Impact of the early COVID-19 pandemic on outcomes in a rural Ugandan neonatal unit: A retrospective cohort study.

BACKGROUND: During the early COVID-19 pandemic travel in Uganda was tightly restricted which affected demand for and access to care for pregnant women and small and sick newborns. In this study we describe changes to neonatal outcomes in one rural central Ugandan newborn unit before and during the early phase of the COVID-19 pandemic.
METHODS: We report outcomes from admissions captured in an electronic dataset of a well-established newborn unit before (September 2019 to March 2020) and during the early COVID-19 period (April-September 2020) as well as two seasonally matched periods one year prior. We report excess mortality as the percent change in mortality over what was expected based on seasonal trends.
FINDINGS: The study included 2,494 patients, 567 of whom were admitted during the early COVID-19 period. During the pandemic admissions decreased by 14%. Patients born outside the facility were older on admission than previously (median 1 day of age vs. admission on the day of birth). There was an increase in admissions with birth asphyxia (22% vs. 15% of patients). Mortality was higher during COVID-19 than previously [16% vs. 11%, p = 0.017]. Patients born outside the facility had a relative increase of 55% above seasonal expected mortality (21% vs. 14%, p = 0.028). During this period patients had decreased antenatal care, restricted transport and difficulty with expenses and support. The hospital had difficulty with maternity staffing and supplies. There was significant community and staff fear of COVID-19.
INTERPRETATION: Increased newborn mortality during the early COVID-19 pandemic at this facility was likely attributed to disruptions affecting maternal and newborn demand for, access to and quality of perinatal healthcare. Lockdown conditions and restrictions to public transit were significant barriers to maternal and newborn wellbeing, and require further focus by national and regional health officials.

Background

The COVID-19 pandemic has stressed health systems around the world. In addition to the massive number of deaths due to infection with the SARS-CoV-2 virus, the pandemic and associated control measures have had a negative impact on primary and essential health care services due to disruptions in health workforce and supply chains, overwhelmed health facilities and decreased care seeking for non-COVID-19 causes [1]. This has resulted in substantial negative effects on human health around the world, particularly among the most vulnerable populations. Much of the progress towards reducing maternal and newborn deaths as well as stillbirth over the last several decades has necessitated health systems strengthening, increasing care seeking and optimizing supply chains for commodities relevant to mothers and babies [2, 3]. Progress towards achieving the Sustainable Development Goals and Every Newborn Action Plan targets for reducing maternal deaths, newborn deaths and stillbirths is expected to slow substantially due to COVID-19 impacts, and may even regress without significant adjustments [3-7]. Therefore, understanding and documenting the indirect effects of the COVID-19 pandemic on newborn health and access to care are crucial to design strategies to address vulnerabilities in the healthcare system.

While direct effects of SARS-CoV-2 infection among mothers or newborns has not been reported as a significant contributor to the overall mortality due to COVID-19, evidence for impact on maternal and newborn services such as access to facility-based deliveries, antenatal care and emergency obstetric care is emerging [8-10]. An early survey by the WHO reported 80% of countries had disruptions to essential health services and these were exacerbated in lower income countries [1]. Little has been published, however, on availability of peripartum care or neonatal outcomes from low resource facilities during the COVID-19 pandemic [11-14].

Over the past decades, Uganda has made significant strides in reducing under-five mortality and maternal deaths; however as of 2019, neonatal mortality had plateaued at 20 deaths per 1000 live births [15]. Twenty five percent of births in Uganda are not delivered by skilled birth attendant, post-natal services remain low and geographical inequalities in access to maternal services exist [16]. It is in this background in which the first case of COVID-19 in Uganda was reported on 21 March 2020 [17]. As a result, the government of Uganda instituted measures to control the spread of the disease including restrictions to movement and a national lockdown that began 30 March and began to ease on 26 May. These restrictions exacerbated existing maternal and newborn service challenges, most notable in decreased ability for pregnant women or parents with a newborn to travel urgently to health facilities. As of May 2021, Uganda had recorded over 43,000 cases of COVID-19 with 357 deaths [18]. Pandemic control measures affecting access to newborn care remain highly dynamic and no country-level data of neonatal survival during this period are available.

We have been prospectively collecting data at one rural Ugandan neonatal unit since 2005 where provision of care for small and sick newborns, including CPAP therapy has been well established. During the early COVID-19 pandemic, this facility was able to obtain personal protective equipment for staff and maintain neonatal care but peripartum mothers had difficulty traveling to the facility due to lockdown. The aim of this study is to describe this facility’s experience with providing peripartum care during the pandemic by utilizing this longitudinal dataset to explore changes to facility-based neonatal outcomes before and during the early phase of the COVID-19 pandemic.

