Journal of the Formosan Medical Association 121 (2022) 1141e1148

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Original Article

Predicting in-hospital length of stay for

very-low-birth-weight preterm infants using
machine learning techniques
Wei-Ting Lin a, Tsung-Yu Wu a, Yen-Ju Chen a, Yu-Shan Chang a,
Chyi-Her Lin a,b, Yuh-Jyh Lin a,*

a
Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National
Cheng-Kung University, Tainan, Taiwan
b
Department of Pediatrics, E-Da Hospital, College of Medicine, I-Shou University, Kaohsiung, Taiwan

Received 28 June 2021; received in revised form 1 September 2021; accepted 24 September 2021

KEYWORDS Background/Purpose: The in-hospital length of stay (LOS) among very-low-birth-weight (VLBW,
Machine learning; BW < 1500 g) infants is an index for care quality and affects medical resource allocation. We
Length of stay; aimed to analyze the LOS among VLBW infants in Taiwan, and to develop and compare the per-
Retrospective study; formance of different LOS prediction models using machine learning (ML) techniques.
Very-low-birth- Methods: This retrospective study illustrated LOS data from VLBW infants born between 2016
weight infants and 2018 registered in the Taiwan Neonatal Network. Among infants discharged alive, contin-
uous variables (LOS or postmenstrual age, PMA) and categorical variables (late and non-late
discharge group) were used as outcome variables to build prediction models. We used 21 early
neonatal variables and six algorithms. The performance was compared using the coefficient of
determination (R2) for continuous variables and area under the curve (AUC) for categorical
variables.
Results: A total of 3519 VLBW infants were included to illustrate the profile of LOS. We found
59% of mortalities occurred within the first 7 days after birth. The median of LOS among sur-
viving and deceased infants was 62 days and 5 days. For the ML prediction models, 2940 infants
were enrolled. Prediction of LOS or PMA had R2 values less than 0.6. Among the prediction
models for prolonged LOS, the logistic regression (ROC: 0.724) and random forest (ROC:
0.712) approach had better performance.

* Corresponding author. Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng-Kung
University, No.138, Sheng Li Road Tainan, Taiwan. Fax: þ886 6 2753083.
E-mail address: ped1@mail.ncku.edu.tw (Y.-J. Lin).

https://doi.org/10.1016/j.jfma.2021.09.018
0929-6646/Copyright ª 2021, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
 W.-T. Lin, T.-Y. Wu, Y.-J. Chen et al.

Conclusion: We provide a benchmark of LOS among VLBW infants in each gestational age group
in Taiwan. ML technique can improve the accuracy of the prediction model of prolonged LOS of
VLBW.
Copyright ª 2021, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).

