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PLOS One logoLink to PLOS One
. 2022 Jun 15;17(6):e0269479. doi: 10.1371/journal.pone.0269479

Referral challenges and outcomes of neonates received at Muhimbili National Hospital, Dar es Salaam, Tanzania

Mpokigwa Kiputa 1,*,#, Nahya Salim 1,*,#, Peter P Kunambi 2, Augustine Massawe 1
Editor: Elsayed Abdelkreem3
PMCID: PMC9200315  PMID: 35704624

Abstract

Background

Functional referral system including pre referral care, access to emergency transport and ensuring continuity of care between facilities is critical for improved newborn health outcome. The neonatal transport system is quite undervalued in many sub Saharan countries, Tanzania included. This study assessed the pre referral care, transport process, ambulance characteristics, admission clinical status and outcomes of referred neonates at Muhimbili National Hospital Upanga, a tertiary facility in Dar es Salaam, Tanzania.

Methods

A descriptive cross sectional study with a longitudinal follow up was conducted from September 2020 to February 2021 including neonates referred to Muhimbili National Hospital. A structured questionnaire was used to collect demographic characteristics and transport factors including pre referral care extracted from the referral documents and through interviewing caregivers or escorting person/nurse. Ambulances were directly observed using a structured checklist on presence, absence and functionality of supportive equipment. All enrolled neonates had a clinical assessment at admission and 48 hours post admission to determine admission clinical status and 48 hours’ clinical outcome as either survived/died.

Results

Out of the 348 neonates assessed during the study period, the median gestation age was 38 weeks (IQR 32, 39) with the mean birth weight of 2455 ± 938 g. Pre referral documentation showed that temperature was measured in 176 (57.1%), oxygen saturation and random blood glucose in only 143 (46.6%) and 116 (36.2%) neonates respectively. Ambulance was used as a means of transportation in 308 (88.5%) neonates. While no ambulance had an incubator only 7 (2.0%) neonates were kept on a Kangaroo Mother Care position. Monitoring enroute was done to only 94 (27%) of the transferred neonates with 169 (54.9%) of health care professionals escorting the neonates lacking training on essential newborn care. On arrival, 115 (33%) were hypothermic, 74 (21.3%) hypoxic, 30 (8.6%) with poor perfusion and 49 (14.1%) hypoglycemic. Hypothermic neonates had an increased chance of dying compared to those who were normothermic (OR = 2.09, 95% CI (1.05–4.20), p = 0.037). The chance of dying among those presenting with hypoxia was almost three times (OR = 2.88, 95%CI (1.44–5.74), p = 0.003) while those with poor perfusion was almost five times (OR = 4.76, 95%CI (1.80–12.58), p = 0.002). Additionally, neonates who had hyperglycemia (RBG > 8.3mmol/l) on arrival had a higher probability of dying compared to those who were euglycemic [(OR = 3.10, 95% CI (1.19–8.09) p = 0.021]. Overall mortality was 22.4% within 48 hours of admission and risk of dying increased as the presence of poor clinical status added on.

Conclusion

Neonatal transportation in Dar es Salaam, Tanzania was observed to be challenging. Pre transfer care and monitoring during transportation was inadequate and this contributed to poor clinical status on admission. Hypothermia, hypoglycemia, hyperglycemia, hypoxia and poor perfusion on admission were associated with increased mortality. Effective referral network is needed for improved neonatal health outcomes. Pre referral supportive care, training of health care professionals, transportation with improved monitoring, clear communication protocol and referral documentation should be invested and effectively utilized.

Introduction

Globally, neonatal mortality rate has decreased from 36.6 deaths per 1000 live birth to 18.0 deaths per 1000 live birth between the year 1990 and 2017 [1]. The rate of decline in sub Saharan Africa needs to be accelerated to achieve the Sustainable Development Goals (SDG’s) by 2030 [1]. In Tanzania, the current neonatal mortality rate is estimated to be 25 deaths per 1000 live birth [2], with institutional deliveries of 76% according to District Health Information Software (DHIS2) of 2018. Considerable efforts have been emphasized on quality facility based care including investment in network of care to facilitate survival [3]. A large number of inter facility transfer is already happening and it is likely to increase.

Referral system challenges such as inadequate transportation, lack of communication, poor documentation and lack of monitoring have been established as factors impeding the stride towards reducing neonatal mortality in developing countries [4]. A well-established referral system is key to transfer neonates to a tertiary care facility [57].

Transportation of a neonate from one facility to another under ideal conditions is still a challenge in many developing countries, Tanzania included. Most of the neonates arrive in poor clinical conditions, which are mostly preventable. Previous studies have shown that hypothermia, hypoglycemia, poor perfusion and hypoxia are associated with increased mortality among transported neonates [812].

There is enough evidence to support that transport by a skilled organized team reduces neonatal morbidity and mortality [9, 13, 14]. The goal of all neonatal transport teams should be transporting a well-stabilized neonate. Pre transport stabilization is crucial; this entails securing the patency of the airway, breathing and circulation. Pre-transport procedures such as establishing an intravenous access should be carried out before arrival of the transport team [15, 16] and continuous monitoring is needed on the way to a higher facility.

Despite the effort to strengthen the referral system in the country and the improvement of health care delivery in terms of infrastructure and manpower, the outcome of referred neonates is still poor. According to raw data collected in 2020 from the tertiary facility, Muhimbili National Hospital (MNH), neonatal mortality among the out-borns is almost twice as high compared to the in-borns admitted at the same neonatal unit.

This study aimed at describing the transport characteristics (i.e. mode of transport, equipment, communication, accompanying personnel, pre referral care and monitoring enroute) for the referred neonates. Additionally, it sought to assess the clinical status at admission in terms of the presence of hypothermia, hypoxia, perfusion and hypoglycemia for the transported neonates to Muhimbili National Hospital (MNH). Furthermore, it determined 48 hours’ outcome and its associated factors in relation to the admission clinical status of referred neonates.

Ethics statement

Permission to carry out the study was sought from Muhimbili University of Health and Allied Sciences (MUHAS) Institutional Review Board (IRB) with an approval number MUHAS-REC-07-2020-306. Written informed consent to participate in the study was sought from both the parent/guardian and health care personnel who escorted the neonate prior to any study procedure. Illiterate parents/ guardians were asked for a witness who participated within the discussion prior to obtaining their thumbprints and witness signature. All neonates received appropriate treatment according to the national treatment guidelines of Tanzania regardless of participation.

Materials and methods

Study area

Muhimbili National Hospital (MNH), Upanga is a tertiary referral centre and teaching hospital receiving patients from the five municipalities in Dar es Salaam (Ilala, Kinondoni, Kigamboni, Ubungo and Temeke) and other upcountry regions. It has a transitional level 2 plus Neonatal Intensive Care Unit (NICU) for caring critically ill neonates. Staff cadres constitutes of 2 neonatologists, 9 pediatricians, 5–10 residents at a time, 3 medical registrars, 9–11 interns and 59 trained nursing staff. The referral annual admissions range between 1440 and 3360 neonates.

Study design

A descriptive cross sectional study with a longitudinal follow up was carried out at Muhimbili National Hospital (MNH), in Dar-es-Salaam region, Tanzania.

Participant recruitment and data collection

All neonates referred to MNH from September 2020 to February 2021 were eligible for enrollment except for neonates with obvious congenital anomalies. A consecutive sampling was used to recruit referred neonates until the required sample size of 349 neonates was met. Sample size was calculated using the expected proportion of referred neonates transported to the neonatal unit of MNH who died in the first week post admission. This was established using a pilot study conducted at MNH prior to this, and was found to be 35%. A sample size of 349 was achieved using the Kish Leslie formula with 95% confidence level and 5% margin of error.

