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Global, Regional, and National Incidence and Mortality
of Neonatal Preterm Birth, 1990-2019
Guiying Cao, PhD; Jue Liu, PhD; Min Liu, PhD
IMPORTANCE Preterm birth complications are the leading cause of death in children younger
than 5 years worldwide. Despite advancing knowledge of risk factors and mechanisms related
to preterm labor, the preterm birth rate has risen in most industrialized countries. Moreover,
the burden of neonatal preterm birth remains unclear across the world.
OBJECTIVE To determine the trends in incidence and mortality of neonatal preterm birth at
the global, regional, and national levels to quantify its burden from 1990 to 2019 using data
from the 2019 Global Burden of Disease study.
DESIGN, SETTING, AND PARTICIPANTS Annual incident cases, deaths, age-standardized
incidence rates (ASIRs), and age-standardized mortality rates (ASMRs) of neonatal preterm
birth between 1990 and 2019 were collected from the 2019 Global Burden of Disease study.
The percentage of relative changes in incident cases and deaths as well as the estimated
annual percentage changes (EAPCs) of ASIRs and ASMRs were calculated to quantify their
temporal trends. Correlations of EAPC of ASIRs and ASMRs with sociodemographic index
(SDI) and universal health coverage index were evaluated by Pearson correlation analyses.
EXPOSURES Infants born alive before 37 completed weeks of gestation between 1990 and
2019.
MAIN OUTCOMES AND MEASURES Incident cases, deaths, ASIRs, and ASMRs of neonatal
preterm birth.
RESULTS Globally, the incident cases of neonatal preterm birth decreased by 5.26% from
16.06 million in 1990 to 15.22 million in 2019, and the deaths decreased by 47.71% from 1.27
million in 1990 to 0.66 million in 2019. The overall ASIR (EAPC = −0.19 [95% CI, −0.27 to
−0.11]) and ASMR (EAPC = −2.09 [95% CI, −1.99 to −2.20]) decreased in this period. The ASIR
of neonatal preterm birth increased by a mean of 0.25% (95% CI, 0.13%-0.38%) in high-SDI
regions from 1990 to 2019. The ASMR of neonatal preterm birth increased by a mean of
2.09% (95% CI, 1.99%-2.20%) in Southern Sub-Saharan Africa in this period. A positive
correlation was observed between EAPC of ASIR and SDI or universal health coverage index
in 2019, while a negative correlation was observed between EAPC in ASMR and SDI or
universal health coverage index in 2019 at national levels.
CONCLUSIONS AND RELEVANCE Preterm birth remains a crucial issue in children worldwide,
with an increasing trend in ASIR in high-SDI regions and in ASMR in Southern Sub-Saharan
Africa between 1990 to 2019. Efforts to reduce both the incidence and mortality of preterm
births are essential.
JAMA Pediatr. doi:10.1001/jamapediatrics.2022.1622
Published online May 31, 2022.
Supplemental content
Author Affiliations: Department of
Epidemiology and Biostatistics,
School of Public Health, Peking
University,Beijing, China.
Corresponding Author: Min Liu,
PhD, Department of Epidemiology
and Biostatistics, School of Public
Health, Peking University, No. 38
Xueyuan Road, Haidian District,
Beijing 100191, China (liumin@
bjmu.edu.cn).
Research
JAMA Pediatrics | Original Investigation
(Reprinted) E1
Downloaded From: https://jamanetwork.com/ on 06/02/2022
Preterm birth is defined as infants born alive before 37
completed weeks of gestation by the World Health Or-
ganization (WHO).
1
Globally, it is estimated that 14.84
million infants were born preterm in 2014, and this number is
rising.
2
The preterm birth rate is 10.6%worldwide, ranging from
8.7% to 13.4% of infants born across regions.
2
In addition, the
preterm birth rate varies significantly across countries, with
an increasing trend in most industrialized countries.
3
For ex-
ample, the preterm birth rate in the US increased from 9.5%
in 1981 to 12.7% in 2005.
3
Preterm birth is truly a global prob-
lem, despite more than 60% of preterm births occuring in Africa
and South Asia.
1
Preterm infants are particularly vulnerable to complica-
tions due to impaired respiration, difficulty in feeding, poor
body temperature regulation, and high risk of infection.
4
Pre-
term birth complications are the leading cause of death in chil-
dren younger than 5 years worldwide and were responsible
for approximately 1 million deaths in 2015.
1
Global efforts to
further reduce mortality in children younger than 5 years de-
mand urgent action based on the data of incidence and mor-
tality of preterm birth at regional and national levels as well
as their associated factors. To our knowledge, there is cur-
rently no study to systematically clarify both the incidence and
mortality of neonatal preterm birth at the global, regional, and
national levels, as well as their association with socioeco-
nomic status. Therefore, we retrieved detailed data on the
incidence and mortality of neonatal preterm birth and socio-
economic status from the 2019 Global Burden of Disease (GBD)
study to determine the global incidence and mortality of
neonatal preterm birth and their associations with socioeco-
nomic status at the national level to provide a more compre-
hensive perspective to make global and regional targeted in-
terventions and health care policies for the prevention and
control of neonatal preterm birth.
Methods
Data Source
The 2019 GBD study modeled nonfatal disease burden using
DisMod-MR version 2.1, a meta-analysis tool that uses a
compartmental model structure with a series of differential
equations that synthesize sparse and heterogeneous epide-
miologic data for nonfatal diseases, including neonatal
disorders.
5
In addition, the GBD study used standardized tools
to generate estimates for the incidence and mortality of most
diseases by age, sex, location, and year.
6,7
In the GBD study,
preterm birth is defined as infants born alive before 37 weeks
of pregnancy according to the WHO.
