Global Burden and Epidemiological Trends of Common Pediatric Neurologic Disorders, 1990-2019

doi:10.21203/rs.3.rs-4956228/v1

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Global Burden and Epidemiological Trends of Common Pediatric Neurologic Disorders, 1990-2019

https://doi.org/10.21203/rs.3.rs-4956228/v1

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Objective: To report the latest estimates of pediatric neurologic disorders by sex, age, geography and sociodemographic index from 1990 to 2019.

Methods：Thirteen major pediatric neurologic disorders were systematically analyzed by sex, year, age and region according to data from Global Burden of Disease Study 2019. The global burden was calculated based on deaths, prevalence, incidence, and disability-adjusted life-years (DALYs) from 1990 to 2019.

Results: In 2019, global burden of pediatric neurologic diseases was responsible for 14.50% all-cause deaths and 13.82% DALYs in people under 20. The most burdensome diseases were noncommunicable disorders neonatal encephalopathy (DALYs 51.7 million. 95%UI 43.7-61.2), neural tube defects (DALYs 7.6 million. 95%UI 5.6-10.8), migraine (7.1 million, 95%UI 4.5-17.9) and idiopathic epilepsy (4.8 million, 95% UI 3.6-6.5); and communicable disorder meningitis (DALYs 12.5 million, 95%UI 10.2-15.6). Spanned from 1990 to 2019, the absolute number sharply decreased in DALYs (-42.9%) and deaths (-46.9%). Some DALYs could be attributed to risk factors lead exposure, low birth weight and short gestation, particular matter pollution, and alcohol use. Migraine rather than meningitis causes the second most DALYs in countries and territories with middle-, high-middle and high- sociodemographic index (SDI).

pediatrics

GBD

encephalopathy

meningitis

migraine

epilepsy

● Pediatric neurologic disorders was responsible for 13.82% DALYs in children in 2019.

● 13 major neurologic disorders were responsible for 92.0 million DALYs in 2019.

● Substantial difference was observed in the disease burden distribution between territories.

● The global burden of disease favorably lightened overtime from 1999 to 2019.

● Take caution that noncommunicable disorders such as migraine increased in DALYs worldwide.

Pediatric neurological disorders are underestimated but increasingly recognized to lead to mortality and disability and contribute significantly to the global burden of disease(1).

There is extreme imbalance between the global burden and the medical resource of pediatric neurology. There is inadequate number of only 0.39 pediatric neurologists per 100,000 population on average worldwide(2). Furthermore, the spectrum and distribution of pediatric disorders is quite different from that in adulthood. Thus, public awareness of the accurate epidemiological data is indispensable for clinicians, decision-makers and societies to promote prophylactic measures, proper treatments and rehabilitation, or support services. However, little established evidence was reported comprehensively on prevalence, incidence, risk factors, disability and mortality.

The Global Burden of Disease Study (GBD) has developed and flourished over the past 30 years, for providing systematic, timely and scientific assessments of 328 major diseases and their 87 risk factors across 204 countries(3). It is annually updated by the Institute for Health Metrics and Evaluation from 1990 to 2019, in order to accurately profile the burden of diseases from the metrics evaluating multiple dimensions. As the pediatric population suffering from important neurologic disorders has not been specially focused, this study aims to estimate the communicable and noncommunicable neurologic disorders from 1990 to 2019, based on the updated version of GBD.

The mortality of birth related disorders, such as neonatal encephalopathy, was far higher than other neurologic disorders (3). As highly age-limited, it is additionally independently analyzed in the newborn.

The global burden of pediatric neurologic disorders was obtained from the GBD study 2019. Briefly, in the GBD study, available statistics was collected from published and unpublished epidemiology data, and collected data (hospitalizations, vital registration, etc.). To unify the evaluation and comparation of mortality and non-fatal disorders, disability-adjusted life-years (DALYs) were calculated as the sum of years lived with disability and years of life lost. Estimations on deaths, prevalence, incidence, and DALYs per 100,000 people from 1990 to 2019 were reported with 95% uncertainty intervals(3, 4). Uncertainty was statistically quantified with the 95% uncertainty intervals (UIs) for each estimate, as capturing the 2.5% and 97.5% values from the distribution. Age-standardized rates were reported along with the absolute numbers to compare across regions, adjusting for the age distribution and demographic difference.