Data was collected day and night using a pretested structured questionnaire designed for the study (S1 File). Data on demographic characteristics of the study participants and pre referral treatment if any were obtained from the referral documents and by interviewing the caregiver or escorting personnel/nurse. The escorting health care personnel was enquired about the transport process including pre transport care and monitoring during transport. Escort team were also asked on whether they received a training on essential newborn care. Data on ambulance characteristics was obtained through direct observation of the transport by looking inside the transport for the presence of necessary equipment using WHO neonatal ambulance checklist [17]. Gestation age, birth weight and date of birth were extracted from the referral documents. Clinical status on admission was measured using TOPS model [1820], whereby;

Temperature was recorded in degrees centigrade and hypothermia defined as an axillary temperature on admission < 36.5°C measured with a digital thermometer (KONIG HC-DT10 Digital Thermometer, United Kingdom). Fever as axillary temperature on admission > 37.5°C.

Oxygen saturation (SPO2) was measured by using the pulse oximeter (ChoiceMMEd fingertip pulse oximeter, manufacturer: Beijing choice electronic technology Co., Ltd. Fuxing road A36 Beijing, 100039 China). Hypoxia was defined as oxygen saturation less than 90% in room air [21].

Perfusion, Capillary Refill Time was recorded by applying gentle pressure on the sternum for 3–5 seconds to cause blanching then the time taken for color to return was measured.

Sugar, Random Blood Glucose was measured by using a haemoglucometer machine (STANDARD™ GlucoNavii® GDH. Manufacturer: SD Biosensor, Inc. Gyeonggi-do, 16690, Republic of Korea). Hypoglycemia was defined as the blood glucose measurement of less than 2.5 mmol/L and hyperglycemia as blood glucose measurement greater than 8.3 mmol/L.

Neonates who were found to be hypoglycemic on admission were given bolus intravenous dextrose, those who were hypoxic received supplemental oxygen according to their needs and those who were hypothermic were kept in a warmer. Neonates who were in shock upon arrival were resuscitated with intravenous fluids according to the hospital protocol. There was room for escalation of care for neonates who needed advanced respiratory support such as ventilating machine.

All enrolled neonates were assessed at 48 hours post admission to capture the early outcome that was defined as survived or died.

Data management and statistical analysis

Data analysis was done using SPSS version 23.0. Dependent variables were admission clinical status as per TOPS model and outcome defined as survival or death of referred neonates at 48 hours post admission. Independent variables were 1. transport factors including mode of transport, presence/functionality of equipment in the transport, accompanying personnel cadre, training status of escorting personnel, monitoring during transport, and pre transport care provided and prior communication 2. Demographic factors: age, sex, birth weight, gestational age, age in days, mode of delivery, Apgar score.

Continuous variables for social-demographic and clinical characteristics of study participants were described using mean and standard deviations or medians and interquartile range depending on normality of distribution. Proportions were presented in bar graphs. Factors with P < 0.2 from univariate analysis were included in the multivariable analysis. Multiple logistic regressions (odds ratio) was used to determine association with clinical outcome. A p-value ≤ 0.05 was considered statistically significant at 95% confidence interval.

Results

Baseline characteristics of the study participants

A total of 349 referred neonates were recruited during the study period, one was excluded from the study due to a congenital anomaly which was incompatible with life (anencephaly). Fig 1 shows the proportion of participants received at Muhimbili National Hospital (MNH), Upanga stratified by referring districts of Dar es Salaam, Tanzania. Out of the 348 neonates, 207 (59.5%) were term babies while 141 (40.5%) were preterm. Majority were male babies 197 (56.6%) with 258 (74.1%) neonates delivered by spontaneous vaginal delivery (SVD) while 85 (24.4%) were born via caesarean section. The median gestation age was 38 weeks (IQR; 32–39) with the mean birth weight of 2455 ± 938 g. The mean age at admission was 1.78 ± 0.757 days. Table 1 describes the socio- demographic and clinical characteristics of the study participants.

Fig 1. Flow of the study participants referred from various districts of Dar es Salaam, Tanzania.

Fig 1

Table 1. Socio-demographic and clinical characteristics of study participants, N = 348.

Characteristic Category Frequency (n) Percent (%)
Sex Male 197 56.6
Female 151 43.4
Age at admission (days)
0–1 229 65.8
2–6 95 27.3
7–28 24 6.9
Mean age at admission (SD) (days) 1.78 (± 0.757)
Gestational age (weeks) <28 25 7.3
28–32 68 19.7
33–36 45 13.0
>37 207 60.0
Median gestational age (week) (IQR) 38 (32–39)
Birth weight (g) Less than 1000 21 6.0
1000–1499 37 10.6
1500–2499 96 27.6
2500+ 194 55.8
Mean birth weight (SD) (g) 2455 (± 938)
Mode of delivery SVD 258 74.1
Breech delivery 4 1.2
Vacuum delivery 1 0.3
Caesarean section 85 24.4
Apgar score at 1st and 5th minutes 0–3 (low) 4 1.1
4–6 (moderately abnormal) 65 18.8
7–10 (reassuring) 279 80.1

Pre transport care and documentation at referring facility

According to data extracted from the referral forms, two hundred and forty-six (79.9%) neonates had an intravenous line inserted prior to transfer. Temperature was measured in 176 (57.1%) neonates before transfer. Oxygen saturation and random blood glucose were measured pre transfer in only 143 (46.6%) and 116 (36.2%) neonates respectively.

Transport process

Communication

Out of 348 neonates who were transferred to the neonatal unit of MNH, in only 26.7% the notification was given prior to transfer.

Escorting personnel

Out of the 340 neonates who were escorted, two hundred and thirty neonates (66.1%) were escorted by the registered nurse. Seventy-five (21.6%) were escorted by the nurse attendant while eight (2.3%) were escorted by a doctor and thirty-two (9.2%) were escorted by the family member. Of the health care professional escorting the neonate, two hundred and nine (66.1%) had no training on essential newborn care.

Access to ambulance service

Majority of the neonates were transported by ambulance 308 (88.5%), followed by private car/taxi 30 (8.6%), public service vehicle 9 (2.6%) and tricyclic motor vehicle 1 (0.3%).

Monitoring during transport

Monitoring was done to only 94 (27%) of the transferred neonates. Of those 69 (73.4%) had their temperature measured. Capillary refill time was monitored in 37 (39.4%) of the transferred neonates while random blood glucose was checked in 27 (28.7%). Just 57 out of 94 (60.6%) had their oxygen monitored during transport.

Warmth during transport

Most of the referred neonates were kept warm using local clothes (Khanga/Kitenge), 233 (67.0%). Only 7 (2.0%) were kept on a Kangaroo Mother Care position, while no neonate was kept in an incubator during transfer.

Reasons for referral

The main reason for transfer was to seek specialized care 164 (47.1%) followed by a lack of newborn unit 65 (18.7%), referred for further investigation 65 (18.7%), lack of equipment 23 (6.6%) and lack of personnel 7 (2.0%).

Ambulance characteristics

For those who came with an ambulance 308, 294 (95.5%) had an oxygen supply, but in 42.5% of those the oxygen delivery system was not functioning. Only 201 (65.3%) had resuscitation equipment such as Ambu bag packed in the ambulances. Resuscitation drugs such as adrenaline were included in 200 (64.9%). Monitoring equipment were not available in 104 (33.8%) ambulances. IV fluids were present in 237 (77.0) while only 184 (59.7%) had suction apparatus. No ambulance had an incubator.

Fig 2 summarizes coverage gap during the referral journey of a newborn in Dar es Salaam, Tanzania.

Fig 2. Coverage gap during the referral journey of a newborn in Dar es Salaam, Tanzania.