Introduction Patients and methods

The survival rates and outcome of very-low-birth-weight
(VLBW, BW < 1500 g) infants have improved with advances
in neonatal resuscitation and management after birth.1e3
As the survival rate improved, medical resources to care
for these VLBW infants increased. In a population-based
study in California, VLBW infants accounted for 0.9% of
cases but 35.7% of hospital costs.4 In-hospital length of stay
(LOS) is one of the factors used to determine the cost and
an index of quality of care.5 There are very few studies on
LOS for VLBW infants in Taiwan, so in this study, we first
illustrated the profile of LOS among VLBW infants in
Taiwan.
Meanwhile, accurate predictions of LOS in early life
would be helpful for resource planning and family coun-
seling.6 It would also be beneficial for both parents and
physicians if an accurate prediction of LOS could be made
early in the infant’s life. On the other hand, “overstay in
hospital” indicates unsuitable utilization of medical re-
sources. It was defined as patients staying longer than 30
days in the hospital based on the Taiwan National Health
Insurance definition. Although this rule is not appropriate
in VLBW infants, it is important to distinguish what
patients may have prolonged LOS to improve quality of care
and develop efficient medical resource planning. In the
previous study, the discharge day of preterm infants was
estimated to be around their estimated date of confine-
ment (EDC).7
Previous studies regarding predicting LOS in preterm
infants were based on conventional statistical
techniques.7e10 These conventional statistical techniques
relied on the hypothesis to determine potential risk fac-
tors.11 In 2010, Hintz et al. concluded in their study that,
“prediction of early or late discharge is poor if only peri-
natal factors are considered.8”
Machine learning (ML) is a novel analytic tool that uses
computers to learn from labeled data rather than a pre-
programmed process. It can be used to analyze a large
number of variables and describe relationships between the
variables and outcomes using different ML algorithms in
complex, nonlinear ways.12,13 The application of ML to
building LOS prediction models in different medical fields
has led to promising results.14,15 However, there are few
reports using ML algorithms to predict LOS in VLBW infants.
The second purpose of this study, therefore, is to develop
LOS prediction models for VLBW infants built using different
ML algorithms and to compare their performance.
Patients and data collection.
The Taiwan Neonatal Network (TNN) was initiated by the
Taiwan Society of Neonatology in 2016. The purpose of this
network is to record the clinical information of infants
whose gestational age was less than 30 weeks or whose
birth body weight was less than 1500 g in order to improve
quality of care. During the study period, there are 28 hos-
pitals participating in the network, including 17 medical
centers and 11 community hospitals in Taiwan. We used
anonymous data from preterm infants born between 2016
and 2018 enrolled in the TNN.
This study has been approved by the Institutional Review
Board of National Cheng Kung University Hospital (B-ER-
109-090).
Data exclusion
We excluded infants based on the following criteria:
1. Birth body weight more than 1500 g.
2. Unknown gestational age or gestation age less than 22
weeks
3. Admission day after 7 days of birth.
4. Severe congenital anomaly.
5. Still in hospital after reaching 1 year of age
6. Transferred to another hospital.
Finally, patients with missing data and deceased infants
were also excluded for the purpose of establishing the LOS
prediction model using a ML technique.
Profile of LOS
We illustrated the profile of LOS using mortality and
gestational age. In this study, LOS was defined as the
number of days post-birth to the infant’s discharge day
(alive or dead).
Variables for ML
For infants discharged alive, 21 variables during the ante-
natal, perinatal, and early neonatal periods were used to
build the LOS prediction model.
Antenatal variables included gestational age, gender,
birth bodyweight, small for gestational age, antenatal

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 Journal of the Formosan Medical Association 121 (2022) 1141e1148

obstetrics visit, antenatal steroid administration, ante- ML approach

natal magnesium sulfate treatment, chorioamnionitis,
maternal hypertension or gestational hypertension, de-
livery mode, and multiple births.
Perinatal variables include birthplace (inborn or out-
born), APGAR scores (1-min and 5-min), and initial
resuscitation at delivery room (DR) such as oxygen supple-
mentation, intubation, chest compression, and use of
epinephrine.
Early neonatal variables include neonatal hypothermia
(body temperature below 36.5  C), early sepsis (bacteremia
in first 3 days), and surfactant use. The gestational age was
recorded as completed gestational age by the best ob-
stetrics estimation either based on the last menstrual cycle
or ultrasonography.
Continuous target variables
LOS was used as the first target variable. We also used
postmenstrual age (PMA) as the second continuous target
variable because the clinical condition and discharge issues
are different for each gestational age.
Categorical target variables
We then categorized infants into 16 groups based on their
gestational age (Table 1). Each gestational age group was
further grouped as a categorical outcome variable using
equal-frequency binning following a previous study.8 The
“Late Discharge Group” was defined as 25% of the infants
with the longest LOS in each gestational age group. The
other 75% of the infants were defined as the “Non-late
Discharge Group.” For example, an infant born with a
gestational age of 24 weeks would be grouped into the
“Late Discharge Group” if his/her LOS was longer than 149
days (Table 1).
We used Waikato Environment for Knowledge Analysis
(Weka) program for ML approach. It is an open-source ML
software collecting different algorithms for performing
statistical analyses in data mining via a graphical user
interface.16e18 In this study, ML was implemented using
Weka3.8.1 to establish the predictive models.
ML algorithms
For the continuous variables, we used six algorithms in
Weka: linear regression, multilayer perceptron, LIBSVM
(support vector machine), IBK (k-nearest neighbors),
REPTree (decision tree), and the random forest approach.
For the categorical variables, we used six algorithms in
Weka: logistic regression, multilayer perceptron, LIBSVM
(support vector machine), IBK (k-nearest neighbors),
REPTree (decision tree), and the random forest approach.
Multilayer perceptron is a class of feedforward artificial
neural networks mimicking human neurons. The neuron
receives signals (input) from other neurons through
weighted connections. Once the output signal weight rea-
ches the” threshold,” the signal propagates to another
neuron until the final output of the signal is completed.
Support vector machine uses multiple dimensional hy-
perplanes to separate each object where the hyperplane
that separates objects by the maximal distance is chosen.
K-Nearest Neighbors determined an object’s class as the
most common class based on its k nearest neighbors. For
example, if K Z 1, the class of the object is assigned to the
class of that single nearest neighbor.
Decision tree is a tree-like model with many bifurcations
with true or false conditions using input variables. It can
display an algorithm to completely separate positive and
negative training input variables.