A total of 12 main pediatric neurologic diseases were involved in this study. Noncommunicable neurologic diseases included brain and other central nervous system (CNS) cancers, neonatal encephalopathy, headache disorders (migraine, tension-type headache), idiopathic epilepsy, idiopathic developmental intellectual disability, neural tubal deficit, multiple sclerosis, motor neuron disease, and other neurological disorders. While communicable diseases included tetanus, meningitis, and encephalitis.

The age limit of pediatrics in this study was set to no more than 20 years old according to the upper age limit of 21 from American Academy of Pediatrics(5). Phases were further divided into newborn (from birth to 1 month of age), infancy (from 1 month to 2 years old), childhood (2 to 12 years old), and adolescence (12 to 21 years old).

The (SDI) indicates the degree of sociodemographic development of countries or territories. It evaluates and synthesis the lag-distributed income per capita, the rate of fertility in females under age of 25, and average schooling years(6). Countries and territories are divided into low SDI, low-middle SDI, middle SDI, high-middle SDI, and high SDI.

The GBD study provides online dataset and assessment for available information through websites (https://vizhub.healthdata.org/gbd-results/, https://vizhub.healthdata.org/gbd-compare/). SDI related data is publicly available through website (https://ghdx.healthdata.org/record/ihme-data/gbd-2019-socio-demographic-index-sdi-1950-2019). Statistical analysis and visualization were performed through the up mentioned online tools and R software (version 4.2.1, http://www.r-project.org). The study is supported by high-performance computing platform of Peking university.

Information about informed consent was previously approved by the Institutional Review Board of the University of Washington and public accessible through http://www.healthdata.org/gbd/2019. No extra identifiable information is included in this study and thus has a waiver of further informed consent.

Overview of Global Pediatric and Newborn Neurologic Disorder Burden, 2019

Considering 2019, the total number of main pediatric neurologic disorders involved in the GBD study were responsible for 92.0 million DALYs and 901.6 thousand deaths (as shown in Table 1) in general pediatrics; 55.3 million DALYs and 621.8 thousand deaths in the newborn.

