Birth Prevalence and Survival of Exomphalosin England and Wales: 2005 to 2011Anna Springett1, Elizabeth S. Draper2, Judith Rankin3, Catherine Rounding4,David Tucker5, Sylvia Stoianova6, Diana Wellesley7, and Joan K. Morris*1

Background: Exomphalos occurs in 2.2 per 10,000 births with 76% of thesebabies surviving to discharge. The aim of this study was to determine thebirth prevalence and survival of babies with this anomaly in England andWales. Methods: Six BINOCAR regional congenital anomaly registers inEngland and Wales (covering 36% of births) between 2005 and 2011provided cases for this study. Cases included live births, stillbirths (241

weeks’ gestation), late miscarriages (20–23 weeks’ gestation), andterminations of pregnancy with fetal anomaly. Results: The overall birthprevalence was 3.8 (95% confidence interval [CI]: 3.6–4.0) per 10,000 births;1.4 (1.2–1.6) for isolated cases, 1.2 (1.1–1.4) for cases with multipleanomalies, and 1.2 (1.1–1.4) for cases with chromosomal anomalies. The livebirth prevalence was 0.8 (0.7–0.9), 0.5 (0.4–0.6), and 0.1 (0.0–0.1) per10,000 live births, respectively. Edwards syndrome, congenital heart defects,and nervous system anomalies were the most common anomalies associatedwith exomphalos. A prenatal diagnosis was made in 83% of isolated, 95% of

multiple, and 99% of chromosomal cases. Fifty-five percent of isolated andmultiple cases were live born, whereas 85% of cases with chromosomalanomalies resulted in a termination of pregnancy with fetal anomaly. The1-year survival of live born babies with an isolated exomphalos was 92%compared with 81% in cases with multiple anomalies and 27% in cases withchromosomal anomalies (p< 0.001). Conclusion: We report a higher birthprevalence than has previously been reported. The proportion of infantssurviving with exomphalos remained unchanged over the time period.

Birth Defects Research (Part A) 100:721–725, 2014.VC 2014 Wiley Periodicals, Inc.

Key words: prevalence; survival; exomphalos; omphalocele; prenatal diagnosis

IntroductionExomphalos (also known as omphalocele) is a defect inthe development of the muscles of the abdominal wall.This results in the intestines, and in giant omphalocele theliver or spleen, remaining outside of the abdomenenclosed within a sac. It is normal for the intestines toprotrude from the abdomen, into the umbilical cord, untilapproximately the tenth week of pregnancy, after whichthey return to inside of the fetal abdomen (Kumar et al.,2008). Children born with exomphalos undergo surgery

soon after birth to place the intestines and other organsback into the abdomen and then close up the hole. Onerecent study by Patel et al. (2009) reported that only 76%of live births survive to discharge.

The birth prevalence has been reported as beingbetween 0.9 and 2.5 per 10,000 births in Europe (Calzo-lari et al., 1995; Tan et al., 1996; Rankin et al., 1999; Bari-sic et al., 2001; McDonnell et al., 2002; Kazaura et al.,2004), between 2.1 and 2.8 per 10,000 births in the USA(Forrester and Merz, 1999; Canfield et al., 2006; Agopianet al., 2009), and 2.9 per 10,000 births in Australia(Byron-Scott et al., 1998). Tan et al. (1996) found a signifi-cant decrease in the prevalence of exomphalos in Englandand Wales between 1987 and 1993; all other studiesfound no statistically significant change over their respec-tive time periods.

The aim of this study was to determine the birth prev-alence of exomphalos in England and Wales and the clini-cal outcomes for these babies from 2005 to 2011, usingdata from the British Isles Network of Congenital AnomalyRegisters (BINOCAR; www.binocar.org).