8,9
The detailed methods
of the modeling strategy and alternative approaches for esti-
mating neonatal preterm birth have been reported in previ-
ous studies.
5-7
The study did not involve human participants
and/or animals; therefore,no ethic s approvalor informed con-
sent was needed.
This study used data of annual incident cases, deaths, age-
standardized incidence rates (ASIRs), and age-standardized
mortality rates (ASMRs) of neonatal preterm birth from 1990
to 2019 by sex, age, and location, collected from the Global
Health Data Exchange query tool.
10
Data were available from
a total of 204 countries and territories, and these were catego-
rized into 5 regions in terms of sociodemographic index (SDI)
and 21 GBD regions according to geographical contiguity. Data
on sociodemographic states, including SDI and universal health
coverage index (UHCI), in 204 countries and territories used
in this study were also collected from the Global Health Data
Exchange query tool.
9
SDI
The SDI is a composite indicator of development status strongly
correlated with health outcomes.
9
It is the geometric mean of
0 to 1 indices of lag distributed income per capita, mean years
of schooling for individuals 15 years and older, and total fer-
tility rate for individuals youngerthan 25 years. A loc ationw ith
an SDI of 0 indicates a theoretical minimum level of develop-
ment status relevant to health outcomes, while a location with
an SDI of 1 indicates a theoretical maximum level.
9
The SDIs
of 204 countries and territories in 2019 are shown in eTable 1
in the Supplement.
UHCI
The UHCI developed following GBD 2019 comprises 23 indi-
cators drawn across a range of health care service areas and is
meant to represent health care needs over the life course.
11
The
indicators of UHCI involved either direct measures of inter-
vention coverage (eg, antiretroviral therapy coverage) or out-
come-based indicators, such as mortality-to-incidence ra-
tios, to approximate access to quality care.
12
The UHCI
indicators are reported on a scale of 0 to 100.
12
The UHCIs of
204 countries and territories in 2019 are shown in eTable 1 in
the Supplement.
Statistical Analysis
We calculated the percentage of relative changes in incident
cases and deaths of neonatal preterm birth and the estimated
Key Points
Question What is the burden of neonatal preterm birth at the
global, regional, and national levels?
Findings In this cross-sectional study using data from the Global
Burden of Disease study, incident cases and deaths of neonatal
preterm birth, overall age-standardized incidence rates (ASIRs),
and age-standardized mortality rates (ASMRs) of neonatal preterm
birth decreased from 1990 to 2019; however, ASIRs and ASMRs
increased in some regions with high sociodemographic index
regions and in Southern Sub-Saharan Africa, respectively. There
was a positive correlation between estimated annual percentage
change of ASIR and sociodemographic index or universal health
coverage index in 2019, while there was a negative correlation
between estimated annual percentage change in ASMR and
sociodemographic index or universal health coverage index in
2019 at the national level.
Meaning Preterm birth remains a crucial issue in children
worldwide and discovery research into the underlying
mechanisms of neonatal preterm birth and the development of
innovative interventions is urgent.
Research Original Investigation Global, Regional, and National Incidence and Mortality of Neonatal Preterm Birth, 1990-2019
E2 JAMA Pediatrics Published online May 31, 2022 (Reprinted) jamapediatrics.com
Downloaded From: https://jamanetwork.com/ on 06/02/2022
annual percentage changes (EAPCs) of ASIRs and ASMRs to
quantify the trends in incidence of neonatal preterm birth. To
compare the incidence and mortality rates of neonatal pre-
term birth across different populations, the ASIRs and ASMRs
were carried out by applying the age-specific rates for each
location, sex, and year to a GBD world standard population to
adjust for potential confounding of age structure.
13
The per-
centage of relative changes in incident cases of neonatal
preterm birth from 1990 to 2019 was calculated by the equa-
tion: percentage of relative changes = (incident cases in
2019 − incident cases in 1990 / incidentc ases in 1990) × 100%.
The percentage of relative changes in deaths of neonatal
preterm birth were calculated using a similar equation. The
EAPC is a summary and widely used measure of the age-
standardized rate trend over a specified time interval. A
regression line was fitted to the natural logarithm of the
age-standardized rate, ie, y = α + βx + ε, where y = ln (age-
standardized rate) and x = calendar year. The EAPC was cal-
culated as 100 × (e
β
− 1) and its 95% CI was calculated to re-
flect the temporal trend in age-standardized rate. The trend
in age-standardized rate is reflected in EAPC value and its 95%
CI age-standardized rate is in an upward trend when the EAPC
and the lower boundary of the 95% CI are positive; con-
versely, age-standardized rate is in a downward trend when
EAPC and the upper boundary of the 95% CI are negative. We
calculated the EAPCs of ASIR and ASMR of neonatal preterm
birth to reflect their temporal trends.
Moreover,the correlations of EAPC of ASIR and ASMR w ith
SDI values (2019) and UHCI (2019) in 204 countries and terri-
tories were evaluated by Pearson correlation analyses to de-
fine the potential factors affecting EAPC. The polynomial
curves were also modeled. All analyses were conducted with
SAS version 9.4 (SAS Institute) and Origin 2019b (OriginLab).
A 2-tailed Pvalue less than .05 was considered statistically
significant.
Results
Global Trend in Incidence and Mortality
of Neonatal Preterm Birth
Globally,the number of incident c ases of neonatalpreterm birth
decreased by 5.26% from 16.06 million in 1990 to 15.22 mil-
lion in 2019, and the number of deaths of neonatal preterm
birth decreased by 47.71% from 1.27 million in 1990 to 0.66 mil-
lion in 2019 (Table 1). The overall ASIR of neonatal pretermbirth
decreased in the same period (EAPC = −0.19 [95% CI, −0.27 to
−0.11]) from 244.19 per 100 000 in 1990 to 234.96 per 100 000
in 2019 (Table 2). The ASMR of neonatal preterm birth de-
creased by a mean of 2.09% (95% CI, 1.99%-2.20%) per year
in the same period (from 19.34 per 100 000 in 1990 to 10.24
per 100 000 in 2019) (Table 2).