Table 1 Length of stay and mortality by gestational age.

Gestational age weeks n (%) Mortality, n (%) LOS of death LOS of alive Difference of days between
Median (25th,75th) Median (25th,75th) EDC and median LOS of discharge
22e37 3519 396 (11.2) 5 (2, 20) 62 (45, 90)
22 39 (1.1) 29 (74.4) 3 (1, 6.5) 138 (125, 183) þ12
23 113 (3.2) 70 (62.0) 2 (1, 5) 135 (113, 170) þ16
24 205 (5.8) 85 (41.5) 4 (2, 18.5) 127 (108,149) þ15
25 261 (7.4) 59 (22.6) 7 (3, 26) 108.5 (95,128) þ3.5
26 282 (8.0) 38 (13.5) 10 (3, 39.75) 93 (83.25,107) þ5
27 377 (10.7) 46 (12.2) 9 (3, 52.25) 83 (69, 101) 8
28 413 (11.7) 27 (6.5) 6 (2.24) 71 (60, 84) 13
29 478 (13.5) 18 (3.8) 6 (2.75, 13.25) 57 (49, 69) 20
30 429 (12.2) 12 (2.8) 13.5 (3, 38.5) 50 (44, 62) 20
31 284 (8.2) 3 (1.1) 25 45 (37, 54) 18
32 246 (7.0) 4 (1.6) 5 42 (35.48) 14
33 174 (4.9) 4 (2.3) 4 38 (32, 47) 11
34 120 (3.4) 0 34 (30.47) 8
35 56 (1.5) 1 (1.8) 4 31 (29.39) 4
36 36 (1.0) 0 34 (28.44) þ6
37 6 (0.2) 0 43 (29.61) þ22
EDC, estimated date of confinement; LOS, length of stay.

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 W.-T. Lin, T.-Y. Wu, Y.-J. Chen et al.

Random forest consists of a multitude of decision trees area). By day 200, almost all infants had been discharged
to avoid the problem of overfitting of one decision (dark-grey area). Notably, the median LOS for infants who
tree.12,13,19,20 died was less than 7 days, especially for those infants with
gestational ages less than 25 weeks, which accounted for
Model evaluation and validation two-thirds of the deceased infants. There were 235 infants
who died (59.3% of all mortalities) within 7 days and 327
To use all available data for training our model, instead of infants who died (82.5% of all mortality) within 30 days. The
splitting the data into training and testing groups, 10-fold number of infants who died on each day in the first 30 days
cross-validation was used. In the 10-fold cross-validation, is shown in Fig. 3.
the data was randomly partitioned into 10 subgroups. Then,
one subgroup was used as the testing group, and the other 9 Comparison of EDC and LOS in surviving infants
subgroups were used as the training groups to build the
prediction model. The process was repeated 10 times using We compared the discharge day of the surviving infants
different subgroups as testing and training groups, and the with their EDC. For infants with the gestational ages
average performance was recorded. Finally, the 10 ranging from 22 to 24 weeks, the median LOS was about
different models were then averaged to obtain the re- 2e3 weeks after EDC. As their gestational age increased,
ported result. the infants were discharged close to or even in advance of
their EDC. Infants with gestational ages ranging from 25 to
Other statistical analyses 27 weeks were discharged around their EDC. Infants with a
gestational age over 28 weeks were discharged 2e3 weeks
before their EDC.
Statistical analyses of patient characteristics were per-
formed using a chi-squared test. Variables with p-values
below 0.05 were considered statistically significant.
The Weka Experiment Environment was used to analyze
the results and determine if one algorithm was statistically
better than the others. Statistical significance refers to the
result of a pairwise comparison of the algorithms using a
standard t-test or the corrected resamples t-test.21 We
used the coefficient of determination (R2) to compare the
predictive capabilities of ML with continuous target vari-
ables. The area under the curve (AUC) of the receiver
operating characteristics (ROC) curve was used as the main
target for the ML performance with the categorical target
variables.8,22

