Gao et al. BMC Pediatrics(2024) 24:537
https://doi.org/10.1186/s12887-024-05016-2

BMC Pediatrics

RESEARCH

Open AccessA real-world study on the treatmentof extremely preterm infants: a multi-center
study in southwest area of Fujian Province
in China
Liang Gao1,2,3†, Dong-mei Chen4†, Hui-ping Yan4, Li-ping Xu5†, Shu-zhen Dai5, Rong-hua Zhong6†, Qi-bing Chen6,
Si-min Ma1,2,3 and Xin-zhu Lin1,2,3*
Abstract
Background Due to regional and cultural differences, the current status of extremely preterm infants(EPIs) treatment
across different areas of mainland China remains unclear. This study investigated the survival rate and incidence ofmajor diseases among EPIs in the southwest area of Fujian province.
Method This retrospective and multicenter study collected perinatal data from EPIs with gestational ages between
22–27+ 6w and born in the southwest area of Fujian province. The study population was divided into 6 groups basedon gestational age at delivery. The primary outcome was the survival status at ordered hospital discharge or correct
gestational age of 40 weeks, and the secondary outcome was the incidence of major diseases. The study analyzed theactual survival status of EPIs in the area.
Result A total of 2004 preterm infants with gestational ages of 22–27+ 6 weeks were enrolled in this study. Amongthem, 1535 cases (76.6%) were born in the delivery room but did not survive, 469 cases (23.4%) were transferred to
the neonatal department for treatment, 101 cases (5.0%) received partial treatment, and 368 cases (18.4%) received
complete treatment. The overall all-cause mortality rate was 84.4% (1691/2004). The survival rate and survival rate
without major serious disease for EPIs who received complete treatment were 85.1% (313/368) and 31.5% (116/318),
respectively. The survival rates for gestational ages 22–22+ 6w, 23–23+ 6w, 24–24+ 6w, 25–25+ 6w, 26–26+ 6w, and
27–27+ 6w were 0%, 0%, 59.1% (13/22), 83% (39/47), 88.8% (87/98), and 89.7% (174/198), respectively. The survival rates
without major serious disease were 0%, 0%, 9.1% (2/22), 19.1% (9/47), 27.6% (27/98), and 40.2% (78/194), respectively.
Conclusion The all-cause mortality of EPIs in the southwest area of Fujian Province remains high, with a significant
number of infants were given up after birth in the delivery room being the main influencing factor. The survival rate†

Liang Gao, Dong-mei Chen, Li-ping Xu and Rong-hua Zhong
contributed equally to this work.
*Correspondence:
Xin-zhu Lin
xinzhufj@163.com
Full list of author information is available at the end of the article© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0
International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you
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Gao et al. BMC Pediatrics(2024) 24:537

Page 2 of 10

of EPIs who received complete treatment at 25–27 weeks in the NICU was similar to that in developed countries.
However, the survival rate without major serious disease was significantly lower compared to high-income countries.
Keywords Extremely preterm infants, Mortality, Survival rate, Survival rate without major serious disease

Introduction
The World Health Organization (WHO) Global Reporton preterm infants first introduced the concept of
extremely preterm infants (EPIs) in 2012, referring topreterm infants with a gestational age < 28 weeks [1]. Thisaccounts for 0.57% of the total number of deliveries andabout 5% of all preterm infants. Due to the extremely
underdeveloped state of their organs, EPIs face a highrisk of death and disease after birth, requiring intensive
and costly care for survival. Disparities in healthcare
resources result in significant regional differences in EPIs
survival rates, with a 90% chance of survival in developed countries compared to only 10% in low-income
countries [2]. The Chinese Neonatal Network retrospectively analyzed data from 2010 to 2019 [3], showingthat the survival rate of infants born at gestational ages
24 to 27 weeks and transferred to the NICU increased
from 56.4% in 2010 to 68.0% in 2019. The survival rates
for infants born at gestational ages 22, 23, 24, 25, 26, and27 weeks were 4.8%, 18.3%, 35.3%, 48.6%, 61.0%, and69.1%, respectively. Cao Yun et al. [4]. have analyzed
data from 9552 cases EPIs from 57 neonatal centers in
Chinese mainland and found that the survival rates andrates of survival without major diseases for EPIs at gestational ages < 24, 24, 25, 26, and 27 weeks were 21.7% vs.
0, 55.8% vs. 7.7%, 75.2% vs. 13%, 87.7% vs. 25.2%, 89.7%
vs. 39.8%, respectively. In high-income countries, EPIs
care is more advanced. A multicenter study in the UnitedStates revealed that out of 10,877 infants born at a gestational age of 22–28 weeks between 2013 and 2018 [5], thesurvival rate at discharge was 78.3%, and the survival rate
at the discharge of preterm infants born at a gestationalage of 22 weeks was 10.9%. The survival rates at dischargeof preterm infants with gestational age of 22 weeks and23 weeks who received active treatment were 30.0% and55.8%, respectively. A 2017 multicenter survey in developed countries like Japan, Sweden, and Australia foundoverall EPIs survival rates ranging from 73–92% [6].
French national studies on EPIs born at gestational ages
23 to 27 weeks from 2011 to 2015 showed severe diseasefree survival rates of 0%, 41.2%, 54.5%, 65.3%, and 71.9%,
respectively [7]. These studies indicate positive outcomesfor EPIs treatment in China, however, preterm birth isstill one of the key issues in maternal and child healthin China [8]. There were two issues persist when compared to developed countries: (1) While the survival rateof EPIs with gestational ages of 26–28 weeks is comparable to developed countries, the survival rate of infants
with gestational ages < 25 weeks, especially those withgestational ages of 22–23+ 6 weeks, remains significantly
lower. (2) The rate of survival without major disease islower than that in developed countries. Due to regionaland cultural differences, the current status of EPIs treatment across different areas of mainland China remains
unclear. Therefore, this real-world study aims to explore
the actual status of EPIs treatment in the four cities inthe southwest of Fujian Province, offering insights into
the development of treatment strategies for this special
population.

