Impact of omphalocele size on associated conditions

Journal of Pediatric Surgery (2008) 43, 2216–2219

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Impact of omphalocele size on associated conditions☆ Hari R. Kumar a , Andrea L. Jester a , Alan P. Ladd b,⁎ a

Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA Division of Pediatric Surgery, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN 46202, USA b

Received 26 August 2008; accepted 29 August 2008

Key words: Omphalocele; Associated congenital anomalies; Defect size; Cardiac defects

Abstract Purpose: Omphalocele is often associated with the presence of other congenital anomalies. Case reports have demonstrated nonclassical associations occurring in smaller omphaloceles. The aim of this study was to determine if omphalocele defect size correlates with the type of anomalies found. Methods: Patient records at a pediatric hospital were retrospectively reviewed for an 8-year period. Data were collected on patient demographics, omphalocele size, and congenital anomalies identified. Size of the abdominal wall defect was determined by either physical examination or operative record of repair. Patient cohorts were designated as those with small (4 cm and less) or large (greater than 4 cm) omphaloceles. Results: Fifty-three cases of omphalocele were observed. Twenty-seven cases were classified as small, with 26 classified as large. A predominance of males was noted in the small omphalocele group (78% vs 42%; P = .01). Intestinal anomalies, including Meckel's diverticulum and intestinal atresia, were only seen in patients with small omphaloceles. Most cardiac anomalies were associated with large omphaloceles (34.6% vs 3.7%; P = .01). Conclusion: Small omphalocele size correlates with an increased prevalence of associated gastrointestinal anomalies, a lower prevalence of cardiac anomalies, and a higher predominance of male sex. © 2008 Elsevier Inc. All rights reserved.

Omphalocele is a congenital midline abdominal wall defect that results in herniation of intraabdominal contents covered by a lining of peritoneum and amnion. The severity of the defect often ranges from a minor herniation of the

Presented at 41st annual meeting of the Pacific Association of Pediatric Surgeons, Jackson Lodge, Grand Teton National Park, Wyoming, June 29-July 3, 2008. ☆ Sponsor PAPS member: James C.Y. Dunn, MD, UCLA Med Ctr, 10833 Le Conte Ave, CHS 72-172, MC 709818, Los Angeles, CA 90095. ⁎ Corresponding author. Tel.: +1 317 274 4682; fax: +1 317 274 4491. E-mail addresses: [email protected] (H.R. Kumar), [email protected] (A.P. Ladd). 0022-3468/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2008.08.050

umbilical cord to a significant protrusion that includes large proportions of intestine and the liver. During week 6 of gestation, the midgut undergoes a physiologic herniation through the umbilicus at which time counterclockwise rotation around the superior mesenteric artery and intestinal elongation occurs. By 10 to 12 weeks, the midgut undergoes reduction into the abdominal cavity where it assumes normal anatomical position. Omphalocele represents a disturbance in this process, although the exact mechanism by which this occurs is not known. Omphalocele is often associated with a constellation of other congenital defects such as Beckwidth-Wiedemann syndrome, pentalogy of Cantrell, and vertebral, anal, cardiac, trachea,

Impact of omphalocele size on associated conditions esophagus, renal, limb association [1-3]. These associated anomalies imply a potential identical, etiologic process as they are often midline defects. Before surgical repair, infants with omphalocele are evaluated for those commonly associated anomalies that may directly impact their perioperative care. Recent clinical experience has identified the presence of abnormalities within patients with small omphaloceles that have not been classically associated with this disorder. Reports within the literature have also noted the presence of nonclassical intestinal anomalies occurring in small omphaloceles [4,5]. Taken together, this suggests the possibility that small omphaloceles may be associated with more nonclassical abnormalities. The purpose of this study was to review our recent institutional experience with omphalocele and determine if size of the abdominal wall defect correlates with the type of congenital malformations found.

