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. Author manuscript; available in PMC: 2022 Sep 7.
Published in final edited form as: Pediatrics. 2020 Jun 17;146(1):e20192623. doi: 10.1542/peds.2019-2623

Global Burden of Childhood Epilepsy, Intellectual Disability, and Sensory Impairments

Bolajoko O Olusanya a,✉, Scott M Wright b, MKC Nair c, Nem-Yun Boo d, Ricardo Halpern e, Hannah Kuper f, Amina A Abubakar g, Nihad A Almasri h, Jalal Arabloo i, Narendra K Arora j, Sophia Backhaus k, Brad D Berman l,m, Cecilia Breinbauer n, Gwen Carr o, Petrus J de Vries p, Christie del Castillo-Hegyi q,r, Aziz Eftekhari s, Melissa J Gladstone t, Rosa A Hoekstra u, Vijaya Kancherla v, Mphelekedzeni C Mulaudzi w, Angelina Kakooza-Mwesige x, Felix A Ogbo y, Helen E Olsen z, Jacob O Olusanya a, Ashok Pandey aa, Maureen E Samms-Vaughan bb, Chiara Servili cc, Amira Shaheen dd, Tracey Smythe f, Donald Wertlieb ee, Andrew N Williams ff, Charles RJ Newton g, Adrian C Davis o, Nicholas J Kassebaum, on behalf of the Global Research on Developmental Disabilities Collaborators (GRDDC)gg
PMCID: PMC7613313  EMSID: EMS152529  PMID: 32554521

Abstract

Background

Estimates of children and adolescents with disabilities worldwide are needed to inform global intervention under the disability-inclusive provisions of the Sustainable Development Goals. We sought to update the most widely reported estimate of 93 million children <15 years with disabilities from the Global Burden of Disease Study 2004.

Methods

We analyzed Global Burden of Disease Study 2017 data on the prevalence of childhood epilepsy, intellectual disability, and vision or hearing loss and on years lived with disability (YLD) derived from systematic reviews, health surveys, hospital and claims databases, cohort studies, and disease-specific registries. Point estimates of the prevalence and YLD and the 95% uncertainty intervals (UIs) around the estimates were assessed.

Results

Globally, 291.2 million (11.2%) of the 2.6 billion children and adolescents (95% UI: 249.9–335.4 million) were estimated to have 1 of the 4 specified disabilities in 2017. The prevalence of these disabilities increased with age from 6.1% among children aged <1 year to 13.9% among adolescents aged 15 to 19 years. A total of 275.2 million (94.5%) lived in low- and middle-income countries, predominantly in South Asia and sub-Saharan Africa. The top 10 countries accounted for 62.3% of all children and adolescents with disabilities. These disabilities accounted for 28.9 million YLD or 19.9% of the overall 145.3 million (95% UI: 106.9–189.7) YLD from all causes among children and adolescents.

Conclusions

The number of children and adolescents with these 4 disabilities is far higher than the 2004 estimate, increases from infancy to adolescence, and accounts for a substantial proportion of all-cause YLD.

The United Nations’ Sustainable Development Goals (SDGs) mandate programs that will ensure inclusive and equitable quality education and promote lifelong learning opportunities for all children and adolescents, including those with disabilities.1 The majority of children with disabilities live in low- and middle-income countries (LMICs)2,3 and are less likely to go to school, or if they do attend school, they are more likely to leave school before completing primary or secondary education, resulting in considerable barriers to work and gainful employment.4–6 They are frequently marginalized in society and are disproportionately vulnerable to neglect, abuse, poverty, and violence.4 Thus, children and adolescents with disabilities are prone to be left behind under the SDGs era without timely and appropriate intervention from early childhood.4,5

Limited global data exist on children and adolescents with disabilities because of insufficient investment in collecting comparable data on different disabilities.6,7 The global prevalence estimates that are most frequently cited by multilateral agencies, such as the World Health Organization (WHO),3,7 the United Nations Children’s Fund,2 the United Nations Educational, Scientific and Cultural Organization,6 the Office of the United Nations High Commissioner for Refugees,8 the World Bank Group,5 and, more recently, the US Agency for International Development,9 were first published in 2008 on the basis of the WHO’s Global Burden of Disease Study (GBD) 2004.10 The GBD estimated that in 2004, at least 93 million children and adolescents (0–15 years) worldwide (5.1% of the global total) lived with a moderate-to-severe disability, and 13 million (0.7%) had a severe disability.10 These estimates were generated from 4 specific impairments that were modeled as sequelae of specific health disorders: epilepsy, intellectual disability, hearing loss, and vision loss. However, the reported estimates excluded children and adolescents with mild impairments and were based on limited data sources. Additionally, the proportion of preschool-aged children with disabilities, who may be the most likely to benefit from early childhood intervention services, was not reported.

Updated and improved estimates of children and adolescents with disabilities are needed to better quantify the disease burden and the resources required to address the needs and rights of these children as mandated by the SDGs,1,11 the Convention on the Rights of the Child,12 the Convention on the Rights of Persons with Disabilities,13 and the subsisting resolution of the World Health Assembly on Disability14 and in line with the International Classification of Functioning, Disability, and Health (ICF).15 Such data are also needed to monitor progress under the SDG era. We, therefore, set out to report the prevalence of childhood epilepsy, intellectual disability, vision loss, or hearing loss among children and adolescents (<20 years) and the associated years lived with disability (YLD) on the basis of data from the GBD 201716,17 to complement and update our earlier report for children <5 years of age from the GBD 2016.18

Methods

The GBD provides estimates of non-fatal outcomes for “impairments” (used interchangeably with “disabilities” in the current article), as part of the annual comprehensive assessment of incidence, prevalence, and YLD for several health conditions across 195 countries and territories. Impairments are defined as sequelae of multiple causes for which better data are available to estimate the overall occurrence than for each underlying cause. Four such impairments are developmental intellectual disability, epilepsy, hearing loss, and vision loss. Case definitions and diagnostic criteria for these impairments were based on International Classification of Diseases, Ninth Revision (ICD-9) and International Classification of Diseases, 10th Revision (ICD-10) codes, complemented with relevant guidelines such as the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition19 and the Guidelines for Epidemiologic Studies on Epilepsy.20 A detailed description of the GBD conceptual framework for epilepsy is reported elsewhere.21 Disorders of intellectual development in the ICD-9 and ICD-10 codes are termed as “developmental intellectual disability” or simply “intellectual disability” in this article and were grouped into 5 bands on the basis of IQ scores: borderline, mild, moderate, severe, and profound intellectual disability. Hearing and visual impairments were similarly classified into bands of severity corresponding to frequency response and visual acuity cutoffs, respectively. These 4 disabilities were selected for comparability with the GBD 2004 estimates for childhood disabilities.