Materials and MethodsData were obtained from six BINOCAR regionalpopulation-based congenital anomaly registers in Englandand Wales. BINOCAR is a network of regional and diseasespecific population-based registers across the British Isles,established in 1996. The aim of BINOCAR is to providecontinuous epidemiological monitoring of the frequency,nature, and outcome of congenital anomalies as well asresearch on possible causes. All births in Wales and 33%

1Centre for Environmental and Preventive Medicine, Queen Mary University ofLondon, London2Department of Health Sciences, University of Leicester, Leicester3Institute of Health & Society, Newcastle University, Newcastle Upon Tyne4National Perinatal Epidemiology Unit, University of Oxford, Oxford5Public Health Wales, Wales6Institute of Child Life and Health, St Michael’s Hospital, Bristol7Faculty of Medicine, University of Southampton and Wessex Clinical GeneticsService, Southampton.

The BINOCAR registers are all funded separately. CARIS (Wales) is fundedby Public Health Wales, CAROBB (Oxford) and NorCAS (Newcastle) werefunded by the Healthcare Quality Improvement Partnership, EMSYCAR(Leicester) was funded by individual Primary Care Trusts, SWCAR (Bristol)was funded by Specialist Commissioners and WANDA (Southampton) wasfunded by the Wessex Clinical Genetics Service.Declaration of conflicting interests: None declared.

*Correspondence to: Joan K. Morris, Centre for Environmental and PreventiveMedicine, Wolfson Institute of Preventive Medicine, Barts and the LondonSchool of Medicine and Dentistry, Queen Mary University of London, London,EC1M 6BQ, UK. E-mail: j.k.morris@qmul.ac.uk

Published online 1 September 2014 in Wiley Online Library (wileyonlinelibrary.com). Doi: 10.1002/bdra.23301

VC 2014 Wiley Periodicals, Inc.

of the births in England are covered by regional congenitalanomaly registers. All the registers follow a commonmethodology for collection and coding of cases. Annualreports are produced on data from these registers for allcongenital anomalies; the most recent is for deliveries in2011 (Springett et al., 2013).

Cases included all affected live births, stillbirths (241

weeks’ gestation), late miscarriages (20–23 weeks’ gesta-tion), and terminations of pregnancy with fetal anomalynotified with a date of delivery/termination between 01January 2005 and 31 December 2011.

To achieve high levels of ascertainment and complete-ness, BINOCAR registers identify cases using active casefinding from multiple sources throughout pregnancy andconfirmation or otherwise at delivery. These sourcesinclude cytogenetic laboratories, post mortem reports,parents, ultrasound departments, delivery suites, obstetricnotes, neonatal units, child health systems, inpatientadministration systems, and pediatric notes. All prenatallysuspected and postnatally confirmed anomalies arerecorded, except certain minor anomalies as defined in theEuropean Surveillance of Congenital Anomalies (EURO-CAT) exclusions list (EUROCAT, 2005). Where the anomalyis prenatally suspected, cases are followed up after deliv-ery to confirm the final diagnosis; only those cases with aconfirmed diagnosis are included in these data. Cases aredefined as isolated (a single anomaly), multiple (wherethey occur with structural anomalies from different bodysystems), or chromosomal (where they occur with chro-mosomal anomalies). Each anomaly is coded using theWorld Health Organization’s International Classification ofDisease 10th Revision.

Prenatal diagnosis was defined as the diagnosis of anyanomaly before delivery. In exomphalos cases occurringwith other anomalies, the prenatal diagnosis may havearisen due to the detection of the other anomaly. Forexample, routine 1st trimester screening for Down syn-drome may diagnose a baby with Down syndrome andexomphalos. We would not be able to distinguish if theexomphalos has been diagnosed prenatally or not. TheNHS Fetal Anomaly Screening Programme (FASP) statedthat from 2010 exomphalos should be one of eleven condi-tions screened for and a prenatal detection rate of 80%should be achieved nationally (FASP, http://fetalanomaly.screening.nhs.uk).

The prevalence of exomphalos in this study was comparedwith the prevalence over the same time period of other Euro-pean registers that are also members of EUROCAT using dataprovided on their website (EUROCAT, www.eurocat-net-work.eu/accessprevalencedata/prevalencetables). Thesedata are presented by country; however, not all of thecountries have 100% coverage by the registers.