Regional Trend in Incidence and Mortality
of Neonatal Preterm Birth
In high-SDI regions, the incident cases of neonatal preterm birth
decreased by 5.00% from 1990 to 2019 (Table 1), whereas the
ASIR of neonatal preterm birth increased in the same period
(EAPC = 0.25 [95% CI, 0.13-0.38]) from 171.30 per 100000 in
1990 to 183.62 per 100 000 in 2019 (Table 2; eFigure 1A in the
Supplement). The ASIR of neonatal preterm birth decreased
in low-, low-middle–, middle-, and middle-high–SDI regions
(Table 2; eFigure 1A in the Supplement). The number of deaths
of neonatal preterm birth decreased by more than 50% in low-
middle–, middle-, middle-high–, and high-SDI regions but in-
creased by 4.62% in low-SDI regions from 1990 to 2019
(Table 1). In low-SDIregions, the growing number of deaths of
neonatal preterm birth was derived from the increased num-
ber of deaths in nearly neonates aged 0 to 6 days (eFigure 2 in
the Supplement). The decreasing number of deaths of neona-
tal preterm birth in low-middle–, middle-, middle-high–, and
high-SDI regions was due to the gradual decrease in the num-
ber of deaths in all neonates, especially in nearly neonates aged
0 to 6 days (eFigure 2 in the Supplement). Across 5 SDI re-
gions, the deaths and ASMR of neonatal preterm birth de-
creased in all regions, with the largest decrease in both deaths
(79.31%) and ASMR (EAPC = −4.60 [95% CI, −4.75 to −4.45])
in middle-high–SDI regions (Table 1, Table 2; eFigure 1B in the
Supplement).
Across the 21 GBD regions, the incident cases of neonatal
preterm birth decreased in 66.7% of the regions (14 GBD
regions) and the deaths of neonatal preterm birth decreased
in 81.0% of the regions (17 regions) from 1990 to 2019, with
the largest decrease both in incident cases (−48.10%) and
deaths (−85.94%) in East Asia (Table 1). The nearly neonates
aged 0 to 6 days accounted for more than 85% of deaths of
neonatal preterm birth globally and approximately 90% in
Central Sub-Saharan Africa (93.57%) and Western Sub-
Saharan Africa (90.37%) in 2019 (eFigure 3 in the Supple-
ment). In addition, the proportions of deaths of neonatal pre-
term birth in 2019 were higher than 20% for late neonates
aged 7 to 28 days in Central Europe (23.74%) and postneo-
nates aged 29 to 364 days in high-income Asia Pacific
(21.88%) (eFigure 3 in the Supplement). Oceania experienced
the largest increase both in incident cases (80.72%) and
deaths (60.39%) from 1990 to 2019 (Table 1). The Caribbean
experienced the most severe threat of incidence of neonatal
preterm birth, with approximately 3 neonatal preterm births
of 1000 populations (ASIR: 314.89 per 100 000) in 2019, fol-
lowed by South Asia (ASIR in 2019: 292.10 per 100 000). For
the mortality of neonatal preterm birth, Western Sub-Saharan
Africa experienced the most severe threat (ASMR: 18.14 per
100 000) in 2019, followed by South Asia (ASMR in 2019:
14.56 per 100 000). The trends in ASIRs of neonatal preterm
birth were heterogeneous across the 21 GBD regions from
1990 to 2019, with the highest increasing trend in high-
income Asia Pacific (EAPC = 0.46 [95% CI, 0.36-0.56]), Cen-
tral Latin America (EAPC = 0.30 [95% CI, 0.26-0.34]), and
Australasia (EAPC = 0.28 [95% CI, 0.17-0.39]) and was stable
in Western Europe and Tropical Latin America (Table 2).
Nearly half of the GBD regions had a decreasing trend in ASIRs
of neonatal preterm birth, such as Andean Latin America, East
Asia, and South Asia (Table 2). The ASMR of neonatal preterm
birth decreased in all GBD regions except Southern Sub-
Saharan Africa (EAPC = 0.62 [95% CI, 0.20-1.03]) from 1990
to 2019 (Table 2).
Global, Regional, and National Incidence and Mortality of Neonatal Preterm Birth, 1990-2019 Original Investigation Research
jamapediatrics.com (Reprinted) JAMA Pediatrics Published online May 31, 2022 E3
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National Trend in Incidence and Mortality
of Neonatal Preterm Birth
For 204 countries and territories, the absolute number of
incident cases of neonatal preterm birth in India (3.10 mil-
lion) and Pakistan (1.04 million) accounted for approxi-
mately one-third of the global incident cases (15.22 million)
in 2019 (eTable 2 in the Supplement). The country with the
most pronounced increase in incident cases of neonatal pre-
term birth was Niger (182.10%), followed by Qatar (176.95%)
(eTable 2 in the Supplement;Figure 1A). The ASIR varies
considerably across the world, with the largest ASIR in
Yemen (545.07 per 100000), followed by Niger (429.64 per
100 000) and Afghanistan (419.12 per 100 000) in 2019
(eTable 2 in the Supplement; Figure 1B). The ASIRs were
deemed to be in a decreasing trend in 101 countries or territo-
ries, with the largest decrease in Mozambique (EAPC = −1.82
[95% CI, −2.05 to −1.58]) (eTable 2 in the Supplement;
Figure 1C). The ASIRs were deemed to be in an increasing
trend in 78 countries or territories, with the largest increase
in Greece (EAPC = 3.91 [95% CI, 3.65-4.18]), followed by
Table 1. Incident Cases and Deaths of Neonatal Preterm Birth in 1990 and 2019 and TheirChange Trends From 1990 to 2019
Characteristic
1990 2019
Relative change,
1990-2019
Incident cases, No.
