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Abstract
Background: Besides survival and recovery, women afflicted with peripartum cardiomyopathy (PPCM) harbor significant apprehension regarding the safety of future pregnancies. Current knowledge regarding the maternal and fetal outcomes in subsequent pregnancies among women with a history of PPCM is sparse. Likewise, there is insufficient medical evidence to provide guidance for women who opt to become pregnant again after experiencing PPCM.
Research Questions: What is the feto-maternal prognosis of subsequent pregnancies following a history of PPCM?
Aims: To describe the fetal and maternal outcomes of subsequent pregnancies following a history of PPCM.
Methods: We included women from the Tanzania PPCM registry who had subsequent pregnancies after PPCM and assessed PPCM recurrence, maternal prognosis, and fetal outcomes.
Results: Among the 870 survivors (286 of whom left ventricular function had returned to normal [group 1] and 584 with persistent left ventricular dysfunction [group 2]), subsequent pregnancies were observed in 121 (13.9%) women (78 in group 1 and 43 in group 2). Forty (51.3%) women in group 1 had PPCM relapse, and during a mean follow-up of 896 days, 34 (85.0%) had complete recovery, 3 (7.5%) had persistent heart failure, and 3 (7.5%) died. In group 2, four (9.3%) women had complete recovery, 32 (74.4%) had persistent heart failure, and 7 (16.3%) died. The infant mortality rate was 23.4%.
Conclusions: After the initial pregnancy complicated by peripartum cardiomyopathy, subsequent pregnancies could lead to PPCM relapse and deleterious feto-maternal outcomes, including death.
| https://www.ahajournals.org/doi/abs/10.1161/circ.150.suppl_1.4114436

Authors: *Naizihijwa G. Majani 1,5 , Pilly Chillo 2, Mkiwa Akida3, Judith Lamosai 6, Deogratias Nkya 1,9, Stella Mongella 1, Zawadi, Kalezi 1 Godwin Sharau 8, Vivienne Mlawi 8 , Peter Kisenge, 7, Mohamed Janabi 7, Diederick E. Grobbee 5 , Martijn. G. Slieker 4

Authors Affiliation:

Department of Pediatric Cardiology, Jakaya Kikwete Cardiac Institute, Dar es Salaam, Tanzania
Department of Internal Medicine, Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania
Department of Pediatrics, Mwananyamala Regional Hospital, Dar es Salaam, Tanzania.
Department of Pediatric Cardiology, Wilhelmina Children’s Hospital, Utrecht, The Netherlands
Julius Global Health, Julius Center for Health Sciences and Primary Care, Utrecht University, Utrecht, The Netherlands
Department of Pediatrics, Muhimbili National Hospital, Dar es Salaam, Tanzania
Department of Adult Cardiology, Jakaya Kikwete Cardiac Institute, Dar es Salaam, Tanzania
Directorate of Surgery, Jakaya Kikwete Cardiac Institute, Dar es Salaam, Tanzania
Department of Pediatrics and Child Health, Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania

*The corresponding author Naizihijwa G. Majani

Keywords: Pulse Oximetry, Newborn screening, Neonatal sepsis, Neonatal mortality, Low resource setting.

Abstract

Background: Pulse oximetry (POX) is commonly used for early detection of Critical Congenital Heart Disease (CCHD) in newborns, but its potential for identifying other life-threatening conditions in low-resource settings is often overlooked. This study examines the role of POX in detecting conditions beyond CCHD in newborns in Dar es Salaam, Tanzania.

Methods: A prospective cohort study was conducted in two Tanzanian hospitals, focusing on identifying CCHD. Pre and post-ductal oxygen saturation (SpO2) readings were taken, and positive screens led to echocardiography evaluations. Newborns with congenital heart disease (CHD) were referred to a cardiac institute, while others were sent to pediatricians for further assessment. Primary outcomes included diagnoses and management strategies for those referred, while secondary outcomes considered hospital stays and survival rates at six months.

Results: Between October 2020 and June 2023, 10,630 newborns were screened, with 51 (0.46%) testing positive for POX. Of these, 29 (59.2%) were referred to paediatricians, resulting in diagnoses of 10 (34.5%) with sepsis, 10 (34.5%) with transient tachypnea, and 8 (27.6%) with persistent pulmonary hypertension of the newborn. The median hospital stay was 9.2 days (IQR: 7–14 days), and the overall mortality rate was 13.8%, with a six-month survival rate of 86.2%. Newborns diagnosed with sepsis showed the highest mortality.

Conclusion: In Tanzania, POX should be utilized as a vital screening tool for both CCHD and other serious neonatal conditions, such as sepsis. Integrating routine POX screening can enable prompt treatment of significant but often asymptomatic conditions in newborns.

What is Known

Pulse oximetry (POX) is commonly used as a non-invasive screening tool for the early detection of CCHD in newborns. There are established protocols designed to identify low oxygen levels, which can indicate potential heart disease.
Most studies have primarily focused on POX’s effectiveness in screening for cardiac conditions. However, its potential for detecting non-cardiac conditions, especially in Low-Middle Income Countries (LMIC), remains largely underexplored.

What this study adds

This study shows that pulse oximetry (POX) can identify several important neonatal conditions beyond critical congenital heart disease (CCHD), including neonatal sepsis, pulmonary hypertension, and transient tachypnea. More than half of the infants flagged by POX required treatment, indicating that POX can act as an early warning system for a wider range of conditions.

