2020 Volume 2 Issue 2 Pages 61-68
BACKGROUND
Omphalocele is frequently detected prenatally worldwide. Nevertheless, little is known about patient demographics, practice pattern and outcomes.
METHODS
We examined patient demographics, treatment options, and outcomes for patients with omphalocele with and without severe chromosomal abnormalities (trisomy 13 and 18), July 2010–March 2016, using a nationwide database in Japan.
RESULTS
Of 399 patients with omphalocele, 89 had trisomy 13 or 18. The average birthweight was 2,449 g, and the average gestational age was 35 weeks; 65% had other congenital associated anomalies, including circulatory and chromosomal anomalies. About 85% of the patients received abdominoplasty. The median length of mechanical ventilation was 5 (0–30) days. The median length of stay (interquartile range) was 45 (21–94) days. Overall, 52% of the patients were discharged to home without home medical care; this percentage was 65% among those without trisomy 13 or 18. In-hospital mortality was 20% for the total sample of patients, while it was 49% for those with trisomy 13 or 18.
CONCLUSIONS
The present study revealed the patient demographics, treatment practices, and discharge status of infants with omphalocele in Japan. This information is useful in aiding decision making on therapeutic strategies by medical staffs and the families of patients with omphalocele.
Omphalocele is a congenital defect of the abdominal wall, with herniation of internal organs covered by a sac. Omphaloceles have a prevalence of one case per 2,500 to 4,000 infants [1–3]. Today, fetuses with omphalocele are frequently detected prenatally because of routine fetal ultrasounds in the late first trimester to mid-second trimester [3, 4]. Therefore, in clinical settings, we should provide information on the prenatal course, associated abnormalities, treatments, and prognoses for expectant mothers with fetal diagnoses of omphalocele. Although several large studies have reported the clinical features of omphalocele in Western countries [5–11], recent data are lacking on the clinical features of omphalocele in Asian countries, including Japan. Furthermore, little is known about actual practice patterns, perioperative management, and discharge status for infants with omphalocele, worldwide.
We therefore conducted this study to examine patient demographics, practice patterns, outcomes, and discharge status of omphalocele, using a Japanese nationwide inpatient database.
We conducted this descriptive study using the Diagnosis Procedure Combination (DPC) database, a nationwide inpatient database that includes administrative claims and discharge data [12]. More than 1,000 hospitals voluntarily contribute to the database, which includes data on approximately seven million inpatients each year. All 82 academic hospitals in Japan are obliged to participate in the database. About 90% of hospitals with neonatal intensive care units are included in this database in Japan [13].
The DPC database includes the following data: unique hospital identification number; patient’s sex, age, body weight at admission and at birth, body height, and gestational age; diagnoses, comorbidities at admission, and complications after admission recorded as textual data in Japanese and using International Classification of Diseases, Tenth Revision (ICD-10) codes [14]; length of stay ; surgical and nonsurgical procedures recorded using the original coding system in Japan; dates of each procedure, drug, blood product or device used during the hospitalization; and discharge status (discharged to home, or other facility, or in-hospital death). A previous study showed that the validity of diagnosis and procedure records in the DPC database was generally high [15].
The present study was based on a secondary analysis of the administrative claims data. The requirement for informed consent was waived because of the anonymous nature of the data. Study approval was obtained from the Institutional Review Board at The University of Tokyo.
We extracted babies (≤2 days old) who were diagnosed with omphalocele (ICD-10 code: Q792) from July 2010 to March 2016. We excluded the following patients: 1) those who were admitted more than 2 days after birth; 2) those who were diagnosed with both omphalocele and gastroschisis; 3) those who were transferred to a different hospital within 2 days of admission; and 4) those with missing data on drugs administered or surgeries.
Treatment outcomes differ depending on the presence or absence of severe chromosomal abnormalities [1]. We divided the eligible patients into those with and without severe chromosomal abnormalities, defined as trisomy 13 (ICD-10 codes: Q91.0–91.3) and trisomy 18 (Q91.4–7).