Table 1

Global Absolute Number of DALYs, Deaths, Incidence, and Prevalence by Neurologic Disorders Category in the General Pediatrics and the Newborn, from 1990 to 2019
	General pediatric neurologic disorders Absolute number (95%UI)			Neurologic disorders in the newborn Absolute number (95%UI)
	1990	2019	Percentage changes	1990	2019	Percentage changes
Neonatal encephalopathy due to birth asphyxia and trauma
DALYs	72,195,971.19(64,852,604.60–80,624,322.34)	51,744,592.74(43,665,350.97-61,218,565.69)	-28(-40 to -14)	69,039,193.42(61,928,233.25-77,577,864.84)	48,982,146.29(41,054,402.07-58,011,632.95)	-29(-41 to -15)
Deaths	808,680.76(726,795.74–903,199.78)	566,975.71(475,535.14–672,551.27)	-30(-42 to -16)	776,846.70(696,824.35–872,944.42)	551,125.50(461,904.67–652,708.35)	-29(-41 to -15)
Prevalence	1,702,681.53(1,143,653.87-2,620,493.56)	4,949,573.46(3,822,876.09-6,319,777.89)	191(124 to 270)	57,623.49(42,338.02-76,446.89)	68,724.03(54,828.33-85,754.18)	19(0 to 38)
Incidence	1,335,110.88(907,226.55-2,086,317.24)	1,378,698.93(963,701.45-2,024,055.52)	3(-7 to 13)	NA
Meningitis
DALYs	29,482,896.57(24,997,569.81-34,563,615.25)	12,520,156.00(10,155,940.94-15,643,463.64)	-58(-66 to -48)	2,721,734.88(2,359,229.07-3,218,865.01)	1,245,826.26(994,471.19-1,614,776.11)	-54(-63 to -42)
Deaths	338,246.10(286,978.20–396,937.81)	143,375.98(116,205.73–179,473.50)	-58(-66 to -47)	30,631.52(26,550.04-36,227.36)	14,019.52(11,190.14-18,172.23)	-54(-63 to -42)
Prevalence	4,139,926.34(3,391,833.94-5,072,692.16)	2,828,646.72(2,360,053.67-3,413,442.30)	-32(-34 to -29)	3,194.53(2,404.58-4,142.62)	2,028.3(1,521.7-2,677.55)	-37(-38 to -35)
Incidence	2,622,895.17(2,023,843.17-3,331,839.87)	1,746,525.38(1,358,866.98-2,221,245.79)	-33(-35 to -32)	134,338.78(96,269.17–182,454.7)	87,345.02(62,254.62–120,909.71)	-35(-36 to -33)
Neural tube defects
DALYs	14,488,597.85(10,319,297.32-10,319,297.32)	7,568,751.03(5,557,266.84-10,819,158.02)	-48(-59 to -33)	7,192,120.14(5,112,757.01-10,111,336.49)	3,592,076.37(2,644,459.1-4,794,914.92)	-50(-61 to -35)
Deaths	162,660.32(115,280.35–261,601.97)	83,754.88(61,422.01–120,454.17)	-49(-59 to -34)	80,910.35(57,519.53–113,774.05)	40,399.01(29,745.14-53,934.26)	-50(-61 to -35)
Prevalence	608,827.17(486,954.81–756,980.80)	709,680.98(567,782.21–888,090.28)	17(13 to 21)	9,867.1(7,481.72-12,583.69)	7,883.25(6,067.74-9,995.66)	-20(-23 to -17)
Incidence	178,690.67(138,868.69–225,524.48)	136,011.48(108,114.43–169,879.66)	-24(-27 to -21)	NA
Migraine
DALYs	5,770,964.99(371,382.79-14,406,040.02)	7,113,885.07(446,726.61-17,854,126.95)	23(19 to 26)	NA
Prevalence	159,486,433.73(118,610,323.21–209,071,547.07)	195,973,649.12(145,585,435.04–257,495,369.55)	23(21 to 25)	NA
Incidence	29,400,151.04(22,672,165.58-36,561,360.76)	35,198,343.20(27,106,858.30–43,950,334.17)	20(18 to 22)	NA
Idiopathic epilepsy
DALYs	5,757,000.42(4,069,571.24-7,366,594.46)	4,797,391.96(3,573,035.46-6,527,370.98)	-17(-32 to 12)	7,817.63(3,763.23-13,554.84)	6,823.78(3,347.49-11,921.63)	-13(-29 to 9)
Deaths	39,071.86(26,395.15-47,796.91)	22,840.05(19,471.42,28,088.55)	-42(-55 to -1)	NA
Prevalence	6,852,990.12(4,758,534.56-9,533,524.74)	8,783,783.04(6,136,726.72-12,142,988.06)	28(9 to 52)	199,434.66(116,016.38–294,093.84)	154,649.95(86,815.97–234,053.04)	-2(-18 to 19)
Incidence	1,143,486.41(703,911.17-1,689,902.55)	1,483,427.68(937,740.45-2,180,902.20)	30(11 to 54)	8,636.89(5,155.01-13,638.9)	10,171.18(6,299.42-15,697.66)	18(0 to 41)
Encephalitis
DALYs	6,852,592.74(5,126,867.93-8,672,018.25)	2,637,125.39(2,138,495.72-3,527,914.05)	-62(-72 to -39)	197,110.38(134,896.8–239,912.19)	125,786.24(97,418.6–159,452.68)	-36(-57 to -2)
Deaths	78,495.96(58,461.14-99,296.81)	30,223.62(24,419.37-40,967.09)	-61(-72 to -38)	2,218.14(1,518.02-2,699.98)	1,415.49(1,096.15-1,794.5)	-36(-57 to -2)