Methods

Study design

Retrospective cohort study of a clinical database.

Study population

Included in this study are patients admitted to the Kiwoko Hospital (KH) neonatal unit during the period of study. There were no exclusion criteria.

Setting

Kiwoko Hospital is a rural, private, not-for-profit secondary level care hospital that acts as a referral center for three districts (total population 1,000,000) in central Uganda. During fiscal year 2019–2020, the perinatal mortality rate in the hospital’s district (Nakaseke) was in the range of 29–42 per 1,000 live births and 19–28 in the two other districts the hospital serves (Nakasongola and Luwero) [19, 20]. The neonatal mortality rate for Uganda was 27 per 1,000 live births [21].

The KH neonatal care unit was established in 2001 and is a regional leader in care of small and sick newborns [22]. The unit admits more than 1,000 patients annually, generally neonates with a gestational age greater than 24 weeks and up to 44 weeks. About half of admitted patients are born at KH and the remainder are “outborn,” or admitted after birth at home or another facility. Outborn patients are treated in the same unit and receive the same care as those born at KH. There are 5–7 nurses on duty each shift, as well as one assigned medical officer and one pediatric physician who round on the patients and are on call each day. Staff generally live on site. Electricity is continuously available with the help of a standby generator. The unit provides thermoregulatory support primarily from radiant warmers and incubators, infection control and treatment, nasogastric and cup feeding, intravenous hydration, phototherapy, blood transfusion, basic laboratory services, oxygen therapy, and pulse oximetry. Improvised bCPAP has been the standard of care for respiratory failure in the unit since 2012 and is assembled using donated RAM nasal cannulas [23]. The unit does not provide surfactant, mechanical ventilation, total parenteral nutrition nor therapeutic hypothermia for birth asphyxia. The national referral hospital is located two hours travel by car and referrals from the Kiwoko NICU are transported free of charge. Admissions via ambulance to KH are assisted by government primary health care subsidies. General care in the neonatal unit is subsidized and families pay for any additional lab tests or imaging. Mothers are offered free accommodation and basic meals during their baby’s stay.

COVID-19 experience

The first COVID-19 tests at Kiwoko hospital were conducted on 5 May 2020 and the first case of COVID-19 was confirmed on 2 August. Following a total of 752 tests of staff, patients and community members, 14 total cases were confirmed before October and transferred to isolation centers. No neonates were denied care and access to and provision of care continued unchanged in the neonatal unit. Mothers were screened for symptoms on entrance to the unit. Experience at KH was determined through interviews with neonatal and maternity unit doctors as well as supervising midwives and nurses (summarized in S1 Table).

Nationally during the 2020 period of the COVID-19 pandemic in Uganda, restrictions included: banning mass gatherings (18 March), closing schools (20 March), suspending public transportation and requiring police presence for private transport (25 March), and a nationwide lockdown with curfew (30 March). All non-essential services and activities were closed in this period [24]. Until 19 April, approval from a Resident District Commissioner was required to move during a medical emergency, and each district had only one Commissioner [25, 26]. Transport restrictions began to ease on 26 May: public transport resumed at half capacity (and increased cost) on 4 June, and the most common form of transport (via motorcycle) resumed on 27 July. Overnight curfews remained in place through the end of 2020.

Dataset

The neonatal unit has maintained an electronic database of all neonatal admissions since late 2012. On admission, nurses record patient and maternal information on a designated bedside form. After discharge, a data entry team extracts additional information from the medical file including treatments and final diagnosis as assigned by the physician at discharge, death, or transfer. Data are manually entered into Epi Info version 7 [27]. The data was exported to STATA v.15 for analysis [28].

Outcome

We utilized this database to explore outcomes from all infants admitted to the neonatal unit during the pre-COVID-19 period (October 2019 through March 2020) and the first six months of the pandemic in Uganda, which we will refer to as the early COVID-19 period, or the COVID-19 period (April through September 2020). These periods were selected to capture the first lockdown period in Uganda (April/May) as well as the subsequent phased relaxation of COVID-19 restrictions (June/July) and then two additional months (August/September) to allow for six month seasonal comparisons with previous years. We also show seasonal variation and pre-existing trends in mortality by reporting outcomes from reference periods one year prior to study periods: Oct 2018 –March 2019 and April–Sep 2019. Death before discharge was the primary outcome- defined as a death as an infant that was admitted to the neonatal unit and died before discharge home.