Materials and methods
Study population

From January 2018 to December 2022, preterm infants
with a gestational age of 22–27+ 6 weeks were born alivein hospitals located in the southwest region of Fujian
province in China, including Xiamen, Quanzhou, Zhangzhou, and Longyan. The four centers were all perinatal
and neonatal treatment centers in the region, equippedwith obstetric wards and neonatal intensive care units.
The neonatal wards were all classified as grade IIIB [9].
The annual deliveries in each center were around 5000–
13,000 cases. A meeting of researchers has been held in
advance to clarify the inclusion and exclusion criteria,
and conform the EpiData software 3.1 for data entry.
Inclusion criteria: (1) Preterm infants with a gestationalage of 22–27+ 6 weeks. (2) Live-born infants delivered inobstetrics department of the four medical centers participating in the study. (3) Preterm infants who weredelivered in other primary hospitals and subsequently
transferred to the four medical centers participating inthe study. Exclusion criteria: Termination of labor due to
medical indications (fatal malformation).
Research method

This study was retrospective and multicenter. Perinatal data of EPIs born in the southwest area of Fujian
province, were collected. The data collected included:(1) Maternal pregnancy data, including demographic, pregnancy, delivery information, and antenatal corticosteroids(ACS). (2) Neonatal characteristics:
gestational age, delivery mode, birth weight, Apgar
score. (3) Neonatal complications: neonatal respiratory distress syndrome (nRDS), necrotizing enterocolitis (NEC), hemodynamically significant patent ductus
arteriosus (hsPDA), early-onset sepsis (EOS), late-onset
sepsis(LOS), neonatal NEC ≥ Bell stage 2, intraventricular hemorrhage (IVH) grade III–IV, periventricularleukomalacia(PVL), retinopathy of prematurity(ROP)Gao et al. BMC Pediatrics(2024) 24:537

requiring intervention, metabolic bone disease of prematurity (MBDP), and parenteral nutrition-associated cholestasis (PNAC), etc., diagnosed based on criteria from
“Practical Neonatology (5th edition)“ [10].According to
the 2018 NICHD criteria for Bronchopulmonary dysplasia (BPD) [11], preterm infants with gestational age of< 32 weeks at a corrected gestational age of 36 weeks had
imaging evidence of substantial lung disease, and needed
different degrees of respiratory support and corresponding levels of FiO2 to maintain arterial oxygen saturation
between 0.90 and 0.95 for at least 3 consecutive days.
Then according to the different respiratory support modeof FiO2 into I, II, III level. (4) Neonatal treatments: This
encompassed feeding patterns, mechanical ventilation,
non-invasive positive pressure ventilation support, postnatal glucocorticoid application, laser or drug intervention for ROP, etc.
The study population was divided into 6 groups basedon gestational age at delivery. The primary outcome was
the survival status at ordered hospital discharge or correct gestational age of 40 weeks. The secondary outcome
was the incidence of major diseases. According to thetreatment received, deceased infants were divided into
three subgroups: (1)EPIs gave up in the delivery room:
These infants were born after induced labor with signs oflife but could not be transferred to the neonatal department for treatment. Unfortunately, they eventually died.
(2)EPIs received partial treatment was defined as those
who were transferred to the neonatal department but
were discharged against medical advice, and the hospital stay less 7 days, and eventually died. (3)Death after
receiving complete treatment covers infants who weredischarged from the hospital against medical advice but
the length of hospital stay was 7 days or more, or later
passed away due to disease-related factors after receiving
active treatment within the first 7 days.
Major serious diseases in this context encompass grade
3–4 IVH, PVL, II to III level BPD, grade 2 or above NEC,
LOS, and ROP requiring intervention. Severe brain injury
is defined as grade 3–4 IVH or PVL.
Statistic method