×10
5
(95% UI)
Deaths, No. × 10
3
(95% UI)
Incident cases, No.
×10
5
(95% UI)
Deaths, No. × 10
3
(95% UI)
Incident
cases, % Deaths, %
Overall 160.62
(159.46-161.90)
1269.04
(1166.14-1383.98)
152.17
(151.11-153.20)
663.52 (560.96-788.95) −5.26 −47.71
Sex
Female 73.42 (72.63-74.30) 560.11 (511.83-613.97) 69.75 (68.97-70.43) 279.57 (237.91-327.32) −5.00 −50.09
Male 87.19 (86.34-88.05) 708.93 (644.55-781.04) 82.42 (81.70-83.18) 383.95 (321.74-463.85) −5.47 −45.84
SDI region
Low NA 250.36 (221.71-283.47) NA 261.93 (214.37-321.60) NA 4.62
Low-middle NA 474.63 (426.84-532.36) NA 237.06 (196.74-280.55) NA −50.05
Middle NA 376.48 (348.51-406.02) NA 124.81 (105.33-147.61) NA −66.85
Middle-high NA 135.26 (122.63-148.39) NA 27.98 (23.74-32.93) NA −79.31
High 9.72 (9.63-9.81) 31.69 (29.80-33.81) 9.11 (9.01-9.21) 11.31 (10.07-12.66) −5.00 −64.31
GBD region
Andean Latin America 1.10 (1.05-1.15) 10.93 (9.51-12.51) 1.08 (1.04-1.13) 4.08 (2.93-5.48) −1.78 −62.67
Australasia 0.22 (0.21-0.23) 0.65 (0.60-0.71) 0.27 (0.26-0.29) 0.25 (0.20-0.31) 25.30 −61.37
Caribbean 1.30 (1.26-1.34) 6.07 (5.28-6.96) 1.23 (1.18-1.27) 3.84 (2.78-5.23) −5.15 −36.68
Central Asia 1.40 (1.36-1.45) 9.34 (8.15-10.65) 1.26 (1.22-1.30) 5.66 (4.63-6.90) −10.16 −39.43
Central Europe 1.21 (1.18-1.23) 7.81 (7.36-8.29) 0.81 (0.79-0.82) 1.21 (0.92-1.52) −33.16 −84.55
Central Latin America 4.23 (4.15-4.31) 39.64 (34.90-44.39) 4.07 (3.99-4.15) 11.58 (8.85-14.60) −3.71 −70.78
Central Sub-Saharan
Africa
2.91 (2.79-3.03) 25.74 (19.70-32.96) 4.50 (4.30-4.70) 27.70 (20.75-36.42) 54.46 7.60
East Asia 19.06 (18.76-19.37) 165.47 (145.14-187.30) 9.89 (9.74-10.05) 23.27 (19.88-27.07) −48.10 −85.94
Eastern Europe 2.13 (2.10-2.16) 8.55 (7.81-9.47) 1.77 (1.75-1.80) 1.52 (1.21-1.88) −16.68 −82.22
Eastern Sub-Saharan
Africa
12.35 (12.16-12.54) 74.62 (64.54-85.04) 17.09 (16.83-17.37) 67.22 (51.93-87.25) 38.39 −9.92
High-income Asia Pacific 1.13 (1.10-1.17) 2.81 (2.50-3.26) 0.88 (0.86-0.90) 0.49 (0.42-0.56) −22.58 −82.52
High-income North
America
4.74 (4.70-4.78) 13.01 (12.37-13.74) 4.72 (4.65-4.78) 6.84 (6.21-7.58) −0.47 −47.40
North Africa and Middle
East
15.07 (14.77-15.41) 178.79 (152.22-212.21) 16.57 (16.24-16.92) 59.66 (47.21-74.22) 9.91 −66.63
Oceania 0.22 (0.21-0.23) 1.47 (1.08-1.90) 0.40 (0.37-0.42) 2.36 (1.57-3.44) 80.72 60.39
South Asia 58.10 (57.12-59.18) 438.60 (381.57-506.46) 46.85 (45.96-47.71) 233.42 (193.68-282.73) −19.37 −46.78
Southeast Asia 12.77 (12.56-12.98) 119.38 (106.73-134.46) 9.63 (9.50-9.78) 44.54 (35.85-54.34) −24.56 −62.69
Southern Latin America 0.57 (0.51-0.63) 7.36 (6.81-7.89) 0.55 (0.53-0.58) 2.31 (1.75-2.96) −2.63 −68.64
Southern Sub-Saharan
Africa
2.13 (2.09-2.17) 10.19 (8.54-11.99) 2.22 (2.17-2.26) 11.11 (8.63-14.66) 4.06 9.00
Tropical Latin America 4.14 (4.06-4.22) 47.02 (40.98-54.29) 3.71 (3.65-3.77) 11.31 (8.98-13.98) −10.38 −75.95
Western Europe 3.45 (3.38-3.52) 9.91 (9.44-10.60) 3.19 (3.12-3.27) 3.21 (2.69-3.80) −7.44 −67.65
Western Sub-Saharan
Africa
12.40 (12.27-12.54) 91.68 (78.21-105.92) 21.50 (21.23-21.78) 141.95 (114.66-175.77) 73.32 54.83
Abbreviations: GBD, Global Burden of Disease; NA, not applicable; SDI, sociodemographic index; UI, uncertainty interval.