Fig 2

Admission clinical status and outcome at the receiving facility, MNH

Seventy-eight neonates (22.4%) died within 48 hours of admission. On arrival, the clinical status of the neonates were as follows; 115 (33%) hypothermic, 74 (21.3%) hypoxic, 30 (8.6%) with poor perfusion and 49 (14.1%) hypoglycemic. Those with hypothermia (< 36.5°C), were two times more likely to die compared to those who were normothermic (OR = 2.09, 95% CI (1.05–4.20), p = 0.037). Thirty-eight (50.7%) of those who had hypoxia (SPO2 < 90%) at arrival died compared to thirty-seven (49.3%) who survived (OR = 2.88, 95%CI (1.44–5.74), p = 0.003). Twenty-one (67.7%) neonates with prolonged capillary refill time (CRT) died compared to ten (32.3%) who survived (OR = 4.76, 95%CI (1.80–12.58), p = 0.002). Out of forty-nine neonates who arrived with hypoglycemia (RBG < 2.5mmol/l) twenty-one (42.9%) died in the first 48 hours (OR = 2.13, 95%CI (0.96–4.74), p = 0.064). Additionally, neonates who had hyperglycemia (RBG > 8.3mmol/l) on arrival were three times more likely to die compared to those who were euglycemic [(OR = 3.10, 95% CI (1.19–8.09) p = 0.021]. Table 2 summarizes the results of univariate and multivariable analysis of factors associated with mortality.

Table 2. Univariate and Multivariate analysis of factors associated with mortality.

Univariate analysis Multivariable analysis
Variable cOR 95% CI P -value aOR 95% CI P -value
Gestational age (weeks)
< 28 7.95 3.19–19.83 < 0.001 3.16 0.77–12.99 0.111
28–33 1.10 0.57–2.15 0.769 0.61 0.22–1.74 0.357
34–36 0.49 0.18–1.30 0.151 0.35 0.11–1.17 0.089
≥ 37 Ref
Weight (Kg)
< 1.0 4.65 1.86–11.59 < 0.001 1.99 0.45–8.74 0.362
1.0–1.4 3.03 1.43–6.41 0.004 2.54 0.70–9.24 0.158
1.5–2.4 1.07 0.57–2.02 0.829 1.56 0.68–3.60 0.293
≥ 2.5 Ref
Temperature ( 0 C)
Hypothermia (< 36.5) 3.65 2.04–6.53 < 0.001 2.09 1.05–4.20 0.037
Fever (> 37.5) 1.62 0.76–3.43 0.209 1.25 0.53–2.96 0.612
Normal (36.5–37.5) Ref
Capillary Refill Time
Prolonged (> 3 seconds) 9.58 4.28–21.44 < 0.001 4.76 1.80–12.58 0.002
Normal (< 3 second) Ref
Oxygen saturation
Hypoxia (< 90%) 5.98 3.41–10.51 < 0.001 2.88 1.44–5.74 0.003
Normal (≥ 90%) Ref
Random blood glucose (mmol/L)
Hypoglycemia (< 2.5) 4.19 2.17–8.07 < 0.001 2.13 0.96–4.74 0.064
Hyperglycemia (> 8.3) 6.87 3.08–15.36 < 0.001 3.10 1.19–8.09 0.021
Normal (2.5–8.3) Ref

Key. cOR: crude odds ratio, aOR: adjusted odds ratio, Ref: Reference category.

The combined effect of poor clinical status on admission in terms of hypoglycemia, hyperglycemia, hypoxia, prolonged CRT and hypothermia were associated with increased mortality as shown in Fig 3.

Fig 3. Combined effect of exposures on newborns mortality outcome at 48 hours post admission at Muhimbili National Hospital.

Fig 3

Discussion

Despite its importance, neonatal transportation has often been overlooked in resource constrained and poor countries like Tanzania [16, 22, 23]. Due to lack of organized neonatal transportation system, most of these neonates arrive in poor clinical condition which influence their outcome negatively [5, 8]. This study assessed the gaps on pre referral care, neonatal transportation, admission clinical status and outcome of the referred neonates at MNH–Upanga, a tertiary facility in Dar es Salaam, Tanzania.

In our study, nineteen percent of the neonates were referred due to lack of a newborn unit in their facilities, seven percent had no equipment while almost half of others were referred for specialized medical or surgical care. Improving level of care in institutions including establishment of well-equipped neonatal units could reduce referrals and mortality of newborns. The ministry of health, Tanzania in collaboration with the Newborn Essential Solutions and Technologies (NEST360) program have been improving neonatal infrastructures, installing equipment and providing in service training to strengthen neonatal care in hospitals across three regions (Dar es Salaam, Mbeya and Moshi) since early 2020. The phase I implementation of NEST 360 program is focusing on regional and tertiary facilities in a stepped wedged approach. While it’s clear that the program is influencing the neonatal care, it’s too early and challenging to link the measurements due to lack of baseline data. Currently, all the three regional referral hospitals in Dar es Salaam have been upgraded to level 2 plus with ongoing quality improvement and mentorship within the region. The findings of this study may provide highlights on baseline data for future studies. Strengthening harmonized health services and investing in coordinated network of care is of paramount importance to ensure safe transfer and survival for those in need.

Pre transport care is pivotal before transfer to a higher facility and is generally agreeable that for a quality transport and desirable outcome, stabilization prior to transfer is mandatory [24]. A study by Narang et al. demonstrated an overall decrease in mortality among neonates in whom lifesaving interventions were done pre referral [25]. In our study, we focused on TOPS model and we noted that temperature was measured in more than half of the neonates prior to transfer. In more than half of the referred neonates neither oxygen saturation nor random blood glucose was measured or documented. Twenty percent of the neonates were transferred without a secured intravenous line which is vital for institution of drugs during resuscitation. In the majority, there was no documentation of what was done, for example to those who were found to be hypothermic. It is clear that poor pre transport care contributed to poor conditions at arrival with subsequent poor outcome. These findings have been documented in previous studies [26, 27]. Knowledge, skills and competence of health professionals is key to saving lives at first level referral facilities, this gap need further attention toward quality newborn care.

Three quarters of the referred neonates were brought in without any notification given to the neonatal unit that could give room for preparation and advice. This finding is similar to the study done by Abdulraheem et al. in Ibadan Nigeria which showed no communication or documented information regarding the clinical stability of any of the neonates prior to transfer [16]. In Tanzania, the referring institution is tasked with providing the escorting personnel and pre referral communication of the case. Our study has shown that in addition to lack of communication, most of the times staff who will render minimal interruption to the hospital running are utilized rather than competent nurses who can support a neonate in the ambulance. Quite a number of neonates were escorted by nurse attendants 73 (21.5%) who were not trained to provide that level of care. Furthermore, this study found more than half of the escorting health care personnel lacking training on essential newborn care. A study done in Jamaica reported one in three of the personnel accompanying the neonate were not skilled in neonatal resuscitation [15]. Transfer of neonates by trained personnel has shown to reduce morbidity and mortality [28]. Improvement in communication system and skills on emergency care is needed.

The preponderance of neonates who were referred to our facility came with hospital organized ambulances at 308 (88.5%) compared to other modes of transport. This is different from studies done in Ghana and Nigeria whereby majority of neonates were brought in by taxis and private vehicles at 36% and 43.9% respectively [16, 23]. The findings are consistent with the study done in the EThekwini health district of KwaZulu-Natal, South Africa whereby all the referrals were transported by ambulance [29]. In Tanzania, ambulance services are cost free in all government owned facilities this could explain why many neonates were brought in using ambulances. Nonetheless, it is worth noting that despite the availability of ambulance, inadequate equipment and functionality were observed. Lack of equipment such as patient monitors impedes actions that could be taken to reverse deterioration during transport. It is not surprising that many neonates arrived at the tertiary hospital in unsteady clinical conditions i.e poor perfusion, hypoxic, hypoglycemic and hypothermic.

Most ambulances had oxygen supply similar to a study done in Bangladesh [30], in our study only 57.5% of the oxygen delivery system were functional. This fact plus lack of monitoring during transport clearly could have contributed to a number of neonates arriving hypoxic at the facility. Similar to our findings, a study by Mehta et al. done in India using the TOPS model established that neonates who had hypoglycemia and prolonged capillary refill time on admission had an overall poor outcome compared to their counterparts [19]. Additionally, we found a number of neonates who were hyperglycemic, had significant higher odds of mortality. These could have been neonates whose blood sugar levels were not monitored and some were given continuous infusion of glucose without any blood glucose check. Monitoring during transportation is critical, ambulance services need to be coordinated.