Statistical analysis was conducted using SPSS 24.0(IBM,IL, USA). Quantitative data with non-normal distribution
were presented as median and interquartile range (IQR),
and between-group comparisons were analyzed using the
Kruskal-Wallis rank-sum test. Count data were expressedas the number of cases and percentage (%). Betweengroup comparisons were performed using Pearson’s chisquare test, continuity correction of Pearson’s chi-square
test, and Fisher’s exact probability method. A significancelevel of P < 0.05 was applied for statistical significance.

Page 3 of 10

ResultGeneral condition

A total of 2004 cases EPIs with a gestational age of
22–27+ 6 weeks were enrolled in the study. Among them,
1121 (55.9%) were male, and 98 (4.9%) were delivered bycesarean section. The number of cases in the gestationalage groups 22–22+ 6w, 23–23+ 6w, 24–24+ 6w, 25–25+ 6w,
26–26+ 6w, and 27–27+ 6w were 189, 223, 407, 428, 357,
and 400 cases, respectively. 1535 cases EPIs were abandoned in the delivery room (76.6%), 469 cases (23.4%)
were transferred to the neonatal department for treatment, 101 cases (5.0%) received partial treatment, and368 cases (18.4%) received complete treatment, as shownin Fig. 1. Among the infants who received complete treatment, 235 cases (63.9%) were male, 58 cases (15.8%) had
mothers who underwent assisted reproductive techniques, 98 cases (26.6%) had multiple pregnancies, and247 cases (67.1%) received more than one dose of glucocorticoids. Significant differences existed in the rates ofreproductive assistance, multiple pregnancies, and ACS
among different gestational age subgroups (P < 0.05), as
shown in Table 1.
We have found that EPIs receiving complete care wereassociated with an older maternal age, a lower incidenceof placental abruption, a higher incidence of prematurerupture of membranes, and a higher rate of ACS, as well
as a higher gestational age and a lower incidence of SGA.
There were no significant differences between gender,
mode of delivery, ART, GDM, HDCP, and multiplets, as
shown in supplemental Table 1.
Care practice

A total of 368 EPIs cases received complete care, and the
proportion of EPIs with complete care in each gestationalage group was as follows: 0%, 3.1% (7/223), 5.4% (22/407),
11% (47/428), 27.5% (98/357), and 48.5% (194/400). This
proportion increased with gestational age (P < 0.05). Outof the 101 patients who were transferred to the NICU but
eventually abandoned treatment, 90 (89.1%) were abandoned due to social factors. Among the 368 patients who
received complete care, 354 (94%) received pulmonary
surfactant (PS), 283 (79.4%) received mechanical ventilation, 146 (39.7%) received postnatal glucocorticoids,
and 41 (13.1%) received interventions for retinopathy ofprematurity (ROP). Additionally, 327 (88.9%) received
breastfeeding, and 230 (62.5%) received human milk
fortifier. Significant differences existed in the rates ofmechanical ventilation, postnatal glucocorticoid use,breastfeeding, and ROP requiring intervention among
different gestational age groups (P < 0.05). There were no
significant differences in the use of PS and human milk
fortifier among different gestational age groups (P > 0.05),
as shown in Table 3.

Gao et al. BMC Pediatrics(2024) 24:537

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Fig. 1 Flow chart. Note: EPIs: Extremely premature infants

Morbidities

Among the 368 EPIs who received complete treatment,
118 cases had grade 3–4 RDS (32.1%), 132 cases had
hsPDA (35.9%), 40 cases had grade 3–4 IVH (10.9%),
255 cases had ROP (69.8%), and 148 cases had II to
III level BPD (40.2%). For EPIs with a gestational age
between 25 and 27 weeks, the incidence of these diseases
decreased with gestational age. Significant differenceswere observed in the incidence of major serious diseases
among different gestational age groups, including grade
3–4 RDS, hsPDA, grade 3–4 IVH, and ROP (P < 0.05).
No significant differences were found in the incidencesof II to III level BPD, grade ≥ 2 NEC, MBDP, PNAC, VAP,
EOS, and LOS among the different gestational age groups(P > 0.05), as shown in Table 2.