Results

Study group

Data from 3791 infants born between 2016 and 2018 in TNN
were screened for eligibility. After exclusion, there were
3519 infants enrolled (Fig. 1).

LOS and mortality rate among VLBW infants in

Taiwan

For all 3519 patients, the mortality rate during the hospital
stay was 11.2%. There were 1825 (51.8%) male infants. The
greatest gestational age was 37 weeks. To ensure privacy,
the actual birth bodyweight of each infant was not recor-
ded; instead, the birth body weight was recorded as 100 g
categories, such as 1000e1100 g. Thus, we were unable to
show the actual mean birth bodyweight of the infants. The
median LOS of all patients was 61 days. The summary of the
LOS profile categorized by mortality and gestational age is
shown in Table 1.
We plotted the cumulative cases against LOS and
demonstrated the result in graphic form,23 as shown in Figure 1 Flow chart illustrating patient selection. GA,
Fig. 2. On day 10, there were no infants discharged, and gestational age; LOS, length of stay; TNN, Taiwan Neonatal
most mortalities occurred before that period (light-gray Network.

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 Journal of the Formosan Medical Association 121 (2022) 1141e1148
Study group for ML
We further excluded 236 infants with missing data and 343
deceased infants. A total of 2940 infants were included for
the purpose of establishing predictive models using ML
(Fig. 1).
Predicting hospital discharge as continuous target
variables
Table 2 shows poor predictive capabilities in terms of pre-
dicting PMA, with coefficients (R2) of less than 0.3 for all ML
algorithms. The performance was better in terms of pre-
dicting LOS, but the best R2 was also less than 0.6. Mean-
while, the mean absolute error (MAE) or the root mean
square error (RMSE) values were more than 14 for all
models.
Predicting hospital discharge as non-late or late
discharge
The characteristics of the infants in each group are shown
in Table 3. Except for gestational age, which was adjusted
in each group, among 20 variables, there were 12 variables
with significant differences: gender, birth bodyweight,
small for gestational age, maternal hypertension or gesta-
tional hypertension, cesarean section, APGAR score 1-min
and 5-min, oxygen at DR, intubation at DR, chest
compression at DR, early sepsis, and surfactant use.
The performance of each ML algorithm is shown in Table 4.
Compared with the other models, the models built using
the logistic regression (AUC Z 0.724) and using the random
forest (AUC Z 0.712) had statistically significant higher AUC
values.
Discussion
In this study, the profile of LOS grouped by mortality and
gestational age among VLBW infants in Taiwan was first
illustrated. According to the results, most mortalities
(59.3% of all mortality) occurred within the first 7 days of
life. Ingram et al. reported that if parents received more
Figure 2 Stacked cumulative cases of death (light-gray
area), in hospital (black area), and discharge (dark-grey area).
LOS, length of stay.
1145
Figure 3 The number of infants that died in the first 30 days
of LOS for each day. LOS, length of stay.
information related to their baby’s likely discharge date, it
improved their perceptions of their baby’s clinical condi-
tion.6 Since mortality is an important determinant of LOS,
and there are high mortality rates (11.2%) among these
patients, it is important to give this information at an
appropriate time.
In clinical practice, we can tell the parents that the
baby’s risk of mortality will decrease if the baby is stable
after seven-day-old, as well as the estimated LOS based on
their gestational age. As shown in Table 1, infants with
gestational ages between 22 and 24 weeks may be dis-
charged 2e3 weeks after their EDC. As the week of gesta-
tional age increases to 27 weeks, the LOS may be shorter
than the time remaining until the EDC. Our results were
similar to a large-population-based study in England, where
infants born at 25e26 weeks were discharged around their
EDC.7
The second part of this study illustrated that ML can help
build accurate models for predicting prolonged LOS among
VLBW infants in their early life but not for exact LOS and
PMA as a continuous variable. For the R2 values of less than
0.6, there were also high MAE and RMSE in the predictive
models for exact LOS and PMA. For predicting prolonged
LOS, models built using a logistic regression and the random
forest had better performance in this study, with AUC
values of 0.724 and 0.712, respectively. This result was
better than the results of a previous report by Hints et al.,
with AUC values ranging from 0.56 to 0.69 in their study.8
Also, one of the strengths of ML is that it can be self-
taught with future added data.13 We believe that as the
patient number increases in the future, more information
on VLBW infants can be provided to the computer, so the
prediction model will become more accurate.
The median LOS of all VLBW infants was 61 days, and
there was significant variability in the LOS among the
different gestational ages, indicating that the current
definition of “overstay in hospital” by the Taiwan National
Health Insurance, which is defined as a LOS longer than 30
days, is not appropriate in this population. However,
“overstay in hospital” is still an important quality index of
hospital performance. Meanwhile, although these infants
are high-risk for early readmission,24 previous studies have
shown early discharge is not associated with higher
 W.-T. Lin, T.-Y. Wu, Y.-J. Chen et al.

