Aynalem 2020@journal - Pone.0235544
Aynalem 2020@journal - Pone.0235544
Aynalem 2020@journal - Pone.0235544
RESEARCH ARTICLE
uploaded the minimal anonymized data set incidence rate was 8.1/100 (95%CI: 7.3, 8.9). Significant predictors of respiratory distress in
necessary to replicate our study findings as a neonates included being male [Adjusted hazard ratio (HR): 2.4 (95%CI: 1.1, 3.1)], born via
Supporting Information file.
caesarean section [AHR: 1.9 (95%CI: 1.6, 2.3)], home delivery [AHR: 2.9 (95%CI: 1.5, 5,2)],
Funding: The authors have also confirmed that no maternal diabetes mellitus (AHR: 2.3 (95%CI: 1.4, 3.6)), preterm birth [AHR: 2.9 (95%CI:
financial funding was received for the study,
authorship, and publication of this article.
1.6, 5.1)], and having an Apgar score of less than 7 [AHR: 3.1 (95%CI: 1.8, 5.0)].
Background
Respiratory distress (RD) is a common problem for newborns immediately following birth. It
is often seen during the transition from fetal to neonatal life. RD typically manifests in new-
borns as tachypnea, intercostal retractions, nasal flaring, audible grunting, and cyanosis. The
successful transition from fetal to neonatal life requires a series of rapid physiologic changes in
the cardiorespiratory systems. These changes result in a redirection of gas exchange from the
placenta to the lungs and requires the replacement of alveolar fluid with air and the onset of
regular breathing [1]. Although RD may be transient in some newborns, if it persists, then
there is a need for proper diagnostic and therapeutic interventions to optimize outcomes and
minimize morbidity.
RD is one of the most common reasons for neonates to be admitted to the neonatal inten-
sive care unit (NICU) [2, 3]. Fifteen percent of term infants and 29% of late preterm infants
admitted to the NICU develop significant respiratory morbidity [4]. This incidence is even
higher for infants born before 34 weeks’ gestation [5]
Certain risk factors increase the likelihood of neonatal RD. Recognized causes of RD in
other low and high resource countries includes; prematurity, low first and fifth minute Apgar
scores, meconium aspiration syndrome, caesarian section delivery, gestational diabetes, mater-
nal chorioamnionitis, premature rupture of membranes [6], and oligohydramnios, as well as
structural lung abnormalities are some predictors identified in previous studies [5, 7–10].
Other common causes include transient tachypnea of the newborn, meconium aspiration syn-
drome, pneumonia, sepsis, pneumothorax, and persistent pulmonary hypertension of the new-
born [11]. In contrast, the risk decreases with each advancing week of gestation and birth
through spontaneous vaginal delivery [12].
Regardless of the cause, if not recognized and managed quickly, RD can escalate to respira-
tory failure, cardiopulmonary arrest, and even death. Therefore, it is imperative that any health
care practitioner caring for newborn infants be able to readily recognize the signs and symp-
toms of RD, differentiate the various causes, and initiate management strategies to prevent sig-
nificant complications or death. Consequently, neonates in need of critical medical attention
are usually admitted to the NICU. These infants tend to be preterm, have a low birth weight,
or have serious medical conditions including RD [13, 14].
Globally, there are different policies, strategies, and programs which work on or advocate
for the prevention and care of preterm neonates and their birth outcomes, including RD, like
the Sustainable Development Goals (SDGs) and the Every Women and Every Child initiative
[15, 16]. Despite these efforts, RD remains among the leading causes of neonatal mortality and
morbidity [17–21]. Indeed, in Ethiopia, RD is the most common cause of neonatal mortality
and morbidity [17–22], resulting in exponentially increasing neonatal care costs within the
first 28 day of life. Additionally, few studies have been conducted in developing countries to
assess RD in these regions, including Ethiopia. Therefore, this study we aimed to determine
the incidence and predictors of RD among neonates who were admitted to the NICU at Black
Lion Specialized Hospital, Ethiopia.