Survival rate and survival rate without major serious
diseases

EPIs had a high risk of postnatal mortality, with an allcause mortality rate of 84.4% (1691/2004) observed in theoverall study cohort. Among the 368 EPIs transferred to
the NICU after birth and provided with comprehensive
treatment, 313 (85.1%) survived. However, these surviving EPIs were at high risk for disease, and only 116 EPIs
(31.5%) managed to remain free from major serious diseases throughout their hospitalization. In addition, thesurvival rate and the survival rate without major severe
diseases increased with gestational age, and the differences between gestational age subgroups were statistically significant (P < 0.05), as shown in Fig. 2.

Gao et al. BMC Pediatrics(2024) 24:537

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Table 1 Characteristics of EPIs with gestation age < 28w receiving complete care22–
22+ 6wn=078(21.2)
938(830,1058) 52(14.2)
235(63.9)84(22.8)-

23–23+ 6w
n=7

24–24+ 6w
n = 22

25–25+ 6
n = 47

26–26+ 6w
n = 9827–27+ 6w
n = 194

Z/χ2

P

1(14.3)520(490,605)
3(42.9)6(85.7)2(28.6)1(4.5)
655(600,700)
5(22.7)16(72.7)4(14.2)1(2.1)
800(750,850)
12(25.5)34(72.3)
8(17)20(20.4)
900(830,993)
16(16.3)
54(55.1)
27(27.6)55(28.4)1020(933,1100)
16(8.2)125(64.4)43(22.2)

23.027170.525
16.8356.528
2.607< 0.001< 0.001
0.001
0.157
0.653

31(27,34)
58(15.8)-28(28,34)
3(42.9)30(26,33.5)
6(28.6)30(28,36)
12(25.5)30(27,33)
16(16.3)

32(27,34)
21(10.9)

2.210
13.094

0.697
0.008

121(32.9)133(36.1)-

5(71.4)2(28.6)9(40.9)8(36.4)19(40.4)23(48.9)32(32.7)32(32.7)

56(28.9)68(35.1)

22.2230.005

114(31.0)-05(22.7)5(10.6)34(34.7)70(36.1)

49(13.3)12(3.3)98(26.6)
122(33.2)22(6.0)-003(42.9)2(28.6)0008(36.4)6(27.3)1(4.5)

6(12.8)2(4.3)
20(42.6)
13(27.7)3(6.4)11(11.2)
6(6.1)
23(23.5)33(33.7)8(8.2)

32(16.5)4(2.1)
44(22.7)
68(35.1)
10(5.2)

5.931
3.854
10.055
1.291
1.254

0.177
0.359
0.034
0.878
0.850

N = 368

Cesarean delivery
Birth weight
SGA
Male
Transferred from anotherhospital
Maternal age
Assisted reproductive
technology
ACSno
Imcomplete
treatment
Completetreatment
GDM
HDCP
Multiplets
PROM
Placental abruption

Data are presented as median(inter quartile range) or n (%); χ2 is the statistic value of the Pearson’s chi-square test or continuity correction of Pearson’s chi-square
test, and Z is the statistic value of the Kruskal-Wallis rank-sum test
Note: EPIs: extremely preterm infants; GDM: Gestational diabetes mellitus; HDCP: Hypertensive disease during pregnancy; ACS: antenatal corticosteroids; SGA: small
for gestational age; PROM: premature rupture of membranes.

Discussion
Discrepancies in the definition of the perinatal period
exist across regions. Presently, China’s definition of theperinatal period adheres to the 1976 WHO standard,
which designates it as gestational age ≥ 28 weeks up to
7 days postpartum, a notable departure from the definitions in developed nations [12]. The current guidelines
from the Chinese Society of Obstetricians and Gynecologists, Chinese Medical Association, classify preterm
infants as those born with a gestational age of 28–36+ 6
weeks [13]. Notably, the guidelines exclude preterm
infants with a gestational age < 28 weeks, which is defined
as a viable age after 24 weeks [14]. Infants born at 22–24
weeks of gestation are regarded as peri-survival infants.
Consequently, due to this considerable discrepancy inChina’s perinatal period definition, these infant deaths
aren’t categorized as neonatal deaths but rather classified as miscarriages, escaping discussion within maternaland child health institutions at all levels. This situation
has fostered a negative disposition among obstetricians
toward the treatment of EPIs. Based on a 2021 cross-sectional survey on obstetricians’ attitudes toward preterm
infant care [15], a mere 27.2% of obstetricians advocatedfor lowering the gestational age threshold for preterm
infant care. Neonatologists, on the other hand, exhibited a relatively higher willingness to treat EPIs. A study
by Li Qiuping et al. [16]. revealed that 63.0% of surveyed