Research Original Investigation Global, Regional, and National Incidence and Mortality of Neonatal Preterm Birth, 1990-2019
E4 JAMAPediatrics Published online May 31, 2022 (Reprinted) jamapediatrics.com
Downloaded From: https://jamanetwork.com/ on 06/02/2022
Table 2. ASIRs and ASMRs of Neonatal Preterm Birth in 1990 and 2019 and TheirChange Trends From 1990 to 2019
Characteristic
No. (95% UI) No. (95% CI)
1990 2019 1990-2019
ASIR per 100 000 ASMR per 100 000 ASIR per 100 000 ASMR per 100 000 EAPC of ASIR EAPC of ASMR
Overall 244.19
(242.43 to 246.14)
19.34
(17.77 to 21.09)
234.96
(233.32 to 236.54)
10.24
(8.66 to 12.18)
−0.19
(−0.27 to −0.11)
−2.09
(−2.20 to −1.99)
Sex
Female 230.89
(228.39 to 233.63)
17.65
(16.13 to 19.34)
223.07
(220.56 to 225.23)
8.94
(7.60 to 10.46)
−0.17
(−0.25 to −0.09)
−2.27
(−2.37 to −2.17)
Male 256.64
(254.13 to 259.16)
20.92
(19.02 to 23.05)
246.06
(243.90 to 248.33)
11.46
(9.60 to 13.84)
−0.20
(−0.29 to −0.12)
−1.96
(−2.06 to −1.86)
SDI region
Low 323.61
(319.41 to 328.41)
22.25
(19.71 to 25.19)
294.30
(290.56 to 297.85)
14.53
(11.89 to 17.83)
−0.32
(−0.39 to −0.25)
−1.32
(−1.38 to −1.26)
Low-middle 302.97
(298.14 to 308.52)
26.25
(23.62 to 29.45)
255.10
(250.61 to 259.26)
13.96
(11.58 to 16.52)
−0.63
(−0.72 to −0.55)
−1.94
(−2.06 to −1.82)
Middle 202.36
(200.41 to 204.43)
18.23
(16.88 to 19.66)
194.49
(192.43 to 196.65)
7.26
(6.13 to 8.58)
−0.17
(−0.20 to −0.14)
−3.02
(−3.21 to −2.83)
Middle-high 174.85
(172.29 to 177.46)
13.58
(12.32 to 14.91)
173.43
(171.06 to 175.93)
3.69
(3.13 to 4.34)
−0.09
(−0.12 to −0.06)
−4.60
(−4.75 to −4.45)
High 171.30
(169.70 to 173.01)
5.57
(5.24 to 5.94)
183.62
(181.60 to 185.68)
2.27
(2.02 to 2.54)
0.25
(0.13 to 0.38)
−2.91
(−3.00 to −2.82)
GBD region
Andean
Latin America
190.40
(181.83 to 199.54)
18.96
(16.49 to 21.71)
171.80
(164.88 to 179.11)
6.47
(4.65 to 8.69)
−0.49
(−0.54 to −0.44)
−3.56
(−3.77 to −3.35)
Australasia 142.27
(135.63 to 149.31)
4.28
(3.96 to 4.68)
153.62
(144.93 to 162.26)
1.42
(1.13 to 1.73)
0.28
(0.17 to 0.39)
−3.05
(−3.44 to −2.66)
Caribbean 298.98
(290.28 to 307.94)
14.00
(12.19 to 16.05)
314.89
(303.19 to 326.29)
9.84
(7.11 to 13.39)
0.12
(0.08 to 0.17)
−1.08
(−1.18 to −0.98)
Central Asia 149.96
(144.96 to 154.52)
9.98
(8.71 to 11.38)
139.38
(134.69 to 144.10)
6.24
(5.11 to 7.61)
−0.33
(−0.37 to −0.30)
−1.35
(−1.73 to −0.96)
Central Europe 150.55
(147.39 to 153.64)
9.67
(9.13 to 10.28)
156.82
(154.09 to 159.69)
2.33
(1.77 to 2.94)
0.12
(0.09 to 0.14)
−4.80
(−5.05 to −4.54)
Central
Latin America
177.97
(174.66 to 181.34)
16.70
(14.71 to 18.70)
192.96
(188.98 to 196.81)
5.48
(4.19 to 6.90)
0.30
(0.26 to 0.34)
−3.82
(−3.99 to −3.64)
Central
Sub-Saharan Africa
228.14
(218.60 to 237.69)
20.24
(15.48 to 25.90)
211.19
(201.75 to 220.77)
13.01
(9.75 to 17.12)
−0.23
(−0.28 to −0.17)
−1.25
(−1.42 to −1.08)
East Asia 158.41
(155.99 to 161.05)
13.74
(12.05 to 15.55)
133.45
(131.36 to 135.55)
3.12
(2.66 to 3.63)
−0.76
(−0.89 to −0.63)
−5.32
(−5.60 to −5.05)
Eastern Europe 151.65
(149.30 to 153.94)
6.06
(5.54 to 6.71)
163.86
(161.57 to 165.90)
1.40
(1.11 to 1.72)
0.36
(0.33 to 0.38)
−5.35
(−5.70 to −5.00)
Eastern
Sub-Saharan Africa
290.05
(285.64 to 294.45)
17.63
(15.25 to 20.11)
253.36
(249.44 to 257.46)
9.98
(7.71 to 12.95)
−0.48
(−0.60 to −0.35)
−1.86
(−1.96 to −1.76)
High-income
Asia Pacific
119.85
(116.45 to 123.67)
2.96
(2.62 to 3.43)
132.50
(129.47 to 135.80)
0.73
(0.64 to 0.83)
0.46
(0.36 to 0.56)
−4.27
(−4.53 to −4.02)
High-income
North America
215.56
(213.75 to 217.53)
5.90
(5.61 to 6.24)
233.97
(230.81 to 237.18)
3.38
(3.07 to 3.75)
0.26
(0.07 to 0.46)
−1.62
(−1.74 to −1.50)
North Africa
and Middle East
268.82
(263.45 to 274.73)
31.99
(27.24 to 37.99)
284.77
(279.15 to 290.74)
10.24
(8.10 to 12.73)
0.17
(0.15 to 0.20)
−3.72
(−3.83 to −3.61)
Oceania 205.92
(194.46 to 217.48)
13.87
(10.20 to 17.87)
201.21
(188.27 to 213.86)
12.01