Methods
Study design, setting, and population
An institution-based retrospective follow-up study was conducted among a cohort of neonates
from the previous consecutive five years (from January 2013 to March 2018). The study was
conducted in Addis Ababa, a capital city of Ethiopia at NICU of black lion hospital. Addis
Ababa has ten sub-cities in which the City lies at an altitude of 7,546 feet (2,300metres). It has
twelve governmental and nine nongovernmental hospitals. The NICU of black lion hospital
ward is able to accommodate a maximum of 60 patients with average of 20–40 patients’ daily
admission. There are on average 5000–6000 annual admissions. The study was conducted
from March to April 1, 2018. The neonatal chart number were taken from the HMIS- data
base. The total patients admitted to NICU from January 2013-last of March 2018 were 5000.
We have found the number of admissions for each year. The samples were proportionally allo-
cated for each year, and with systematics sampling; the study participants of each year were
selected as follows. First, numbering the units of each year on the frame from 1 to N (N = total
admission of each year), then we determine the sampling interval (K) by dividing the number
of units in the population by the desired sample size of each year (n = sample size of each year)
which gives 8. Then number between one and 8 at random was selected (2 were selected). This
number is called the random start and the first number included in the sample. Then later
Selection was conducted every 8th unit after that first number. Our source population was all
neonates admitted to the NICU at the Black Lion Specialized Hospital, Ethiopia. All neonates
who were admitted to the NICU in the previous five consecutive years (from January 2013 to
March 2018) were considered as the study population.
Eligibility criteria
All targeted neonates’ medical cards documented in the previous five years from the study
period were recruited and those with incomplete cards were excluded.
Study variables
Dependent variable. Incidence of RD
Independent variables. Socio-demographic factors. Neonatal-related variables included
age at admission, gestational age, sex, the weight of the neonate, date of NICU admission and
discharge. Maternal-related variables were age and residency.
Gynecologic-obstetric related factors. Antenatal care (ANC) follow up, gravidity, parity,
mode of delivery, multiple pregnancies, PROM, preeclampsia, abruption placenta, and breast-
feeding initiation.
Medical disorders in mother. Hypertension, diabetes mellitus (DM), human immune virus/
acquired immune deficiency syndrome (HIV)/(AIDS).
Neonatal outcome condition. Apgar score, sepsis, jaundice, hypothermia, prenatal asphyxia
(PNA), hypoglycemia, meningitis, esophageal atresia.
Data collection tools. A pretested checklist was used to collect the required data from the
neonates’ charts. The checklist was translated to the local language of Amharic and back to
English. The consistency of this translation was checked to ensure its accuracy. Data were col-
lected by reviewing the complete patients’ cards from the previous five consecutive years from
the study period. RD was confirmed by reviewing neonate medical charts.
Data quality control. Data quality was assured by designing proper data abstraction tools.
The checklist was evaluated by experienced researchers. The data collection instrument was
pretested on 5% of the sample size. Rigorous training was given regarding the data abstraction
checklist and data collection process for both data collectors and supervisors. During the data
collection time, close supervision and monitoring were carried out by the supervisors and
investigator. Double data entry was also done using Epi Data 4.2.0 software.
Data processing, analysis, and presentation. Before analysis, data was cleaned, edited, and
coded. Any errors identified at this time were corrected after review of the original data using
the code numbers that we had assigned during the data collection period. Data were entered
using Epi-Data version 4.2.0 and analyzed using STATA 14 statistical software. Incidence den-
sity rate (IDR) was calculated for the entire study period. Subsequently, the number of cases of
RD within the follow-up period was divided by the total person-time at risk on follow-up and
reported per 100-person day. Kaplan-Meier survival curves were used to estimate the mean
survival time and the log-rank tests were used to compare survival curves. Proportional hazard
assumption was tested both graphically and through the Schoenfeld residual test for all predic-
tors, revealing that the proportional hazard assumption was met. After checking this assump-
tion, by comparing models, a more effective hazard model was selected using the log
likelihood ratio (LR) test and the Akaike Information Criterion (AIC). In this parametric
approach, the baseline hazard and the vector of its parameters were assessed together with the
regression coefficients. The best-fit model was chosen using AIC; selecting those having the
smallest AIC. Subsequently, parametric models were completed for neonates to ascertain the
possible predictors. Variables having a p-value less than or equal to 0.05 in the bivariate analy-
sis were fitted to the multivariable Gompertz hazard distribution regression model with a 95%
confidence interval. A p-value less than 0.05 was considered statistically significant.