Prevalence	1,306,967.46(974,697.60-1,656,616.24)	990,027.79(763,956.66-1,226,322.75)	-24(-27 to -20)	353.61(284.86-433.42)	238.8(189.58-294.58)	-32(-34 to -31)
Incidence	836,957.32(682,355.61–999,374.12)	699,110.95(566,567.49–846,455.84)	-16(-18 to -14)	13,975.66(11,080.93-17,181.57)	9,641.56(7,594.37-11,984.83)	-31(-33 to -30)
Idiopathic developmental intellectal Disability
DALYs	2,115,377.71(1,133,346.80-3,431,375.42)	2,073,433.44(1,090,159.65-3,419,390.70)	-2(-6 to 1)	7,683.71(3,522.51-13,406.04)	6,039.97(2,724.99-10,783.38)	-21(-25 to -19)
Prevalence	51,299,492.20(33,027,969.23-70,160,259.48)	50,565,740.87(31,511,221.04-69,928,783.21)	-1(-5 to 0)	199,434.66(116,016.38–294,093.84)	154,649.95(86,815.97–234,053.04)	-2(-18 to 19)
Brain and CNS cancer
DALYs	2,452,770.91(1,619,066.68- 3,947,887.26)	1,923,038.31(1,474,554.21-2,248,519.03)	-22(-57 to 15)	67,807.98(36,212.73-98,103.59)	51,931.97(31,266.61-71,334.19)	-23(-56 to 20)
Deaths	29,734.77(19,858.92-47,584.62)	23,538.03(18,050.51-27,496.22)	-21(-56 to 15)	758.55(405.15-1098.71)	580.08(349.7-796.78)	-24(-56 to 20)
Prevalence	153,334.46(111,452.83–233,819.18)	212,459.23(164,908.50–245,556.21)	39(-28 to 91)	3,760.11(2,197.8-5,241.34)	4,241.26(2,747.17-5,381.56)	13(-39 to 78)
Incidence	47,373.13(32,635.92-74,710.65)	47,600.95(36,572.25-55,194.61)	0(-46 to 44)	1,238.1(680.93-1,776.37)	1,036.73(646.83-1,370.12)	-16(-53 to 32)
Other neurological disorders
DALYs	1,533,318.32(1,174,185.16-1,914,416.55)	1,824,850.71(1,350,271.27-2,429,088.48)	19(2 to 41)	NA
Deaths	10,985.15(8,714.17-12,613.68)	9,082.29(7,373.83-11,137.21)	-17(-31 to 2)	NA
Prevalence	12,108.39(6,668.18-19,101.48)	14,274.37(7,860.00–22,776.31)	18(15 to 22)	NA
Tetanus
DALYs	19,934,636(16,454,114.21-23,433,611.95)	1,811,279.66(1,356,730.46-2,639,664.49)	-91(-93 to -85)	14,936,197.22(11,985,279.15-17,561,803.62)	1,264,399.23(929,930.67–1957,736.68)	-92(-94 to -85)
Deaths	226,657.11(187,202.86–266,312.24)	20,793.73(15,573.66-30,249.14)	-91(-93 to -85)	168,091.81(134,892.21–197,643.86)	14,229.29(10,464.52-22,030.27)	-92(-94 to -85)
Prevalence	94,877.31(74,568.17–118,979.63)	27,043.94(19,762.34-35,286.06)	-71(-75 to -68)	20,827.33(14,589.05-28,610.59)	1,586.58(1,037.82-2,380.06)	-92(-95 to -88)
Incidence	511,239.76(385,097.55–667,505.07)	43,463.34(29,558.09-64,293.78)	-91(-94 to -87)	37,0885.29(267,831.81–497,794.24)	27,170.55(17,693.69-41,344.43)	-93(-95 to -88)
Tension-type headache
DALYs	473,767.10(72,364.25-2,485,438.24)	571,130.09(86,353.53-2,889,355.61)	21(15 to 26)	NA
Prevalence	337,574,706.43(250,590,257.65–444,250,424.16)	403,936,012.92(298,847,724.71–532,658,149.47)	20(18 to 21)	NA
Incidence	149,568,826.87(113,754,280.61–186,195,098.83)	177,277,563.47(135,276,615.30–221,353,292.37)	19(17 to 20)	NA
Motor neuron disease
DALYs	197,300.61(171,805.79–233,242.35)	84,105.28(74,848.93-94,205.68)	-57(-65 to -49)	2,856.55(2,468.28-3,424.89)	1,847.8(1,572.19-2,153.99)	-35(-50 to -20)
Deaths	2,205.97(1,914.88-2,607.16)	897.09(800.82-1,017.38)	-59(-67 to -52)	32.14(27.77–38.54)	20.79(17.69–24.23)	-35(-50 to -20)
Prevalence	37,921.06(27,835.66-49,094.13)	42,311.13(31,175.61-54,790.15S)	12(9 to 14)	5.47(3.75–7.59)	4.89(3.27–6.91)	-11(-13 to -8)
Incidence	8,132.16(6,146.03-10,331.14)	7,947.38(5,922.15-10,238.03)	-2(-5 to 0)	161.72(111.85-223.15)	143.64(97.57-201.88)	-11(-14 to -9)
Multiple sclerosis
DALYs	17,023.83(6,299.76-28,705.48)	16,321.44(6,885.67-41,649.52)	-4(-49 to 109)	NA
Deaths	150.99(28.20-291.22)	129.63(28.16-432.22)	-14(-63 to 133)	NA
Prevalence	18,874.72(12,315.23-27,898.08)	22,205.42(14,792.28-32,288.59)	18(14 to 22)	NA
Incidence	5,553.96(3,956.30-7,850.53)	4,659.83(3,211.34-6,733.95)	19(15 to 25)	NA
Total^[1]
DALYs	161,272,218.23	92,048,935.73	-42.9	94,172,521.90	55,276,877.91	-41.3
Deaths	1,696,888.98	901,611.02	-46.9	1,059,521.35	621,789.68	-41.3
Abbreviations: DALY: disability-adjusted life-year; NA: not available; UI: uncertainty interval; CNS: central nervous system