The detailed methodologic techniques used for estimating the burden of each impairment have been reported previously16–18 and are presented in the Supplemental Information. In brief, the estimation for each condition started with the compilation of all available data inputs from systematic reviews of the literature, hospital and claims databases, health surveys, case notification systems, cohort studies, and multinational survey data. All input data for GBD 2017 are available at the Global Health Data Exchange (http://ghdx.healthdata.org/gbd-2017/data-input-sources). A total of 1675 sources were analyzed for data on the prevalence of intellectual disability (57), hearing loss (355), epilepsy (455), and vision loss (808). Efforts were made to (1) optimize the comparability of data derived from various sources by using different methods, (2) find a consistent set of estimates across prevalence data, and (3) generate estimates for locations with sparse or no data by using available information from other locations combined with covariates. Prevalence estimates were produced by using DisMod-MR 2.1, a statistical modeling technique developed for the GBD project (Supplemental Fig 5).22 This is a Bayesian meta-regression tool that synthesizes epidemiological data for fatal and non-fatal health outcomes from disparate settings and sources, adjusting for different case definitions, diagnostic criteria, or sampling methods, to generate internally consistent estimates by geographical location, year, age group, and sex. The validity of DisMod has been widely reported.16–18,22

YLD, defined as the years of life lived with a condition in a less than ideal health state, are designed to provide a comparable measure of disease burden across diverse health conditions and impairments rather than a measure of functional status, as described in ICF.15 To calculate YLD for the 4 disabilities, the estimated prevalence of each disability was multiplied by an assigned disability weight. Disability weights are the population assessment of magnitude of health loss from specific health outcomes measured on a scale from 0 to 1, in which 0 equals a state of perfect health and 1 equals death. The disability weights were estimated from multicountry population-based surveys, as described in detail elsewhere.18,23

The global estimates of the prevalence and YLD for the 4 disabilities in children and adolescents were disaggregated by age group (children: <1, 1–4, 5–9 years; adolescents: 10–14 and 15–19 years), sex, and geographical regions (high-income North America, Western Europe, Central and Eastern Europe and Central Asia, Latin America and the Caribbean, Southeast and East Asia and Oceania, South Asia, Sub-Saharan Africa, and North Africa and the Middle East). The selected locations are not geopolitical units, but groupings of countries created by GBD for analytical purposes. All computations in the GBD were conducted 1000 times to propagate uncertainty around the estimates for prevalence and YLD. At every step in the modeling process, the distributions were assessed for the sampling error of data inputs, the uncertainty of data corrections for measurement errors, the uncertainty in coefficients from model fit, and the uncertainty of severity distributions and disability weights. The corresponding uncertainty intervals (UIs) for prevalence and YLD estimates of the 4 disabilities were defined at the 2.5th and 97.5th value of 1000 draws. As with all GBD articles, the substantive data that formed the basis of this analysis16,17 adhered to the Guidelines for Accurate and Transparent Health Estimates Reporting, which include recommendations on the documentation of data sources, estimation methods, statistical analysis, and statistical code.24

Results

Globally, the population of children and adolescents was ~2.6 billion in 2017, of whom 291.2 million (95% UI: 249.9–335.4), or 11.2% (95% UI: 10.0–12.5), were estimated to have 1 of the 4 disabilities examined (Tables 1–4). Approximately 152.3 million (52.3%) were male, although the sex pattern varied across the disabilities. The prevalence of these disabilities increased with age, from 6.1% among all the ~138 million children aged <1 year to 13.9% among the roughly 616 million adolescents aged 15 to 19 years. A total of 16 million (95% UI: 13.4–18.9 [5.5%]) lived in high-income countries, and 275.2 million (95% UI: 236.4–316.5 [94.5%]) lived in LMIC. Of all the children and adolescents with disabilities, 8.4 million (2.9%) were aged <1 year, 47.9 million (16.4%) were aged 1 to 4 years, 73.5 million (25.2%) were aged 5 to 9 years, 75.9 million (26.1%) were aged 10 to 14 years, and 85.6 million (29.4%) were aged 15 to 19 years. Thus, a total of 205.6 million (70.6%) were <15 years of age. These 4 disabilities accounted for 28.9 million YLD (or 19.9%) of the overall 145.3 million (95% UI: 106.9–189.7) YLD among children and adolescents from all causes of fatal and non-fatal outcomes included in the GBD 2017.

Table 1. Global and Regional Age-Specific Prevalence of and YLD for Epilepsy in 2017.