(8.01 to 17.48)
−0.09
(−0.14 to −0.04)
−0.35
(−0.44 to −0.26)
South Asia 338.16
(332.46 to 344.46)
25.62
(22.31 to 29.57)
292.10
(286.55 to 297.51)
14.56
(12.08 to 17.64)
−0.52
(−0.60 to −0.45)
−1.64
(−1.77 to −1.50)
Southeast Asia 211.47
(208.08 to 214.93)
19.80
(17.70 to 22.30)
184.13
(181.59 to 186.93)
8.51
(6.85 to 10.38)
−0.48
(−0.49 to −0.46)
−2.84
(−2.93 to −2.74)
Southern
Latin America
113.24
(102.07 to 125.58)
14.67
(13.56 to 15.71)
119.31
(113.65 to 124.75)
4.97
(3.77 to 6.37)
0.25
(0.22 to 0.28)
−3.50
(−3.63 to −3.37)
Southern
Sub-Saharan Africa
289.10
(283.41 to 295.04)
13.85
(11.61 to 16.29)
278.40
(272.49 to 284.35)
13.95
(10.84 to 18.42)
−0.16
(−0.24 to −0.08)
0.62
(0.20 to 1.03)
Tropical
Latin America
241.73
(237.41 to 246.47)
27.50
(23.97 to 31.76)
239.95
(236.52 to 243.71)
7.30
(5.79 to 9.02)
0.02
(−0.01 to 0.04)
−4.48
(−4.59 to −4.37)
Western Europe 154.83
(151.70 to 158.09)
4.43
(4.22 to 4.74)
154.27
(150.64 to 157.90)
1.54
(1.29 to 1.83)
−0.01
(−0.04 to 0.01)
−3.45
(−3.60 to −3.31)
Western
Sub-Saharan Africa
290.02
(286.89 to 293.26)
21.51
(18.35 to 24.85)
274.32
(270.86 to 277.93)
18.14
(14.65 to 22.46)
−0.19
(−0.22 to −0.16)
−0.48
(−0.55 to −0.41)
Abbreviations: ASIR, age-standardized incidence rate; ASMR, age-standardized mortality rate; EAPC, estimated annual percentage change;
GBD, Global Burden of Disease; SDI, sociodemographic index; UI, uncertainty interval.
Global, Regional, and National Incidence and Mortality of Neonatal Preterm Birth, 1990-2019 Original Investigation Research
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Bahrain (EAPC = 1.84 [95% CI, 1.69-1.99]) (eTable 2 in the
Supplement; Figure 1C). The ASIRs remained stable in 25
countries or territories, such as Afghanistan, Cameroon, and
Italy (eTable 2 in the Supplement).
The most pronounced increase in deaths of neonatal
preterm birth was observed in Niger (105.52%), followed by
Papua New Guinea (90.45%), while the most pronounced de-
crease was detected in Cook Islands (97.15%) (eTable 3 in the
Supplement;Figure 2A). The ASMR of neonatal preterm birth
varied significantly across 204 countries and territories, with
the largest ASMR in Sudan (ASMR: 25.54 per 100 000), Central
African Republic (ASMR: 23.51 per 100 000), and Mali (ASMR:
23.10 per 100 000) in 2019 (eTable 3 in the Supplement;
Figure 2B). The ASMRs were deemed to be in a decreasing trend
Figure 1. Global Trends in the Incidence of Neonatal Preterm Birth in 204 Countries and Territories
Albania:
67.71%
Greece:
EAPC
=
3.19
Niger:
182.10%
Niger:
ASIR
=
429.64
Qatar:
176.95%
Yemen:
ASIR
=
545.07
Afghanistan:
ASIR
=
419.12
Bahrain:
EAPC
=
1.84
Mozambique:
EAPC
=
–1.82
25-70 Decrease
<25 Decrease
<25 Increase
25-50 Increase
≥50 Increase
<150
150-199
200-249
250-299
≥300
<–0.4
–0.4 to –0.2
–0.2 to 0
0 to 0.2
≥0.2
ASIR in 2019 (per 100
000 population)
B
EAPC of ASIR
C
Change in incident cases, %
A
The percentage of relative change in
incident cases of neonatal preterm
birth between 1990 and 2019 (A),
age-standardized incidence rates
(ASIRs) of neonatal preterm birth in
2019 (B), and estimated annual
percentage changes (EAPCs) of ASIRs
of neonatal preterm birth from 1990
to 2019 (C) are reported.
Research Original Investigation Global, Regional, and National Incidence and Mortality of Neonatal Preterm Birth, 1990-2019
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in 186 countries or territories, with the largest decrease in Cook
Islands (EAPC = −10.23 [95% CI, −11.01 to −9.45]) (eTable 3 in
the Supplement; Figure 2C). The ASMRs were deemed to be in-
creasing in 7 countries or territories, with the largest increase
in Guam (EAPC = 1.93 [95% CI, 1.45-2.41]), followed by South
Africa (EAPC = 0.90 [95% CI, 0.30-1.50]). The ASIRs remained
stable in 11 countries or territories, such as Azerbaijan, Cote
d’Ivoire, and Burkina Faso (eTable 3 in the Supplement).