Dar es Salaam has a tropical climate located 16m above sea level with an average annual temperature of 26.1°C. Despite this fact, one third of the neonates were hypothermic on admission which was associated with increased mortality. This finding is similar to studies done in low resource settings in Ghana and India where almost half of the neonates were found to be hypothermic [23, 25]. A study which was done on the same setting in 2003 by Manji et al. found a threefold increase in mortality and morbidity among hypothermic neonates [11]. Hypothermia in our study was contributed by lack of monitoring during transport and inferior means of maintaining warmth as more than two third of the referred neonates were covered by only light local clothes such as khanga and kitenge. Most facilities could not afford incubators in their ambulance, nevertheless the practice of KMC which has been shown to be cheap and effective in preventing hypothermia was observed in only 2% of the transferred neonates. In a study conducted by Rathod et al., in southern India, KMC practice was not observed at all [22].

The overall mortality of neonates 48 hours post admission was 22%. Furthermore, a correlation between poor clinical status on admission in terms of hypoxia, hypothermia, hyperglycemia and poor perfusion with increased risk of mortality 48 hours post admission has been demostarted in previous studies [912]. For example, persistent hypothermia in newborns can lead to complications such as infection, hypoglycemia, and metabolic acidosis, and increase the risk of late-onset sepsis [31, 32]. Managing hypothermia and maintaining a healthy temperature in neonates is essential to survival of the particularly vulnerable newborn [31, 33]. All these are preventable conditions, if tackled appropriately could increase survival of the newborns.

Overall, this study demonstrates inadequate pre transport care, documentation and lack of monitoring enroute contributing to poor clinical conditions of neonates at admission. Emphasis has to be placed on having coordinated ambulance services, strengthening referral system and pre referral care to neonatal transportation. Additionally, ensuring continuous training to health care workers on neonatal resuscitation and essential newborn care is key. Regional and national coordination is needed to strengthen the referral system network.

Our study may have been exposed to recall bias as some of the information relied on the escorting health personnel. Hawthorne effect can’t be ignored as the behaviors might have changed on the course of the study including improvement in the referral and transportation of neonates as they become aware they are being observed. Limitation in recording full data due to poor/incomplete documentation based on the referral forms, consequently contributed to the inadequate data of pre-referral care assessment, reasons for referral and monitoring enroute information. Despite the limitations, the findings reflect the gaps of referral system which need to be improved for quality care of newborns at the primary and secondary levels. Further studies are required to learn on barriers and facilitators of effective referral at all levels of care. All efforts should be done to ensure every small and sick newborn with condition(s) that cannot be managed effectively with available resources receive appropriate, timely referral through integrated newborn service pathways with continuity of quality care, including provisional of warmth using cost effective measures such as KMC during transportation.

Supporting information

S1 File. Structured questionnaire English version.

(DOCX)

S1 Data

(XLSX)

Acknowledgments

The authors acknowledge all staff at Muhimbili National Hospital, all caregivers/guardians of neonates, escorting persons and nurses who made this study possible to accomplish what we have. We are particularly obliged to Dr. Robert Moshiro and all members of Peadiatrics and Child Health Department at MNH and MUHAS. We would like to dedicate this work to our mentor, neonatologist, a father and a neonatal champion in Tanzania, the Late Dr. Augustine Massawe. May his soul rest in peace, Amin.

Data Availability

All relevant data are within the paper and its supporting information files.

Funding Statement

This study received no financial support, it was part of the academic completion requirement supported by the Government of Tanzania through the Ministry of Health, Community Development, Gender, Elderly and Children at Muhimbili University of Health and Allied Sciences, MUHAS.

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Decision Letter 0

Elsayed Abdelkreem

2 Feb 2022

PONE-D-21-40535Referral Challenges and Outcomes of Neonates Received at Muhimbili National Hospital, Dar es Salaam, Tanzania.PLOS ONE

Dear Dr. KIPUTA,

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**********

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Reviewer #1: Yes

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**********

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**********

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**********

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Reviewer #1: Referral Challenges and Outcomes of Neonates Received at Muhimbili National Hospital, Dar es Salaam, Tanzania

PONE-D-21-40535

I would like to congratulate the authors for a good work done. I have some minor concerns which may improve upon the quality of the manuscript.

1. Introduction: lines 72-73 stated “About half of neonates die within the first 24 hours after birth and 75% in the first seven days of life” Please check this information and present it appropriately. You mean; about half of all neonatal deaths occur within the first 24 hours……

2. Participant recruitment and data collection: line 126 stated that: “Data was collected day and night…”. Were there any difference in outcome when day or night referrals were considered

3. Neonatal age in days at time of admission was not reported. This is important to understand the outcome measure presented in the study

4. Results section monitoring during transport: lines 183-184: “Blood circulation was monitored in 37 (39.4%) of the transferred neonates…..”. How was it done and how was this assessed.

5. Table 1: presented “Apgar score 1st and 5 minutes” however only single measurement was presented. A little explanation would dispel the confusion.

Reviewer #2: General comment

This would have been an important study that contributes to the understanding of the Referral Challenges and Outcomes of Neonates Received at Muhimbili National Hospital, Dares Salaam, Tanzania. However, there are minor flaws in the method of the study, discussion and grammar that need a revision before publication.

Specific comments

1. In abstract section, it needs more elaboration in why the study is needed/ gap of the study, As much as possible avoid acronyms in the abstract and rewrite the abstract in very short and precise way particularly in the result section.

2. Pay great attention for punctuations.

3. In introduction section, would start with the global and regional/ continent evidence on neonatal mortality and relate it with how referral contributes. One paragraph which describes why this study is needed. Generally, introduction lacks coherence of ideas, world to Tanzania figure of neonatal mortality, gap of the study, clear description of clinical outcome of referral neonates in previous study. Introduction needs substantial modification.

4. In materials and methods,

Study area: Add the number of physician, nurses and other health care professionals working in neonatal ward and NICU. It gives an insight for why high burden of neonatal death; Is because of shortage of HCW or not? You stated the number of admission but we can’t get patient-to-physician proportion.

• In line 147, it states as “All enrolled neonates were assessed at 48 hours post admission to capture the early outcome that was defined as survived or died” what is your baseline reference? If there is, cite it.

5. Result

• In line 157, it states as “ A total of 349 referred neonates were screened during the study period, one was excluded from the study due to a congenital anomaly which was incompatible with life (anencephaly).” How it could be? You already excluded the known congenital anomalies before including in the study.

• In line 161, “258 (74.1%) were delivered by Spontaneous Vertex Delivery (SVD) while 85 (24.4%) were born via caesarean section.” Rewrite this.

• What is the rationale behind to use median/mean and IQR and SD? You used median for GA and mean for BWt….

• In line 176, it states as “thirty-two (9.4%) were escorted by the family member.” In method section, you stated that the pre transfer data and transportation data/monitoring during transportation were taken from accompanying personnel/escort personnel. My question is how did you collect data from those who escorted by the family member? They don’t know about the pre transfer treatments and monitoring process.

• In line 208-211, Twenty-one (67.7%) neonates with prolonged capillary refill time (CRT) died compared to ten (32.3%) who survived (OR=4.76, 95%CI (1.80-12.58), p=0.002)”. This sentence is hard to follow. Consider revision. Either describes using odds ratio or proportion in the whole document.

6. The discussion is inadequate and need to be revised thoroughly. Your independent variables were not well stated as compared to other findings with possible justification. Contributing factors are not discussed in detail as compared to previous studies. It doesn’t tell us the discovery and how these results contribute to the current debate and policies in the research specific context and beyond.

In table 2: Is you used univariate or bivariate? Which one do you think appropriate? What is difference b/n multivariate analysis and multivariable analysis? Which one is appropriate for your study?

Generally, give much concern for grammar, punctuation, capitalization and flow of ideas.