Birth prevalence rates per 10,000 total births and thepercentages are presented with 95% confidence intervalscalculated using the binomial distribution. Mean values

were compared using t tests and survival rates were com-pared using chi-squared tests. Multilevel logistic regressionwas used to test for trends within each register over time.All analyses were performed using STATA 12 statisticalsoftware.

ResultsBIRTH PREVALENCE

In the 7-year period, 2005 to 2011, a total of 671 caseswith exomphalos were reported to the six BINOCAR regis-ters; 247 (37%) isolated cases, 211 (31%) multiple cases,and 213 (32%) chromosomal cases. The overall birth prev-alence for exomphalos was 3.8 per 10,000 births (95%confidence interval [CI], 3.6–4.1). The birth prevalence forisolated exomphalos cases was 1.4 per 10,000 births (95%CI, 1.2–1.6), 1.2 per 10,000 births (95% CI, 1.1–1.4) formultiple cases, and 1.2 per 10,000 births (95% CI, 1.1–1.4) for chromosomal cases. The overall birth prevalencefor exomphalos in England and Wales was one of the high-est in Europe (Fig. 1).

The overall live birth prevalence for exomphalos was1.3 per 10,000 live births (95% CI, 1.2–1.5). The live birthprevalence for isolated cases was 0.8 per 10,000 livebirths (95% CI, 0.7–0.9), 0.5 per 10,000 live births (95%CI, 0.4–0.6) for multiple cases, and 0.1 per 10,000 livebirths (95% CI, 0.0–0.1) for chromosomal cases.

There has been no significant change in the birth or livebirth prevalence in exomphalos cases over the last 7 years.

SAMPLE CHARACTERISTICS

The mean maternal age at delivery for isolated exompha-los cases was 29.2 years (SD5 6.8; range 15–46 years)which was comparable to the population mean maternalage of 29.7 years (ONS, 2011). For multiple cases, themean was 28.4 years (SD5 6.6; range 16–43 years) which

FIGURE 1. Birth prevalence of exomphalos in 18 European countries: 2005 to 2011.

Note: UK includes the same registers as in this study. Data from EUROCAT

prevalence tables http://www.eurocatnetwork. eu/accessprevalencedata/

prevalencetables, data uploaded 12/12/2013.

722 EXOMPHALOS IN ENGLAND AND WALES: 2005 TO 2011

was significantly (p5 0.004) younger than the populationmean and for chromosomal cases it was 33.8 years(SD5 6.5; 19–45) which was significantly (p< 0.001)older than the population mean.

Males are more commonly affected by exomphalos;62% each of isolated and chromosomal cases and 58% ofmultiple cases were male.

ASSOCIATED ANOMALIES

The anomalies associated with exomphalos are listed inTable 1. The most common associated anomalies wereEdwards syndrome in 21% of all cases, congenital heartdefects in 17%, and nervous system anomalies in 14%.

PREGNANCY OUTCOME

The majority of isolated exomphalos cases were live born(55%); however, only 39% of multiple cases and 7% ofchromosomal cases were live born. The majority of preg-nancies with multiple and chromosomal exomphalos casesended in a termination of pregnancy with fetal anomaly(54% and 85%, respectively; Table 2).

The 1-year survival of live born babies with an isolatedexomphalos was 92% compared with 81% in multiple and27% in chromosomal cases (p< 0.001). The overall 1-yearsurvival of all live born babies with exomphalos was 84%.There has been no significant change in the survival oflive born babies with exomphalos over the past 7 years.

Of the babies born alive, 70% of isolated exomphaloscases, 71% of multiple cases, and 75% of chromosomal caseswere born preterm (<37 weeks’ gestation). There was nosignificant difference in the 1-year survival between live bornbabies delivered preterm or at term in the three groups ofcases (88% vs. 94% in isolated cases, 81% vs. 76% in multi-ple cases and 33% vs. 0% in chromosomal cases).