We investigated the patients’ background demographics including sex and gestational age (in weeks), body weight (at birth or at admission), and other associated malformation. Gestational age was categorized as <28 weeks (extremely preterm), 28–31 weeks (very preterm), 32–36 weeks (preterm), or ≥37 weeks (term). Body weight at birth or admission was categorized as <1,000 g (extremely low birthweight), 1,000 g–1,499 g (very low birthweight), 1,500 g–2,499 g (low birthweight), 2,500 g–3,999 g (normal birthweight), or ≥4,000 g (high birthweight).
We identified the following associated malformations from the Japanese text-based diagnoses or the relevant ICD-10 codes: congenital malformations of the nervous system (ICD-10 codes: Q00–07); eye, ear, face, or neck (Q10–18); circulatory system (Q20–28); respiratory system (Q30–34); cleft lip or cleft palate (Q35–37); digestive system without gastroschisis (Q38–45); genital organs (Q50–56); urinary system (Q60–64); musculoskeletal system (Q65–79); other congenital malformations (Q80–89); trisomy 21 (Q90); other chromosomal abnormalities (Q92–99); pentalogy of Cantrell (Japanese textual diagnosis); cloaca exstrophy (Japanese textual diagnosis); and Beckwith–Wiedemann syndrome (Japanese textual diagnosis).
We carried out investigation of practice patterns for treating omphalocele in terms of using catecholamines (dopamine, noradrenaline, adrenaline, dobutamine), blood transfusion (red blood cells, fresh-frozen plasma, and platelets), immunoglobulin, albumin, antithrombin anti-disseminated intravascular coagulation drugs, anti-apnea drugs (aminophylline, anhydrous caffeine, theophylline), and surfactants. Supportive measures included central venous catheterization, mechanical ventilation (with nitric oxide and with extracorporeal membrane oxygenation), and phototherapy for infantile jaundice. We examined length of stay, length of intensive care unit stay, age (in days) at start of enteral feeding, age (in days) at start of full enteral feeding, and total hospitalization costs. We also examined requirements for home medical care after discharge—for example, home parenteral nutrition, enteral feeding (i.e. gastrostomy, transnasal tube), tracheostomy, home respirator, and home oxygen therapy. We also investigated 1-year readmission rates and the proportion of ileus or bowel obstruction (ICD-10 codes: K561-2, K564-7, K660, K913) as a reason for 1-year readmission.
STATISTICAL ANALYSESWe used chi-square tests and Fisher’s exact tests to compare proportions for categorical variables (such as sex and diagnosis), and t-tests and Mann–Whitney U tests to compare averages or median values for continuous variables (such as body height). All tests were two-tailed, and p values less than 0.05 were considered statistically significant. All statistical analyses were conducted using Stata/MP 14.0 (Stata Corp., College Station, TX, USA).
A total of 456 inpatients were diagnosed with omphalocele within 2 days of birth during the study period. We excluded patients who were diagnosed with both omphalocele and gastroschisis (n = 3), those who were transferred to another hospital within 2 days of admission (n = 23), and those with missing data on surgery or drugs administered (n = 31). We identified a total of 399 eligible patients, 89 (22%) of whom had trisomy 13 or 18.
Table 1 shows the patients’ demographics. The number of males was larger than the number of females. The averages (standard deviations) of gestational age and birthweight were 35 (6.5) weeks and 2,449 (767) g, respectively. Prematurity (<37 weeks of gestation) was recorded among 163 (41%) patients. Overall, 52% of the patients had low birthweight (<2,500 g).
