Data from INMPR (Table 1) shows that of all deaths (n=4044) aged 0-14 years registered in the ROI during the period, (2006-2016), 58.6% (n=2368) had a RD diagnosis. When stratified by age category: neonates, 55.6% (1140/2050), post-neonates, 57.8% (450/778), children aged 1-4 years, 63.9% (337/527), children aged 5-9 years, 69.3% (219/316), children aged 10-14 years, 59.5% (222/373) had a RD. There was a significantly higher proportion of RD patients among registered paediatric deaths (58.6%) than expected (4.1%) Z=52.7876, p<0.00001. There was no analysis of significance undertaken by stratified age groups as there are no estimates of RD onset in each of these age categories.
Table 2 Categorisation of all registered deaths < 15 years by Rare Disease category and age 2006-2016
Neonatal (0-28 days)Post-neonatal (29 days < 1 year) Children (1-14 years) Total
Rare Disease Category Number of cases [%] Number of cases [%] Number of cases [%]
Rare disease sub-category
Rare Disease (n) (n) (n)
Birth Defects 588 [51.58%] 147 [32.67%] 93 [11.95%] 828
Rare development defect during embryogenesis
Anencephaly (93) (<5) ___
Multiple congenital anomalies (73) (11) ___
Renal agenesis (52) ___ ___
Congenital diaphragmatic hernia (38) (10) (<5)
Hydrops fetalis (13) ___ ___
Holoprosencephaly (11) (<5) (<5)
Omphalocele (9) ___ ___
VACTERL/VATER association (8) ___ (<5)
Esophageal atresia (8) (<5) ___
Spina bifida (8) (<5) (7)
Congenital hydrocephalus (6) (<5) (5)
Renal hypoplasia (5) ___ (<5)
Other defect during embryogenesis (116) (28) (4)
Rare congenital heart malformations
Hypoplastic left heart (67) (22) (7)
Tetralogy of fallot (6) (<5) (<5)
Truncus arteriosus (5) (<5) ___
Ebstein malformation (<5) (<5) (<5)
Congenital valvular dysplasia (<5) (<5) ___
Aorta coarctation (<5) (<5) (<5)
Other rare congenital heart malformation (61) (53) (19)
Rare Genetic 346 [30.3%] 192 [42.67%] 249 [32.01%] 787
Chromosomal anomaly
Trisomy 18 (114) (31) (<5)
Trisomy 21 (29) (36) (22)
Trisomy 13 (64) (10) (<5)
22q11.2 deletion syndrome (6) (<5) (<5)
Pallister-Killian syndrome (<5) (<5) (<5)
Triploidy (<5) ___ ___
Wolf-Hirschhorn syndrome (<5) ___ (<5)
Turner syndrome (<5) (<5) ___
Other chromosomal anomaly (21) (16) (27)
Inborn errors of metabolism
Mitochondrial disease (6) (7) (21)
Alpers syndrome ___ ___ (11)
Leigh syndrome (<5) (<5) (10)
Batten disease ___ ___ (<5)
Hurler syndrome ___ (<5) (<5)
Other inborn errors of metabolism (9) (24) (30)
Rare neurologic disease
Schizencephaly ___ ___ (6)
Spinal Muscular Atrophy ___ (17) (6)
Muscular dystrophy (<5) ___ (6)
Rett syndrome ___ ___ (6)
Aicardi-Goutieres Syndrome ___ ___ (<5)
Other rare neurologic disease ___ (16) (29)
Cystic Fibrosis (<5) (11)
Rare endocrine disease (<5) __ (5)
Rare hematologic disease (5) (<5) (5)
Rare immune disease __ (5)
Other rare genetic (86) (24) (29)
Rare Neoplastic 10 [0.88%] 11 [2.44%] 265 [34.06%] 286
Acute lymphoblastic leukemia __ (<5) (27)
Neuroblastoma __ __ (26)
Rhabdoid tumour __ (<5) (6)
Medulloblastoma (<5) __ (12)
Glioma (<5) (<5) (11)
Astrocytoma (<5) (<5) (12)
Teratoma (<5) __ __
Other rare neoplastic (4) (2) (171)
Rare Infectious 116 [10.18%] 43 [9.56%] 39 [5.01%] 198
Sepsis in premature infants (102) (27) (<5)
Meningitis (<5) (9) 28
Pertussis __ (6) __
Congenital Herpes simplex virus infection (<5) __ (<5)
Congenital toxoplasmosis (<5) __ __
Fetal cytomegalovirus syndrome (<5) __ (<5)
Other rare infectious (4) (1) (8)
Other 80 [7.02%] 57 [12.67%] 132 [16.97%] 269
Cardiomyopathy (12) (20) (25)
Cerebral Palsy __ (<5) (52)
Epilepsy __ (<5) (23)
Other rare disease (68) (30) (32)
Total 1140 [100%] 450 [100%] 778 [100%] 2368
Categories where case numbers are less than 5 have been accounted for as <5 to avoid disclosure issues.
(Table 2). The most common RD diagnoses across all age groups include trisomy 18 (n=147,6.2%), hypoplastic left heart (n=96, 4.1%), anencephaly (n=94, 3.9%) and trisomy 13 (n=77, 3.2%). Deaths due to birth defects (n=588, 51.5%) and rare infections (n=116, 10.1%) were the most common causes among neonates. Of the birth defect cases, 73/588 (12.4%) had multiple congenital anomalies. Of the infectious cases, the highest number were due to sepsis in premature infants (n=102, 87.9%). Rare genetic disorders had the highest category in the post-neonatal period and rare neoplastic disorders were most frequently represented in the older age group of 1-14 years. Within the category ‘Other’, there were 54 (2.2%) cases of cerebral palsy, 57 (2.4%) cases of cardiomyopathy and 27 (1.1%) cases of epilepsy.
A comparison was undertaken of the RD cases identified in this study (n=2368) versus the number of RD cases identified if only the ICD-10 coding was used. Use of the ICD-10 code in isolation of the narrative record identified only 995 rare disease cases (42%), meaning that Orphacodes use would have been required to capture 1373 (58%) of RD cases.
NQAIS Clinical summary analysis of the in-patient healthcare burden of RD patients is shown in Table 3. RD patients accounted for 66% of the children less than 15 years who died in hospital during the 2-year study period, significantly higher than the expected 4.1% (Z=46.6 P<0.0001). These RD patients had significantly longer length of stay than the non-RD in-hospital deaths. The median length of stay for RD patients was 5 days while it was 2 days for non-RD cases. The 66% of the patients who had a RD, used 87% of all bed days (Z=7.96 P<0.0001) and 83% of the intensive care unit days (Z=5.17 P<0.0001) in the period of hospitalisation prior to their death.
Table 3 National hospital data of children <15years discharged deceased in Ireland for the period January 2015-December 2016 with analysis of bed usage.
Number of Deaths Total Length of stay (LOS) Standard bed LOS ICU Total LOS
number of patients (%) number of days (%)[Median LOS] number of days (%) number of days (%)
All patients 365 (100%) 5566.5 (100%) [3 days] 1527.5 (100%) 4039 (100%)
RD patients 240 (66%) 4845.0 (87%) [5 days] 1504.0 (98.5%) 3341 (83%)
Non-RD patients 125 (34%) 721.5 (13%) [2 days] 23.5 (1.5%) 698 (17%)
Z score testing Z=46.6 P<0.0001* Z=7.96 P<0.0001* Z=5.17 P<0.0001*
*p<0.0001 for the Z score testing the hypothesis that there is a difference in the proportion of children with a RD in national hospital data compared to the expected proportion from children with RD in the general population.