Prenatally diagnosed omphaloceles: Report of 92 cases and association with Beckwith-Wiedemann syndrome.

OBJECTIVE: Describe the prevalence, perinatal and long-term outcomes of Beckwith-Wiedemann syndrome (BWS) among prenatally detected omphaloceles. METHODS: All prenatally diagnosed omphaloceles from 2010 to 2015 within a single tertiary care centre were identified. An echocardiogram and detailed fetal ultrasound were performed, and amniocentesis was offered with karyotype/microarray analysis and BWS molecular testing. Perinatal, neonatal, and long-term outcomes were retrieved for BWS cases. RESULTS: Among 92 omphaloceles, 62 had additional anomalies. Abnormal karyotypes were identified in 23/62 (37%) non-isolated and 2/30 (7%) isolated cases. One BWS case (5%) was identified among non-isolated omphaloceles and six BWS cases (37.5%) were identified among isolated omphaloceles after exclusion of aneuploidy. Among 19 BWS cases, 21% were conceived by ART. All omphaloceles underwent primary closure. Prenatally, macrosomia and polyhydramnios were seen in 42%. Macroglossia and nephromegaly were more commonly detected postnatally. Preterm birth occurred in 10/19 (53%) cases and cesarean deliveries were performed in 7/19 (40%) cases. Overall mortality was 20% (4/19). Embryonal tumors were diagnosed in 2/16 (12.5%) children, and neurodevelopmental outcomes were normal in 9/12 (75%) survivors. CONCLUSIONS: After excluding aneuploidy, BWS was identified in 37.5% and 5% of isolated and non-isolated omphaloceles, respectively. Omphaloceles were small-moderate size with good long-term surgical and neurodevelopmental outcomes when isolated.

Common pathogenesis for sirenomelia, OEIS complex, limb-body wall defect, and other malformations of caudal structures.

Decades of clinical, pathological, and epidemiological study and the recent application of advanced microarray and gene sequencing technologies have led to an understanding of the causes and pathogenesis of most recognized patterns of malformation. Still, there remain a number of patterns of malformation whose pathogenesis has not been established. Six such patterns of malformation are sirenomelia, VACTERL association, OEIS complex, limb-body wall defect (LBWD), urorectal septum malformation (URSM) sequence, and MURCS association, all of which predominantly affect caudal structures. On the basis of the overlap of the component malformations, the co-occurrence in individual fetuses, and the findings on fetal examination, a common pathogenesis is proposed for these patterns of malformation. The presence of a single artery in the umbilical cord provides a visible clue to the pathogenesis of all cases of sirenomelia and 30%-50% of cases of VACTERL association, OEIS complex, URSM sequence, and LBWD. The single artery is formed by a coalescence of arteries that supply the yolk sac, arises from the descending aorta high in the abdominal cavity, and redirects blood flow from the developing caudal structures of the embryo to the placenta. This phenomenon during embryogenesis is termed vitelline vascular steal.

Turbulent Cerebrospinal Fluid Flow in Enlarging Terminal Myelocystocele.

Terminal myelocystocele is a rare type of neural tube malformation, consisting of a skin-covered lumbosacral mass, highly associated with other complex abdominal malformations within the OIES complex (omphalocele, imperforate anus, exstrophy of the cloaca and spinal defects). We present a case of a premature female with an extensive lumbosacral mass at birth, as well as an omphalocele, cloacal exstrophy, renal abnormalities, and sacral agenesis. Lumbar magnetic resonance imaging revealed a meningocele sac herniating through the bone defects and containing a syringocele sac. Advanced imaging techniques showed turbulent cerebrospinal fluid flow. At control, 4 weeks later, the defect doubled in size. The myelocystocele sac was evacuated and closed, and the patient persisted with paraparesis. The role of cerebrospinal fluid flow analysis is well established in Chiari-type malformations, in which turbulent flow within the syrinx is related to a better outcome after surgery. It is possible that the same principle could be applied to other spinal malformations, as shown in this case of terminal myelocystocele.

Comprehensive Echocardiographic Assessment of Ventricular Function and Pulmonary Pressure in the Neonatal Omphalocele Population.