| Without Trisomy 13 or 18 (N = 310) | With Trisomy 13 or 18 (N = 89) | Total (N = 399) | |
|---|---|---|---|
| Sex, n (%) | |||
| Male | 184 (59.4) | 60 (67.4) | 244 (61.2) |
| Gestational age (in weeks), average (standard deviation) | 35 (7.3) | 36 (2.7) | 35 (6.5) |
| Gestational age category (in weeks), n (%) | |||
| Extremely preterm (<28) | 14 (4.5) | 0 (0.0) | 14 (3.5) |
| Very preterm (28–31) | 11 (3.5) | 5 (5.6) | 16 (4.0) |
| Moderate to late preterm (32–36) | 106 (34.2) | 27 (30.3) | 133 (33.3) |
| Term (≥37) | 153 (49.4) | 54 (60.7) | 207 (51.9) |
| Missing | 26 (8.4) | 3 (3.4) | 29 (7.3) |
| Birthweight (g), average (standard deviation) | 2,554 (767) | 2,084 (646) | 2,449 (767) |
| Birthweight category (g), n (%) | |||
| Extremely low birthweight infant (<1,000 g) | 7 (2.3) | 2 (2.2) | 9 (2.3) |
| Very low birthweight infant (1,000–1,499 g) | 17 (5.5) | 13 (14.6) | 30 (7.5) |
| Low birthweight infant (1,500–2,499 g) | 114 (36.8) | 55 (61.8) | 169 (42.4) |
| Normal birthweight infant (2,500–3,999 g) | 162 (52.3) | 18 (20.2) | 180 (45.1) |
| High birthweight infant (≥4,000 g) | 8 (2.6) | 1 (1.1) | 9 (2.3) |
| Missing | 2 (0.6) | 0 (0.0) | 9 (2.3) |
| Associated anomaly, n (%) | |||
| Any anomaly | 172 (55.5) | 89 (100) | 261 (65.4) |
| Nervous system | 17 (5.5) | 9 (10.1) | 26 (6.5) |
| Eye, ear, face, or neck | 4 (1.3) | 3 (3.4) | 7 (1.8) |
| Circulatory system | 62 (20.0) | 66 (74.2) | 128 (32.1) |
| Cardiac anomaly with operation during same hospitalization | 20 (6.5) | 10 (11.2) | 30 (7.5) |
| Respiratory system | 19 (6.1) | 6 (6.7) | 25 (6.3) |
| Cleft lip or cleft palate | 7 (2.3) | 13 (14.6) | 20 (5.0) |
| Digestive system | 62 (20.0) | 21 (23.6) | 83 (20.8) |
| Genital organs | 20 (6.5) | 2 (2.2) | 22 (5.5) |
| Urinary system | 26 (8.4) | 1 (1.1) | 27 (6.8) |
| Musculoskeletal system | 33 (10.6) | 11 (12.4) | 44 (11.0) |
| Other | 29 (9.4) | 4 (4.5) | 33 (8.3) |
| Typical syndrome, n (%) | |||
| Pentalogy of Cantrell | 6 (1.9) | 0 (0.0) | 6 (1.5) |
| Cloaca exstrophy | 14 (4.5) | 0 (0.0) | 14 (3.5) |
| Beckwith–Wiedemann syndrome | 14 (4.5) | 0 (0.0) | 14 (3.5) |
| Chromosomal anomaly, n (%) | |||
| Any chromosomal anomaly | 12 (3.9) | 89 (100) | 101 (25.3) |
| Trisomy 21 | 7 (2.3) | 0 (0.0) | 7 (1.8) |
| Trisomy 13 | 0 (0.0) | 52 (58.4) | 53 (13.3) |
| Trisomy 18 | 0 (0.0) | 37 (41.6) | 37 (9.3) |
| Unspecified or other | 5 (1.6) | 0 (0.0) | 5 (1.3) |
Associated anomalies were detected in 261 (65%) patients. Physical abnormalities were observed in 63% of the patients: in the circulatory system for 128 (32%) patients, in the digestive system for 83 (21%), and in the musculoskeletal system for 44 (11%). Details of the circulatory anomalies were as follows: 57 patients (14%) had a ventricular septal defect, 56 (14%) had an atrial septal defect, 36 (9.0%) had patent ductus arteriosus, 18 (4.5%) had tetralogy of Fallot, 18 (4.5%) had double outlet right ventricle, 13 (3.3%) had coarctation of the aorta or interruption of aortic arch, 5 (1.3%) had hypoplastic left heart syndrome, 4 (1.0%) had an atrioventricular septal defect, and 4 (1.0%) had pulmonary valve stenosis. A chromosomal abnormality was found among 101 (25%) patients, 53 (13%) patients had trisomy 13, 37 (9.7%) had trisomy 18, and 7 (1.5%) had trisomy 21.