Ethical consideration. Ethical clearance was obtained from Addis Ababa University, College
of health science ethical review board. Letters of cooperation were written to Black Lion Spe-
cialized Hospital by the ethical review board members and subsequently permission was
obtained from the clinical director and relevant department and unit heads of the hospital.
Since the study was conducted by taking appropriate information from medical chart, it will
not inflict any harm on the patients. The name or any other identifying information was not
be recorded on the checklist and all information that was taken from the chart was kept strictly
confidential and in a safe place.
Following these approvals, access to the medical charts was provided and we did our utmost
to maintain participant confidentiality by storing in a file cabinet and kept in a key and locked
system with computer pass ward.
Operational definition
Event (neonatal RD). The presence of two or more of the following signs: an abnormal
respiratory rate (tachypnea > 60 breaths/min, bradypnea < 30 breaths/minute, respiratory
pauses, or apnea) or signs of labored breathing (expiratory grunting, nasal flaring, intercostal
recessions, xyphoid recessions), with or without cyanosis.
RD. presence of two or more of the following signs: an abnormal respiratory rate, expira-
tory grunting, nasal flaring, chest wall recessions, and cyanosis as per patient chart
information.
Results
Characteristics of neonates
Among 604 neonatal charts reviewed, 571 (94.5%) records met the enrollment criteria and
were included in the final analysis. Of this group, 299 (52.34%) of the study participants were
males. Neonates in the late neonatal period accounted for more than half of the study partici-
pants. The mean age of the cohort at the time of admission to the NICU was 3 days ± 3.72 stan-
dard deviation (SD). More than half of the neonates admitted to the NICU were diagnosed
with neonatal sepsis, but other common causes of admission were jaundice, hypothermia, and
PNA (Table 1). In addition, the common types of RD for neonatal admission were RDS or hya-
line membrane diseases (Fig 1).
Table 1. Characteristics of neonates admitted to the NICU at Black Lion Specialized Hospital, Ethiopia, (n = 571).
Characteristics Category Frequency (%)
Sex Male 299 (52.34)
Female 272 (47.66)
Gestational age (weeks) <37 239 (41.8)
�37 332 (58.2)
Neonates weight (g) <2500 243 (42.6)
�2500 328 (57.4)
Hypothermia Yes 180 (31.5)
No 391 (68.5)
Sepsis Yes 260 (45.5)
No 247(43.3)
Jaundice Yes 202 (35.4)
No 369 (64.6)
1st minute Apgar <7 337 (59.0)
�7 234 (41)
https://doi.org/10.1371/journal.pone.0235544.t001
medical diagnosis of maternal diseases, 250 (43.8%) had PROM, (43.8%) had HIV/AIDS
(13.5%), and (10.7%) had DM. The results of this study also indicated that the majority [402
(70.4%)] of neonates were born to mothers who had an ANC follow-up. (Table 2).
Table 2. Socio-demographic and obstetric characteristics of mothers of neonates admitted to the NICU at Black
Lion Specialized Hospital, Ethiopia, (n = 571).
Characteristics Category Frequency (%)
ANC follow-up Yes 402(70.4)
No 169(29.6)
Maternal age (years) <20 61(10.9)
20–34 426 (74.6)
>34 84 (14.7)
Place of delivery Home 194(34)
Health institution 377(66.0)
Multiple pregnancy Yes 49(8.5)
No 522(91.5)
PROM Yes 250(43.8)
No 321(56.2)
HIV/AIDS Yes 76(13.3)
No 495(86.7)
Maternal DM Yes 61(10.7)
No 510(89.3)
https://doi.org/10.1371/journal.pone.0235544.t002
Fig 2. Overall Kaplan-Meier survival estimate of neonates with RD admitted to the NICU at Black Lion Specialized Hospital, Ethiopia.
https://doi.org/10.1371/journal.pone.0235544.g002
Fig 3. Kaplan-Meier survival curves of neonates with RD with respect to A) PROM, B) PNA, C) maternal HIV/AIDS, and D) mode of
delivery.
https://doi.org/10.1371/journal.pone.0235544.g003
Fig 4. The Cox-Snell residual Nelson-Aalen cumulative hazard graph on neonates with RDS admitted to the NICU at Black Lion Specialized
Hospital, Ethiopia.
https://doi.org/10.1371/journal.pone.0235544.g004
parametric exponential (AIC = 987.5) and Weibull (AIC = 686.9) semi-parametric Cox-pro-
portional hazard (AIC = 1123.54) models (Fig 4).