2217 Table 1 Demographic data of patients with small vs large omphaloceles Variable

Omphalocele ≤4 cm (n = 27)

Omphalocele N4 cm (n = 26)

P

Gestational age (median wk) Sex Female Male Race White Other

38

37

.05

6 21

15 11

.01

21 6

21 5

1.00

2. Results 2.1. Omphalocele size correlates with sex

1. Methods Admission and billing records from a tertiary care pediatric hospital were retrospectively reviewed with institutional review board approval (EX0708-19) from a period of July 1, 1999, to June 30, 2007. Patients were identified through electronic database search by International Classification of Diseases, Ninth Edition, code 756.79 (other congenital anomalies of abdominal wall) and/or Current Procedural Terminology (CPT) codes 49,600 (repair of small omphalocele, with primary closure) and 49,605 (repair of large omphalocele or gastroschisis; with or without prosthesis). Records were then reviewed to verify the diagnosis of omphalocele for patient incorporation into our study population. Information regarding patient demographics, size of omphalocele defect, and other congenital anomalies were compiled into an electronic database. Patients identified with omphalocele were separated into 2 groups as follows: small (4 cm or less) and large (greater than 4 cm). Size of the abdominal wall opening was determined either by reported physical examination at the time of initial assessment or by documented intraoperative findings correlated against the operative CPT codes. Congenital anomalies were identified through reported physical examination, imaging, or laboratory testing. All imaging were reviewed including radiographs, ultrasounds, and echocardiograms. Patent ductus arteriosus, patent foramen ovale, and hydronephrosis were ruled out as associated anomalies unless they were of clinical significance or required intervention. All calculations were performed using GraphPad Prism 4 (GraphPad software, San Diego, Calif). A Fisher's Exact test was used for statistical comparison of categorical variables between the groups. A Mann-Whitney test was used for statistical comparison of continuous variables between the groups. A P value of less than .05 was considered to be of statistical significance.

There were a total of 53 patients with omphalocele for the 8-year period; 27 of these infants were found to have small omphaloceles (4 cm or less), whereas 26 infants were found to have large omphaloceles (greater than 4 cm). The demographic data, which include gestational age, sex, and race, are presented in Table 1. Patients of the male sex were more likely to have small omphaloceles, whereas those of the female sex were more likely to have large omphaloceles. There was no difference between groups in race.

2.2. Omphalocele size correlates with the type of congenital abnormalities present The variety of malformations present within each group is listed in Table 2. Intestinal malformations were only seen within the small omphalocele group. This group had 4 infants with Meckel's diverticulum, 1 with ileal atresia, and 1 with colonic atresia. Infants with small omphaloceles also presented with more brain and craniofacial defects, although this trend did not approach statistical significance. Infants with large omphaloceles were more likely to have cardiac defects. This population also exhibited diaphragm defects, which were not seen within the small omphalocele group; this association was slightly above the threshold for statistical significance.

3. Discussion Previous reports have noted nonclassical abnormalities within small omphaloceles. Wakhlu and Wakhlu [4], in their series of 45 infants with omphaloceles less than 5 cm, found 8 patients with Meckel's diverticulum, 7 with malrotation and intestinal volvulus, and 1 with ileal atresia. A case report by Salomon et al [5] described an infant with a 2-cm omphalocele noted on prenatal ultrasound with no other associated sonographic anomalies; however at the time of

2218

H.R. Kumar et al.

Table 2 Congenital anomalies by organ system or syndrome associated with small vs large omphaloceles Type of anomaly

Omphalocele Omphalocele P ≤4 cm (n = 27) N4 cm (n = 26)

Brain Hydrocephalus Corpus callosum agenesis Septum pallucidum agenesis Craniofacial Skin tags Isolated cleft lip or palate Multiple craniofacial anomalies Neural tube Meningomyelocele Lumbar vertebral dysplasia Cardiac Isolated Ventricular Septal Defect Multiple cardiac defects Diaphragm Morgagni hernia Diaphragm eventration Paraesophageal hernia Intestinal Meckel's diverticulum Colonic atresia Ileal atresia Liver Benign vascular lesion 2-vessel umbilical cord Renal Renal cysts Vesicoureteral reflux Kidney malformation Genitalia Undescended testis Limb Rocker bottom feet Club foot Pentalogy of Cantrell BeckwidthWiedemann Chromosomal Trisomy 13 Trisomy 18 Trisomy 21