Other variables

The analysis was further stratified by inborn/outborn status. Patients were classified as ‘inborn’ if they were born at KH while others were classified as ‘outborn’ (born at another facility, at home or on the way to the hospital). Birthweight-specific and diagnosis-specific mortalities were also computed. When birthweight was unknown, admission weight was used if the patient was admitted within 3 days of birth. Gestational age is not reliably available from this dataset and is therefore not reported for this study. Primary diagnoses were assigned by doctor at patient discharge, transfer, or death. Additional data on availability of health workforce in the neonatal unit was retrospectively reported by the nurse in-charge.

Statistical analysis

The mortality rate pre and during the early COVID-19 period was computed as a proportion of infants who died to the total number of infants admitted to the unit in the same period. To determine the potential impact of the COVID-19 pandemic on neonatal mortality in the unit, we computed the relative change in mortality rate between two time periods of the same months for the 2 sequential years. Proportion tests were used to compare the rates between two time periods of the same months.

Ethical considerations

Human Subjects Approval was obtained from Makerere University School of Public Health Institutional Review Board (protocol number 917) and approved by the Uganda National Council for Science and Technology (registration number SS813ES). The data were fully anonymized before accessed by the research team and the ethics committee waived the requirement for informed consent. The University of Washington institutional review board designated this as an exempt study.

Results

The study included 2,494 patients admitted during the period of study and admissions during each period are shown in Table 1. A total of 567 patients were admitted during the early COVID-19 period (April-Sept 2020) representing a 14% decrease in admissions compared to the same period in the preceding year (April-Sept 2019). Out of 2,494 patients included in the analysis, 49% (1,234) were outborn (born elsewhere and admitted to the KH unit). Proportion of outborn patients decreased during the early COVID-19 period, as shown in Fig 1. Five patients did not have inborn/outborn status recorded, and these were excluded from the stratified analyses by birth location. The average daily census increased during the early COVID-19 period to 42.3 (sd 6.3) from a range of 38.6–41.6 in the periods before COVID-19.

Table 1

Admissions per period, unit census and staffing levels.

	Reference periods		pre-COVID-19 period	Early COVID-19 period
Date range	Oct 2018 –Mar 2019	April–Sep 2019	Oct 2019 –Mar 2020	April–Sep 2020
Number of patients admitted (n)	649	659	619	567
Outborn n (%)	326 (50.1%)	323 (49.1%)	321 (51.6%)	264 (46.1%)
Average Daily Census (sd)	38.6 (4.9)	41.3 (6.6)	41.6 (5.3)	42.3 (6.3)
Nurses per shift	5	5	5	5

Fig 1

Admissions by birth location.

Proportion of admissions of outborn patients decreased to 46.1% during the early COVID period (April–September 2020) from 51.6% pre-COVID (October 2019 to March 2020). All transport was banned or tightly limited during April and May and public transport was costly and restricted during June and July. “Outborn” refers to patients born outside KH. “Inborn” includes those born at KH.

Maternal and neonatal demographics are shown in Table 2. Nineteen percent (474/2,494) of patients had missing birth weight and admission weight was used as proxy for 400 of this group.

Table 2

Maternal and neonatal demographics and clinical characteristics during pre-COVID (October 19 –March 20) and early COVID periods (April–September 2020) by birth location.