Reviewer #3: The study titled Referral Challenges and Outcomes of Neonates Received at Muhimbili National

Hospital, Dar es Salaam, Tanzania explored problems for preparation, care during transport and outcome in terms of death with in 48 hours, a crucial issue that are under addressed in countries like Tanzania. This findings will guide to plan for way forward to achieve SDG.

in line 180 , spelling mistake, seems it will be taxi. others seem good

Reviewer #4: Dear authors,

This manuscript describes the outcome of neonates referred to tertiary care hospital and identification of underlying factors for poor outcome. The topic is very important particularly from point of view of high NMR in developing countries. However, there are some serious flaws in the paper which need to rectify before further processing:

First of all, the authors need to work on the English language written in the paper for grammar, and syntax of the sentences.

Please clarify that whether all babies were born at hospitals, if it is so, then, please elaborate the infrastructure available at these peripheral hospitals where child births have taken place. Please add whether these neonates were referred from a single health facility or multiple hospitals.

Also, please add following information:

Referral indications: Please describe the approach used to determine indication for referral. Please explain whether this information was extracted from cards with details of parameters used in referral cards. Sometime, the indications listed are not necessarily mutually exclusive” e.g. need for mechanical ventilation may overlap with prematurity or birth asphyxia. If there was more than one indication, how was this treated analytically?

What definitions did you use for classification of period of gestation, birth asphyxia, and severity of hypothermia (like moderate or severe?)

Gestational age is frequently poorly recorded and/or women present late to care. The accurate determination of gestational age or classification of prematurity is critically important as your results present approximately 40% prematurity. Please identify this specifically for weight as well – it is extremely important to know if these were scale weights at birth and what was done for home births (if any).

The authors have not included any information about the comparison between the referred neonates that lived and those that died. Please add information that describes this comparison.

Do you have any information about timeliness of referrals or care provided before referrals? In final discussion and conclusions, you have mentioned that the peripheral center and pre-referral stabilization is needed as well as upgrades. While this may be true, you do not present sufficient information in the manuscript to lead to this recommendation. Also explain about the duration of stay for neonates at referring facility and treatment provided before referral.

Please add duration transport as well distance travelled by neonates and perform statistical analysis of this factor also.

As the sample size 348, in order to know if this sample is representative for the whole study population, it would be needed more information regarding hospital and setting. What is the population size attended by this hospital, how many neonatal admission by year this hospital has and how many are inborn and how many outborn. This would give us a roughly idea if the sample size is enough to be representative for the whole population. Also what is the NMR in this hospital or at least in the region (authors have given the national NMR but likely the regional is different). Please also write exact number of the neonates at every place where percentage is used.

Explain in a better way how the factors affecting the outcome of neonates were identified. What kind of analysis was done to determine significance of parameters? The significance level indicated was for what? Whether only those parameters having significant values on univariate analysis were included in multivariate analysis?

In LMICs, antenatal screening is one of the important factors in identification of high risk pregnancies, but surprisingly this information was missed in manuscript.

There are no details of referral challenges that might be faced during referral of neonates in the region as you have stated in your title. Please add this information in your result section. Please provide some information about the ambulance services available to the patients. Is it provided free of cost, remains available 24x7 and what type training was given to the escort persons.

Since this paper focuses on the transfer of the infants, specific recommendations should be made in the discussion regarding improvements, e.g. how can stabilization prior to transfer be improved, what additional training do the emergency staff require, etc

Please add a segment what type of interventions were required in neonates immediately on arrival in emergency room at your center.

Also add what is the neonatal mortality rates observed at authors center for inborn babies. Is mortality same for inborn and outborns?

Line 72: Neonatal age is the most vulnerable period in human life with neonatal mortality contributing up to 47% of overall under-five deaths. Please give reference for this statement. Is this represent global figure or data from you country?

Line 74-75: Most of these conditions, up to 75% are preventable through effective equitable measures such as early detection and timely management. Most of these conditions, up to 75% are preventable through effective equitable measures such as early detection and timely management. Please add reference.

Line 128: Since data was collected from referral cards, please give the details of the data/parameters recorded in referral cards

Line 183-184: Blood circulation was monitored 184 in 37 (39.4%) of the transferred neonates. Please elaborate how blood circulation was measured during transfer.

Best wishes,

**********

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

Reviewer #4: No

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Attachment

Submitted filename: PONE-D-21-40535 (1).pdf

PLoS One. 2022 Jun 15;17(6):e0269479. doi: 10.1371/journal.pone.0269479.r002

Author response to Decision Letter 0


17 Mar 2022

PONE-D-21-40535

Referral Challenges and Outcomes of Neonates Received at Muhimbili National Hospital, Dar es Salaam, Tanzania.

PLOS ONE

March 17, 2022

Dear editors,

We are grateful to have received your email dated 2nd February 2022, containing the reviewers’ comments pertaining our manuscript titled “Referral Challenges and Outcomes of Neonates Received at Muhimbili National Hospital, Dar es Salaam, Tanzania”

We are thankful to the reviewers for taking their time to assess our manuscript. We have addressed all the concerns raised by the independent peer reviewers. Those have improved the overall quality of our manuscript.

Please find below our point-by-point response, clearly indicating how and where in the manuscript changes have been made (line numbers). To assist you in readily tracking our amendments, we included a marked up copy of the manuscript that highlights changes made to the original version. We also enclose a “clean” version of the revised manuscript as supporting information.

We very much hope that this revised version of our manuscript will now be suitable for publication in PLOS medicine. We look forward to hearing from you.

Yours Sincerely,

Dr Mpokigwa Kiputa

Reviewer #1: Referral Challenges and Outcomes of Neonates Received at Muhimbili National Hospital, Dar es Salaam, Tanzania

PONE-D-21-40535

I would like to congratulate the authors for a good work done. I have some minor concerns which may improve upon the quality of the manuscript.

Thank you for the congratulatory note.

1. Introduction: lines 72-73 stated “About half of neonates die within the first 24 hours after birth and 75% in the first seven days of life” Please check this information and present it appropriately. You mean; about half of all neonatal deaths occur within the first 24 hours……

In light of your comment we have improved and updated the introduction part.

2. Participant recruitment and data collection: line 126 stated that: “Data was collected day and night…” Were there any difference in outcome when day or night referrals were considered?

The statement sought to address the fact that neonates were recruited 24/7. Based on your comment we have reanalyzed the data and found out there was no significant difference in outcome during the day Vs night referral. However, we didn’t add this factors in the analysis as we didn’t extract and record exact time of death as a variable.

3. Neonatal age in days at time of admission was not reported. This is important to understand the outcome measure presented in the study.

Categories of neonatal age in days at the time of admission has been updated in Table 1: Socio-demographic and clinical characteristics of study participants.

4. Results section monitoring during transport: lines 183-184: “Blood circulation was monitored in 37 (39.4%) of the transferred neonates…..” How was it done and how was this assessed.

Perfusion monitoring was assessed by asking the escorting health personnel if he/she checked the capillary refill time as part of monitoring during transport. The questionnaire is shared as supplementary materials and the methodology section updated accordingly.

5. Table 1: presented “Apgar score 1st and 5 minutes” however only single measurement was presented. A little explanation would dispel the confusion.

On the contrary it was two measurement presented e.g. (7-10), meaning the Apgar score was 7 in the 1st minute and 10 in the 5th minute. Table 1 has been revised to clarify the information. Thank you for noting this confusion.

Reviewer #2: General comment

This would have been an important study that contributes to the understanding of the Referral Challenges and Outcomes of Neonates Received at Muhimbili National Hospital, Dares Salaam, Tanzania. However, there are minor flaws in the method of the study, discussion and grammar that need a revision before publication.

Thank you for appreciating the importance of this study. The authors have addressed all comments and updated the manuscript accordingly.

1. In abstract section, it needs more elaboration in why the study is needed/ gap of the study, as much as possible avoid acronyms in the abstract and rewrite the abstract in very short and precise way particularly in the result section.

Elaboration on why the study is needed has been added, acronyms have been deferred and the abstract section have been re written as suggested. The results section in the abstract has been shorten.

2. Pay great attention for punctuations.

Point noted. The revised manuscript took great consideration on punctuation.