Table 2 shows the treatment options for omphalocele. We excluded 19 patients who died within 2 days of admission. About 13% of the patients received conservative treatment without operation. Overall, 265 patients (70%) underwent abdominoplasty once, and 175 patients (46%) underwent a first operation on their day of birth. There was no significant difference in the number of operations or age at first operation between the patients with and without trisomy 13 or 18. The use of mechanical ventilation was documented for 275 patients (72%), and blood transfusion was documented for 202 (53%). There was no significant difference in the use of mechanical ventilation, catecholamine, blood transfusion, anti-disseminated intravascular coagulation drugs, and surfactants between the patients with and without trisomy 13 or 18. The percentages phototherapy use for infantile jaundice and anti-apnea drugs were significantly higher for patients with trisomy 13 or 18 than for those without these conditions.
| Without Trisomy 13 or 18 (N = 301) | With Trisomy 13 or 18 (N = 79) | Total* (N = 380) | P-value | |
|---|---|---|---|---|
| Number of operations | 0.18 | |||
| 0 (conservative treatment) | 40 (13.3) | 11 (13.9) | 51 (13.4) | |
| 1 | 203 (67.4) | 62 (78.5) | 265 (69.7) | |
| ≥2 | 58 (19.3) | 6 (7.6) | 64 (16.8) | |
| Age (in days) at first operation | 0.98 | |||
| On birthday | 139 (46.2) | 36 (45.6) | 175 (46.1) | |
| After birthday | 122 (40.5) | 32 (40.5) | 154 (40.5) | |
| Conservative treatment | 40 (13.3) | 11 (13.9) | 51 (13.4) | |
| Mechanical ventilation | 209 (69.4) | 66 (83.5) | 275 (72.4) | 0.02 |
| Requiring nitric oxide | 15 (5.0) | 3 (3.8) | 18 (4.7) | 1.00 |
| Catecholamine use | 135 (44.9) | 37 (46.8) | 172 (45.3) | 0.75 |
| Dopamine | 121 (40.2) | 33 (41.8) | 154 (40.5) | 0.8 |
| Noradrenaline | 6 (2.0) | 1 (1.3) | 7 (1.8) | 1.00 |
| Adrenaline | 47 (15.6) | 22 (27.8) | 69 (18.2) | 0.02 |
| Dobutamine | 73 (24.3) | 22 (27.8) | 95 (25.0) | 0.51 |
| Blood transfusion | 157 (52.2) | 45 (57.0) | 202 (53.2) | 0.53 |
| Red blood cells | 83 (27.6) | 27 (34.2) | 110 (28.9) | 0.25 |
| Fresh frozen plasma | 55 (18.3) | 15 (19.0) | 70 (18.4) | 0.87 |
| Platelets | 25 (8.3) | 9 (11.4) | 34 (8.9) | 0.38 |
| Albumin | 140 (46.5) | 26 (32.9) | 166 (43.7) | 0.03 |
| Immunoglobulin | 31 (10.3) | 13 (16.5) | 44 (11.6) | 0.17 |
| Insertion of central venous catheter | 224 (74.4) | 63 (79.7) | 287 (75.5) | 0.38 |
| Use of anti-DIC drugs | 12 (4.0) | 4 (5.1) | 16 (4.2) | 0.75 |
| Use of anti-apnea drugs | 24 (8.0) | 15 (19.0) | 39 (10.3) | 0.007 |
| Use of surfactants | 36 (12.0) | 12 (15.2) | 48 (12.6) | 0.44 |
| Phototherapy for infantile jaundice | 125 (41.5) | 49 (62.0) | 174 (45.8) | 0.001 |
Abbreviation: DIC, disseminated intravascular coagulation.
Data are presented as n (%).
* Nineteen patients were excluded because of death within 2 days of admission.