No. (95% UI)
1–4 y 5–9 y 10–14 y 15–19 y <20 y
High-income North America
  Prevalence 131 803 (107432–159399) 199 970 (157 616–246 093) 216420 (168 746–265 722) 216711 (171 356–265789) 789737 (632 514–948 176)
    Cases per 100000 767 (625–927) 890 (701–1095) 920 (717–1129) 920 (727–1128) 867 (695–1041)
  YLD 51 974 (37 050–69 051) 75 662 (53 611–104 677) 79999 (55802–109880) 77882 (54 747–107 040) 295570 (211 251–403410)
    Rate per 100 000 302 (216–402) 337 (238–466) 340 (237–467) 331 (232–454) 325 (232–443)
Western Europe
  Prevalence 126 468 (100 007–156 598) 188 957 (144 255–237 135) 196335 (151 269–242173 202926 (1 57 762–249 314) 739 764 (574 153–903 671)
    Cases per 100000 712 (563–882) 803 (613–1008) 845 (651–1042) 865 (673–1063) 802 (622–979)
  YLD 48 964 (34429–67 257) 70 905 (49 050–98 578) 72145 (49296–98731) 72 754 (50 216–100 092) 274 710 (192 230–373 788)
    Rate per 100 000 276 (194–379) 301 (209–419) 310 (212–425) 310 (214–427) 298 (208–405)
Central Europe, Eastern
  Europe, and Central Asia
  Prevalence 189 861 (156 308–226 756) 275 179 (221 331–336 004) 256 698 (207 995–311 453) 247 331 (203 706–297 748) 1 004098 (839 357–1 194942)
    Cases per 100000 837 (689–1000) 1001 (805–1222) 1066 (864–1293) 1083 (892–1304) 980 (820–1167)
  YLD 83 351 (60 394–108 332) 117909 (86 351–153 388) 108160 (78 760–144448) 102209 (75 128–136 169) 427 137 (315 890–554 788)
    Rate per 100000 368 (266–478) 429 (314–558) 449 (327–600) 448 (329–596) 417 (308–542)
Latin America and the Caribbean
  Prevalence 449 630 (370 510–548 055) 575 028 (459 495–713 720) 609379 (483 554–749 149) 672 801 (550 138–818 731) 2 420 438 (1 972 412–2917913)
    Cases per 100000 1106 (911 –1348) 1163 (929–1443) 1237 (981–1521) 1347 (1101–1639) 1213 (988–1462)
  YLD 196 721 (145 687–256 747) 245 611 (178 296–324 113) 253267 (184956–339349) 267238 (198 161–357 961) 1 013 135 (747 175–1338725)
    Rate per 100000 484 (358–631) 497 (361–655) 514 (375–689) 535 (397–717) 508 (374–671)
Southeast Asia, East Asia, and Oceania
  Prevalence 737 521 (605 450–893 982) 945 540 (750 994–1 164 348) 958185 (773 663–1 184098) 962 589 (783 522–1 177 510) 3 793 040 (3141 571–4560916)
    Cases per 100000 664 (545–804) 701 (557–863) 703 (567–868) 692 (563–846) 687 (569–826)
  YLD 331 971 (248 485–440 416) 420 846 (308 919–561 459) 423461 (308930–564083) 419 264 (308 153–556 904) 1 681 681 (1267440–2163937)
    Rate per 100000 299 (224–396) 312 (229–416) 310 (227–414) 301 (221–400) 305 (230–392)
South Asia
  Prevalence 1 134129 (892519–1 402382) 1 592310 (1216 048–2021 679) 1 626 659 (1 248 656–2 046 161) 1 626 693 (1 279 219–2 022 196) 6 207 938 (5071 432–7483407)
    Cases per 100000 804 (633–994) 889 (679–1129) 915 (702–1151) 914 (719–1136) 875 (715–1055)
  YLD 547600 (384538–732918) 760878 (545 412–1 049 013) 772 626 (562 422–1 054172) 760804 (549 690–1 019 818) 2 952 475 (2180425–3869281)
    Rate per 100 000 388 (273–519) 425 (304–586) 434 (316–593) 428 (309–573) 416 (307–545)
Sub-Saharan Africa
  Prevalence 1 324612 (1 044953–1 668665) 1 445 699 (1 089 817–1 874924) 1 327 538 (1 012 314–1 723 209) 1 174 404 (905 551–1 483 284) 5 610 340 (4407396–7044475)
    Cases per 100000 1027 (810–1294) 980 (739–1271) 1017 (776–1321) 1062 (819–1341) 1016 (799–1276)
  YLD 631 083 (455159–836628) 654 829 (453 942–909 475) 594 123 (408 058–828 262) 513862 (358 361–705 617) 2 561 263 (1 817398–3446823)
    Rate per 100 000 489 (353–649) 444 (308–617) 455 (313–635) 465 (324–638) 464 (329–624)
North Africa and the Middle East
  Prevalence 529020 (425793–647712) 605 404 (476 471–745 640) 513 903 (406 382–628 706) 439 954 (351 097–534 851) 2216563 (1 779 281–2 654 106)
    Cases per 100000 1025 (825–1255) 980 (771–1207) 908 (718–1111) 838 (669–1019) 942 (756–1128)
  YLD 236221 (173908–315055) 264 780 (193 166–360 277) 224 422 (163 680–298 144) 190429 (137 334–255 005) 975171 (719368–1 300 365)
    Rate per 100000 458 (337–611) 429 (313–583) 397 (289–527) 363 (262–486) 415 (306–553)
Global
  Prevalence 4704742 (3906017–5688824) 5951 176 (4 780 635–7 281 786) 5 825 559 (4 699 604–7 042 917) 5 674377 (4 682 960–6 831 607) 23251 109 (19477175–27607857
    Cases per 100000 867 (720–1048) 900 (723–1101) 916 (739–1107) 920 (760–1108) 896 (751–1064)
  YLD 2161 753 (1 622637–2784049) 2 661 547 (1 961 247–3478308) 2 576 792 (1 943 858–3 419 294) 2 456 333 (1 856830–3223372) 10371 105 (7852990–13253967)
    Rate per 100000 398 (299–513) 403 (297–526) 405 (306–537) 398 (301–523) 400 (303–511)
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Table 4. Global and Regional Age-Specific Prevalence of and YLD for Vision Loss in 2017.