pediatricians believed that the lower limit for actively
resuscitating EPIs should be set at 25 weeks or lower.
They endorsed a reduction in the lower gestational age
threshold for preterm infant care. The overall willingness
within this group to treat EPIs was markedly higher thanthat of obstetricians, yet still lower than that of pediatricians in developed countries [17]. The existing cognitive
bias among obstetricians and pediatricians toward EPIs
care is undoubtedly exerting a detrimental influence on
the care of extremely preterm infants at younger gestational ages. The national perinatal academic community
has acknowledged this reality, prompting the Society of
Perinatal Medicine to propose that active care be provided to EPIs over 24 weeks of age, while EPIs between
22 and 23 weeks of age are not eligible for active care.
This decision should involve comprehensive consultation
with parents [18].
The willingness of obstetricians and family members
plays a pivotal role in determining whether EPIs areadmitted to the neonatal intensive care unit for treatment. The elevated risk of adverse outcomes and concerns about substantial financial burden constitutesignificant factors influencing treatment decisions forthese preterm infants [19, 20], both from the perspective of parents and medical staff. Our study revealed thatmerely 23.4% of EPIs in the region were transferred to the
NICU, and a strikingly high 76.6% abandonment rate wasGao et al. BMC Pediatrics(2024) 24:537

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Table 2 Morbidites and survival in EPIs with gestation age < 28w receiving complete care
23–23+ 6w
n=72(28.6)1(14.3)4(57.1)
2(28.6)1(14.3)01(14.3)1(14.3)24–24+ 6w
n = 224(18.2)9(40.9)9(40.9)10(45.5)1(4.5)
9(40.9)11(50)
4(18.2)

25–25+ 6
n = 474(8.5)
18(38.3)25(53.2)
24(51.1)4(8.5)
24(51.1)
39(83)
8(17.0)

26–26+ 6w
n = 9815(15.3)
49(50)
34(34.7)
47(48)
7(7.1)
35(35.7)
76(77.6)
16(16.3)

27–27+ 6w
n = 194
21(10.8)
127(65.5)46(23.7)
65(33.5)9(4.6)
64(33)
130(67)13(6.7)Z/χ2P

46(12.5)
204(55.4)
118(32.1)
148(40.2)
22(6.0)132(35.9)255(69.8)41(13.1)

22–22+ 6w
n=0-

25.796< 0.001

9/030
3.265
9.500
20.38010.209

0.056
0.443
0.045
< 0.0010.027

29(7.9)84(22.8)40(10.9)63(17.1)
21(5.7)68(18.5)34(9.2)52(14.1)
221(60.1)-

02(28.6)2(28.6)1(14.3)1(14.3)1(14.3)2(28.6)1(14.3)3(42.9)1(4.5)
7(31.8)6(27.3)3(13.6)1(4.5)
1(4.5)
2(9.1)
2(9.1)
16(72.7)4(8.5)
16(34)
6(12.8)15(31.9)5(10.6)4(8.5)
5(10.6)4(8.5)
32(68.1)

12(12.2)
21(21.4)
10(10.2)
17(17.3)
2(2)21(21.4)8(8.2)
18(18.4)64(65.3)

12(6.2)38(19.6)16(8.2)29(14.9)12(6.2)41(21.1)
17(8.8)27(13.9)
106(54.6)

3.410
5.418
9.355
3.710
6.468
7.350
3.396
2.949
11.743

0.445
0.247
0.040
0.576
0.126
0.096
0.439
0.542
0.008

N = 368
RDS

0
1
2
II to III level BPD
VAP
hsPDA
ROP
ROP requiring
intervention
NEC ≥ 2
BI
IVH ≥ 3
PVL
MBDP
PNAC
EOS
LOS
Morbidities ofmajor serious
diseaseAll-causemortality
Survival rate of
EPIs transfered to
NICU
Survival rate of
EPIs received
complete care
Survival rate of
EPIs withoutmajor serious
diseases

1691/2004(84.4) 189/189(100) 223/223(100) 394/407(96.8) 389/428(90.9) 270/357(75.6) 226/400(56.5) 394.360 < 0.001
313/469(66.7)

0013/38(34.2)

39/75(52)87/124(70.2)

174/216(80.6) 75.708< 0.001

313(85.1)-

013(59.1)

39(83.0)87(88.8)

174(89.7)

38.718< 0.001116(31.5)-

02(9.1)

9(19.1)27(27.6)

78(40.2)

19.1420.001

Data are presented as median(inter quartile range) or n (%); χ2 is the statistic value of the Pearson’s chi-square test or continuity correction of Pearson’s chi-square
test, and Z is the statistic value of the Kruskal-Wallis rank-sum test.
Note: EPIs: extremely preterm infants; RDS: neonatal respiratory distress syndrome, 2 refers to the grade 3–4 RDS; EOS: early onset sepsis; LOS later onset sepsis;
NEC: necrotizing enterocolitis; hsPDA: hemodynamically significant patent ductus arteriosus; BPD: bronchopulmonary dysplasia; BI: brain injury. ROP: retinopathyof prematurity; MBDP: metabolic bone disease of prematurity; PNAC: parenteral nutrition-associated cholestasis.