Table 3 shows the outcomes of omphalocele. We excluded 19 patients who died within 2 days of admission. The median length of stay was significantly longer for patients with trisomy 13 or 18 than for those without these conditions (Without trisomy 13 or 18: 38 days, with trisomy 13 or 18: 66 days, p < 0.001; p < 0.001). Regarding enteral feeding, we excluded 23 patients with missing data. Age at the start of full enteral feeding differed significantly between the two groups (19 vs. 45 days; p < 0.001). The median length of mechanical ventilation was 17 days for patients with trisomy 13 or 18, whereas it was 4 days for those without trisomy 13 or 18.
| Without Trisomy 13 or 18 (N = 301) | With Trisomy 13 or 18 (N = 79) | Total* (N = 380) | P-value | |
|---|---|---|---|---|
| Length of stay (in days) median (IQR) | 38 (19–83) | 66 (39–130) | 45 (21–94) | <0.001 |
| Length of ICU stay, n (%) | 0.03 | |||
| <2 weeks | 101 (33.6) | 16 (20.3) | 117 (30.8) | |
| 2–3 weeks | 106 (35.2) | 27 (34.2) | 133 (35.0) | |
| ≥4 weeks | 94 (31.2) | 36(45.6) | 130 (34.2) | |
| Age at start of enteral feeding (in days), median (IQR) | 2 (1–7) | 4 (1–12) | 3 (1–8) | 0.26 |
| Age at start of full enteral feeding (in days), median (IQR)† | 19 (9–56) | 45 (24–129) | 26 (10–73) | <0.001 |
| Length of mechanical ventilation (in days), median (IQR) | 4 (0–18) | 17 (2–52) | 5 (0–30) | <0.001 |
| Total hospitalization costs (in United States dollars), median (IQR) | 35,439 (20,446–61,449) | 46,738 (34,330–77,160) | 38,139 (21,668–133,727) | <0.001 |
Abbreviations: IQR, interquartile range; ICU, intensive care unit.
* Nineteen patients were excluded because of death within 2 days of admission.
† Three patients were excluded because of discharge to home with parenteral nutrition.
Table 4 shows discharge and readmission status. Mortality was 20% (81 patients) for the full group of patients, whereas it was 49% for patients with trisomy 13 or 18. In the group without trisomy 13 or 18, about 65% of omphalocele infants were discharged to home without home medical care. However, only 6.7% of the patients in the group with trisomy 13 or 18 who were discharged to home did not require home medical care. The percentage of discharges to home with home medical care was 18% (72 patients) for the total group of patients; of these patients, 58 required tube feeding, 22 required home oxygen therapy, 14 required tracheostomies, and 14 required home respirators. There were 124 patients (44%) who were readmitted within one year of discharge; 8 patients (2.9%) were readmitted because of ileus or bowel obstruction.
| Without Trisomy 13 or 18 (N = 310) | With Trisomy 13 or 18 (N = 89) | Total (N = 399) | P-value | |
|---|---|---|---|---|
| Discharge status | ||||
| Discharge to home without home medical care* | 202 (65.2) | 6 (6.7) | 208 (52.1) | <0.001 |
| Discharge to home with home medical care* | 41 (13.2) | 31 (34.8) | 72 (18.0) | <0.001 |
| Tube feeding | 31 (10.0) | 27 (30.3) | 58 (14.5) | <0.001 |
| Home parenteral nutrition | 1 (0.3) | 0 (0.0) | 1 (0.3) | 1.00 |
| Home oxygen therapy | 11 (3.5) | 11 (12.4) | 22 (5.5) | 0.003 |
| Tracheostomy | 8 (2.6) | 6 (6.7) | 14 (3.5) | 0.09 |
| Home respirator | 8 (2.6) | 6 (6.7) | 14 (3.5) | 0.09 |
| Discharge to other facilities | 29 (9.4) | 8 (9.0) | 37 (9.3) | 1.00 |
| In-hospital death | 37 (11.9) | 44 (49.4) | 81 (20.3) | <0.001 |
| Missing | 1 (0.3) | 0 (0.0) | 1 (0.3) | |
| Readmission within one year from discharge† | 99 (40.7) | 25 (67.6) | 124 (44.3) | 0.003 |
| because of ileus or bowel obstruction | 8 (3.3) | 0 (0.0) | 8 (2.9) | 0.60 |
Data are presented as n (%).