  No. (95% UI)
1–4 y 5–9 y 10–14 y 15 –19 y <20 y
High-income North America
  Prevalence 152 623 (118137–187434) 290 067 (216 569–380 633) 325 847 (245 317–433 303) 332 019 (260 911–415 580) 1 114 609 (893 445–1 366 118)
    Cases per 100 000 888 (687–1090) 1290 (963–1693) 1385 (1042–1841) 1409 (1107–1764) 1224 (981–1501)
  YLD 6825 (4491–9800) 12 497 (7946–18 913) 13 922 (9109–20 643) 14080 (9443–20 526) 48069 (31 567–70 783)
    Rate per 100 000 40 (26–57) 56 (35–84) 59 (39–88) 60 (40–87) 53 (35–78)
Western Europe
  Prevalence 276 367 (198 687–374997) 517 470 (353 529–726 275) 525 529 (358 367–760 147) 518 419 (371 643–710 943) 1 863 897 (1 406 494–2 458 616)
    Cases per 100 000 1556 (11 19–211 1) 2200 (1503–3088) 2261 (1542–3271) 2211 (1585–3031) 2020 (1524–2664)
  YLD 12 670 (8363–18 679) 22 999 (14 561–35 761) 23 903 (15 661 –36 263) 24 246 (16 137–35 060) 85 277 (56 719–126 152)
    Rate per 100 000 71 (47–105) 98 (62–152) 103 (67–156) 103 (69–149) 92 (61–137)
Central Europe, Eastern Europe, and Central Asia
  Prevalence 564 728 (440 263–703 012) 941 642 (717 458–1 223 861) 868 204 (677 153–1 113574) 846 765 (688 153–1 039 601) 3 283 489 (2 696 872–3 979 988)
    Cases per 100 000 2490 (1941–3100) 3424 (2609–4450) 3605 (2812–4624) 3709 (3014–4553) 3206 (2633–3886)
  YLD 23 331 (15 339–33908) 37 060 (23 671–57 112) 33 650 (22 175–50 785) 32 090 (21 729–46 690) 129096 (86 179–190 154)
    Rate per 100 000 103 (68–150) 135 (86–208) 140 (92–211) 141 (95–204) 126 (84–186)
Latin America and the Caribbean
  Prevalence 740 115 (608 175–891 456) 1 382 342 (1 139 624–1 686 144) 1 722 148 (1 458 855–2 078 414) 2 134 390 (1 864 828–2 454466) 6 060 394 (5 274074–6 953 437)
    Cases per 100 000 1820 (1495–2192) 2795 (2305–3410) 3495 (2961–4218) 4273 (3733–4914) 3037 (2643–3484)
  YLD 35 105 (24 358–49 102) 56 438 (38 220–82 876) 63 224 (43 422–93 124) 71 838 (49 073–102 168) 231 800 (161 066–330 075)
    Rate per 100 000 86 (60–121) 114 (77–168) 128 (88–189) 144 (98–205) 116 (81 –165)
Southeast Asia, East Asia, and Oceania
  Prevalence 2 249 931 (1 808000–2 713 770) 3 932 438 (3 111 842–4917097) 4413 990 (3 605469–5 471 494) 4 703 742 (4018 023–5 517 485) 15 585 040 (13 235 355–18 269 625)
    Cases per 100 000 2024 (1627–2442) 2914 (2306–3644) 3236 (2644–4012) 3379 (2887–3964) 2823 (2397–3309)
  YLD 109 196 (76 200–153 579) 166 445 (111 487–245 186) 176 644 (121 421–254986) 181 132 (126 902–254 871) 653 115 (455 897–924467)
Rate per 100 000 98 (69–138) 123 (83–182) 130 (89–187) 130 (91–183) 118 (83–167)
South Asia
  Prevalence 3 774616 (3 077 028–4508 330) 6 439 687 (5 251 987–7 862 31 1) 7 183 140 (6 119 227–8 571 685) 8 143 890 (7 174906–9 255 169) 26 038 313 (22 730 901–29 883 169)
    Cases per 100 000 2675 (2181–3195) 3595 (2932–4389) 4039 (3441–4820) 4577 (4032–5201) 3671 (3205–4213)
  YLD 165 553 (113090–235 319) 245 087 (163 525–364047) 249 088 (168 740–368 544) 261 408 (181 428–376 079) 948 988 (648 070–1 367 226)
    Rate per 100 000 117 (80–167) 137 (91–203) 140 (95–207) 147 (102–211) 134 (91–193)
Sub-Saharan Africa
  Prevalence 2 648 821 (2 192 343–3 177 168) 4 543 637 (3 814 398–5 446 542) 4907 105 (4 263 876–5 738 216) 4973 223 (4439 848–5 562 714) 17 405 890 (15 387972–19 716012)
    Cases per 100 000 2055 (1700–2464) 3081 (2587–3693) 3761 (3268–4398) 4496 (4014–5029) 3154 (2788–3572)
  YLD 129 586 (91 767–177 285) 178 202 (122 692–257 198) 172 247 (1 19 122–245 839) 161 966 (113 190–226 755) 667 326 (471 998–937 436)
    Rate per 100000 101 (71–138) 121 (83–174) 132 (91 –188) 146 (102–205) 121 (86–170)
North Africa and the Middle East
  Prevalence 1 270 261 (1 006 150–1 584 554) 2 128 785 (1 665 430–2 721 426) 2 186 398 (1 774129–2 745 766) 2 218 003 (1 877 690–2 634071) 7 960 528 (6 721 789–9 429 083)
    Cases per 100 000 2462 (1950–3071) 3446 (2696–4405) 3864 (3136–4853) 4224 (3576–5017) 3384 (2858–4009)
  YLD 56 999 (38 277–81 141) 82 725 (53 508–125 192) 79 230 (53 191–119 232) 76 351 (52 324–1 10 075) 304 847 (206 858–442 931)
    Rate per 100 000 110 (74–157) 134 (87–203) 140 (94–211) 145 (100–210) 130 (88–188)
Global
  Prevalence 11 902 507 (9 685 418–14 340 209) 20584553 (16 619 635–25 501 975) 22 554407 (18 878 363–27 433 881) 24339696 (21 124978–28 083 187) 80 857 974 (69 402 207–94059 458)
    Cases per 100 000 2193 (1785–2642) 3113 (2514–3857) 3545 (2967–4312) 3948 (3427–4556) 3116 (2675–3625)
  YLD 549 006 (378 690–770 472) 818 335 (546 869–1 207 657) 829363 (566 152–1 214034) 842 676 (582 361–1 198 086) 3 133 280 (2 171 484–4467 090)
    Rate per 100 000 101 (70–142) 124 (83–183) 130 (89–191) 137 (94–194) 121 (84–172)
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The prevalence of hearing loss rose from 0.9% among children aged <1 year to 5.9% (95% UI: 5.4%–6.5%) among adolescents aged 15 to 19 years (Fig 1). Vision loss rose from 1.1% among children aged <1 year to 3.9% (95% UI: 3.4%–4.6%) among adolescents aged 15 to 19 years. The prevalence of intellectual disability and epilepsy remained largely constant at ~3% and 0.9%, respectively, in all age groups. Among all children and adolescents, the disability-specific prevalence was 0.9% (95% UI: 0.8%–1.1%) for epilepsy, 3.2% (95% UI: 2.5%–3.9%) for intellectual disability, 3.1% (95% UI: 2.7%–3.6%) for vision loss, and 4.0% (95% UI: 3.7%–4.3%) for hearing loss. However, epilepsy and intellectual disability were associated with the highest YLD in all age groups, which were significantly higher than sensory disabilities.

Figure 1. Global age-specific prevalence of and YLD for childhood epilepsy, intellectual disability, hearing loss and vision loss in 2017.