Predictors of RD
The univariate and multivariable parametric Gompertz hazard distribution regression model
was used to identify predictors of RD in neonates from admission to discharge in the NICU.
Findings from the bivariate analysis showed that gestational weight, being male, having no
antenatal follow-up, multiple pregnancies, neonates born via caesarean section, home delivery,
PROM, maternal DM, maternal HIV/AIDS, preterm birth, neonatal sepsis, and an Apgar
score of less than 7 were significantly associated with the time to discharge of neonates with
RD. However, in the multivariable analysis, being male, neonates born via caesarean section,
home delivery, maternal DM, preterm birth, neonatal sepsis, PROM, and an Apgar score of
less than 7 were the factors which continued as statistically significant predictors of RD. The
hazard ratio for RD in male neonates was 2.4 times higher than their female counterparts
[AHR: 2.4 (95%CI: 1.1, 3.1)]. The current study also showed that the hazard ratio for RD
among neonates born via caesarean section had nearly two times the risk compared to neo-
nates born vaginally [AHR: 1.9 (95%CI: 1.6, 2.3)]. In this study, the risk of RD in neonates
born at home was almost three times higher than those delivered at a health institution [AHR:
2.9 (95%CI: 1.5, 5,2)]. This result also indicated that neonates delivered from mothers who had
DM had a 2.3 times higher risk of RD as compared with their non-DM counterparts [AHR 2.3
(95%CI: 1.4, 3.6)]. Moreover, as the gestational age increases by one week the rate of RD
Table 3. Gompertz hazard model for predictors of RD among neonates admitted to the NICU at Black Lion Specialized Hospital, Ethiopia (N = 571).
Predictor Category RD (n, %) Censored (%) Total (%) CHR (95%CI) AHR (95%CI)
Mother’s age (years) <20 50 (20.4) 69 (21.2) 119 (10.9) 1.5 (0.97, 2.4) 1.4 (1.3, 1.9)
20–34 107 (43.7) 44 (13.5) 151 (74.6) 1
�34 88 (35.9) 213 (78.4) 301 (14.7) 2.7 (1.18, 3.4) 2.8(1.8, 3.3)
Sex Female 171 (48.6) 101 (46.2.) 272 (47.6) 1
Male 181 (51.4) 118 (53.8) 299 (52.4) 1.7 (1.2, 2.3) �� 2.4 (1.1, 3.1) �
Place of delivery Home 3.14 (2.3, 5.2) 2.9 (1.5, 5.2) �
Health institution 1
ANC follow up Yes 56 (22.8) 113 (34.7) 169 (29.6) 0.4 (0.3, 0.5) �� 0.8 (0.54, 1.19)
No 189 (77.2) 213 (65.3) 402 (70.4) 1
Multiple pregnancy Yes 23 (9.4) 26 (8) 49 (8.5) 1.6 (1.1, 2.1) �� 1.1 (0.9, 1.6)
No 22 (90.6) 300 (92) 351 (91.5) 1
PROM Yes 143 (58.4) 107 (32.8) 250 (43.8) 1.5 (1.1, 2.0) � 1.1(1.8, 1.5) �
No 102 (41.6) 219 (67.2) 321 (56.2) 1
Mode of delivery Caesarean section 132 (53.8) 103 (31.6) 235 (41.2) 1.6 (1.2, 2.2) �� 1.9 (1.6, 2.3)
Vaginal Caesarean section 113 (46.2) 223 (68.4) 336 (58.8) 1
HIV/AIDS Yes 35 (14.3) 41 (12.6) 76 (13.3) 1.9 (1.3, 2.7) �� 1.5(0.9, 2.5)
No 210 (85.7) 285 (87.4) 495 (86.7) 1