Correlations of EAPC of ASIR and ASMR With SDI and UHCI
A significant positive correlation was detected between EAPC
of ASIR of neonatal preterm birth and SDI in 2019 (ρ = 0.41;
Figure 2. Global Trends in the Mortality of Neonatal Preterm Birth in 204 Countries and Territories
Niger:
105.52%
Papua New Guinea:
90.45%
Cook Islands:
97.15%
South Africa:
EAPC
=
0.90
Guam:
EAPC
=
1.93
<2.5
2.5-4.9
5.0-7.4
7.5-9.9
≥10
80-100 Decrease 60-80 Decrease 40-60 Decrease <40 Decrease ≥0 Increase
<–4.5 –4.5 to –3.0 –3.0 to –1.5 –1.5 to 0 ≥0
Mali:
ASMR
=
23.10
Central African Republic:
ASMR
=
23.51
Sudan:
ASMR
=
25.24
ASMR in 2019 (per 100
000 population)
B
EAPC of ASMR
C
Change in deaths, %
A
Cook Islands:
EAPC = –10.23 The percentage of relative change in
deaths of neonatal preterm birth
between 1990 and 2019 (A),
age-standardized mortality rates
(ASMRs) of neonatal preterm birth in
2019 (B), and estimated annual
percentage change (EAPCs) of
ASMRs of neonatal preterm birth
from 1990 to 2019 (C) are reported.
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P< .001) and UHCI in 2019 (ρ = 0.38; P< .001) (Figure 3A and
B). Surprisingly, a significant negative correlation was de-
tected between EAPC of ASMR of neonatal preterm birth and
SDI in 2019 (ρ = −0.42; P< .001) and UHCI in 2019 (ρ = −0.47;
P< .001) (Figure 3C and D).
Discussion
To our knowledge, this is the first comprehensive assessment
of the global landscape, long-term trends, and regional differ-
ences in the incidence and mortality of neonatal preterm
birth, as well as the association with socioeconomic status at
the national level, using data from the 2019 GBD study. In this
study, we found that the global ASIR and ASMR of neonatal
preterm birth decreased by a mean of 0.19% and 1.52% per
year from 1990 to 2019, respectively. Meanwhile, the global
absolute number of incident cases and deaths of neonatal pre-
term birth also decreased by 5.26% and 47.71% worldwide in
this period, respectively. For SDI regions, the ASIRs of neona-
tal preterm birth increased in high-SDI regions by a mean of
0.25% per year from 1990 to 2019. The ASMR of neonatal pre-
term birth increased by a mean of 2.09% per year in Southern
Sub-Saharan Africa in this period. Oceania experienced the
largest increase both in the number of incident cases (82.72%)
and deaths (60.39%) of neonatal preterm birth. Notably, we
found a positive association of EAPC of ASIR with SDI or UHCI
in 2019 and a negative association of EAPC of ASMR with SDI
or UHCI in 2019 at the national level.
Preterm birth is an important perinatal health problem,
contributing to increased mortality risk of children younger
than 5 years directly and maternal mortality indirectly.
9,14,15
Thus, reducing the incidence and mortality of preterm birth
is significant. A better understanding of the incidence and mor-
tality of preterm birth at the regional and national levels is
needed to improve access to effective obstetric and neonatal
care. In line with the decreasing trend in the global preterm
birth rate,
3
this current study found a decreasing trend in the
ASIR and ASMR of neonatal preterm birth worldwide. This is
largely attributed to improvements in maternal and newborn
health care.
16,17
Infant mortality from preterm birth can be re-
duced through interventions delivered to the birthing parent
before or during pregnancy and to the preterm infant after
birth.
4
The progress in the frequency of the presence of a skilled
birth attendant at birth in many countriespresents a major op-
portunity to reduce intrapartum stillbirth and neonatal
mortality.
16
In addition, high-quality health care for female in-
dividuals is also essential in the prevention of neonatal pre-
term birth.
2
Finally, improvements in nutritional status and
medical interventions for reducing preterm birth are also ben-
eficial for reducing the incidence and mortality of preterm
birth.
16
This study found that the ASIRs and ASMRs of neonatal
preterm birth varied significantly across regions and nations.
We found an increasing trend in the ASIR and a decreasing
trend in the ASMR in high-SDI regions between 1990 and 2019,
which was especially common in high-income countries, such
as Greece, Bahrain, Japan, the UK, and the US. However, this
study observed opposite trends in the ASIR and ASMR in some
low-income countries: the ASMR of neonatal preterm birth in-
creased but the ASIR of neonatal preterm birth decreased in
Southern Sub-Saharan Africa. Similar to our findings, several
previous studies reported that the incidence of preterm birth
increased in high-income countries in the past 2 decades.