3. In introduction section, would start with the global and regional/ continent evidence on neonatal mortality and relate it with how referral contributes. One paragraph which describes why this study is needed. Generally, introduction lacks coherence of ideas, world to Tanzania figure of neonatal mortality, gap of the study, clear description of clinical outcome of referral neonates in previous study. Introduction needs substantial modification.

Modification have been made as suggested with a focused introduction highlighting the burden of neonatal mortality, referral care gaps, and significance of this study. Also we have included factors identified in previous studies to pose referral challenges and how they are associated with neonatal mortality.

4. In materials and methods

Study area: Add the number of physician, nurses and other health care professionals working in neonatal ward and NICU. It gives an insight for why high burden of neonatal death; is it because of shortage of HCW or not? You stated the number of admission but we can’t get patient-to-physician proportion.

The number of staff, cadre working at neonatal unit and NICU has been added in materials and methods section to provide an insight on the NICU capacity.

5. In line 147, it states as “All enrolled neonates were assessed at 48 hours post admission to capture the early outcome that was defined as survived or died” what is your baseline reference? If there is, cite it.

Regarding the early outcome assessment, we had no baseline reference to refer but we have included overall mortality at Muhimbili tertiary hospital.

6. Result

In line 157, it states as “A total of 349 referred neonates were screened during the study period, one was excluded from the study due to a congenital anomaly which was incompatible with life (anencephaly).” How it could be? You already excluded the known congenital anomalies before including in the study

This is a valid point. We changed the statement to read as follows;

A total of 349 referred neonates were recruited during the study period, one was excluded from the study due to a congenital anomaly which was incompatible with life (anencephaly).

In line 161, “258 (74.1%) were delivered by Spontaneous Vertex Delivery (SVD) while 85 (24.4%) were born via caesarean section.” Rewrite this.

Thank you for pointing this, the sentence has been rewritten.

What is the rationale behind to use median/mean and IQR and SD? You used median for GA and mean for BWT….

Mean was used for data with normal distribution and median for skewed data like gestational age.

In line 176, it states as “thirty-two (9.4%) were escorted by the family member.” In method section, you stated that the pre transfer data and transportation data/monitoring during transportation were taken from accompanying personnel/escort personnel. My question is how did you collect data from those who escorted by the family member? They don’t know about the pre transfer treatments and monitoring process.

The pre transfer data were collected from the referral notes/other documents. Those escorted by family members were not in a position to provide information on monitoring during transportation, hence not applicable. Only health care personnel were asked about the pre transport and monitoring during transport.

In line 208-211, Twenty-one (67.7%) neonates with prolonged capillary refill time (CRT) died compared to ten (32.3%) who survived (OR=4.76, 95%CI (1.80-12.58), p=0.002)”. This sentence is hard to follow. Consider revision. Either describes using odds ratio or proportion in the whole document.

Revision have been done and odds ratio used to compare the outcome. Most of the text has been changed in the manuscript considering your comments.

7. The discussion is inadequate and need to be revised thoroughly. Your independent variables were not well stated as compared to other findings with possible justification. Contributing factors are not discussed in detail as compared to previous studies. It doesn’t tell us the discovery and how these results contribute to the current debate and policies in the research specific context and beyond.

Revisions have been made to the discussion section. This study has highlighted the coverage gap during the referral of a newborn and how poor clinical status on admission influence the outcome. We have explained these facts together with the challenges which have not been reported before in our setting. It’s our hope the publication of this findings will influence policies in the region and beyond.

In table 2: you used univariate or bivariate? Which one do you think is appropriate? What is difference b/n multivariate analysis and multivariable analysis? Which one is appropriate for your study?

In Table 2 we used univariate analysis taking one independent variable at a time in relation to the outcome. Multivariate analysis provides more objective approach for studying the effect of covariates on the binary outcome as fitted in the model. It addresses both categorical and continuous covariates. Model selection increases power of detection, from that point of view multivariable analysis is appropriate to be used in our study.

Generally, give much concern for grammar, punctuation, capitalization and flow of ideas.

The comment has been taken. In our revised manuscript we have given much attention to grammar, punctuation and flow of ideas.

Reviewer #3:

The study titled Referral Challenges and Outcomes of Neonates Received at Muhimbili national hospital, Dar es Salaam, Tanzania explored problems for preparation, care during transport and outcome in terms of death within 48 hours, a crucial issue that are under addressed in countries like Tanzania. These findings will guide to plan for way forward to achieve SDG.

Thank you for the encouraging remarks.

In line 180, spelling mistake, seems it will be taxi. Others seem good

The spelling mistake corrected accordingly in the manuscript.

Reviewer #4

This manuscript describes the outcome of neonates referred to tertiary care hospital and identification of underlying factors for poor outcome. The topic is very important particularly from point of view of high NMR in developing countries. However, there are some serious flaws in the paper which need to rectify before further processing:

Thank you for acknowledging the importance of the topic, we have addressed all comments provided.

1. First of all, the authors need to work on the English language written in the paper for grammar, and syntax of the sentences.

In our revised manuscript we have given great attention to details regarding grammar and syntax of the sentences.

2. Please clarify that whether all babies were born at hospitals, if it is so, then, please elaborate the infrastructure available at these peripheral hospitals where child births have taken place. Please add whether these neonates were referred from a single health facility or multiple hospitals.

In Tanzania, most women deliver at health facility (83% as per One plan III report, 76% as per DHIS2 (2018)). In this study, we didn’t enquire on specific delivery place but in most cases babies are sent to health centers for assessment and vaccination post-delivery.

It was noted that few babies at the time of admission were escorted by family members (9.4%). Majority of neonates were referred from health facilities; Figure 1 shows the flow of study participants referred from various districts of Dar es Salaam. The details of infrastructure/capacity of peripheral hospitals has been added in the introduction and methodology section.

3. Referral indications: Please describe the approach used to determine indication for referral. Please explain whether this information was extracted from cards with details of parameters used in referral cards. Sometime, the indications listed are not necessarily mutually exclusive” e.g. need for mechanical ventilation may overlap with prematurity or birth asphyxia. If there was more than one indication, how was this treated analytically?

The information regarding indication for referral was extracted from referral notes. This information was captured at the time of admission before any further history was taken. We noted poor documentation of pre referral information including pre referral care provided.

Figure 2 shows the coverage gaps on what parameters have been documented as measured.

Nationally, we still have a gap on harmonization of documentation used for neonatal care. The ongoing Newborn Essential Solutions and Technologies (NEST) program is working towards achieving this. This might be considered as one of our weaknesses but Figure 2 shows pre transport care and the clinical admission status of all neonates received using the TOPS model rather than admission diagnoses. These are common preventable conditions which contributes to neonatal mortality and has to be checked and tackled in every admission/referral.

4. What definitions did you use for classification of period of gestation, birth asphyxia, and severity of hypothermia (like moderate or severe?)

Gestational age is frequently poorly recorded and/or women present late to care. The accurate determination of gestational age or classification of prematurity is critically important as your results present approximately 40% prematurity. Please identify this specifically for weight as well – it is extremely important to know if these were scale weights at birth and what was done for home births (if any).

The cut points used for gestation age and hypothermia were according to the WHO definition. The assessment of Birth Asphyxia was out of the scope of our study, we didn’t utilize clinical diagnoses in our analyses.

Gestational age was calculated by assessing the date of the last normal menstrual period or using the obstetric ultrasound report if available. Then this information was compared to the one recorded in the Reproductive and child health clinic card.

The birth weight reported were all scale weight from the respective facilities. The validation of birth weight measurement is not within the scope of this study. The results of previous study conducted in Tanzania ‘EN BIRTH study’; can provide further information on coverage and quality measurements in routine information system.

5. The authors have not included any information about the comparison between the referred neonates that lived and those that died. Please add information that describes this comparison.

Thank you for the comment, we compared the referred neonates that lived Vs those died in terms of clinic status at admission. Figure 3 shows the combined effect of clinical status at admission and neonatal outcome.