	All Patients		Inborn Patients		Outborn Patients
	pre-COVID (n = 619) %	COVID (n = 567) %	pre-COVID (n = 296) %	COVID (n = 303) %	pre-COVID (n = 321) %	COVID (n = 264) %
Maternal Demographics
Median maternal age (years, IQR)	25 (20–29)	24 (20–29)	25 (21.5–29)	24 (21–30)	24 (20.29)	23 (20–28)
Antenatal care visits (mean, SD)	2.6 (1.3)	2.6 (1.3)	2.6 (1.3)	2.6 (1.3)	2.5 (1.2)	2.5 (1.3)
Mode of transport to facility:			(pregnant mother)		(newborn)
Motorcycle	51.8	44.8	55.7	50.5	48.0	38.3
Taxi/Special hire	29.6	27.9	30.7	28.4	29.3	27.3
Ambulance	15.8	24.7	9.5	17.5	21.8	32.9
Bicycle or foot	0.8	1.8	1.0	2.3	0.6	1.1
Unknown	1.9	0.9	3.7	1.3	0.3	0.4
Lives outside district	67.2	67.2	64.5	65.3	69.8	69.3
Type of birth attendant
Doctor	27.1	27.0	44.3	42.6	11.2	9.1
Midwife/Nurse	65.3	66.7	55.7	57.4	74.4	77.3
Traditional birth attendant	1.8	1.9	-	-	3.4	4.2
Family member	4.0	2.8	-	-	7.5	6.1
Unknown/other	1.8	1.6	-	-	3.4	3.4
Birth location					(n = 585)
Another facility	-	-	-	-	86.3	88.6
Home	-	-	-	-	11.5	9.5
On the way to hospital	-	-	-	-	2.2	1.9
Cesarean section	25.8	27.0	42.9	41.9	10.0	9.8
Singleton birth	82.2	82.4	81.4	79.9	82.9	85.2
Infant characteristics
Female	45.4	43.9	46.6	43.6	44.6	44.3
Age at admission (days)	-	-	-	-	0 (0–2)	1 (0–2)
Median (IQR)
Mean (SD)	-	-	-	-	2.5 (5.6)	3.2 (8.8)
Low birthweight (<2.5kg)	51.5	51.8	53.7	58.1	49.5	44.7
Very low birthweight (<1.5kg)	14.4	15.7	11.5	17.2	17.1	14.0
Primary diagnosis
Prematurity/LBW	47.7	46.9	50.3	52.8	45.2	40.1
Birth asphyxia	15.0	22.4	12.2	17.5	17.4	28.0
Infection	21.8	18.9	17.6	17.2	25.9	20.8
Other	15.5	11.8	19.9	12.6	11.5	11.0
Clinical Course
Therapies received:
Phototherapy	34.3	44.3	30.1	42.6	38.1	46.2
Blood transfusion	4.8	2.5	3.7	1.6	5.9	3.4
Bubble CPAP	14.0	15.7	13.8	16.5	14.3	14.8

▯Yellow highlighted cells show trends of particular clinical significance.

As seen in Table 2, during the early COVID-19 period admitted patients were born to younger mothers (median of 24 vs. 25 years). Both expectant mothers and newborns were more likely to be transported via ambulance or on foot during COVID-19.

Outborn patients during the early COVID-19 period were admitted on average one day later than pre-COVID-19 (median admission at 1 day of age vs. on the day of birth). Outborns admitted were less likely to have been born at home (9.5% vs 11.5%), and their births were less likely to be attended by a doctor (9% vs. 11%) (Table 2).

There was an increased proportion of admission with birth asphyxia, most notably among outborn patients (28% from 17% pre-COVID-19). Concurrently, outborn admissions were less likely to have a diagnosis of prematurity (40% down from 45%) or infection (21% from 26%). Inborn admissions had an increased proportion due to low birthweight (58% from 54%) and very low birthweight (17% from 11%) while these decreased among outborn patients (Table 2).

All patients were more likely to be treated with phototherapy (44% up from 34%) and less likely to receive a blood transfusion (3% down from 5%). Bubble CPAP therapy, however, was used more frequently in only inborn patients (17% vs. 14%) during the pandemic and likely corresponds to the increase in prematurity among this group (Table 2).

Mortality significantly differed between the COVID-19 period and pre-COVID-19 periods [15.7% (89/567) vs. 11.1% (69/619), p = 0.017]. Fig 2 illustrates mortality pre-COVID-19 and during the early COVID-19 period compared with the reference periods one year prior to allow for seasonally appropriate trends. When we compared mortality pre-COVID and the reference period of the same months, mortality increased proportionally by 5.7% while during COVID, mortality increased proportionally by 41.4% compared to the reference period. Therefore an excess mortality of 35.7% (41.4–5.7%) occurred during the early COVID-19 period.

Fig 2

Newborn mortality by birth location including expected mortality trend (dotted lines) without the COVID-19 pandemic based on seasonally matched periods prior to COVID-19.

Excess mortality is the amount of mortality seen above what would be expected for trend, calculated as the relative difference between periods divided by mortality in the reference period. 1,234 patients were outborn (born outside Kiwoko hospital) and 1,260 born at Kiwoko (inborn) during the periods of study.

Among the inborn patients, mortality pre-COVID was 7.8 per 100 hospital admissions while during COVID, mortality was 10.9 per 100 hospital admissions. Mortality increased by 20.0% pre-COVID when compared to the reference period, however during COVID, mortality increased by 25.3%. Therefore an excess mortality of 5.3% (25.3% - 20.0%) among inborn patients occurred during the early COVID-19 period.