Table 2 The performance of each machine learning algorithm for LOS and PMA.
Linear regression Multilayer perceptron LIBSVM IBK REPTree Random Forest
2
LOS R 0.57 0.345 0.572 0.309 0.56 0.573
MAE 15.40 20.64 14.50 21.82 15.46 15.35
RMSE 25.73 38.07 26.40 37.48 26.03 25.65
PMA R2 0.243 0.062 0.241 0.063 0.244 0.243
MAE 15.40 20.94 14.50 21.35 15.34 15.38
RMSE 25.73 38.04 26.40 36.77 25.71 25.82
LOS, length of stay; PMA, postmenstrual age; LIBSVM, support vector machine; IBK, k-nearest neighbors; REPTree, decision tree; MAE,
mean absolute error; R,2 coefficient of determination; RMSE, root mean square error.

readmission frequency.25 Our results may provide a refer-
ence for determining “overstay in hospital” in Taiwan
among this population.
An accurate prolonged LOS prediction model can help
improve quality of care in clinical practice. For example,
if a patient was predicted to be “non-late discharge”
after birth but stayed in the hospital longer than ex-
pected, we should analyze the reasons why the prolonged
LOS occurred. On the other hand, physicians need to
distinguish infants with higher risk for prolonged LOS for
general resource planning. Physicians can plan in advance
to have adequate beds, equipment, and medical staff in
the neonatal intensive care units as soon as a VLBW infant
is born.
Furthermore, a previous study showed that later mor-
bidities, such as bronchopulmonary dysplasia or surgery for
necrotizing enterocolitis, are factors contributing to the
predictive models for LOS.8 However, later morbidities

Table 3 Characteristics of the infants used for algorithm training.