Maternal DM Yes 39 (15.9) 22 (6.7) 61 (10.7) 2.4 (1.6, 3.5) �� 2.3 (1.4, 3.6) ��
No 206 (84.1) 304 (93.3) 510 (89.3) 1
Sepsis Yes 189 (77.1) 122 (37.4) 311 (54.5) 2.2 (1.6, 3.1) �� 1.6 (1.1, 2.4) ��
No 56 (22.9) 204 (62.6) 260 (45.5) 1
GA <37 23 (13.5) 8 31 (5.4) 6.3 (3.9, 10.2) �� 2.9 (1.6, 5.1) ��
�37 61 (35.9) 271 (67.6) 332 (58.1) 1
Neonatal weight (g) <1000 22 (12.9) 11 33 (5.8) 3.8 (1.9, 7.5) �� 1.9 (0.9, 4.3)
1000–1500 56 (32.9) 99 (24.7) 155 (27.1) 1.3 (0.7, 2.4) 0.8 (0.41, 1.6)
1500–2500 84 (49.4) 257 (64.1) 341 (59.7) 1.1 (0.6, 1.9) 0.8 (0.4, 1.4)
�2500 8 34 (8.5) 42 (7.4) 1
First minute Apgar Score <7 154 (90.6) 283 (70.5) 437 (76.5) 3.2 (1.9, 5.4) � 3.1 (1.8, 5.0) �
�7 16 118 (29.5) 134 (23.5) 1
Fifth minute Apgar score <7 128 (75.2) 131 (32.7) 259 (45.4) 3.8 (2.7, 5.4) �� 1.81 (1.3, 4.8) ��
�7 42 (24.8) 270 (67.3) 312 (54.6) 1
https://doi.org/10.1371/journal.pone.0235544.t003
decreased by 10% [AHR: 2.9 (95%CI: 1.6, 5.1)]. The risk of RD also increased threefold for a
neonate who had an Apgar score of less than 7 as compared with one having an Apgar score
greater than or equal to 7 [AHR: 3.1 (95%CI: 1.8, 5.0)]. Additionally, neonatal sepsis increases
the risk of RD by 60% [AHR: 1.6 (95%CI: 1.1, 2.4)]. The last predictor for RD was to be born
from mothers experiencing PROM, with neonates having a 1.11.1(1.8,1.5) times higher risk of
RD than their counterparts not experiencing PROM [AHR: 1.1 (95%CI: 1.8, 1.5)] (Table 3).
Discussion
In the current study, the overall proportion of neonates with RD admitted to the Black Lion
Specialized Hospital NICU was 42.9% (95%CI: 39.3–46.1%). This finding is in line with a
study conducted in the Republic of China [23]. However, our finding is higher than studies
conducted in several countries including Nepal (34%) [24], India (33.4%) [10], Egypt (34.3%)
[25], Pakistan (4.6%) [26], Northern Italy (20.1%) [27], and Portugal (8.83%) [28]. Variance
noted in these studies may have been due to differences in the study settings which maybe
more advanced maternal newborn care services in some locations than in others. Additionally,
sample size, study design, and population socio-demographic characteristics may also lead to
the differences observed between studies. Interestingly, the prevalence of RD found in this
study was lower than studies from Saudi Arabia (54.7%) [8], Cameroon (47.5%) [7], and
Poland (54.29%) [29]. These differences may reflect the quality/qualifications of staff, public
awareness to attended births, and cultural beliefs.
Based on the current finding, the overall incidence of RD was 8.1 per 100 neonate-days
(95%CI: 7.3, 8.9). The common causes of RD in our study were RDS and meconium aspira-
tion, which is similar to previous findings from Nepal and Egypt [24, 25].