Table 3 Care practices in preterm infants with gestation age < 28w receiving complete care22–
22+ 6wn=0469/2004(23.4) 2/189(1)368/2004(18.4) 0
90/101(89.1)
2/2(100)

23–23+ 6w
n=7

29(20,43.3)-

3731(21,62)

34(17,54)27.5(28,41.3)

29(20,44)

2.912

0.573

327(88.9)230(62.5)345(94)283(79.4)
146(39.7)-2(28.6)1(14.3)7(100)
7(100)
1(14.3)16(72.7)9(40.9)22(100)22(100)11(50)

39(83)
30(63.8)45(95.7)
43(91.5)31(66)

86(87.8)64(65.3)
90(91.8)
73(74.5)40(40.8)

184(94.8)
126(64.9)
175(90.2)
138(71.1)
63(32.5)

29.832
11.5452.985
25.94531.969< 0.0010.018
0.516< 0.001< 0.001N = 368

EPIs transfered to NICU
EPIs received complete care
EPIs abandoned for Socioeconomic considerations
The time of initiating feeding, hBreast-feeding
Human milk fortifier
PS
IMV
Postnatal corticosteroids

24–24+ 6w
n = 22

25–25+ 6
n = 47

26–26+ 6w
n = 9827–27+ 6w
n = 194

χ2

P

14/223(6.3) 38/407(9.3) 75/428(17.5) 124/357(34.7) 216/400(54)375.212 < 0.001
7/223(3.1) 22/407(5.4) 47/428(11.0) 98/357(27.5) 194/400(48.5) 400.137 < 0.001
7/7(100)
14/16(87.5) 25/28(89.3) 23/26(88.5)
19/22(86.4)
1.225
0.990

Data are presented as n (%); χ2 is the statistic value of the Pearson’s chi-square test or continuity correction of Pearson’s chi-square test.
Note: EPIs: extremely preterm infants; IMV: Invasive mechanical ventilation; PS: pulmonary surfactant; NICU: neonatal intensive care unit.

Gao et al. BMC Pediatrics(2024) 24:537

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Fig. 2 Survival rate of extremely preterm infants receiving complete carerecorded in the delivery room. This finding closely aligns
with Zhang et al.‘s observations [21], who reported datafrom a single center indicating that 73% of EPIs were notadmitted to the NICU for treatment. Most of these cases
arose from non-medical inductions, and in theory, therisk of mortality could be substantially reduced if these
infants received comprehensive care. Even among thosetransferred to the NICU, a portion was eventually discontinued from treatment due to non-medical reasons,and merely 18.4% of the cases ultimately underwent complete treatment. Notably, the proportions of receiving
complete treatment within the 22–24w group were 0%,3.1%, and 5.4%, respectively. This indicates a considerable shortfall in providing complete medical treatment toa large number of infants at the fringes of viability, contrasting starkly with high-income countries. A Japanesestudy unveiled that approximately 50% of EPIs with a gestational age of 22–23 weeks received active care [22]. The
United States has witnessed a notable upsurge in active
treatment for live births occurring between 22 weeks and
25 weeks of gestation, with around 52% of infants in thisgestational age bracket benefiting from active care [23].
Moreover, our study uncovered that gender also emerged
as a decisive factor influencing the active provision oftreatment. In our study, male infants constituted 55.9%(1121/2004) of the cohort, yet the proportion of maleinfants transferred to the NICU and receiving comprehensive treatment was significantly higher (63.9%). Considering the distinct cultural norms within our region,differing parental preferences for male infants led to agreater willingness to shoulder the costs of hospitalization, and had a higher tolerance for their long-term poor
prognosis.