Summarized information on pediatric and newborn neurologic burden of diseases is detailed in Table 1. Currently, in general pediatrics, four most burdensome diseases based on DALYs were neonatal encephalopathy (DALYs 51.7 million. 95%UI 43.7–61.2), meningitis (12.5 million, 95%UI 10.2–15.6), neural tube defects (7.6 million. 95%UI 5.6–10.8), migraine (7.1 million, 95%UI 4.5–17.9) and idiopathic epilepsy (4.8 million, 95% UI 3.6–6.5). In the newborn, neonatal encephalopathy (DALYs 49.0 million. 95%UI 41.1–58.0), neural tube defects (3.6milion, 95%UI 2.64–4.79), tetanus (1.3milion, 95%UI 0.93–1.96), meningitis (1.2milion, 95%UI 0.99–1.61), and encephalitis (0.13 million, 95%UI 0.10–0.16) were the top five burden measured by DALYs.

The leading causes of death in pediatric population were neonatal encephalopathy (567.0 thousand. 95%UI 475.53-672.55), meningitis (143.4 thousand, 95%UI 116.21-179.47), neural tube defects (83.8 thousand, 95%UI 61.42-120.45), encephalitis (30.2 thousand, 95% UI 24.42–40.97), brain and CNS cancer (23.5 thousand, 95%UI 18.05–27.50), and idiopathic epilepsy (22.8 thousand, 95%UI 19.47–28.09); while in the newborn were neonatal encephalopathy (551.1 thousand. 95%UI 461.90-652.71), tetanus (168.1 thousand, 95%UI 134.89-197.64), neural tube defects (80.9 thousand, 95%UI 57.52-113.77), and meningitis (30.6 thousand, 95%UI 26.55–36.23).