* Home medical care includes tube feeding, home oxygen therapy, and home parenteral nutrition.
† 119 patients were excluded because of death or discharge to other than home.
We examined 399 patients with omphalocele using a nationwide inpatient database in Japan. The percentages of associated anomalies and chromosomal anomalies for the total sample were 65% and 25%, respectively. In-hospital mortality was 20%. About 52% of the patients were discharged to home without home medical care. Our study provides an overview of patient demographics, treatment options, and outcomes for omphalocele.
Previous studies have shown that omphalocele is likely to be associated with multiple anomalies and chromosomal or genetic abnormalities. Associated anomalies were reported in 35%–83% of cases in previous studies [4–10], whereas these were found in 65% of the patients in the present study. Associated anomalies in the circulatory system were reported in 11%–41% in previous studies [5–10], whereas these were found in 32% of the patients in the present study. Previous findings for associated chromosomal anomalies ranged widely, with previous studies reporting them in 9%–32% of cases [5, 6, 9, 16, 17]; these were found in 25% of the patients in the present study. Beckwith–Wiedemann syndrome has previously been documented in 6%–8% of cases [5, 7, 8], the present study found this syndrome in 3.5% of the patients. According to previous studies, omphalocele patients are more likely to have circulatory anomalies and chromosomal anomalies compared with other anomalies, which is in line with the present study’s findings. Past findings on mortality also vary widely, with reports of mortality of 16%–32% in previous studies [9–11, 17]; it was 20% in the present study. This finding may be plausible because the percentage with chromosomal abnormalities and neonatal mortality can be affected by the proportions of in-utero death and spontaneous abortion. Differences between countries in the proportions of elective termination following prenatal diagnosis of anomalies may exist, because late selective abortion is allowed in Europe, unlike in Japan [18], and there may be differences in fetal palliative care [19–21].
To our knowledge, there have been no previous large-scale reports on the discharge status of patients with omphalocele. This study showed that 13% of patients required home medical care at discharge, even in the group without trisomy 13 or 18. Only 6.7% of the patients did not require any home medical care at discharge in the group with trisomy 13 or 18. These data suggest that a social home medical care system is necessary to support patients’ discharge to home. The incidence of the need for home medical device in trisomy 13 or 18 infants with omphalocele in this study was similar in those without omphalocele in a previous study [13]. The previous study reported in-hospital mortality to be 53% for patients with trisomy 13 or 18 who were admitted <7 days after birth, whereas it was about 50% in the present study. The proportion of patients discharged to home was previously reported to be about 36%, whereas it was about 42% in the present study.
To our knowledge, there is no recent data with a large sample size about clinical features and practice pattern of omphalocele in Asian countries, including Japan. It is therefore difficult for pediatricians and pediatric surgeons to give enough information on omphalocele to guardians in Japan. At present, physicians are obliged to provide guardians with limited information based on sparse data, other countries’ data, or one’s own experience. Our large and reliable data will help physicians to guide guardians.
The present study has several limitations that should be pointed out. First, we were unable to get information on outpatients because of data availability. Information on frequency of outpatients and long-term prognoses are important to understand guardians’ burdens. A future prospective study that examines this information is needed. Second, we were unable to evaluate detailed surgical methods (e.g., intended primary or secondary closure, fascial or flap closure). Third, we could not confirm the direct cause of death (omphalocele, associated anomaly, complication, etc.). Fourth, there was no information about the prenatal diagnosis of congenital anomaly in this database, which may have affected the choice of ambitious care by parents [22, 23].
This Japanese large retrospective cohort study using a nationwide inpatient database showed that 22% of patients had severe chromosomal anomalies, 65% had associated anomalies, and half of the total sample of patients were discharged to home without home medical care. Our findings provide practical information to medical staffs and families of patients with omphalocele.
This work was supported by grants from the Ministry of Health, Labour and Welfare, Japan (H29-Policy-Designated-009 and H29-ICT-General-004) and the Ministry of Education, Culture, Sports, Science and Technology, Japan (17H04141).