Non-Late (n Z 2218) Late (n Z 722) P value
Gender, Boy 1109 (50%) 398 (55.1%) 0.017
Birth bodyweight, g <0.001
<500 10 (0.5%) 13 (1.8%)
500-1000 649 (29.2%) 359 (49.7%)
1000-1500 1559 (70.3%) 350 (48.5%)
Small for gestational age 848 (38.2%) 400 (55.4%) <0.001
Antenatal obstetrics visit 2207 (99.5%) 716 (99.2%) 0.454
Antenatal steroid 1843 (83.1%) 597 (82.7%) 0.801
Antenatal magnesium sulfate 1221 (55.0%) 381 (55.8%) 0.285
Chorioamnionitis 290 (13.1%) 103 (14.3%) 0.414
Maternal hypertension or gestational hypertension 627 (28.3%) 242 (33.5%) 0.007
Cesarean section 1626 (73.3%) 560 (77.6%) 0.023
Multiple births 668 (30.1%) 213 (29.5%) 0.754
Outborn 155 (7.0%) 56 (7.8%) 0.487
APGAR scores (1-min) <0.001
0-3 242 (10.9%) 116 (16.1%)
4-6 911 (41.1%) 341 (47.2%)
7-10 1065 (48.0%) 265 (36.7%)
APGAR scores (5-min) 0.001
0-3 42 (1.9%) 19 (2.6%)
4-6 222 (10.0%) 105 (14.5%)
7-10 1954 (88.1%) 598 (82.8%)
Oxygen at DR 2017 (90.9%) 694 (96.1%) <0.001
Intubation at DR 516 (23.3%) 249 (34.5%) <0.001
Chest compression at DR 54 (2.4%) 35 (4.8%) 0.001
Epinephrine at DR 46 (2.1%) 24 (3.3%) 0.076
Hypothermiaa 1437 (64.8%) 469 (65.0%) 0.934
Early sepsisb 34 (1.5%) 25 (3.5%) 0.001
Surfactant use 621 (28.0%) 320 (44.3%) <0.001
Value are number (%); DR, delivery room.
a
Body temperature <36.5  C.
b
Bacteremia noted in first 3 days of life.

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 Journal of the Formosan Medical Association 121 (2022) 1141e1148

Table 4 The performance of each machine learning algorithm for the target categorical variables.
Logistic regression Multilayer perceptron LIBSVM IBK REPTree Random Forest
a a a a
AUC 0.724 0.647 0.591 0.574 0.686 0.712
Precision 0.761 0.713a 0.794 0.681a 0.745 0.744
Recall 0.783 0.736a 0.791 0.687a 0.774 0.773
F-measure 0.744 0.721a 0.739 0.684a 0.733 0.739
AUC, area under the curve; LIBSVM, support vector machine; IBK, k-nearest neighbors; REPTree, decision tree.
a
Statistical significance compared with the logistic regression (p-value<0.05).

were mostly observed later in this study population and
after the great majority of the deaths had already
occurred. In practice, it is appropriate to include these
later morbidities to build an explanatory model, but it is
inappropriate to build a prediction model for LOS.26
There are several limitations in this study. This study
included 17 medical centers and 11 community hospitals in
Taiwan. The individual discharge criteria for each hospital
may vary and is a confounding factor in this study. Ideally,
each hospital should have a predictive LOS model for its
patient population and distinctive discharge criteria, but
the low patient number in each hospital made it difficult to
develop a robust model. We attempted to illustrate the LOS
among VLBW infants in Taiwan at a national level to serve
as a reference for acceptable LOS. To build prediction
models, we should provide all collectible variables for ML to
avoid missing important predictors. There were, however,
some variables unavailable in this study. In the TNN data-
base, some of the important variables were recorded
without the actual time when the event occurred such as
intraventricular hemorrhage, surgical necrotizing entero-
colitis and treatment for patent ductus arteriosus. Some
variables were not recorded in the database such as
maternal gestational diabetes mellitus, formula feeding or
breast milk feeding, and use of probiotics. Finally, due to
the limited patient number, we used all patient data to
build the prediction model. Although a 10-fold cross-
validation was used to avoid the problem of over-fitting in
ML, we did not have an external validation for the
model evaluation. In a future study, we hope to have more
patients with more variables to improve the accuracy of the
proposed prediction model.
ML is a novel technology in many fields, including
building prediction models in the field of neonatology.
Further study is needed to validate the use of ML in pre-
diction models in this special population.
Conclusion
An accurate LOS prediction model in a VLBW baby’s early life
can be used in the parents counseling and in general resource
planning for physicians. Our study provides a benchmark of
LOS among VLBW infants in each gestational age group in
Taiwan. We also demonstrated that the ML technique can
improve the accuracy of the prediction mode of prolonged LOS
in their early life. Further study is needed to externally vali-
date these models in terms of predicting LOS.
Declaration of any potential financial and
nonfinancial conflicts of interest
1. This work has not been supported by any funding.
2. The authors have no conflicts of interest relevant to this
article.
Acknowledgments
We thank for members and administrator of Taiwan
Neonatal Network and the research nurses and residents of
the 28 participating hospitals for their help in the regis-
tration and data collection.
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