TIMING OF DIAGNOSIS

A prenatal diagnosis was made in 84% of isolated exom-phalos cases, 96% of multiple cases and 99% of

TABLE 1. Most Common Congenital Anomalies Associated with Exomphalos:2005 to 2011

Associated anomalies NumberPercentage[95% CI]

All cases 671 100

No associated anomalies 247 37 [33–41]

Associated anomalies 424 63 [59–67]

Chromosomal 213 32 [28–35]

Edwards syndrome 144 21 [19–25]

Patau syndrome 30 4 [3–6]

Turner syndrome 10 1 [1–3]

Down syndrome 7 1 [1–2]

Congenital heart defects 115 17 [14–20]

VSD 41 6 [5–8]

Severe CHD 31 5 [3–6]

ASD 17 3 [2–4]

AVSD 9 1 [1–3]

Nervous system 95 14 [12–17]

Neural tube defects 56 8 [6–11]

Anencephalus 36 5 [4–7]

Encephalocele 7 1 [1–2]

Spina bifida 13 2 [1–3]

Hydrocephalus 10 1 [1–3]

Arhinencephaly/

holoprosencephaly

15 2 [1–4]

Limb 78 12 [9–14]

Limb reduction 27 4 [3–6]

Club foot – talipes equinovarus 19 3 [2–4]

Polydactyly 15 2 [1–4]

Urinary 56 8 [6–11]

Bladder exstrophy and/or

epispadia

17 3 [2–4]

Congenital hydronephrosis 11 2 [1–3]

Digestive system 53 8 [6–10]

Ano-rectal atresia and stenosis 24 4 [2–5]

Diaphragmatic hernia 14 2 [1–3]

Genetic syndromes 1 microdeletions 32 5 [3–7]

Genital 26 4 [3–6]

Indeterminate sex 10 1 [1–3]

Hypospadia 9 1 [1–3]

Respiratory 20 3 [2–5]

Oro-facial clefts 19 3 [2–4]

TABLE 1. Continued

Associated anomalies NumberPercentage[95% CI]

Cleft lip with or without

cleft palate

14 2 [1–3]

Some cases may have more than one other anomaly, accounting forthe total number of anomalies being higher than the total numberof cases of associated anomalies. “Most common” means a percent-age of over 1%. Severe CHD includes: common arterial truncus,transposition of great vessels, single ventricle, AVSD, tetralogy ofFallot, pulmonary valve atresia, tricuspid atresia and stenosis,Ebstein’s anomaly, hypoplastic right heart, aortic valve atresia/ste-nosis, hypoplastic left heart, coarctation of aorta, total anomalouspulmonary venous return.

ASD, atrial septal defect; AVSD, atrioventricular septal defect; CHD,congenital heart defect; VSD, ventricular septal defect.

BIRTH DEFECTS RESEARCH (PART A) 100:721–725 (2014) 723

chromosomal cases (Table 3). All of these detection ratesexceed the NHS Fetal Anomaly Screening Programme tar-get of 80%. In those cases diagnosed prenatally, 90% ofisolated, 89% of multiple, and 93% of chromosomal exom-phalos cases were diagnosed before 23 weeks.

The 1-year survival of live born babies was comparablebetween those diagnosed prenatally and postnatally in thethree groups of cases (89% vs. 100% in isolated cases,80% vs. 83% in multiple cases and 25% vs. 50% in chro-mosomal cases).

Three out of the six congenital anomaly registers wereable to provide data on whether the individual anomalieswere diagnosed prenatally. Of the multiple cases prenatallydiagnosed, exomphalos was not suspected in five cases(6%) and of the chromosomal cases prenatally diagnosedit was not suspected in three cases (3%).

DiscussionThe prevalence of exomphalos in this study was 3.8 per10,000 births and no significant change was seen over the7 years of the study. The 1-year survival was significantlydifferent depending on the associated anomalies; 92% inisolated cases, 81% in multiple cases and 27% in chromo-somal cases. There was no significant difference in the

survival within these three groups between babies bornpreterm or at term and diagnosed pre- or postnatally.

The strength of this study is that it is based on robustpopulation-based data from six regional congenital anom-aly registers across England and Wales covering 36% ofall births. The registers ensure high case ascertainment bynotification from multiple sources and follow a commonmethodology for collection and coding of cases.