Among outborn patients, the excess mortality was 55.2% (55.9- -0.7%). Further, mortality among the outborn infants significantly differs during early COVID compared to the immediate pre-COVID period (21.2% vs. 14.3%, p = 0.028).

Table 3 shows increased mortality during the COVID-19 period among almost all categories of diagnosis and birthweight. Mortality among inborn patients with prematurity increased from 8.7% pre to 13.7%. Mortality among the smallest inborn patients (<1.5kg birthweight) was increased from 26.5% to 38.5% while other categories of birthweight among inborns remained unchanged. Outborn patients, however, had significantly increased mortality in all major categories of birthweight- patients <1.5k up through 4kg.

Table 3

Mortality by birth location, birthweight and diagnosis during early COVID and pre-COVID periods.

	Inborn Patients				Outborn Patients
	pre-COVID period (Oct 19—Mar 20) n = 296		Early COVID period (April–Sep 20) n = 303		pre-COVID period (Oct 19—Mar 20) n = 321		Early COVID period (April–Sep 20) n = 264
Birth Location
	(23/296)	7.8%	(33/303)	10.9%	(46/321)	14.3%	(56/264)*	21.2%
Diagnosis
Prematurity/ low birthweight	(13/149)	8.7%	(22/160)	13.7%	(18/145)	12.4%	(15/106)	14.1%
Birth asphyxia	(5/36)	13.9%	(8/53)	15.1%	(19/58)	33.9%	(25/69)	35.1%
Infection	(0/52)	0%	(1/52)	1.9%	(8/83)	9.6%	(8/55)	14.5%
Birthweight
<1.5 kg	(9/34)	26.5%	(20/52)	38.5%	(12/55)	21.8%	(13/37)	35.1%
1.5 to 2.49 kg	(6/125)	4.8%	(5/124)	4.0%	(6/104)	5.8%	(10/81)	12.3%
2.5 to 4kg	(8/126)	6.3%	(8/119)	6.7%	(21/131)	16.0%	(28/122)	23.0%
>4 kg	(0/11)	-	(0/8)	-	(1/5)	20.0%	(2/12)	16.7%

*p< 0.05. ▯Yellow highlighted cells show trends of particularly clinical significance.

Table 4 summarizes the impact of reported maternal child health impacts globally and how they affected KH. Descriptions and data from KH on these topics are found in S1 Table.

Table 4

Summary of impacts on maternal child and health reported globally during the early COVID-19 pandemic and the experience at Kiwoko hospital.

Kiwoko Impacted	Kiwoko not impacted
Maternity
Restricted transport for mothers[1, 29, 30]	Increased adolescent pregnancy[31, 39]
Decreased antenatal care[1, 31–34]	Increased stillbirth[2, 32, 39]
Decreased facility birth[1, 6, 8, 12, 30, 33–35]	Decreased cesarean sections[39]
Increased births at home or with traditional birth attendant[36]	Restricted personal protective equipment (PPE)[1, 8, 30]
Decreased availability of labor medications [32, 37]
Decreased staffing levels[1, 3, 8, 38]
Neonatal Unit
Restricted transport for babies[1, 29, 30]	Decreased staffing levels[1, 3, 8, 38]
Decreased neonatal intensive care admissions[14, 32, 40]	Restricted supplies/ personal protective equipment (PPE)[1, 8, 30]
Decreased outborn admissions[8, 41]	Decreased kangaroo mother care (KMC)[8, 44]
Increased preterm birth[14, 32]
Increased birth asphyxia[14]
Decreased blood supply[1]
Increased facility neonatal mortality[12, 40, 42]
Decreased facility-based infant follow-up[8, 43]
Parents
Decreased maternal support by family at hospital[8]
Difficulty with medical expenses/ food security[1, 24, 31, 40]
Staff and Community
Staff COVID-19 fear[3, 8]
Community fear of COVID-19 at facilities[8, 33, 34]

Discussion

Mortality and admissions with birth asphyxia increased while outborn admissions decreased in this rural Ugandan neonatal unit during the first six months of the COVID-19 pandemic. The pandemic was associated with a relative increase in mortality by 36% and 55% excess mortality above seasonal trends among outborn patients. This increased mortality is likely attributed to disruptions due to the pandemic affecting maternal and newborn demand for, access to and quality of peripartum healthcare [45].