Figure 1

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South Asia accounted for the highest prevalence of intellectual disability (6.0% [95% UI: 4.5%–7.5%]), hearing loss (4.7% [95% UI: 4.3%–5.0%]), and vision loss (3.7% [95% UI: 3.2%–4.2%]), whereas Latin America and the Caribbean recorded the highest prevalence of epilepsy (1.2% [95% UI: 1.0%–1.5%]), as shown in Fig 2. Epilepsy was least prevalent in Southeast and East Asia and Oceania (0.7% [95% UI: 0.6%–0.8%]), and intellectual disability was least prevalent in Latin America and the Caribbean (1.6% [95% UI: 1.3%–1.9%]), whereas vision loss(1.2% [95% UI: 1.0%–1.5%]) and hearing loss (2.2% [95% UI: 2.1%–2.4%] were least prevalent in high-income North America. South Asia (0.6% [95% UI: 0.4%–0.7%]) and Latin America and the Caribbean (0.5% [95% UI: 0.4%–0.7%]) were associated with the highest YLD rates for intellectual disability and epilepsy, respectively. South Asia (107.8 million or 37.5%) and sub-Saharan Africa (59.8 million or 20.5%) accounted for more than half of all children and adolescents with disabilities (Fig 3). High-income North America (5.6 million or 1.9%) and Western Europe (6.2 million or 2.1%) accounted for the lowest population of children and adolescents with disabilities.

Figure 2. Regional prevalence of and YLD for childhood epilepsy, intellectual disability, hearing loss and vision loss in 2017.

Figure 2

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Figure 3.

Figure 3

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Regional ranking of childhood epilepsy, intellectual disability, hearing loss, and vision loss by severity among children and adolescents based on estimates of prevalence and YLD in 2017. Colors correspond to the ranking of disability by severity, with dark red indicating the most common disability and dark green indicating the least common disability for the location indicated. The numbers inside each box indicate the ranking.

Globally, mild intellectual disability (IQ scores of 50–69) was the most prevalent disability, and mild vision loss was the least prevalent disability among the 4 types of disability (Fig 3). Within regions, mild hearing loss was the most common disability in all regions except Central and Eastern Europe and Central Asia and Southeast and East Asia and Oceania. Mild vision loss was the least prevalent disability in all regions.

Severe epilepsy and severe intellectual disability were the 2 most common disabilities with the highest YLD globally and in all regions. The burden of epilepsy was more concentrated in Mexico, Colombia, and Venezuela in Latin America and was more concentrated in Gabon, the Republic of the Congo, and Angola in sub-Saharan Africa (Fig 4).

Figure 4. Global distribution of childhood epilepsy, intellectual disability, hearing loss and vision loss in 2017.

Figure 4

Figure 4

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A, Epilepsy, both sexes, <20 years, 2017, prevalent cases per 100 000. B, Developmental intellectual disability, both sexes, <20 years, 2017, prevalent cases per 100 000. C, Hearing loss, both sexes, <20 years, 2017, prevalent cases per 100 000. D, Blindness and vision impairment, both sexes, <20 years, 2017, prevalent cases per 100 000.

Intellectual disability had the highest prevalence in India (South Asia), Afghanistan, and Yemen (Middle East). Hearing loss was most prevalent in Madagascar (sub-Saharan Africa) and Myanmar (Southeast Asia), whereas vision loss was more widespread and had the highest prevalence in South Sudan, the Central African Republic (sub-Saharan Africa), and Papua New Guinea (Oceania).

The top 10 countries accounted for 52.8% of all children and adolescents with epilepsy, 68.0% of children and adolescents with intellectual disability, 62.0% of children and adolescents with hearing loss, and 59.4% of children and adolescents with vision loss (Supplemental Fig 6). The top 10 countries accounted for 62.3% of all children and adolescents with these disabilities. These countries also accounted for at least 53.5% of the YLD associated with these conditions. India and China had the highest population of children and adolescents with any disability, with their associated YLD. The United States was the only high-income country among the top 10 countries for any disability. However, in terms of the highest prevalence and YLD rates per population, countries with the highest prevalence were Gabon for epilepsy, India for intellectual disability, Madagascar for hearing loss, and Israel for vision loss. The underlying causes or risk factors and their ICD-9 and ICD-10 codes that formed the basis of the reported estimates for all disabilities in the GBD 2017, as well as their contributions to the aggregate estimate for each disability, are summarized in Supplemental Fig 7.

Discussion

Our primary aim was to update the global estimate of children and adolescents with disabilities previously attributed to the GBD 2004 and still widely reported in the literature.2–9 Although, in our study, we did not capture the full spectrum of all possible childhood disabilities, our analysis reveals that the number of children and adolescents with disabilities is at least 291 million globally and that the prevalence increases with age. Among children and adolescents <15 years, the estimate of children and adolescents with these 4 disabilities is more than twice the 2004 estimate of 93 million. The substantially higher estimate can be attributed to several factors besides the modest impact of the ~6.6% and 4.1% rise in the global population of children and adolescents <15 and <20 years, respectively, between 2004 and 2017.25 Firstly, the number and variety of data sources used in generating estimates have increased substantially since 2004. Secondly, the modeling techniques have improved significantly on the basis of expert contributions from an increasing number of institutional and individual collaborators from 146 countries.26 Thirdly, consistent with the classification recommended by the ICF, the GBD 2017 estimates include disabilities of varying degrees of severity from slight or mild to profound for each disability. Lastly, there is now an internationally agreed on framework for evaluating estimates of health from statistical modeling, which has been strictly followed by the GBD since 2015.24

The GBD modeling efforts are meant to bridge a critical gap in the epidemiology of developmental disorders resulting from several conceptual and operational challenges in measuring disabilities in children and adolescents.27,28 As with most health conditions, the dearth of population-based data for specific disabilities, especially in LMIC, has compelled a growing reliance on the statistical estimation of health outcomes as an interim step to guide health policy and intervention. The implicit philosophy underpinning these efforts is that the absence of conventional epidemiological data is not evidence of the absence of a health condition. Thus, GBD is an essential, independent, and up-to-date source of alternative data for policy-makers and decision-makers in global health, especially for countries with poor or no data.2,3