The overall birth prevalence of exomphalos was 3.8per 10,000 (95% CI, 3.6–4.1) which was higher than theprevalence in previous register-based studies in Europe,USA and Australia (Calzolari et al., 1995; Tan et al., 1996;Byron-Scott et al., 1998; Rankin et al., 1999; Forrester andMerz, 1999; Barisic et al., 2001; McDonnell et al., 2002;Kazaura et al., 2004; Canfield et al., 2006; Agopian et al.,2009) all covering time periods before the data in thisstudy. Comparing the prevalence to other European coun-tries in the same time period as this study (Fig. 1), showsthat England and Wales has one of the highest prevalencerates but five countries have a higher rate between 4.1and 5.2 per 10,000 births. There was no significant changein the prevalence over the 7 years which is consistentwith previous studies (Byron-Scott et al., 1998; Forresterand Merz, 1999; Rankin et al., 1999; McDonnell et al.,2002; Kazaura et al., 2004) except an earlier study by Tan

TABLE 2. Pregnancy Outcome and Survival of All Cases of Exomphalos: 2005 to 2011

Outcome

Isolated Multiple Chromosomal

Number Percentage [95% CI] Number Percentage [95% CI] Number Percentage [95% CI]

TOPFA 94 38 [32–44] 113 54 [47–60] 181 85 [80–89]

Late miscarriage (20–23 weeks) 9 4 [2–7] 3 1 [0–4] 2 1 [0–3]

Stillbirth (241 weeks) 8 3 [2–6] 12 6 [3–10] 15 7 [4–11]

Live birth 136 55 [49–61] 83 39 [33–46] 15 7 [4–11]

1 year survival 125 92 [86–95] 67 81 [71–88] 4 27 [11–52]

TOPFA, termination of pregnancy with fetal anomaly.

TABLE 3. Timing of Diagnosis of All Cases of Exomphalos: 2005 to 2011

Isolated Multiple Chromosomal

Number Percentage [95% CI] Number Percentage [95% CI] Number Percentage [95% CI]

Prenatal 208 84 [79–88] 202 96 [92–98] 210 99 [96–100]

<14 weeks 101 41 [35–47] 92 44 [37–50] 119 56 [49–62]

14–22 weeks 86 35 [29–41] 87 41 [35–48] 76 36 [30–42]

231 weeks 12 5 [3–8] 12 6 [3–10] 6 3 [1–6]

Not known 9 4 [2–7] 11 5 [3–9] 9 4 [2–8]

Postnatal 35 14 [10–19] 7 3 [2–7] 2 1 [0–3]

Not known 4 2 [1–4] 2 1 [0–3] 1 0 [0–3]

724 EXOMPHALOS IN ENGLAND AND WALES: 2005 TO 2011

et al. (1996) for England and Wales between 1987 and1993 which showed a significant decrease. This decreasemay well be the result of terminations being performedbecause of associated prenatally diagnosed anomalies.

This study has shown that 63% of exomphalos casesare associated with other anomalies. This is comparable toprevious literature reporting between 31% and 77% ofcases with associated anomalies (St-Vil et al., 1996; Fisheret al., 1996; Dunn and Fonkalsrud, 1997; Boyd et al.,1998; Rankin et al., 1999; Heider et al., 2004; Blazer et al.,2004; Groves et al., 2006). The proportion of exomphaloscases associated with a chromosomal anomaly was 32%which is higher than the range of 3% to 31% reported inprevious literature. The proportion of exomphalos casesassociated with a congenital heart defect was 17% andwith central nervous system anomalies was 14%, whichare comparable to the previous literature reporting 6% to34%, and 8% to 16%, respectively.

The overall 1-year survival of all live born babies withexomphalos was 84%, which is comparable to the propor-tion (87.2%) found in a study by Tennant et al. (2010)looking at the survival of children with congenital anoma-lies in the Northern England BINOCAR register between1985 and 2003. It is of concern that the survival rate hasnot improved over time and that the occurrence of a pre-natal diagnosis does not appear to help in the manage-ment of such babies.

ConclusionsWe report a higher birth prevalence than has previouslybeen reported which has not changed over the past 7years. The survival of infants with exomphalos alsoremains unchanged.

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