The most prevalent diseases were tension-type headache (403.9 million, 95%UI 298.8-532.7), migraine (196.0 million, 95%UI 145.6-257.5), idiopathic developmental intellectual disability (50.6 million, 95%UI 31.5–69.9) and idiopathic epilepsy (8.8 million, 95%UI 6.1–12.1). In the newborn, considering prevalence or incidence, the most prevalent disorders were idiopathic developmental intellectual disability (prevalence 1546 thousand, 95%UI 86.82-234.05), meningitis (incidence 87.3 thousand, 95%UI 62.25-120.91), neonatal encephalopathy (prevalence 68.7, 95%UI 54.82–85.75), tetanus (incidence 27.2 thousand, 95%UI 17.69–41.34) and idiopathic epilepsy (prevalence 19.9 thousand, 95%UI 10.67–32.98).

Changes in the Global Pediatric and Newborn Neurologic Disorder Burden, from 1990 to 2019

The total burden of both pediatric and newborn neurologic disorders has largely decreased through the past 30 years by -42.9% and − 41.3%, measured by DALYs, respectively (Table 1). Deaths changes were around − 46.9% and − 41.3%. The considerable amount of change was mainly attributed to the control of neonatal encephalopathy and communicable diseases. Tetanus (DALYs changed by -91%, 95%UI -93 to -85), encephalitis (DALYs changed by -62%, 95%UI -72 to -39), and meningitis (DALYs changed by -58%, 95%UI -66 to -48) marked the top three of percentage change in the pediatric neurologic burden. In the newborn, tetanus (DALYs changed by -92%, 95%UI -94 to -85), meningitis (DALYs changed by -54%, 95%UI -63 to -42), and neural tube defects (DALYs changed by -50%, 95%UI -61 to -35) decreased the most in percentage. However, an increase in DALYs were observed in migraine (DALYs changed by 23%, 95%UI 19 to 26), tension-type headache (DALYs changed by 21%, 95%UI 15 to 26) and other neurological disorders (DALYs changed by 19%, 95%UI 2 to 41). In the newborn, favorably, no disorder was observed to increase in DALYs or deaths, although idiopathic epilepsy increased in incidence (incidence changed by 18%, 95%UI 0 to 41), as well as brain and CNS cancer increased in prevalence (prevalence changed by 13%, 95%UI -39 to 78).

Global Pediatric Neurologic Disorder Burden by Sex and Age

The distribution of global pediatric neurologic disorders by sex and age is shown in Fig. 1 (Except for neonatal encephalopathy, because age distribution less meaningful). Generally, both DALYs and Deaths decreased spanned from 1990 to 2019.Meningitis was responsible for the most DALYs in both boys and girls from 1 to 9 years old. Migraine accounted for the most DALYs in both sexes in the 10- to 19-year-olds. There were more girls than boys suffered from migraine in the period. Idiopathic epilepsy maintained the second cause for DALYs from 5 to 19 years old in both sexes with a slight male predominance. Considering deaths, meningitis was always the leading cause from 1 to 19 years old, in both sexes.

Substantial difference in DALYs were observed between boys and girls. The male-to-female ratio was calculated as shown in Table 2. Across the neurologic disorders observed, brain and CNS cancer (male-to-female ratio 1.42), neonatal encephalopathy (1.39), meningitis (1.22), idiopathic epilepsy (1.22) were more likely to increase DALYs in boys; multiple sclerosis (male-to-female ratio 0.43), migraine (0.64), and tension-type headache (0.89) were more likely to affect girls.

