principles of patients' autonomy and doctors' duty of competence moving the boundaries between experimental surgery, therapeutic innovation and standard care. In addition, the technical success of a fetal intervention can only rarely fully predict the postnatal outcome. Managing uncertainty regarding long-term morbidity and the possibility for fetal therapy to change the risk of perinatal death into that of severe handicap remains a critical factor affecting women's choice for TOP as an alternative to fetal therapy. Copyright © 2011 John Wiley & Sons, Ltd.     

Integration of noninvasive prenatal prediction of fetal blood group into clinical prenatal care

Incompatibility of red blood cell blood group antigens between a pregnant woman and her fetus can cause maternal immunization and, consequently, hemolytic disease of the fetus and newborn. Noninvasive prenatal testing of cell-free fetal DNA can be used to assess the risk of hemolytic disease of the fetus and newborn to fetuses of immunized women. Prediction of the fetal RhD type has been very successful and is now integrated into clinical practice to assist in the management of the pregnancies of RhD immunized women. In addition, noninvasive prediction of the fetal RhD type can be applied to guide targeted prenatal prophylaxis, thus avoiding unnecessary exposure to anti-D in pregnant women. The analytical aspect of noninvasive fetal RHD typing is very robust and accurate, and its routine utilization has demonstrated high sensitivities for fetal RHD detection. A high compliance with administering anti-D is essential for obtaining a clinical effect. Noninvasive fetal typing of RHC/c, RHE/e, and KEL may become more widely used in the future. © 2014 John Wiley & Sons, Ltd.     

Rapid prenatal diagnosis of Patau's syndrome in a fetus with an abdominal wall defect by 72 hour culture of cells from amniotic fluid

A woman in the 32nd week of pregnancy was referred for investigation because of fetal abnormalities, including an abdominal wall defect, detected by ultrasonography. In view of the increased risk of chromosome abnormality, amniocentesis was performed to enable informed decisions about the management of the pregnancy and delivery to be taken. Cells from the liquor were inoculated into standard lymphocyte culture medium and incubated for 72 h. Slides with a high mitotic index and good quality metaphases, comparable to those from a blood culture, were obtained after harvesting. Cytogenetic analysis showed the karyotype to be 46,XY,—14,+t(13ql4q), which is consistent with Patau's syndrome. This technique appears to be an option for rapid karyotyping in cases of abdominal wall defect, where a chromosomal abnormality is suspected.     

Prenatal ultrasonic findings in congenital chloride diarrhoea

In 3 fetuses affected by congenital chloride diarrhoea there were characteristic prenatal ultrasonic findings. In all cases the fetal abdominal cavity was filled with distended loops of fetal intestine, the fetal stomach was of normal size and polyhydramnios was present. The prenatal ultrasonic findings in this metabolic inherited disease are identical to those caused by mechanical obstruction of the distal fetal intestine. Whenever these findings are encountered prenatally, the possibility of chloride diarrhoea should be considered, because therapy with electrolytes is needed rather than the surgical intervention required in mechanical intestinal obstruction.     

Noninvasive prenatal diagnosis of fetal blood group phenotypes: current practice and future prospects

Fetuses of women with alloantibodies to RhD (D) are at risk from hemolytic disease of the fetus and newborn, but only if the fetal red cells are D-positive. In such pregnancies, it is beneficial to determine fetal D type, as this will affect the management of the pregnancy. It is possible to predict, with a high level of accuracy, fetal blood group phenotypes from genotyping tests on fetal DNA. The best source is the small quantity of fetal DNA in the blood of pregnant women, as this avoids the requirement for invasive procedures of amniocentesis or chorionic villus sampling (CVS). Many laboratories worldwide now provide noninvasive fetal D genotyping as a routine service for alloimmunized women, and some also test for c, E, C and K. In many countries, anti-D immunoglobulin injections are offered to D-negative pregnant women, to reduce the chances of prenatal immunization, even though up to 40% of these women will have a D-negative fetus. High-throughput, noninvasive fetal D genotyping technologies are being developed so that unnecessary treatment of pregnant women can be avoided. Trials suggest that fetal D typing of all D-negative pregnant women is feasible and should become common practice in the near future. Copyright © 2008 John Wiley & Sons, Ltd.     

In utero sonographic diagnosis of a communicating enteric duplication cyst in a giant omphalocele

Enteric duplications are rare lesions, and relatively few cases have been diagnosed prenatally. We present, to our knowledge, the first case of an associated communicating ileal duplication cyst in a huge omphalocele diagnosed prenatally. The prenatal ultrasound findings revealed four features of the cystic lesion including peristaltic movements of the cystic wall, communication between the cyst and normal bowel lumen, intra-cystic echogenic contents, and echogenic mesenteric tissue (fat) close to the cyst. These distinct characteristics helped us to make a firm in utero diagnosis. Copyright © 2001 John Wiley & Sons, Ltd.     

Prenatal karyotyping in malformed fetuses

Experience with prenatal karyotyping of 237 fetuses with sonographic evidence of malformation is reported. Abnormal karyotype was found in 40 cases (16-8 per cent): chromosomal aberrations were found in 19 of the 178 fetuses with an isolated structural anomaly (10-6 per cent) and in 21 of the 59 fetuses with multiple malformations (35-6 per cent). Detailed cytogenetic and morphological information concerning fetuses affected by omphalocele, duodenal atresia, hydrocephalus, multicystic kidney, unilateral hydronephrosis and cystic hygroma is reported. The need for a very careful ultrasound evaluation of fetal anatomy in these pregnancies is stressed, as the risk of a chromosomal anomaly depends mainly on the existence of more than one ultrasonically diagnosed structural defect.     