We also found that the early COVID-19 period was associated with fewer admissions but increased daily census suggesting longer lengths of stay. Inborn patients were more likely to be preterm or very low birthweight and be treated with bubble CPAP. Outborn admissions decreased, were older on admission and were less likely to be delivered by a doctor. All patients were more likely to have birth asphyxia and be treated with phototherapy. These finding suggest increased patient acuity and aligns with resultant increased mortality during this period.

In Uganda, lockdown in April and May and restricted, expensive public motorcycle transit through July created significant barriers to transport that exacerbated existing delays to maternal and neonatal care, including delayed decision to seek care and prolonged time to reach to care [41, 45]. Increased mortality among newborns in this setting due to the indirect effects of the pandemic could quickly dwarf the direct mortality rate from COVID-19 infections, and likely did so in 2020. Although primary data is sparse, other sites have also reported increased facility-based neonatal deaths during COVID-19 lockdown periods, especially among outborn patients [12, 14, 42]. Heterogeneity in mortality among sites suggests the indirect impacts of COVID-19 are context-specific [41]. The experience at KH is described in Table 4 and S1 Table. KH was resourced to provide sufficient personal protective equipment to staff and parents in the neonatal unit, was able to adequately space mothers staying in on-campus quarters, and isolated patients demonstrating COVID-19 symptoms. This ability to respond to the pandemic beyond baseline newborn resources and outcomes at KH that exceed many other facilities in Uganda, may explain why outcomes could have been worse elsewhere.

Proportion of admissions due to prematurity was increased among inborn babies but not among outborns. With single facility data we cannot infer population-level changes in prematurity rates during the pandemic as other regions have, but decreased admissions of outborn premature infants suggests they may have died before reaching KH or were less likely to be transferred from other facilities [2, 11]. Mothers who did deliver at KH may have been triaged from the community for their risk of preterm delivery while others delivered elsewhere. Despite their birth location, the smallest patients (<1.5kg) had increased mortality which reveals the fragile survival of these patients at baseline.

Limitations to this study include the fluidity and dynamic nature of impacts of the early pandemic on demand for, access to and provision of quality maternal and newborn care services. For example, transportation impacts were greatest early in the COVID-19 study period due to lockdown restrictions, but further impacts on quality of care in the hospital may have been later in the period when COVID-19 was diagnosed locally and affected maternity staffing, community morale and supply chain of obstetric medications. This analysis does not capture subsequent months during the COVID-19 pandemic, including Uganda’s peak in infections in December 2020 and most recent wave in June 2021 [46]. Finally, we could not account for all impacts on maternal and newborn health, as impacts to antenatal care may impact the health of the baby independent of the neonatal care, either during the newborn period or later in life.

Strengths of the study include the stable care model of the KH neonatal unit and the established dataset with ability to make comparisons with reference years to account for seasonal trends.

COVID-19-related disruptions to the provision of child health service and outcomes, including the impact on immunizations and primary health care, have been well documented [39, 43]. This study is among few reporting impact to essential maternal/newborn care including access to safe delivery and transfer to neonatal inpatient care [8, 11–14, 32, 40, 47]. We report the pandemic’s disruptions to outcomes for small and sick newborns, who are among the most vulnerable humans and accounted for one fifth of childhood deaths pre-pandemic [15]. The World Health Organization has highlighted the importance of evaluation of health care vulnerabilities and modifications that will allow the continuation of essential health services during the pandemic [48]. Reducing impacts on vulnerable newborns in the continued pandemic will take coordinated and deliberate actions by policymakers, countries, and regional public health officials to ensure that access and quality to maternal and newborn health services are prioritized and optimized.

Impacts on maternal child and health reported globally during the early COVID-19 pandemic and their experience at Kiwoko hospital.

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14 Jul 2021

PONE-D-21-20950

Outcomes in a Rural Ugandan Neonatal Unit Before and During the Early COVID-19 Pandemic: a Retrospective Cohort Study

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. 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 #1: Yes

Reviewer #2: Yes

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

Reviewer #1: No

Reviewer #2: No

**********

3. 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 #1: Yes

Reviewer #2: No

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4. 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 #1: Yes

Reviewer #2: No

**********

5. 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 #1: Title: Outcomes in a Rural Ugandan Neonatal Unit Before and During the Early COVID-19 Pandemic: a Retrospective Cohort Study (manuscript number: PONE-D-21-20950)

Review by Ermias Sisay Chanie /MSc in pediatrics and Child health Nursing)

Debre Tabor University, Debre Tabor, Ethiopia

Thanks for give an opportunity to plos one chief editors to reviewing this article. This research is important on reducing neonatal mortality and morbidity in worldwide in general and in study ara in particular, in the meantime it is one of the international concerns. African countries including Ugandan works to reduce the mortality of neonate through monitoring and evaluation the ‘’outcomes neonate in Neonatal Unit”.