OBJECTIVE: Pulmonary hypertension (PH) has been described in the neonatal omphalocele population. This study was aimed to describe cardiac function and PH severity using echocardiography in newborns with giant omphalocele (GO) and with non-GO and determine if right ventricular (RV) dysfunction is associated with mortality. STUDY DESIGN: Retrospective, single-center analysis of first echocardiography among neonatal omphalocele patients born between 2004 and 2017 was conducted. Multivariate logistic and univariate Cox's regression was constructed to measure hazard ratio (HR) for death outcome. RESULTS: There were 32 newborns, of whom 18 were GO and 7 died. GO had increased systolic pulmonary arterial to systolic systemic blood pressure ratio (97% [isosystemic] vs. 73% [three-fourths systemic] p = 0.03). RV performance parameters (tricuspid annular plane excursion, HR = 0.40; fractional area change, HR = 0.90; and RV peak global longitudinal strain, HR = 1.39) were associated with mortality. These RV performance parameters remained associated in a multiple logistic regression accounting for gestational age and GO status. The overall population had abnormal eccentricity index and pulmonary artery acceleration time to RV ejection time ratio, two markers of PH. CONCLUSION: Patients with omphalocele have increased pulmonary pressure, with GO being worse than non-GO. RV dysfunction at initial echocardiography was significantly associated with mortality.

[Protruding omentum with umbilical fluid leakage in a patient with liver cirrhosis]. / Een vrouw met vetweefsel uit haar navel.

A 57 year old woman with a history of liver cirrhosis and ascites presented with serous exudate spontaneously leaking from a ruptured umbilical hernia, also known as Flood syndrome. This syndrome is a rare complication of decompensated liver cirrhosis and is associated with high mortality. In this specific case, there was also omentum protruding through the umbilical hernia which limited the outflow of ascites. Patient was successfully treated with antibiotics and consecutive open primary hernia repair without mesh implantation.

Long term complications and outcomes in omphalocele.

After a diagnosis of omphalocele during pregnancy, questions regarding long-term prognosis are of primary importance for parents. It is imperative that their questions are answered with substantiated data to promote confident decisions for their children. They frequently express concerns regarding long-term survival, quality of life, need for more operations, feeding issues, motor and cognitive development, cosmesis, and the unique difficulties of giant omphaloceles. The available outcome studies that address these questions are discussed.

Relationship Between Physiological Umbilical Herniation and Liver Morphogenesis During the Human Embryonic Period: A Morphological and Morphometric Study.

It is widely hypothesized that physiological umbilical herniation (PUH) in humans occurs, because the liver occupies a large space in the abdominal cavity, which pushes the intestine into the extraembryonic coelom during the embryonic period. We have recently shown the presence of the intestinal loop in the extraembryonic coelom in embryos with liver malformation. Here, we analyzed the relationship between the liver and the PUH at Carnegie stage 21 of four embryos with liver malformation, including two with hypogenesis (HY1, HY2) and two with agenesis (AG1, AG2), using phase-contrast X-ray computed tomography and compared them with two control embryos. The intestinal loop morphology in the malformed embryos differed from that in the control embryos, except in HY1. The length of the digestive tract in the extraembryonic coelom of the embryos with liver malformation was similar to or longer than that of the controls. The rate of intestinal loop lengthening in the extraembryonic coelom compared with that of the total digestive tract in all embryos with liver malformation was similar to or higher than that of the controls. The estimated total abdominal cavity volume in the embryos with liver malformation was considerably smaller than that of the controls, while the intestinal volume was similar. The cardia and proximal portion of the pancreas connecting to the duodenum were located at almost identical positions in all the embryos, whereas other parts of the upper digestive tract deviated in the embryos with abnormal livers. Thus, our results provided evidence that PUH occurred independently of liver volume. Anat Rec, 302:1968-1976, 2019. © 2019 American Association for Anatomy.

Omphalocele: from diagnosis to growth and development at 2 years of age.