6. Do you have any information about timeliness of referrals or care provided before referrals? In final discussion and conclusions, you have mentioned that the peripheral center and pre-referral stabilization is needed as well as upgrades. While this may be true, you do not present sufficient information in the manuscript to lead to this recommendation. Also explain about the duration of stay for neonates at referring facility and treatment provided before referral. Please add duration transport as well distance travelled by neonates and perform statistical analysis of this factor also.

Pre referral care has been presented in the result section and summarized using the TOPS model in Figure 2. The timeliness of referral, the duration of stay at referring facilities, duration of transport and the distance travelled were difficult to ascertain in our study as they were not recorded anywhere. The information we collected were within the provision of care provided. To analyze the above factors, we will need to design another study which cut across the whole referral network system including assessment at the peripheral facilities.

The comment has been taken for designing further studies.

7. As the sample size 348, in order to know if this sample is representative for the whole study population, it would be needed more information regarding hospital and setting. What is the population size attended by this hospital, how many neonatal admissions by year this hospital has and how many are inborn and how many outborn. This would give us a roughly idea if the sample size is enough to be representative for the whole population. Also what is the NMR in this hospital or at least in the region (authors have given the national NMR but likely the regional is different). Please also write exact number of the neonates at every place where percentage is used.

The annual neonatal admission by year ranges between 1440 and 3360 neonates. This has been reported under the material and methods section. There is currently no study which has established the NMR at Muhimbili National Hospital or Dar es Salaam region. The crude data from the ministry of health reports, 2018- 2019 shows Dar es Salaam region being the number one contributor of neonatal mortality with an average neonatal mortality of 14.6 per 1000 facility births.

In a revised manuscript the exact number of neonates have been written in every place where percentage is used.

8. Explain in a better way how the factors affecting the outcome of neonates were identified. What kind of analysis was done to determine significance of parameters? The significance level indicated was for what? Whether only those parameters having significant values on univariate analysis were included in multivariate analysis?

From a univariate analysis, factors with P value < 0.2 were included in the final multivariable model. The significance level was indicated for outcome defined as death, hence only those parameters with significant value on univariate analysis were included in multivariable analysis.

9. In LMICs, antenatal screening is one of the important factors in identification of high risk pregnancies, but surprisingly this information was missed in manuscript.

We agree about the importance of antenatal screening but the information is beyond the scope of our study. It could be true that high risk pregnancies have been referred early but with high number of facility deliveries, strengthening referral system is needed.

10. There are no details of referral challenges that might be faced during referral of neonates in the region as you have stated in your title. Please add this information in your result section. Please provide some information about the ambulance services available to the patients. Is it provided free of cost, remains available 24x7 and what type training was given to the escort persons.

In most Government health facilities, the ambulance service is free of cost and yes it is available 24/7. This information has been added in the introduction and discussion section as needed.

Currently, there is no harmonized referral network and trainings but the escort nurses come from the respective units of referring facilities and are supposed to be trained on skills and competences at least for essential newborn care if not comprehensive care.

The referral challenges are reported in Figure 2 in the results section. The information regarding the type of training given to the escort personnel is reported in the discussion section.

11. Since this paper focuses on the transfer of the infants, specific recommendations should be made in the discussion regarding improvements, e.g. how can stabilization prior to transfer be improved, what additional training do the emergency staff require, etc

Specific recommendations regarding improvements on pre transfer care and stabilization is found in the discussion section. The whole discussion has been revised accordingly.

12. Please add a segment what type of interventions were required in neonates immediately on arrival in emergency room at your center

The segment has been added in the material and methods section. It reads as follows;

Neonates who were found to be hypoglycemic on admission were given bolus intravenous dextrose, those who were hypoxic received supplemental oxygen according to their needs and those who were hypothermic were kept in a warmer. Neonates who were in shock upon arrival were resuscitated with intravenous fluids according to the hospital protocol. There was room for escalation of care for neonates who needed advanced respiratory support such as ventilating machine.

Additionally, the clinical admission status found in the cases have been presented in the results and discussed in the manuscript.

13. Also add what is the neonatal mortality rates observed at authors center for inborn babies. Is mortality same for inborn and outborns?

The information has been added in the introduction section, it reads as follows;

According to raw data from the MNH, neonatal mortality among the out-borns is almost twice as higher compared to the in-borns admitted at the same neonatal unit.

14. Line 72: Neonatal age is the most vulnerable period in human life with neonatal mortality contributing up to 47% of overall under-five deaths. Please give reference for this statement. Is this represent global figure or data from you country?

Reference have been provided accordingly and introduction section revised.

15. Line 74-75: Most of these conditions, up to 75% are preventable through effective equitable measures such as early detection and timely management. Please add reference.

The statement has been modified it is no longer available in the manuscript. The point has been noted.

16. Line 128: Since data was collected from referral cards, please give the details of the data/parameters recorded in referral cards

Line 135-137: Data on demographic characteristics of the study participants and pre referral treatment if any were extracted from referral cards. There are variations of the referral forms used by the referring facilities. Currently, the Newborn Essential Solutions and Technologies (NEST) program is working towards achieving this.

17. Line 183-184: Blood circulation was monitored 184 in 37 (39.4%) of the transferred neonates. Please elaborate how blood circulation was measured during transfer.

Blood circulation was monitored by checking the capillary refill time periodically. To remove the confusion, the sentence has been modified to read as follows;

Capillary refill time was monitored in 37 (39.4%) of the transferred neonates while Random blood glucose was checked in 27 (28.7%).

Attachment

Submitted filename: Response to Reviewers.docx

Decision Letter 1

Elsayed Abdelkreem

18 Apr 2022

PONE-D-21-40535R1Referral Challenges and Outcomes of Neonates Received at Muhimbili National Hospital, Dar es Salaam, Tanzania.PLOS ONE

Dear Dr. KIPUTA,

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Elsayed Abdelkreem, MD, PhD

Academic Editor

PLOS ONE

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Comments to the Author

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Reviewer #1: All comments have been addressed

Reviewer #4: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

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Reviewer #4: Yes

**********

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Reviewer #1: Yes

Reviewer #4: Yes

**********

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Reviewer #1: Yes

Reviewer #4: Yes

**********

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Reviewer #4: Yes

**********

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Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: All my comments have been addressed. I would like to congratulate the authors for a good work done.

Reviewer #4: Dear authors,

Thank you for addressing my queries in detail and submission of revisions. Authors have improved the manuscript very nicely, but I have some minor issue:

1. Although grammar part had been improved but please look on use of unnecessary capital words. Line 166: Model, line 185: Spontaneous Vaginal Delivery.

2. Main issue is with the inadequacy of the data analysis for primary aim of the study.

In abstract part (background section, line 24): Authors claim “This study assessed the pre-referral care……”.

However, as per the information provided in result section (line 189), no details of prereferral care have been given by the authors. The information just describes the numbers of neonates having IV-line insertion, temperature measurement, oxygen saturation and blood glucose monitoring.

Same point had been highlighted in the response letter points number 3 and 6 regarding inadequacy of documentations in referral cards.

I will suggest author to add this point (i.e. inadequate assessment of prereferral care) in limitations sections, please.

3. In abstract part, result section line 44-49 need to be rephrased while reporting odd’s ratios and p-value. Please avoid repeated use of odds of dying or likely to die repeatedly as this can be easily understandable from odd’s ratio against each variable.

4. In conclusion part, line 58-59; Please shift this line from conclusion to discussion part. This is not a finding of this study but may serve as future recommendation.

5. Line 213: I request to the authors to state indications of referral more explicitly rather than mentioning “seek specialized care, lack of newborn unit or lack of equipment”, which are very vague.

6. As authors have acknowledged in response letter at points number 3, 6 and 9th, there are some limitations in recording full data. So, please add these statements in the limitations section at the end of manuscript.

7. Please avoid repetition of the facts “no ambulance had an incubator” at line 211-212, line 222.

Best wishes,

**********

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PLoS One. 2022 Jun 15;17(6):e0269479. doi: 10.1371/journal.pone.0269479.r004

Author response to Decision Letter 1


17 May 2022

PONE-D-21-40535R1

Referral Challenges and Outcomes of Neonates Received at Muhimbili National Hospital, Dar es Salaam, Tanzania.