Minor

1. General English: The review recommends the article be copyedited to improve language and grammar used

2. Check the table number frequency, percentage and p- value for each column

Major concern

Title

1. In my point of view the title better to modified based on your conclusion, since it focuses on the impact of COVID-19 in “maternal and newborn demand for, access to and quality of peripartum healthcare’’ etc.

2. Rural vs Neonatal Unit? I am not clear with it. I am not expected neonatal unit in rural area.

Introduction

1. In my view, better to focus on your objective, which mean the effect of COVID-19 on maternal health, or neonatal health or healthcare system in general

2. Try to show any attempting solution to reduce the burden of COVID-19 related to your objective in the study rea

3. The identified gaps before conducting the study? And the implication of the study to fill the appreciated gaps

Methods

1. Discuss about your study populations vs source population of the study participant clearly

2. your Inclusion criteria vs Exclusion criteria of the study participant clearly

3. Better to included data set in statical analysis and try to explore about descriptive statics that was used etc.…?

4. Adding about goodness of fit and model fitness?

Reviewer #2: Abstract is too long and should not exceed 300 words for The PLOS ONE. Please describe clearly the main objective of this study and summarize the most important results and their significance.

Introduction:

The overall aim of this study and whether that aim was achieved are missing.

Methods:

The role of the funding source should not be in the method section

The statistical analysis to compare the groups are missing or incorrect (proportion tests?)

Results:

Fig 1. It should clarify the term “outborn” and “inborn” in the legend

Table 2. the “+-“ should replace the points in all numbers. Same for the text across the manuscript

p-values should be added to the table. The statistical analysis should be described in the table.

Figure 2 legend should describe the sample size and the statistical analysis used. It should not repeat the results of the figure. It also should specify the term inborn and outborn.

**********

6. 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 #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

6 Oct 2021

Response to Reviewers

Reviewer #1:

Minor

1. General English: The review recommends the article be copyedited to improve language and grammar used

We appreciate this recommendation. Our goal is to be grammatically accurate. The English language/grammar use has been edited where appropriate. If the editors have further suggestions for optimizing grammar we are open to them.

2. Check the table number frequency, percentage and p- value for each column

These have been checked, please see discussion of p values in response to reviewer 2 below.

Major concern

Title

1. In my point of view the title better to modified based on your conclusion, since it focuses on the impact of COVID-19 in “maternal and newborn demand for, access to and quality of peripartum healthcare’’ etc.

The title has been modified to “Impact of the early COVID-19 Pandemic on Outcomes in a Rural Ugandan Neonatal Unit: a Retrospective Study”. Although we agree with the reviewer that the impact on “maternal and newborn demand for, access to and quality of peripartum healthcare” is important we did not have any direct measures of this so do not feel comfortable including it in the title.

2. Rural vs Neonatal Unit? I am not clear with it. I am not expected neonatal unit in rural area.

As the reviewer notes, it is unusual, however Kiwoko hospital is a secondary neonatal unit in a rural area. Due to its clinical reputation, it has become a referral unit for three districts in central Uganda.

Introduction

1. In my view, better to focus on your objective, which mean the effect of COVID-19 on maternal health, or neonatal health or healthcare system in general

The introduction text has been updated to focus on the effect on maternal/neonatal health and the healthcare system in general:

“An early survey by the WHO reported 80% of countries had disruptions to essential health services and these were exacerbated in lower income countries. Little has been published, however, on low resource facility based neonatal outcomes from low resource facilities during the COVID-19 pandemic, nor describing experiences of peripartum care availability.“

2. Try to show any attempting solution to reduce the burden of COVID-19 related to your objective in the study rea

We added to the introduction: “During the early COVID-19 pandemic, this facility was able to obtain personal protective equipment for staff and maintain neonatal care but peripartum mothers had difficulty traveling to the facility due to lockdown.”

3. The identified gaps before conducting the study? And the implication of the study to fill the appreciated gaps

We added “Pandemic control measures affecting access to newborn care remain highly dynamic and no country-level data of neonatal survival during this period are available.”