OBJECTIVES: To compare the prenatal frame of reference of omphalocele (ie, survival of fetuses) with that after birth (ie, survival of liveborn neonates), and to assess physical growth and neurodevelopment in children with minor or giant omphalocele up to 2 years of age. DESIGN: We included fetuses and neonates diagnosed in 2000-2012. Physical growth (SD scores, SDS) and mental and motor development at 12 and 24 months were analysed using general linear models, and outcomes were compared with reference norms. Giant omphalocele was defined as defect ≥5 cm, with liver protruding. RESULTS: We included 145 fetuses and neonates. Of 126 (87%) who were diagnosed prenatally, 50 (40%) were liveborn and 35 (28%) survived at least 2 years. Nineteen (13%) neonates were diagnosed after birth. Of the 69 liveborn neonates, 52 (75%) survived and 42 children (81% of survivors) were followed longitudinally. At 24 months, mean (95% CI) height and weight SDS were significantly below 0 in both minor (height: -0.57 (-1.05 to -0.09); weight: -0.86 (-1.35 to -0.37)) and giant omphalocele (height: -1.32 (-2.10 to -0.54); weight: -1.58 (-2.37 to -0.79)). Mental development was comparable with reference norms in both groups. Motor function delay was found significantly more often in children with giant omphalocele (82%) than in those with minor omphalocele (21%, P=0.002). CONCLUSIONS: The prenatal and postnatal frames of reference of omphalocele differ considerably; a multidisciplinary approach in parental counselling is recommended. As many children with giant omphalocele had delayed motor development, we recommend close monitoring of these children and early referral to physical therapy.

Evaluation of the effect of umbilical hernias on play behaviors in growing pigs.

Umbilical hernias (UH) are common in pigs and are an animal welfare concern. This study used an assessment of play behavior to evaluate the welfare of pigs with UH. Twenty-one grower pigs with UH and 17 without hernias (WUH) were assigned to 16 playing groups (PG) of 2 or 3 pigs (with at least 1 UH pig per PG). The time each animal was engaged in any of the defined playing behaviors for locomotor/social or toy play behaviors was recorded. Mixed Poisson or negative binomial and linear models were used to determine the effect of UH and day of session, accounting for the cluster of pigs within groups, on the frequency of each play behavior, and playing times. Pigs with UH had the same frequency of most play behaviors and playing times as pigs without hernias. There was no indication that the presence of UH-affected play behavior or performance in pigs.

Évaluation de l'effet des hernies ombilicales sur les comportements de jeu chez les porcs en croissance. Les hernies ombilicales (HO) sont communes chez les porcs et elles représentent une préoccupation liée au bien-être animal. Cette étude a utilisé une évaluation du comportement de jeu afin d'évaluer le bien-être des porcs ayant une HO. Vingt-et-un porcs en croissance ayant une HO et 17 sans hernies (SHO) ont été assignés à 16 groupes de jeu (GJ) de 2 ou 3 porcs (avec au moins 1 porc HO par GJ). Le temps consacré par chaque animal pour participer à l'un des comportements de jeu définis pour les comportements de jeu de locomotion/social ou de jouet a été consigné. Des modèles mixtes de Poisson ou binomiaux et linéaires négatifs ont été utilisés pour déterminer l'effet de HO et le jour de la séance, en tenant compte des regroupements de porcs au sein des groupes, de la fréquence de chaque comportement de jeu et des moments de jeu. Les porcs avec une HO avait la même fréquence pour la plupart des comportements de jeu et des moments de jeu que les porcs SHO. Il n'y avait aucune indication que la présence d'une HO affectait le comportement de jeu ou la performance des porcs.(Traduit par Isabelle Vallières).

Clinical and risk factor analysis of cloacal defects in the National Birth Defects Prevention Study.

Cloacal exstrophy (CE) and persistent cloaca (PC) (alternatively termed urorectal septum malformation sequence [URSMS]), represent two major cloacal defects (CDs). Clinical characteristics and risk factors often are studied for both defects combined, rather than exploring if these defects have different etiologies. We enumerated clinical features for 47 CE and 54 PC (inclusive of URSMS) cases from the National Birth Defects Prevention Study. Thirty-three CE cases were classified as isolated and 14 as multiple (presence of unassociated major defects); respective totals for PC cases were 26 and 28. We compared selected child and maternal characteristics between 11,829 non-malformed controls and CE and PC cases using chi-square or Fisher's exact tests. Compared to controls, CE and PC cases were statistically more likely (p < 0.05) to be preterm; CE cases were more likely to be multiple births. We conducted logistic regression analysis to estimate odds ratios and 95% confidence intervals for any CD, CE, and PC with selected self-reported maternal prepregnancy and periconceptional (one month prior to 3 months following conception) exposures. In crude and adjusted analyses, we observed significant positive associations for any CD, CE, and PC with use of any fertility medication or assisted reproductive technology procedure. Significant positive associations observed only in crude analyses were any CD with maternal obesity or use of progesterone, any CD and CE with any x-ray, and any CD and PC with use of folate antagonist medications. Our findings provide some of the first insights into potential differing etiologies for CE and PC.