Therefore, it is necessary to enhance the awarenessof obstetricians and pediatricians regarding the treatment of EPIs and promote equal access to medical carefor female infants. The age of these EPIs mothers was 31(27, 34) years old, and 15.8% of them conceived throughassisted reproductive technology. This suggests that thesemothers were older, with nearly one-sixth of them conceived through assisted reproductive technology. Therefore, treating these infants is of practical significance forthese older mothers with pregnancy difficulties.
EPIs were at an extremely high risk of death after birth.
The overall survival rate of EPIs in this study was only
15.6%, but the survival rate of EPIs transferred to the
NICU after birth and receiving complete treatment was
85.1%. Hence, a large number of EPIs were abandonedin the delivery room, significantly affecting the survival
rate of EPIs. The study indicated that the survival rateof EPIs and the survival rate free from major diseases
increased significantly with gestational age in this region.
National data from 2019 indicated that the survival ratesof EPIs with gestational ages < 24 weeks, 24 weeks, 25
weeks, 26 weeks, and 27 weeks were 21.7%, 55.8%, 75.2%,
87.7%, and 89.7%, respectively [4]. Data from 233 cases
EPIs with gestational ages of 22–25 weeks at Shenzhen
Maternal and Child Health Hospital from 2015 to 2021
showed an overall survival rate of 61.8% [24]. According
to a study by the Child Health and Human Development
Neonatal Research Network, from 2006 to 2011, 4987
EPIs were born at 26 and 24 weeks, with survival rates
of 81.55% and 76%, respectively, without severe sequelae.
The survival rates without mild and severe sequelae were
59% and 30%, respectively [25]. In a study of preterm
infants born at gestational ages of 22–28 weeks in the UK

Gao et al. BMC Pediatrics(2024) 24:537

region of Wales, the overall survival rate of infants after
live birth was approximately 71.8% [26]. Accordingly, we
found that the survival rate of EPIs with gestational ages
over 25 weeks in southwest Fujian Province was morethan 83%, which was close to the average level of China
and the level of developed countries. However, there still
exists a significant gap in the survival rate without serious
diseases compared to developed countries. Furthermore,
the survival rate of EPIs at gestational ages of 22–24
weeks was still significantly low. Even with active treatment, their survival status could not be improved. Therefore, improving the survival rate without major serious
diseases and the success rate of peri-survival infants isthe direction of future efforts.
EPIs were at risk of many diseases after birth [27]. Ourstudies have found that the lower the gestational age, thehigher the incidence of early-life diseases, such as grade
3–4 RDS, where gestational age follows a similar doseresponse relationship. However, for diseases that frequently occur later in hospitalization, like II to III level
BPD, ROP, NEC, BI, LOS, hsPDA, MBDP, PNAC, etc.,
the incidence did not decrease with increasing gestational age. This appears to contradict medical common
knowledge. Considering potential causes, most of theperi-survival marginal infants died shortly after birth,
before reaching the corrected gestational age or the highincidence age of these diseases. Consequently, the incidence of these diseases in this population is relatively
low compared to the actual situation. We found that in
EPIs born at gestational ages of 25–27 weeks, with higher
survival rates, the incidence of major severe diseases
decreased with gestational age. This reduction in risk led
to a decrease in the risk of death during hospitalization,
as evidenced by a progressive increase in the survival rateof EPIs without major serious diseases with increasinggestational age.
Reasonable perinatal interventions could enhance theshort-term and long-term prognosis of EPIs [18]. ACS
were effective prenatal interventions to improve perinatal outcomes in EPIs. This study revealed that 67.1%(247/368) of pregnant women received at least one doseof corticosteroids before delivery, and the rate of ACS
usage gradually increased with gestational age. This rate
was similar to the 71.1% rate of ACS use in EPIs reportedby the Chinese Neonatal Network in 2021 [4]. In developed countries, this proportion has risen from 64% in the
1990s to stabilize at over 70%. Moreover, in some highresource countries, more than 85% of pregnant womenwith a gestational age of 24–28 weeks received ACS [7,28, 29]. For pregnant women facing inevitable prematuredelivery before 34 weeks’ gestation, glucocorticoid usage
has been recommended [14, 30]. However, for EPIs witha very low gestational age, obstetric guidelines do not recommend routine ACS use for mothers with a gestational