Methods

1. Discuss about your study populations vs source population of the study participant clearly

We added “Study Population- Included in this study are patients admitted to the Kiwoko Hospital (KH) neonatal unit during the period of study. There were no exclusion criteria.” The “setting” section goes on to describe the type patients admitted to this unit and the typical provision of care in the unit.

2. your Inclusion criteria vs Exclusion criteria of the study participant clearly

See added text in response to #1 above re: inclusion/exclusion criteria.

3. Better to included data set in statical analysis and try to explore about descriptive statics that was used etc.…?

The dataset is now uploaded in accordance with journal requirements. We agree with the reviewer and focused on descriptive statistics in this report. If further suggestions can be considered, please clarify these.

4. Adding about goodness of fit and model fitness?

We did not use a model in this analysis.

Reviewer #2:

Abstract is too long and should not exceed 300 words for The PLOS ONE. Please describe clearly the main objective of this study and summarize the most important results and their significance.

Thank you for this guidance. The abstract is now < 300 words. It has been revised to better describe the objective and most important results and their significance.

Introduction:

The overall aim of this study and whether that aim was achieved are missing.

The introduction has been revised to better describe the aim:

“The aim of this study is to describe this facility’s experience with providing peripartum care during the pandemic by utilizing this longitudinal dataset to explore changes to facility-based neonatal outcomes before and during the early phase of the COVID-19 pandemic.”

Methods:

The role of the funding source should not be in the method section

It has been removed.

The statistical analysis to compare the groups are missing or incorrect (proportion tests?)

As suggested by the reviewer, we used a proportion test to compare the groups. This is described in the methods:

“Statistical analysis

The mortality rate pre and during the early COVID-19 period was computed as a proportion of infants who died to the total number of infants admitted to the unit in the same period. To determine the potential impact of the COVID-19 pandemic on neonatal mortality in the unit, we computed the relative change in mortality rate between two time periods of the same months for the 2 sequential years. Proportion tests were used to compare the rates between two time periods of the same months. “

Results:

Fig 1. It should clarify the term “outborn” and “inborn” in the legend

The figure legend has been updated with:

“Outborn” refers to patients born outside KH. “Inborn” includes those born at KH.”

Table 2. the “+-“ should replace the points in all numbers. Same for the text across the manuscript

p-values should be added to the table. The statistical analysis should be described in the table.

- The decimal points have been revised throughout the tables and manuscript

- We appreciate the comment and have discussed among our authors but respectfully disagree with the style of including p values in table 2 which describes demographic characteristics in the two time periods. P values may be misleading in comparing groups from two different periods given the seasonal nature of neonatal mortality and would be at risk of type 2 errors.

If the editorial team feels a formal comparison of the demographics is important to our manuscript, we would ask to change this table to a comparison of seasonally matched periods (ie comparing April to September 2020 with April to September 2019). However, we feel the most important data to show is immediately prior to the COVID-19 pandemic. Formal appropriate comparisons of mortality adjusting for seasonal trends are later in the manuscript.

Figure 2 legend should describe the sample size and the statistical analysis used. It should not repeat the results of the figure. It also should specify the term inborn and outborn.

- FIgure 2 legend now:

- no longer repeats the results of the figure

- includes “1,234 patients were outborn (born outside Kiwoko hospital) and 1,260 born at Kiwoko (inborn) during the periods of study.“

- includes “Excess mortality is the amount of mortality seen above what would be expected for trend, calculated as the relative difference between periods divided by mortality in the reference period.”

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

This has been done.

Submitted filename: 21.docx

Click here for additional data file.

2 Nov 2021

Impact of the Early COVID-19 Pandemic on Outcomes in a Rural Ugandan Neonatal Unit: a Retrospective Cohort Study

PONE-D-21-20950R1

Dear Dr. Hedstrom,

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,

Robert Jeenchen Chen, MD, MPH

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 #1: All comments have been addressed

Reviewer #2: 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 #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: 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 #1: Yes

Reviewer #2: 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 #1: Yes

Reviewer #2: (No Response)

**********

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 #1: 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.

Thank you very much indeed

Reviewer #2: (No Response)

**********

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 #1: No

Reviewer #2: No

4 Nov 2021

PONE-D-21-20950R1

Impact of the early COVID-19 Pandemic on Outcomes in a Rural Ugandan Neonatal Unit: a Retrospective Cohort Study

Dear Dr. Hedstrom:

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.

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on behalf of

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