PLOS ONE

May 17, 2022

Dear editors,

We are grateful to have received your email dated 19th April 2022, containing the reviewers’ comments pertaining our manuscript titled “Referral Challenges and Outcomes of Neonates Received at Muhimbili National Hospital, Dar es Salaam, Tanzania”

We are appreciative to the reviewers for taking their time to assess our manuscript a second time after our first review response. We have addressed all the concerns raised by the independent peer reviewers and improved the overall quality of our manuscript.

Please find below point-by-point response, clearly indicating how and where in the manuscript changes have been made (line numbers). To assist you in readily tracking our amendments, we included a marked up copy of the manuscript that highlights changes made to the original version. We also enclose a “clean” version of the revised manuscript. All comments from the reviewers (previous and current comments) have been integrated into the manuscript itself (not only in the response letter). Study limitations, conclusion and recommendations revised accordingly. Reviewers’ responses are highlighted in the manuscript.

Additional edits to reformat the manuscript have been done and can be observed with track changes and summarized in the response to comments letter specifying sections and line numbers as per no. 8 below. Kindly note that, these edits do not alter any information as per reviewers comments but rather improve the organization and grammar of the manuscript.

We very much hope that this revised version of the manuscript will now be suitable for publication in PLOS medicine. We look forward to hearing from you.

Yours Sincerely,

Dr Mpokigwa Kiputa

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Thank you for the comment, reference list has not been updated and remains as per previous edits according to initial reviewer’s comments.

Reviewer #1: All my comments have been addressed. I would like to congratulate the authors for a good work done.

Thank you for the congratulatory note. We really do appreciate your time invested to improve the quality of the manuscript.

Reviewer #4: Dear authors, Thank you for addressing my queries in detail and submission of revisions. Authors have improved the manuscript very nicely, but I have some minor issue:

Thank you for the positive remarks

1. Although grammar part had been improved but please look on use of unnecessary capital words. Line 166: Model, line 185: Spontaneous Vaginal Delivery.

Thanks for noticing. The capitalization errors have been addressed accordingly in line 169 and line 188 in the manuscript. The whole manuscript was revised and other font edits have been made in line 146, 147 and 158.

2. Main issue is with the inadequacy of the data analysis for primary aim of the study.

In abstract part (background section, line 24): Authors claim “This study assessed the pre-referral care……”

However, as per the information provided in result section (line 189), no details of pre referral care have been given by the authors. The information just describes the numbers of neonates having IV-line insertion, temperature measurement, oxygen saturation and blood glucose monitoring.

Same point had been highlighted in the response letter points number 3 and 6 regarding inadequacy of documentations in referral cards.

I will suggest author to add this point (i.e. inadequate assessment of pre referral care) in limitations sections, please.

Pre referral care entails stabilization of the sick neonate prior to transfer according to the S.T.A.B.L.E (Sugar, Temperature, Airway, Blood pressure, Lab work and Emotional support) program. It was developed by Kristine Karlesen in 1980s as part of research project. Henceforth adopted worldwide as a standard practice.

Establishing an IV access, temperature measurement, oxygen saturation and blood glucose monitoring is part of the pre referral care as it was laid out in our study using the TOPS model. Although we agree that to a certain extent it was inadequate given the fact that not all parameters were assessed and no direct assessment was carried out at the referring centers. In this study, pre referral care assessment was based on documentation provided from the referral notes.

In limitations section line 347-349, this point has been added on and it now reads as follows;

Limitation in recording full data due to poor/incomplete documentation based on the referral forms, consequently contributed to the inadequate data of pre-referral care assessment, reasons for referral and monitoring enroute information

In addition, the methodology section in the abstract has been updated accordingly, please refer to line 29, 30 and 34 to match line 137 -139 in the main manuscript (highlighted yellow for easier tracing)

3. In abstract part, result section line 44-49 need to be rephrased while reporting odd’s ratios and p-value. Please avoid repeated use of odds of dying or likely to die repeatedly as this can be easily understandable from odd’s ratio against each variable

The statement in result section line 45-51 has been rephrased and it now reads as follows;

Hypothermic neonates had an increased chance of dying compared to those who were normothermic (OR=2.09, 95% CI (1.05-4.20), p=0.037). The chance of dying among those presenting with hypoxia was almost three times (OR=2.88, 95%CI (1.44-5.74), p=0.003) while those with poor perfusion was almost five times (OR=4.76, 95%CI (1.80-12.58), p=0.002). Additionally, neonates who had hyperglycemia (RBG > 8.3mmol/l) on arrival had a higher probability of dying compared to those who were euglycemic [(OR= 3.10, 95% CI (1.19 – 8.09) p=0.021].

4. In conclusion part, line 58-59; please shift this line from conclusion to discussion part. This is not a finding of this study but may serve as future recommendation.

We agree with this observation. The line aforementioned has been removed from the conclusion part and added to recommendation line 355-356 in the main manuscript

5. Line 213: I request to the authors to state indications of referral more explicitly rather than mentioning “seek specialized care, lack of newborn unit or lack of equipment”, which are very vague.

The indications for referral were extracted from the referral notes at the time of admission before any further history was taken. Unfortunately, the reasoning were clustered and no much information provided. This has been addressed as one of the limitations of our study. Documentation using standard harmonized forms is a critical and currently NEST 360 program is working on improving all forms including introducing inpatient neonatal register.

The study limitation has been updated to accommodate this information and it reads as

Limitation in recording full data due to poor/incomplete documentation based on the referral forms, consequently contributed to the inadequate data of pre-referral care assessment, reasons for referral and monitoring enroute information. Please refer to line 347 – 349.

6. As authors have acknowledged in response letter at points number 3, 6 and 9th, there are some limitations in recording full data. So, please add these statements in the limitations section at the end of manuscript.

The statement has been added accordingly in line 347-349 in the limitation section. It reads as follows;

Limitation in recording full data due to poor/incomplete documentation based on the referral forms, consequently contributed to the inadequate data of pre-referral care assessment, reasons for referral and monitoring enroute information. Please refer to line 344 – 346 in the manuscript.

7. Please avoid repetition of the facts “no ambulance had an incubator” at line 211-212, line 222.

The aforementioned line 211 which now stands as line 214 had been modified accordingly to avoid repetitions. The edits have been made in the manuscript.

8. Additional edits of grammar, font and some wordings have been made in the manuscript for the purpose of clarity. They are on track changes and summarized per section and line numbers below. All the edits are cosmetic and do not alter previously revised manuscript.

Abstract – line 26, 34, 41, and 60

Introduction – line 105

Materials and Methods - line 120, 123, 124, 146, 147, 158, 169, 175 and 177

Results – 185, 192, 193 and 228

Discussion – 251, 275, 285, 290, 302, 305, 325, 326, 339, 352 and 354

Attachment

Submitted filename: Response to reviewers.docx

Decision Letter 2

Elsayed Abdelkreem

23 May 2022

Referral Challenges and Outcomes of Neonates Received at Muhimbili National Hospital, Dar es Salaam, Tanzania.

PONE-D-21-40535R2

Dear Dr. KIPUTA,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Elsayed Abdelkreem, MD, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #4: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #4: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #4: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #4: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #4: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #4: Dear authors,

Thank you for revising the manuscript and addressing my queries. I am satisfied with the revisions submitted. Improving the neonatal survival in a low resource settings is major area of concern for the health policy makers all over the world. Authors need to be commended for addressing this topic.

Thank you,

Best wishes,

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #4: No

Acceptance letter

Elsayed Abdelkreem

27 May 2022

PONE-D-21-40535R2

Referral Challenges and Outcomes of Neonates Received at Muhimbili National Hospital, Dar es Salaam, Tanzania

Dear Dr. Kiputa:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

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on behalf of

Dr. Elsayed Abdelkreem

Academic Editor

PLOS ONE

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