However, it is helpful to evaluate the plausibility of the GBD estimates in the absence of comparable global estimates from other reputable sources. The global estimate of 0.9% (95% UI: 0.8%–1.1%) for epilepsy among all children and adolescents appears plausible on the basis of evidence in the literature, suggesting a global prevalence of between 0.5% and 1%.29,30 In addition, the estimate of 1.0% (95% UI: 0.8%–1.3%) for sub-Saharan Africa is consistent with the 0.9% reported in the most comprehensive systematic review on epilepsy to date from this region.31 The GBD estimate for intellectual disability of 3.2% (95% UI: 2.5%–3.9%) was higher than the estimate of 1.8% reported in 1 meta-analysis of population-based studies, possibly because of the inclusion of children and adolescents with comorbid autism spectrum disorder and cerebral palsy secondary to neonatal encephalopathy in the GBD.32,33 South Asia substantially contributed to the reported global estimates for intellectual disability, and the age-specific GBD estimates for this region are supported by a recent robust population-based study from India in which a prevalence of 5.2% was reported.34 Sensory disabilities are perhaps the most researched childhood disabilities worldwide. Several studies in school-aged children support the reported estimates for vision loss and hearing loss, with most suggesting that the GBD estimates were conservative.35–38 For example, in 1 systematic review of childhood hearing loss, a prevalence of between 0.8% and 46.7% was reported across 26 well-conducted studies from different regions,36 whereas 2 population-based studies from Canada and the United Sates revealed estimates of between 4.5% and 7.9%, compared with a GBD estimate of 2.2% for North America. More crucially, these findings underscore the need to develop local capacity toward early identification and timely on-going support for children and adolescents with any disability and their families, especially in high-burden LMIC. The unique challenges faced by children with disabilities as they transition into adolescence also need to be recognized and addressed.39

This study has several limitations worth emphasizing. Most importantly, our main finding must be regarded as a conservative estimate of children with disabilities in general because this study was restricted to 4 conditions. The inclusion of conditions such as cerebral palsy without comorbid intellectual disability would have increased the reported estimates in our article. Additionally, the GBD 2017 has methodologic limitations that have been extensively described in previous publications in accordance with the Guidelines for Accurate and Transparent Health Estimates Reporting.16–18 For example, the 95% UIs around estimates for regions with sparse data are still wide. Most of the uncertainty in the YLD estimates results from the current limitations in the determination of disability weights that may be minimized in the future by removing some of the ambiguities in lay descriptions and increasing the volume of survey data. In addition, despite the continuous efforts toward improving the GBD methodology, concerns remain on estimating the prevalence of disabilities solely as sequelae of health conditions.2,3,40 Furthermore, the estimates do not fully reflect the complex and dynamic relationship between health conditions and contextual personal or environmental factors, as envisaged under the ICF, and so provide a limited picture of disability.15 Finally, it was difficult to completely and precisely account for children with multiple disabilities and across multiple developmental domains. These considerations reveal the need for complementary nationally representative disability data, such as those published periodically by the United Nations Children’s Fund and the WHO, that can be used as additional data inputs for the GBD. Although estimates of disabilities from both statistical modeling and household surveys are not definitive, they reflect current knowledge and the best available evidence to inform policies and interventions.

Conclusions

In the most recent GBD, it is shown that the number of children and adolescents with disabilities globally far exceeds the estimate in 2004. The burden of disability is substantial from early childhood and corroborates our earlier report on the need to address the quality of life of many beneficiaries of the child survival programs during the era of the Millennium Development Goals (2000–2015).18 The risk likely to be faced by the affected children and adolescents of not realizing their full potential, especially in LMIC, as envisaged under the SDGs era, is real and disturbing. Regardless of the inherent limitations of modeled estimates, the findings from our analysis are plausible and insightful. These findings shed light on the high and growing health needs among child survivors that warrant significant investments and should be a wake-up call to public health leaders and advocates globally. A committed global leadership will ensure that these and other vulnerable children and adolescents are truly not left behind in accordance with the obligations under the Convention on the Rights of the Child and the Convention on the Rights of Persons with Disabilities.

Supplementary Material

Supplementary Information

What’s Known On This Subject

The World Disability Report 2011 indicated that at least 93 million (~5.1%) children <15 years old had a moderate-to-severe disability and 13 million (0.7%) had a severe disability on the basis of the Global Burden of Disease Study 2004.

What This Study Adds

More than 291 million children aged <20 years had epilepsy and intellectual and sensory disabilities in 2017. The top 10 countries accounted for 62% of the children with these disabilities, and 95% lived in low and middle income countries.

Table 2. Global and Regional Age-Specific Prevalence of and YLD for Intellectual Disability in 2017.