This study found that there were multiple predictors of RD in neonates from Ethiopia,
including preterm birth, caesarean section delivery, Apgar score < 7, sepsis, PROM, maternal
DM, and home delivery. The risk of RD in male neonates was 2.4 times higher than their
female counterparts; a finding which was also found in studies done in China [28] and Camer-
oon [7]. This aligns with the fact that male neonates have higher levels of circulating testoster-
one than females, which may be associated with differences in pulmonary biomechanics and
vascular development. For those neonates delivered via caesarean section there was a nearly
two times higher risk of developing RD than in non-caesarean births. This was also found in
neonate studies from China [23], Cameroon [7], and Italy [30]. Moreover, we found that the
risk of RD for neonates born at home was almost three times higher than those delivered at a
health institution.
Mothers with DM bore infants 2.3 times more likely to develop RD than non-DM mothers,
which is 2again a finding supported by research done in China [31]. It is possible that this
relates to the fact that these neonates have plentiful glucose stores, but develop hypoglycemia
because of high insulin secretion induced by maternal and fetal hyperglycemia.
Our study also found that preterm neonates had a threefold greater likelihood of RD than
those who were term births, which aligns with work from Cameron [7] and Italy [30]. This
finding seems to coincide with the positive association between gestational age and fetal devel-
opment, thereby reducing complications as the level of prematurity is lessened. Additionally,
those neonates born premature often have immature lung structures which might delay intra-
pulmonary fluid absorption, a deficiency in pulmonary surfactant, and inefficient gas
exchange. The risk of RD was also increased by threefold in neonates who had an Apgar score
less than 7, which has been previously reported in other studies [7]. Finally, neonatal sepsis
was significantly associated with the risk of developing RD as was found in Nepal and Egypt,
[24, 25].
Limitations
Since the data were collected from secondary source; some important predictors such as socio-
economic factors like nutritional status of mother, educational level, birth interval might be
missed which will have a significant on RD. The study area covers only TASH; its generaliz-
ability to all hospitals of the city and Ethiopia is may not be possible and this might also
decrease our precision.
Conclusion
RD was found to be a major public health problem for neonates that were admitted to NICU
of Black Lion Specialized Hospital. Those neonates delivered at home, delivered through cae-
sarean section, born preterm, who had an Apgar score < 7, or were born from diabetic moth-
ers were most likely to develop RD. Thus, to actively reduce the risk of the development of RD
in neonates, medical professionals should support pregnant mother’s health wherever possible
and encourage those mothers to give birth in health care institutions, especially in premature
birth situations.
Supporting information
S1 Text. STROBE Statement—Checklist of items that should be included in reports of
cohort studies.
(DOCX)
S2 Text. Checklist used to assess incidence of RD and its predictors.
(DOCX)
S1 Table.
(DOCX)
Acknowledgments
We would like to thank black lion hospital neonatal ward staffs, card extractors, and data col-
lectors whose assistance was invaluable to our completion of the study. our gratitude also goes
to doctor Ryan Bell (CEO and Chief Editor Excision Editing) who have made an extensive edi-
tion in our manuscript.
Author Contributions
Conceptualization: Yared Asmare Aynalem, Pammla Margaret Petrucka.
Data curation: Yared Asmare Aynalem, Hussien Mekonen, Tadesse Yirga Akalu, Pammla
Margaret Petrucka.
Formal analysis: Yared Asmare Aynalem, Hussien Mekonen, Pammla Margaret Petrucka.
Investigation: Yared Asmare Aynalem, Hussien Mekonen.
Methodology: Yared Asmare Aynalem, Pammla Margaret Petrucka.
Project administration: Yared Asmare Aynalem, Tesfa Dejenie Habtewold.
Resources: Tesfa Dejenie Habtewold.
Software: Yared Asmare Aynalem, Tesfa Dejenie Habtewold, Aklilu Endalamaw, Wondime-
neh Shibabaw Shiferaw.
Supervision: Yared Asmare Aynalem, Tadesse Yirga Akalu, Aklilu Endalamaw.
Validation: Yared Asmare Aynalem, Wondimeneh Shibabaw Shiferaw.
Visualization: Yared Asmare Aynalem, Wondimeneh Shibabaw Shiferaw.
Writing – original draft: Yared Asmare Aynalem, Aklilu Endalamaw, Wondimeneh Shiba-
baw Shiferaw.
Writing – review & editing: Yared Asmare Aynalem, Tadesse Yirga Akalu, Wondimeneh Shi-
babaw Shiferaw.
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