Table 2

2019 Global Absolute Number of DALYs of Boys and Girls and Male-to-Female Ratio by Neurologic Disorders Category
Neurological disorders	DALYs		Male-to-female ratio
Neurological disorders	Boys(95%UI)	Girls(95%UI)	Male-to-female ratio
Neonatal encephalopathy	30,109,582.25(24,723,169.51,24,723,169.51)	21,635,010.49(18,445,050.27,25,366,465.49)	1.39
MENINGITIS	6,884,033(5,533,137 to 8,770,391)	5,636,123(4,465,211 to 7,085,775)	1.22
Migraine	2,774,321(184,944 to 6,787,803)	4,339,564(259,949 to 10,880,682)	0.64
Neural tube defects	3,653,421(2,333,180 to 5,753,921)	3,915,330(2,682,655 to 5,840,959)	0.93
Idiopathic epilepsy	2,635,282(1,959,082 to 3,581,660)	2,162,110(1,593,397 to 2,944,522)	1.22
Encephalitis	1,425,549(1,120,770 to 1,971,500)	1,211,577(950,885 to 1,745,403)	1.18
Brain and cNS cancer	1,128,697(801,339 to 1,387,876)	794,341(606,847 to 923,279)	1.42
Idiopathic developmental intellectual disability	1,087,779(563,381 to 1,800,506)	985,655(529,692 to 1,618,885)	1.10
Other neurological disorders	1,022,307(768,995 to 1,346,638)	802,543(563,422 to 1,085,403)	1.27
Tetanus	978,013(709,688 to 1,583,337)	833,266(602,018 to 1,220,891)	1.17
Tension-type headache	269,231(35,810 to 1,536,397)	301,899(50,629 to 1,392,303)	0.89
Motor neuron disease	45,701(39,999 to 52,465)	38,404(33,940 to 43,438)	1.19
Multiple sclerosis	4,922(2,253 to 10,480)	11,400(4,575 to 34,390)	0.43
Abbreviations: DALY: disability-adjusted life-year; CNS: central nervous system

Global Pediatric Neurologic Burden Attributed to Risk Factors, 1990 and 2019

In the pediatric neurologic disorders studied, neonatal encephalopathy, meningitis, encephalitis, idiopathic epilepsy and intellectual disability could attribute to risk factors according to GBD 2019. As shown in Fig. 2, low birth weight and short gestation, lead exposure, particular matter pollution, and alcohol use were the major risk factors accounting for DALYs in both 1990 and 2019.

Distribution of Global Pediatric Neurologic Burden Under Geographic and SDI Difference

Distribution of each disorder in a world map is shown in Appendix. There was substantial difference in the burden distribution between countries and territories. The trend of distribution of DALYs according to SDI is shown in Fig. 3. Disorders associated with the most DALYs (neonatal encephalopathy, meningitis, migraine, neural tube defects) were observed to affect areas with lower SDI generally. According to DALYs, the ranking of disorders is shown in Fig. 4. Neonatal encephalopathy was the top burden in all over the world. Except for neonatal encephalopathy, meningitis was the leading burden in low and low-middle SDI areas rather than middle, high-middle and high SDI areas. Migraine was the most burdensome disorder in high, high-middle and middle SDI areas after neonatal encephalopathy. DALYs caused by neural tube defects and idiopathic epilepsy are generally high in overall countries and territories. Brain and CNS cancer is more burdensome in areas with relatively higher SDI.

The global pediatric neurologic burden has steadily improved from 1990 to 2019 according to the study, especially in the newborn and in communicable diseases. The total burden of pediatric neurologic disorders was responsible for 14.50% all-cause deaths and 13.82% DALYs in people under 20 globally in 2019. Of the 13 major pediatric neurologic disorders included, neonatal encephalopathy and meningitis remain the leading cause of noncommunicable and communicable mortality and DALYs, respectively, although a substantial decline overtime observed.

Considering the past 30 years, there was remarkable decrease in infectious diseases. Tetanus, encephalitis and meningitis marked the top 3 of decrease in DALYs over the diseases studied. The impressive progress may be attributed to the improved access to lower-cost diagnostics and therapeutics, increased availability for vaccines and antibiotics, and improved social support for the survivors(7). This decline of infectious diseases is excessively inspiring as they also contributed significantly to newborn deaths and DALYs improvements.

As hypothesized by the GBD collaboration, the major global burden has shifted from communicable disorders to noncommunicable disorders(8). Most noncommunicable common pediatric neurologic disorders also declined in DALYs and deaths, such as neonatal encephalopathy, idiopathic epilepsy and brain and CNS cancer. However, frustratingly, the DALYs caused by migraine and tension-type headache increased by about 20% in total number from 1990 to 2019. The increase could not be eliminated by the population growth. Also, pediatric headache disorders seem to be more burdensome in countries and territories with higher SDI, indicating an increasing need to promote effective and innovative prevention and intervention in headache disorders. The highly prevalent and burdensome disease deserves more attention and resources, as prophylactic, abortive treatment and education might be cost-effective(9).