  No. (95% UI)
1–4 y 5–9 y 10–14 y 15–19 y <20 y
High-income North America
  Prevalence 312 301 (242 878–382 044) 406 645 (316 939–500 868) 421 064 (328 142–518 193) 414992 (323 170–511 232) 1 631108 (1 272 711–2 004 735)
    Cases per 100 000 1817 (1413–2223) 1809 (1410–2228) 1789 (1394–2202) 1761 (1372–2170) 1792 (1398–2202)
  YLD 56 625 (42 735–71 313) 75 118 (55 834–96 354) 77 205 (57 942–99 252) 74 525 (55 493–94 510) 296 285 (222 764–374979)
    Rate per 100 000 329 (249–415) 334 (248–429) 328 (246–422) 316 (236–401) 325 (245–412)
Western Europe
  Prevalence 306 760 (244 393–366 154) 407 635 (323 805–486 663) 398 547 (316 114–476 539) 394 895 (315 514–472 494) 1 581 607 (1 257 082–1 888 734)
    Cases per 100 000 1727 (1376–2062) 1733 (1377–2069) 1715 (1360–2051) 1684 (1345–2015) 1714 (1362–2047)
  YLD 58 830 (44 214–76 755) 79 235 (59 655–103 358) 77 719 (58 698–102 767) 76 870 (57 392–100 563) 306 181 (231 706–397 589)
    Rate per 100 000 331 (249–432) 337 (254–439) 334 (253–442) 328 (245–429) 332 (251–431)
Central Europe, Eastern Europe, and Central Asia
  Prevalence 464 555 (372 176–551 946) 566 007 (456 083–671 043) 490 842 (396 378–579 410) 456 221 (369 000–539 606) 2 085 228 (1 684 719–2 467 164)
    Cases per 100 000 2048 (1641–2434) 2058 (1658–2440) 2038 (1646–2406) 1998 (1616–2363) 2036 (1645–2409)
  YLD 96 975 (74084–123 808) 123 931 (93 748–158 428) 108 941 (82 212–141 470) 100 356 (75 919–129 790) 450 975 (344 233–576 327)
Rate per 100 000 428 (327–546) 451 (341–576) 452 (341–587) 440 (333–568) 440 (336–563)
Latin America and the Caribbean
  Prevalence 672 585 (546 288–790 809) 793 565 (640 531–936 587) 771 280 (620 371–911 461) 757 768 (609 956–895 890) 3 170 947 (2 566 782–3 741 437)
    Cases per 100 000 1654 (1343–1944) 1605 (1295–1894) 1565 (1259–1850) 1517 (1221–1794) 1589 (1286–1875)
  YLD 163 130 (122 299–205 398) 192 502 (141 828–249 593) 186 842 (138 637–245 523) 180 520 (133 886–238 899) 765 956 (572 889–985 737)
    Rate per 100 000 401 (301 –505) 389 (287–505) 379 (281–498) 361 (268–478) 384 (287–494)
Southeast Asia, East Asia, and Oceania
  Prevalence 1 989 600 (1 551 695–2 417 553) 2 388 846 (1 858 076–2 909 389) 2 366 591 (1 837 990–2 863 620) 2 342 392 (1 825 186–2 833 713) 9635177 (7 508 265–1 1 680 166)
    Cases per 100 000 1790 (1396–2175) 1770 (1377–2156) 1735 (1348–2100) 1683 (1311–2036) 1745 (1360–21 16)
  YLD 338 527 (261 223–424 819) 409 425 (314267–510283) 406 080 (315 679–509 454) 400 529 (312 259–498 027) 1 647 992 (1 282 960–2 052 003)
    Rate per 100 000 305 (235–382) 303 (233–378) 298 (231–374) 288 (224–358) 299 (232–372)
South Asia
  Prevalence 8 814255 (6 626 639–10 976 227) 10915694 (8 235 801–13 631 549) 10 497 333 (7918 391–13093 706) 10 172 283 (7 644 114–12 708 838) 42 491 040 (31 992 788–53 01 1 21 1)
    Cases per 100 000 6247 (4696–7779) 6093 (4597–7610) 5903 (4453–7363) 5717 (4296–7142) 5990 (4510–7474)
  YLD 810 729 (612 510–1 052 819) 1 038 830 (788 263–1 334037) 1 020 827 (777147–1 297 493) 987 227 (753 048–1 252 961) 4042 934 (3 097 570–5 160 238)
Rate per 100 000 575 (434–746) 580 (440–745) 574 (437–730) 555 (423–704) 570 (437–727)
Sub-Saharan Africa
  Prevalence 3 165 296 (2 481 170–3 837 016) 3 334 212 (2 597 892–4095 851) 2 843 521 (2 215 008–3 491 657) 2 321 894 (1 805 326–2 855 238) 12 578 273 (9 852 736–15 399 332)
    Cases per 100 000 2455 (1924–2976) 2261 (1762–2777) 2179 (1698–2676) 2099 (1632–2581) 2279 (1785–2790)
  YLD 537 270 (403 404–681 216) 502 903 (371 463–654997) 427 855 (318 385–563 513) 344 876 (257 747–450 141) 1 978 503 (1 492 394–2 545 605)
Rate per 100 000 417 (313–528) 341 (252–444) 328 (244–432) 312 (233–407) 358 (270–461)
North Africa and the Middle East
  Prevalence 2 095 975 (1 607 222–2 594440) 2 407 074 (1 843 226–2 986 253) 2 134977 (1 635 729–2 648 684) 1 888 277 (1 448 419–2 345 875) 9 063 331 (6 947 456–11 240448)
    Cases per 100 000 4062 (31 15–5028) 3896 (2984–4834) 3773 (2891–4681) 3596 (2759–4468) 3853 (2954–4779)
  YLD 247 026 (186 292–312 698) 277 132 (211 358–354 743) 244 547 (186 614–310 299) 214982 (164447–274 406) 1 049 302 (801 194–1 335 594)
    Rate per 100 000 479 (361 –606) 449 (342–574) 432 (330–548) 409 (313–523) 446 (341–568)
Global
  Prevalence 18 008 445 (13 909 115–22144997) 21 463 907 (16 582 655–26 376 300) 20 163 862 (15 573 910–24 783 030) 19 007 495 (14 683 193–23 427 643) 83 209 866 (64448 368–102 067 901)
    Cases per 100 000 3318 (2563–4080) 3246 (2508–3989) 3169 (2448–3895) 3083 (2382–3800) 3207 (2484–3934)
  YLD 2 349 727 (1 817 711–2 945 999) 2 754 614 (2 1 18 761–3 466 366) 2 603 898 (2 016 091–3 243 552) 2 437 342 (1 889 411–3 031 441) 10 753 999 (8 286 290–13 378933)
    Rate per 100 000 433 (335–543) 417 (320–524) 409 (317–510) 395 (306–492) 414 (319–516)
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Table 3. Global and Regional Age-Specific Prevalence of and YLD for Hearing Loss in 2017.