3,8,18,19
Several possible factors contributing to but not completely ex-
plaining this increasing trend in the ASIR of neonatal preterm
Figure 3. Estimated Annual Percentage Changes (EAPCs) of Age-StandardizedIncidence Rates (ASIRs)
and Age-Standardized Mortality Rates (ASMRs) in Neonatal Preterm Birth at the Country and Territorial Levels
ρ= 0.41; P<.001
ρ= –0.42; P<.001 ρ= –0.47; P<.001
ρ= 0.38; P<.001
EAPC of ASIR
4
3
2
1
0
–1
–2
–3
SDI in 2019
Incidence of neonatal preterm birth
A
0 0.2 0.4 0.6 0.8 1.0
EAPC of ASIR
4
3
2
1
0
–1
–2
–3
UHCI in 2019
0 20 40 60 80 100
EAPC of ASMR
4
2
0
–2
–4
–6
–8
–10
SDI in 2019
Mortality of neonatal preterm birth
B
0 0.2 0.4 0.6 0.8 1.0
EAPC of ASMR
4
2
0
–2
–4
–6
–8
–10
UHCI in 2019
0 20 40 60 80 100
1000 000
750000
500000
25000
Incident cases
in 2019
1000 000
750000
500000
25000
Incident cases
in 2019
60000
45000
30000
15000
Deaths in
2019
60000
45000
30000
15000
Deaths in
2019 The incident cases and deaths of
neonatal preterm birth from 204
countries and territories in 2019 are
represented by circles. The size of the
circles increased with the incident
cases or deaths of neonatal preterm
birth. The ρ indices and Pvalues were
derived from Pearson correlation
analysis. SDI indicates
sociodemographic index;
UHCI, universal health coverage
index.
Research Original Investigation Global, Regional, and National Incidence and Mortality of Neonatal Preterm Birth, 1990-2019
E8 JAMA Pediatrics Published online May 31, 2022 (Reprinted) jamapediatrics.com
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birth include increasing rates of multiple births, increases in the
proportion of births among individuals older than 34 years,
greater use of assisted reproduction techniques, and changes
in clinical practices, such as greater use of elective cesarean
delivery.
9,20,21
For example, the increasing age of individuals
giving birth in North America causes more maternal compli-
cations and cesarean deliveries and ultimately leads to an in-
creased risk of preterm birth.
9
In addition, the increasing use
of ultrasonography rather than the date of the last menstrual
period to estimate gestational age may have resulted in larger
numbers of births being classified as preterm.
9
In high-income
countries, the reduction in mortality rates in infants who were
born preterm has been driven largely byimproved maternal and
newborn health care.
4
One previous study reported that pre-
term survival rates have increased in high-income countries,
while preterm newborns still die because of a lack of adequate
newborn care in many low-income and middle-income
countries.
2
Almost all births are attended by skilled staff and 50%
of the neonates of less than 24 weeks’ gestation survive in high-
income countries, whereas even the neonates older than 32
weeks’ gestation have only a 50% chance of survival owing to
lack of available resources and/orlow quality of specialized c are
in low-income countries.
22
In high-income countries, admin-
istration of antenatal steroids is standard care for birthing par-
ents with anticipated preterm labor,which has been verified to
be very effective in preventingneonatal mortality; however, the
coverage of antenatal steroid therapy remains low in low- and
middle-income countries.
23
In addition, intrauterine infection
or lack of availability of drugs, such as tocolytic agents, might
contribute to an increased risk of preterm birth and deaths of
neonatal preterm birth in low-income countries.
9
Thus, the de-
velopment of interventions to reduce neonatalpreterm birth is
urgently needed for all countries, especially low-incomecoun-
tries where the incidence of neonatal preterm birth is high and
the trend in mortality of neonatal preterm birth is increasing.
These findings highlight the urgent need for discovery re-
search into the underlying mechanisms of neonatal preterm
birth and the development of innovative interventions.
Limitations
This current study comprehensively assessed the global land-
scape, long-term trends, and regional differences in the inci-
dence and mortality of neonatal preterm birth as well as the
association with socioeconomic status using data from GBD
estimates, which fill a gap where actual data on disease bur-
den are sparse or unavailable. However, several limitations
should be noted. First, the availability of data and the quality
of available data limited the accuracy and robustness of the
estimates of the incidence of mortality of neonatal preterm
birth in the modeling, which might lead to bias when na-
tional surveillance and population-based studies were lack-
ing. Second, data of gestational ages were not available in the
GBD study; thus, we cannot further analyze the trends in in-
cidence and mortality of neonatal preterm birth according to
different gestational ages. Third, EAPC in ASIRs and ASMRs as
well as the relative changein the number of inc ident cases and
deaths were used to assess its long-term trends from 1990 to
2019, which might mask the recent short-term trends that re-
flected the effectiveness of the recent prevention interven-
tions of preterm birth. Finally, the contribution of the causes
of preterm birth is unknown globally.
Conclusions
In summary,the global ASIR and ASMR of preterm birth gradu-
ally decreased from 1990 to 2019, while the ASIR increased in
high SDI region and the ASMR increased in Southern Sub-
Saharan Africa in this period. Preterm birth remains a crucial
issue in children, both in high- and low-resource countries.
Thus, efforts to reduce both the incidence and mortality of pre-
term births are essential worldwide.
ARTICLE INFORMATION
Accepted for Publication: March 9, 2022.
Published Online: May 31, 2022.
doi:10.1001/jamapediatrics.2022.1622
Open Access: This is an open access article
distributed under the terms of the CC-BY License.
©2022CaoGetal.JAMA Pediatrics.
Author Contributions: Dr M. Liu had full access to
all of the data in the study and takes responsibility
for the integrity of the data and the accuracy of the
data analysis.
Concept and design: All authors.
Acquisition, analysis, or interpretation of data: Cao.
Drafting of the manuscript: Cao.
Critical revision of the manuscript for important
intellectual content: All authors.
Statistical analysis: Cao, M. Liu.
Obtained funding: All authors.
Administrative, technical, or material support:
All authors.
Supervision: All authors.
Conflict of Interest Disclosures: None reported.
Funding/Support: This work was funded by
National Key R&D Program of China (grant
2021ZD0114104).
Role of the Funder/Sponsor:The funder had no
role in the design and conduct of the study;
collection, management, analysis, and
interpretation of the data; preparation, review, or
approval of the manuscript; and decision to submit
the manuscript for publication.
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