The burden of selected disorders could be attributed to the risk factors studied in GBD 2019. Low birth weight and short gestation (mainly owning to child and maternal malnutrition), particular matter pollution, lead exposure, and alcohol use were the most significant risk factors accounting for DALYs. Through comparation between 1990 and 2019, the influence of the up mentioned factors has been alleviated. To mention, lead exposure still largely accounts for 55.76% idiopathic developmental intellectual disability up to 2019. Low birth weight and short gestation, mainly associated with child and maternal malnutrition, was the most significant risk factor for neonatal encephalopathy.

There is sexual difference in the global burden of pediatric disorders. Brain and CNS cancer was most likely to affect boys than girls with a male-to-female ratio of 1.42, which is in accordance with sufficient previous studies(10, 11). While multiple sclerosis caused more DALYs in girls with a male-to-female ratio of 0.43 and its susceptibility of female predominance was well known(12). To mention, tension-type headache appears much less likely to affect girls with a male-to-female ratio of 0.89.

The spectrum of disorders was rather different in countries and territories with different SDI. Neonatal encephalopathy was always the top cause of DALYs in areas with any SDI. Meningitis remains the second cause in areas with relatively lower SDI, however, has declined far behind noncommunicable disease in high-SDI areas. Migraine, idiopathic epilepsy, brain and CNS cancer are becoming most burdensome especially in areas with middle to high SDI. Neural tube defects seemed to be less burdensome in areas with higher SDI. Meanwhile, tension-type headache is more predominant in high SDI areas.

During the past three decades, the global burden of pediatric neurologic disorders has largely improved owning to effective prophylactic measures, interventions, and public services, especially when considering communicable diseases. Also, inspiringly, the newborn deaths and DALYs sharply decreased by 41.3%. However, selective disorders, in particular migraine, likely increased in causing DALYs, thus deserve more attention and effort. We are shifting to an era of controlling noncommunicable diseases where resource and innovation are in urgent requirement in the region of pediatric neurologic disorders.

The global burden of pediatric neurologic diseases has largely improved, especially for communicable diseases through the past 30 years. However, selective disorders, in particular migraine, increased in causing DALYs and thus deserve more attention and resource. Further control of related risk factors, public education, prophylactic measures and social service about pediatric neurologic disorders are warranted.

Acknowledgements

We sincerely acknowledge the GBD study collaboration for providing public available noncommercial access to the GBD study. And we acknowledge thanks to Xiao Ming’s team ([email protected]) for their advice in the analysis procedure. The study is supported by high-performance computing platform of Peking university.

Disclosure Statement

Hongyuan Chu is a member of the GBD study collaboration.

Ethical Approval

Funding

No funding was received for this study.

Author Contribution

Hongyuan Chu is the single author for this study.

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Calculated by summing neurologic diseases, brain and other CNS cancers, idiopathic developmental intellectual disability, neural tubal deficit, tetanus, meningitis, and encephalitis manually

No competing interests reported.

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Global Burden and Epidemiological Trends of Common Pediatric Neurologic Disorders, 1990-2019

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Abstract

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What This Paper Adds

INTRODUCTION

METHODS

RESULTS

Overview of Global Pediatric and Newborn Neurologic Disorder Burden, 2019

Changes in the Global Pediatric and Newborn Neurologic Disorder Burden, from 1990 to 2019

Global Pediatric Neurologic Disorder Burden by Sex and Age

Global Pediatric Neurologic Burden Attributed to Risk Factors, 1990 and 2019

Distribution of Global Pediatric Neurologic Burden Under Geographic and SDI Difference

DISCUSSION

Conclusion

Declarations

Author Contribution

References

Footnotes

Additional Declarations

Supplementary Files

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