  No. (95% UI)
1–4 y 5–9 y 10–14 y 15–19 y <20 y
High-income North America
  Prevalence 258 142 (225 327–295 461) 478 573 (426 090–537 100) 526 205 (471 867–585 743) 733 490 (664 602–818 883) 2 017 260 (1 870 427–2 183 386)
    Cases per 100 000 1502 (1311–1719) 2129 (1895–2389) 2236 (2005–2489) 3113 (2821–3475) 2216 (2054–2398)
  YLD 12 408 (8680–17 110) 22 325 (15 402–30 559) 26 443 (18 237–36 819) 30 600 (21 450–41 400) 93 525 (65 864–126 933)
Rate per 100 000 72 (50–100) 99 (69–136) 112 (77–156) 130 (91–176) 103 (72–139)
Western Europe
  Prevalence 226 464 (198 409–259 596) 454 724 (401 634–515 000) 510 865 (453 338–573 776) 854951 (768 534–958 165) 2 064471 (1 900 504–2 243 406)
    Cases per 100 000 1275 (1 1 17–1462) 1933 (1708–2190) 2198 (1951–2469) 3646 (3277–4086) 2237 (2059–2431)
  YLD 9166 (6304–12 735) 16 542 (1 1 121–23 162) 18 457 (12 695–25 847) 24027 (16478–34 327) 69 441 (48 083–96 832)
Rate per 100 000 52 (35–72) 70 (47–98) 79 (55–111) 102 (70–146) 75 (52–105)
Central Europe, Eastern Europe, and Central Asia
  Prevalence 446 534 (393 229–505 136) 867 575 (761 631–978 052) 853 600 (759 658–961 526) 1 156 592 (1 039 959–1 289 852) 3 355 115 (3 098 21 1–3 626 580)
    Cases per 100 000 1969 (1734–2227) 3155 (2769–3556) 3545 (3155–3993) 5066 (4555–5649) 3276 (3025–3541)
  YLD 19 754 (13 847–27 355) 34 888 (23 943–48 270) 34 657 (23 805–47 919) 38 964 (27 198–53 796) 130 484 (91 327–179 383)
    Rate per 100 000 87 (61–121) 127 (87–176) 144 (99–199) 171 (119–236) 127 (89–175)
Latin America and the Caribbean
  Prevalence 843 578 (744 767–954 872) 1 640 439 (1 443 332–1 839 080) 1 853 695 (1 648 833–2 080 510) 2 670 666 (2 406 587–2 973 854) 7 076 049 (6 546 644–7 652 670)
    Cases per 100 000 2074 (1831–2348) 3317 (2919–3719) 3762 (3347–4223) 5347 (4818–5954) 3546 (3280–3835)
  YLD 36 917 (25 862–51 437) 64 279 (43 830–88 858) 72 599 (50 013–101 588) 87 004 (60 705–120 938) 265 671 (184402–365 704)
    Rate per 100 000 91 (64–126) 130 (89–180) 147 (102–206) 174 (122–242) 133 (92–183)
Southeast Asia, East Asia, and Oceania
  Prevalence 2 937 855 (2 637 971–3 247 557 5 847 100 (5 185 984–6 566 636) 6 652 840 (5 969 283–7 447 327) 9 517 169 (8 599 529–10 544 702) 25 253 888 (23 356 813–27 245 250)
    Cases per 100 000 2643 (2374–2922) 4333 (3844–4867) 4878 (4377–5460) 6837 (6178–7575) 4574 (4231–4935)
  YLD 147 715 (103 706–203 433) 258 411 (179 943–352 506) 295 134 (205 286–407 958) 346 117 (242 624–475054) 1 070 358 (750 476–1 466 477)
    Rate per 100 000 133 (93–183) 192 (133–261) 216 (151–299) 249 (174–341) 194 (136–266)
South Asia
  Prevalence 3 931 287 (3 566 450–4 315 347) 7 908 429 (7 057 869–8 818 810) 8 847 058 (7 976 611–9 814130) 12 033 855 (10927 238–13 319010) 33 081 529 (30 758 299–35 615 041)
    Cases per 100 000 2786 (2528–3058) 4415 (3940–4923) 4975 (4485–5519) 6763 (6141–7485) 4664 (4336–5021)
  YLD 209 056 (146 539–286 880) 359 966 (252 910–485 91 1) 399 390 (275 291–552 742) 457 025 (321 410–630 307) 1 455 912 (1 023 230–1 979 015)
    Rate per 100 000 148 (104–203) 201 (141 –271) 225 (155–311) 257 (181 –354) 205 (144–279)
Sub-Saharan Africa
  Prevalence 3 694 805 (3 352 273–4064 331) 6 576 843 (5 912 292–7 295 890) 6 363 670 (5 763 444–7 037 152) 7182174 (6 591 941–7 868 098) 24 215 356 (22 583 51 1–25 985 485)
    Cases per 100 000 2866 (2600–3152) 4460 (4009–4947) 4877 (4417–5393) 6493 (5959–7113) 4387 (4092–4708)
  YLD 239 641 (167 087–325 126) 355 441 (249 963–475 154) 348 323 (244 318–470 735) 331 536 (234 376–448 129) 1 320 256 (937 865–1 765 546)
Rate per 100 000 186 (130–252) 241 (170–322) 267 (187–361) 300 (212–405) 239 (170–320)
North Africa and the Middle East
  Prevalence 751 019 (652 720–873 241) 1 405 634 (1 230 855–1 586 991) 1 443 894 (1 271 286–1 632 521) 1 941 910 (1 732 125–2 175 269) 5 591 434 (5 144 265–6 077 669)
    Cases per 100 000 455 (1265–1692) 2275 (1992–2569) 2552 (2247–2885) 3699 (3299–4143) 2377 (2187–2584)
  YLD 30 533 (20 961–42 481) 54000 (36 989–74 896) 56 630 (38 685–79 072) 63 515 (43 877–88 736) 207 788 (144685–286 606)
    Rate per 100 000 59 (41–82) 87 (60–121) 100 (68–140) 121 (84–169) 88 (62–122)
Global
  Prevalence 13 244 864 (11 950 478–14 667 046) 25 468 776 (22 734486–28 377 208) 27 358 599 (24 627 508–30 360 794) 36 577 235(33 265 797–40 257 224) 103 904 538 (96 545 635–11 1 630 666)
    Cases per 100 000 2440 (2202–2703) 3852 (3438–4292) 4300 (3871–4772) 5933 (5396–6530) 4005 (3721–4302)
  YLD 711 795 (499 549–978 438) 1 177 588 (826 177–1 586 023) 1 264 660 (880 741–1 742 484) 1 395 869 (982 697–1 908 896) 4 662 724 (3 290 463–6 304 785)
Rate per 100 000 131 (92–180) 178 (125–240) 199 (138–274) 226 (159–310) 180 (127–243)
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Acknowledgements

We thank Christopher J.L. Murray, Theo Vos, and Mohsen Naghavi of the Institute for Health Metrics and Evaluation for their overall guidance of the substantive GBD study that formed the basis of this analysis.

Funding

No external funding was received by any of the authors for this work. The substantive data that formed the basis of this article and the open access charge were funded by the Bill & Melinda Gates Foundation. This article is licensed under the Creative Commons Attribution 4.0 International License. The named authors alone are responsible for the views expressed in this publication.

Abbreviations

GBD

Global Burden of Disease Study

ICD-9

International Classification of Disease, Ninth Revision

ICD-10

International Classification of Disease, 10th Revision

ICF

International Classification of Functioning, Disability, and Health

LMIC

low- and middle-income countries

SDG

sustainable development goal

UI

uncertainty interval

WHO

World Health Organization

YLD

years lived with disability

Footnotes

Financial Disclosure: Dr Kassebaum reports personal fees and nonfinancial support from Vifor Pharma Group outside the submitted work; the other authors have indicated they have no financial relationships relevant to this article to disclose.

Potential Conflict Of Interest: The authors have indicated they have no potential conflicts of interest to disclose.

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