High-resolution array genomic hybridization in prenatal diagnosis

Array genomic hybridization (AGH) can detect chromosomal gains or losses that are 100 times smaller than those identifiable by conventional cytogenetic methods. Genome-wide AGH can identify genomic imbalance that causes birth defects and mental retardation at least twice as frequently as conventional cytogenetic analysis. Using AGH as a prenatal test for fetal genomic imbalance offers the promise of detecting pathogenic gain or loss of genomic material more quickly and much more frequently than current methods. However, the chance of finding a result of uncertain clinical significance is much greater than with conventional cytogenetic analysis, and the benefit–cost ratio of doing AGH in addition to conventional cytogenetic analysis in pregnancies at high risk for Down syndrome is likely to be poor. Very little is known about the natural history and range of clinical variability associated with most pathogenic submicroscopic copy number variants (CNVs). It seems doubtful that patients can be adequately counseled for prenatal AGH testing in most cases because the risks and benefits are unknown. At present, AGH should be offered for prenatal diagnosis only if the pregnancy is at especially high risk of having a pathogenic CNV or if AGH is being done as part of a clinical trial. Copyright © 2008 John Wiley & Sons, Ltd.     

Detection of fetal structural abnormalities at the 11–14 week ultrasound scan

The aim of this study was to evaluate the detection of fetal structural abnormalities by the 11–14 week scan. 2853 pregnant women were submitted to a routine ultrasound scan between the 11th and 14th week and the fetal skull, brain, spine, abdominal wall, limbs, stomach and bladder were examined. Following the scans the patientes were examined in the second or third trimester of pregnancy. An isolated increased nuchal translucency was not considered an abnormality. However, these patients had an early echocardiography assessment. Fetal structural abnormalities were classified as major or minor and of early or late onset. A total of 130 (4.6%) defects were identified and 29 (22.3%) of these were diagnosed at the 11–14 week scan, including nine cardiac defects associated with increased nuchal translucency. The antenatal ultrasound detection rate was 71.5%, and 31.2% were detected in the first-trimester assessment. 78.8% of the major defects were diagnosed by the prenatal scan and 37.8% by the 11–14 week scan. Fetal structural abnormalities at the 11–14 week scan were detected in approximately 22.3% of the cases, therefore, a second-trimester anomaly scan is important in routine antenatal care to increase the prenatal detection of fetal defects. Copyright © 2002 John Wiley & Sons, Ltd.     

Fetal cholecystomegaly: A prenatal marker of aneuploidy

The fetal gall bladder can now be easily identified during the second and third trimesters using high-resolution ultrasonography. In this report we present eight fetuses with an enlarged gall bladder detected on prenatal ultrasonography at a mean gestational age of 24.6 weeks (range 19–31 weeks). Additional ultrasonographic findings were present in four cases: fetal anomalies and intrauterine growth retardation in three and polyhydramnios in one. Of those cases associated with fetal anomalies, one woman underwent amniocentesis at 21 weeks revealing trisomy 18. The other two declined prenatal karyotyping; neonatal karyotyping revealed trisomy 13 in one and trisomy 18 in the other. Although an enlarged fetal gall bladder can be a normal variant in the second and third trimesters, the prenatal detection of cholecystomegaly should prompt a search for associated anomalies and other markers of aneuploidy. If found, prenatal karyotyping should be considered.     

Organ targeted prenatal gene therapy—how far are we?

Prenatal gene therapy aims to deliver genes to cells and tissues early in prenatal life, allowing correction of a genetic defect, before long-term tissue damage has occurred. In contrast to postnatal gene therapy, prenatal application can target genes to a large population of dividing stem cells, and the smaller fetal size allows a higher vector-to-target cell ratio to be achieved. Early-gestation delivery may allow the development of immune tolerance to the transgenic protein which would facilitate postnatal repeat vector administration if needed. Targeting particular organs will depend on manipulating the vector to achieve selective tropism and on choosing the most appropriate gestational age and injection method for fetal delivery. Intra-amniotic injection reaches the skin, and other organs that are bathed in the fluid however since gene transfer to the lung and gut is usually poor more direct injection methods will be needed. Delivery to the liver and blood can be achieved by systemic delivery via the umbilical vein or peritoneal cavity. Gene transfer to the central nervous system in the fetus is difficult but newer vectors are available that transduce neuronal tissue even after systemic delivery. Copyright © 2011 John Wiley & Sons, Ltd.     

Triploidy: Pregnancy complications and clinical findings in seven cases

Seven cases of triploidy were encountered by the Prenatal Diagnosis Program at Dartmouth–Hitchcock Medical Center over an 8-year period through associated pregnancy complications. We describe the characteristic findings that facilitate prenatal diagnosis and management. Our experience includes fetuses with major central nervous system abnormalities (spina bifida aperta, holoprosencephaly) and anterior abdominal wall defects, which are detectable with routine prenatal diagnostic screening examinations (ultrasound and AFP). In addition, we stress the importance of recognizing obstetric complications and associated cystic placental changes, which are quite common among triploid conceptuses. Molar changes associated with triploidy have a more benign prognosis than that associated with diploid moles. Such molar changes may relate to the presence of a diploid paternal chromosome complement. The usefulness of cytofluorometric DNA determinations in helping to confirm a clinical suspicion of triploidy is emphasized. These cases are presented in an effort to facilitate prenatal recognition and management of this common cytogenetic condition and prevent unnecessary Caesarean section deliveries.