3 (11.1%) 1 1

0 (0%) 0 0

1

0

5 (18.5%) 1 1

1 (3.8%) 0 0

3

1

1 (3.7%) 1 0

1 (3.8%) 0 1

1.00

1 (3.7%) 0

9 (34.6%) 2

.01

1

7

0 (0%) 0 0

4 (15.3%) 2 1

0

1

6 (22.2%) 4

0 (0%) 0

1 1 1 (3.7%) 1

0 0 0 (0%) 0

2 (7.4%)

1 (3.8%)

1.00

2 (7.4%) 1 1 0

1 (3.8%) 0 0 1

1.00

0 (0%) 0 2 (7.4%) 1 1 0 (0%)

1 (3.8%) 1 2 (7.7%) 2 0 2 (7.7%)

.49

3 (11.1%)

1 (3.8%)

.61

1 (3.7%) 1 0 0

2 (7.7%) 1 1 0

1.00

.24

.19

.05

.02

1.00

1.00

.49

Table 2 (continued) Type of anomaly

Omphalocele Omphalocele P ≤4 cm (n = 27) N4 cm (n = 26)

Other Tracheomalacia Thyroid agenesis Ovarian cyst

2 (7.4%) 1 1 0

1 (3.8%) 0 0 1

1.00

surgical repair, the infant was found to have ileal atresia. Our study is novel in that it progresses beyond these casual observations and definitively demonstrates that intestinal anomalies are distinctly associated with smaller omphaloceles. Of equal importance are the revelations that male sex is associated with small omphaloceles, and cardiac defects are primarily associated with large omphaloceles. This study may help to elucidate the difference in prognosis between small and large omphaloceles. Studies have demonstrated that small omphaloceles and the presence of few anomalies have the best overall prognosis among omphaloceles as a whole [6-8]. Small omphaloceles have far fewer cardiac defects that may explain their better prognosis, as severe cardiac defects portend a poorer prognosis [9,10]. Although the findings of this study are intriguing, the study is limited by its retrospective nature. Our determination of omphalocele size relied upon a nonstandardized method of measurement reported within the initial physical examination and/or operative findings. In an attempt to correct for the deficiencies in this method, we also examined CPT coding that stratifies repair of omphalocele based on the size of the defect. Another criticism of this study would be the lack of uniformity in preoperative testing, with some infants undergoing ultrasounds and radiographs at outside institutions. A more controlled, prospective study would eliminate these weaknesses and be useful in confirming our results. Regardless of the limitations of this study, the findings are of relevance to clinicians. The current approach used to screen for concurrent anomalies may miss the intestinal anomalies present within small omphaloceles. As has been demonstrated, these small omphaloceles are more than just simple “hernias of the cord” and are associated with their own distinct variety of anomalies when compared to larger omphaloceles. The surgeon must then be cognizant of the potential for undetected intestinal anomalies to be present at the time of surgical correction of small omphaloceles. Lastly, this study may add to our understanding of the pathogenesis of omphalocele. The timing of midgut development is known, but the aberrations that take place to result in the formation of an omphalocele are poorly understood. Development of the midgut does not take place in isolation, and many other organ systems are concurrently maturing. The correlation that sex and certain anomalies are preferentially present in small vs large omphaloceles suggests that these organ systems and sexual differentiation may potentially influence the formation of

Impact of omphalocele size on associated conditions omphalocele development. Our data regarding the unique associations to the size of omphalocele may also imply different etiologic processes in the formation of small vs large omphalocele defects. An examination of this possibility warrants further contemplation, especially from a basic science perspective. These observations suggest that omphalocele size correlates with sex and type of other congenital abnormalities present. Male sex and intestinal defects are associated with small omphaloceles. Female sex and cardiac defects are more associated with larger omphaloceles.

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