Is 1p36 deletion associated with anterior body wall defects?

Epispadias and exstrophy of the cloaca, also known as OEIS complex (omphalocele, exstrophy, imperforate anus, spinal defects), respectively constitute the most benign and severe ends of the bladder exstrophy-epispadias complex (BEEC) spectrum. In 2009, El-Hattab et al. reported the first patient with OEIS complex associated with a chromosome 1p36 deletion. Here we report a second patient with 1p36 deletion who also has classic bladder exstrophy, supporting the possible role of genes in this region in the development of BEEC. The absence of omphalocele and imperforate anus in our patient places him toward classic bladder exstrophy while presence of spina bifida and the absence of coccyx suggest an overlap with OEIS complex. An additional differential diagnosis is the pentalogy of Cantrell in our patient as he also has a diaphragmatic hernia and an incomplete sternum. This is the second observation of a ventral midline birth defect in association with 1p36 deletion syndrome, following El-Hattab et al.'s report [2009]. The three genes (NOCL2, DVL1, and MMP23B) discussed as possible candidates are also among the deleted ones in our patient, supporting the possible role of these genes in BEEC spectrum. © 2016 Wiley Periodicals, Inc.

Intestinal Rotation and Physiological Umbilical Herniation During the Embryonic Period.

Drastic changes occur during the formation of the intestinal loop (IL), including elongation, physiological umbilical herniation (PUH), and midgut rotation. Fifty-four sets of magnetic resonance images of embryos between Carnegie stage (CS) 14 and CS 23 were used to reconstruct embryonic digestive tract in three dimensions in the Amira program. Elongation, PUH, and rotation were quantified in relation to the proximal part of the superior mesenteric artery (SMA), designated as the origin. Up to CS 16, IL rotation was initially observed as a slight deviation of the duodenum and colorectum from the median plane. The PUH was noticeable after CS 17. At CS 18, the IL showed a hairpin-like structure, with the SMA running parallel to the straight part and the cecum located to the left. After CS 19, the IL began to form a complex structure as a result of the rapid growth of the small intestinal portion. By CS 20, the IL starting point had moved from the right cranial region to an area caudal to the origin, though elongation of the duodenum was not conspicuous-this was a change of almost 180° in position. The end of the IL remained in roughly the same place, to the left of and caudal to the origin. Notably, the IL rotated around the origin only during earlier stages and gradually moved away, running transversely after CS 19. The movements of the IL may be explained as the result of differential growth, suggesting that IL rotation is passive.

Gastroesophageal reflux and congenital gastrointestinal malformations.

Although the outcome of newborns with surgical congenital diseases (e.g., diaphragmatic hernia; esophageal atresia; omphalocele; gastroschisis) has improved rapidly with recent advances in perinatal intensive care and surgery, infant survivors often require intensive treatment after birth, have prolonged hospitalizations, and, after discharge, may have long-term sequelae including gastro-intestinal comorbidities, above all, gastroesophageal reflux (GER). This condition involves the involuntary retrograde passage of gastric contents into the esophagus, with or without regurgitation or vomiting. It is a well-recognized condition, typical of infants, with an incidence of 85%, which usually resolves after physiological maturation of the lower esophageal sphincter and lengthening of the intra-abdominal esophagus, in the first few months after birth. Although the exact cause of abnormal esophageal function in congenital defects is not clearly understood, it has been hypothesized that common (increased intra-abdominal pressure after closure of the abdominal defect) and/or specific (e.g., motility disturbance of the upper gastrointestinal tract, damage of esophageal peristaltic pump) pathological mechanisms may play a role in the etiology of GER in patients with birth defects. Improvement of knowledge could positively impact the long-term prognosis of patients with surgical congenital diseases. The present manuscript provides a literature review focused on pathological and clinical characteristics of GER in patients who have undergone surgical treatment for congenital abdominal malformations.

Class II pentalogy of Cantrell.