Page 8 of 10

age of < 23 weeks. Consequently, there is a low rate of
ACS use in infants with a gestational age of < 24 weeks.
However, other studies have shown that the smaller thegestational age, the greater the benefit of preterm infants,suggesting that EPIs may be the group with the greatest
benefit from ACS use. Moreover, ACS use at “any” time
could help improve long-term quality of life for EPIs
[31]. The low rate of cesarean delivery (4.9%) in the study
population was considered to be related to the high rateof abandonment among EPIs with a gestational age less
26 weeks, during the delivery of these women cesareandelivery was a secondary option for obstetricians. Among
EPIs received complete care, 79.4% had received invasive
mechanical ventilation, and 94% had received PS. The
breastfeeding rate increased with gestational age. Given
that parents possess a strong desire to treat preterm
infants with a higher gestational age, they exhibit greater
compliance and provide ample breast milk. An increasein breastfeeding rates would be beneficial to improve theprognosis of EPIs.
In short, the mortality risk of peri-survival infants inthe southwest region of Fujian Province was markedly
high. It is crucial to enhance the perinatal managementof EPI, facilitate communication between obstetricians
and pediatricians, and involve neonatologists actively in
pre-delivery consultations. This will furnish parents andobstetricians with more comprehensive and accurate
information about the success rate and prognosis of EPIs
treatment in their region, thereby reducing the abandonment rate in delivery rooms and offering more medical treatment opportunities. ACS should be promptly
administered when unavoidable delivery approaches to
expedite fetal maturation. Upon admission of premature infants to the NICU, referring to the best neonatalmanagement strategy [32], providing respiratory support,
and utilizing exogenous pulmonary surfactant should be
pursued vigorously to develop personalized nursing andassessment plans for EPIs. This will enhance both shortterm and long-term prognoses.
Inevitably, this study was retrospective and encompassed data from all pregnant women and infants undergoing obstetric induction and obstetric delivery. Detailed
analysis of pregnancy complications for some women
undergoing obstetric induction was not feasible, possibly
affecting accuracy of the results.

Conclusion
The all-cause mortality rate of EPIs in the southwest
area of Fujian Province remained high, with a significant
proportion being abandoned in the delivery room. The
survival rate of EPIs born at 25–27 weeks and receiving
complete NICU care is comparable to that of developed
countries. However, the rates of survival without major
severe diseases and the survival rate of peri-survival

Gao et al. BMC Pediatrics(2024) 24:537

infants were markedly lower than those in high-income
countries.

Supplementary Information

The online version contains supplementary material available at https://doi.
org/10.1186/s12887-024-05016-2.

Page 9 of 10

4

Department of Neonatology, Quanzhou Maternity and Children’s
Hospital, Quanzhou 362000, China
5
Department of Neonatology, Zhangzhou Affiliated Hospital of Fujian
Medical University, Zhangzhou 363000, China
6
Department of Neonatology, Longyan First Hospital Affiliated to Fujian
Medical University, Longyan 364000, China
Received: 20 December 2023 / Accepted: 15 August 2024

Supplementary Material 1
Acknowledgements
The authors thank the neonatal units in the following hospitals and centers
for providing help for this survey : Clinical key specialty of FujianProvince(Specialty in neonatology); Department of Neonatology, Women andChildren’s Hospital, School of Medicine, Xiamen, Fujian, China (Liang Gao,
Si-min Ma, Xin-Zhu Lin); Department of Neonatology, Quanzhou Maternity
and Children’s Hospital, Quanzhou, Fujian, China (Dong-Mei Chen, Hui-pingYan); Department of Neonatology, Zhangzhou Affiliated Hospital of Fujian
Medical University, Zhangzhou, Fujian, China(Li-ping Xu, Shu-zhen Dai);
Department of Neonatology, Longyan First Hospital Affiliated to Fujian
Medical University, Longyan, Fujian, China(Rong-hua Zhong, Qi-bing Chen).
In addition, thanks the obstetricians from the above four medical centers fortheir support in this study. This study was also supported by Project of Clinical
key specialty of Fujian Province（Specialty in neonatology）.
Author contributions
XZL conceptualized and designed the study, reviewed and revised themanuscript, and approved the final manuscript. LG, DMC, LPX and RHZ
collected data and performed the data analysis, drafted the initial manuscript,
and approved the final manuscript. SMM, HPY, SZD, and QBC coordinatedand supervised data collection at their own sites and approved the final
manuscript.
Funding
This research was funded by Guidance Project of Xiamen Science andTechnology Plan (grant number 3502Z20214ZD1232); Guidance Project of
Xiamen Science and Technology Plan (grant number 3502Z20214ZD1225);
Natural Science Foundation of Fujian Province (grant number: 2022D004).
Data availability
The datasets used during the current study are available from thecorresponding author upon reasonable request.

Declarations
Ethics approval and consent to participate
The research protocol was approved by the Ethics Committee of Women andChildren’s Hospital affiliated to Xiamen University/Xiamen Maternal and Child
Health Hospital (Batch number kY-2023-089-K01). Consent to participate andfor publication all participants gave written informed consent. The informed
consent was obtained from the families of the children.
Competing interests
The authors declare no competing interests.
Consent to participate and for publication
All data published here received consent for publication.
Conflict of interest
The authors declare that there is no conflict of interest.
Author details
1
Department of Neonatology, Women and Children’s Hospital, School of
Medicine, Xiamen university, Xiamen 361003, China
2
Xiamen key laboratory of perinatal-neonatal infection, Xiamen
361003, China
3
Xiamen Clinical Research Center for Perinatal Medicine, Xiamen
361003, China

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