BACKGROUND: Pentalogy of Cantrell is a rare syndrome, first described by Cantrell and co-workers in 1958. The syndrome is characterized by the presence of five major congenital defects involving the diaphragm, abdominal wall, the diaphragmatic pericardium, lower sternum and various congenital intra-cardiac abnormalities. The syndrome has never been reported in Tanzania, although may have been reported from other African countries. Survival rate of the complete form of pentalogy of Cantrell is as low as 20%, but recent studies have reported normal growth achieved by 6 years of age where corrective surgeries were done; showing that surgical repair early in life is essential for survival. CASE PRESENTATION: The African baby residing in Tanzania was referred from a district hospital on the second day of life. She was noted to have a huge omphalocele and ectopia cordis covered by a thin membrane, with bowels visible through the membrane and the cardiac impulse visible just below the epigastrium. Despite the physical anomaly, she appeared to saturate well in room air and had stable vitals. Her chest X-ray revealed the absence of the lower segments of the sternum and echocardiography showed multiple intra-cardiac defects. Based on these findings, the diagnosis of pentalogy of Cantrell was reached. On her fifth day of life, the neonate was noted to have signs of cardiac failure characterized by easy fatigability and restlessness during feeding. Cardiac failure treatment was initiated and she was discharged on parents' request on the second week of life. Due to inadequate facilities to undertake this complex corrective surgery, arrangements were being made to refer her abroad. In the meantime, her growth and development was satisfactory until the age of 9 months, when she ran out of the medications and succumbed to death. Her parents could no longer afford transport cost to attend the monthly clinic visits, where the infant was getting free medication refill. CONCLUSIONS: The case reported here highlights that in resource limited settings; poor outcome in infants with complex congenital anomalies is a function of multiple factors. However, we believe that surgery would have averted mortality in this 9-month-old female infant. We hope to be able to manage these cases better in future following the recent establishment of cardiac surgery facilities at Muhimbili National Hospital.

Systemic hypertension in giant omphalocele: An underappreciated association.

PURPOSE: To evaluate the incidence, severity and duration of systemic hypertension in infants born with giant omphalocele (GO). METHODS: A retrospective review of patients born from 2003 through 2013 with a GO or intestinal atresia (control population) and managed at a single institution was performed. The hospital course was reviewed including all blood pressures, method of omphalocele repair, requirement for antihypertensive medications and renal function. RESULTS: Forty-five GO and 20 control patients met criteria for the study. Thirty-three GO patients underwent Schuster repair and 12 GO patients underwent delayed repair after epithelialization. Overall, 78% of GO patients had episodes of hypertension (82% Schuster and 67% delayed repair) compared to 15% of control patients (P<0.001). The majority of episodes were transient and occurred in the postoperative period (97%). Hypertension was persistent in 4 GO patients. These patients required antihypertensive medication at discharge, which was discontinued as an outpatient. No patient demonstrated significant evidence of renal abnormalities as indicated by renal ultrasound, urinalysis and/or serum creatinine level at the time of hypertension. CONCLUSION: Episodes of systemic hypertension are frequent in patients with GO. Episodes are often post-operative, transient and can be present in patients undergoing either a delayed or Schuster repair. A small subset of patients will have persistent hypertension requiring antihypertensive medication that can be weaned off in an outpatient setting.

Clinical and genetic investigation of 17 Japanese patients with hyperekplexia.

AIM: The aim of the study was to determine clinical and genetic characteristics of Japanese patients with hyperekplexia. METHOD: Clinical courses, responses to antiepileptic drugs, outcomes, and genetic testing were investigated in 17 Japanese patients (nine males, eight females, median age 1y, range birth-45y) with hyperekplexia. RESULTS: In all patients, muscle stiffness and startle responses appeared soon after birth. Only seven patients were diagnosed with hyperekplexia before 1 year of age. Seven patients had been misdiagnosed with other disorders such as epilepsy and adult-onset anxiety neurosis. Umbilical/inguinal hernias were seen in 10 patients. Life-threatening events were noted in four patients. Clonazepam was the most effective drug. Muscle stiffness completely disappeared in 12 patients before 5 years of age, whereas startle responses resolved in only three patients. Mutations in the GLRA1 and GLRB genes were identified in 16 patients and one patient respectively. In 14 patients, the mutation showed autosomal dominant inheritance; in the other three, inheritance was autosomal recessive. p.R271Q of GLRA1 was the most frequent mutation, found in 10 patients. Novel mutations, p.A272P and p.A384P of GLRA1, were detected. Clinical severity and outcome varied even in the same family. INTERPRETATION: Early correct diagnosis is essential for prevention of accidental injuries and to provide appropriate treatments for hyperekplexia. Clonazepam is effective, although the time taken for startle responses to resolve varied.