Impact

In low-resource settings where comprehensive neonatal care is limited, pulse oximetry (POX) can be a vital tool for identifying newborns who need urgent medical attention before symptoms appear. By incorporating POX into routine newborn screening programs and addressing a wider range of neonatal conditions, there is significant potential to reduce neonatal morbidity and mortality.

Introduction

Pulse oximetry (POX) is a simple, cheap and noninvasive tool used for early detection of critical congenital heart disease (CCHD) (1,2). It helps identify structural heart anomalies and guides clinical management decisions. Its usefulness, cost-effectiveness, and accuracy have been widely studied, and it is now a standard of care for newborns in many high-income countries (HIC) (1-5). In these countries, CCHD is the second leading cause of infant deaths, making early diagnosis and intervention critical for reducing neonatal morbidity and mortality (6,7).

Childhood survival remains a critical global health concern. Despite significant strides in reducing under-five mortality, credits to international efforts, such as the Millennium Development Goals and later Sustainable Development Goals (SDGs), neonatal mortality rates remain alarmingly high, especially in low resource settings (10-14). To address this ongoing challenge, there is an urgent need for targeted interventions aimed at advancing neonatal care and achieving further reductions in newborn deaths (8,9).

One area that requires attention is the current detection methods for newborn illnesses. The diagnostic capabilities available in well-resourced healthcare facilities are often lacking in low-middle-income countries (LMIC); furthermore, nonspecific presentations and early post-delivery discharge practices in these settings potentially fail to identify early-onset diseases, resulting in delayed diagnosis and unfavorable outcomes (8, 9, 10,15,23). POX, a vital sign equivalent, has not been thoroughly investigated in this context (23). Since the 1990s, researchers have been exploring the possible roles of POX in identifying CCHD (18). Some early studies on newborn screening for CCHD suggested that false positives from POX could actually indicate other serious conditions, making it potentially useful in low-resource countries (1,2,19-21). With less than a handful of reported reports of the usefulness of this diagnostic tool, the practical application of this knowledge has yet to be widely studied (15-17). Needless to say, as the outcomes for newborns undergoing this screening can vary widely depending on the abnormalities detected, it is crucial to study the impact of POX on detected pathologies so as to improve clinical protocols and ensure appropriate newborn care.

The purpose of this study, therefore, is to explore the benefits of using POX to detect non-cardiac conditions that could pose significant risks to neonatal health. We will delve into how early interventions for identified newborn illnesses can impact outcomes. Our main goal is to highlight the importance of using POX as a standard of care to improve the overall quality of newborn care in these settings.

Methods

Study Design and Study Setting

This prospective cohort study was conducted in Dar es Salaam, Tanzania, and focused on two government-owned hospitals that offer tertiary and secondary care. These hospitals are Muhimbili National Hospital (MNH) and Mwananyamala Referral Hospital (MRH). MNH is a tertiary referral center equipped with a neonatal Intensive Care Unit (NICU), a kangaroo mother care unit, and a neonatal ward that can accommodate up to 100 newborns. MRH, a regional secondary care facility located about 6 km from MNH, has a 10-bed NICU, a kangaroo mother care unit, and a neonatal ward with a capacity for 30 newborns. These two hospitals provide a good representation of tertiary and secondary-level health facilities in Tanzania. The full primary study protocol was previously published (44). Briefly in here, the study was conducted from October 2020 to June 2023 at MNH and from June 2022 to June 2023 in MRH, screening a total of 10,630 newborns. All newborns meeting the inclusion criteria were systematically enrolled and screened. These were all asymptomatic full-term or near-term newborns (gestational age >35 weeks) delivered at the two hospitals and admitted to regular newborn nurseries who were at least 12 hours old or prior to discharge. Newborns delivered before 35 weeks, or those admitted to the NICU due to severe illness or malformations, were excluded, as these infants undergo extensive investigations and are less likely to be missed for evaluation.

Routine newborn care at MNH and MRH

Postnatal newborn examination and femoral pulse palpation are not routine practices at both hospitals. In a well-baby nursery, asymptomatic newborns are nursed with their mother for observation, routinely weighed, and receive the first dose of immunisation before discharge under the observation of nursing staff. If a nurse suspects a baby on visual assessment is not well or the mother reports complaints, a medical doctor is consulted.

Enrolment and Pulse Oximetry Screening

The POX screening was conducted according to the US Newborn Screening Program protocol (1). It was performed by a nurse, intern doctor, or student, and readings were taken from the right hand and one foot using the Bistos (BT-710, Korea) device with a neonatal sensor. The full screening protocol for this study has been published for reference (44).

Data Collection

Data were collected at the time of screening and during echocardiography, including demographic information, echocardiogram results, referral patterns, diagnoses, treatment regimens, and length of hospital stay. Echocardiographic diagnoses were categorised into CCHD, other Congenital Heart Diseases (CHD), Pulmonary Hypertension and normal Echocardiogram. Pulmonary Hypertension was estimated by measurement of Tricuspid regurgitation and an estimated RVSP of more than 2/3 of systemic pressure was regarded positive for pulmonary hypertension. Treatment interventions were recorded, focusing on the management of persistent pulmonary hypertension of newborns (PPHN), transient tachypnoea of the newborn (TTN) and neonatal sepsis. The diagnosis of sepsis was based on clinical signs and symptoms complemented by other investigations such as full blood count, C-reactive protein, blood cultures and chest x-rays whenever needed and per guided protocol of MNH and MRH on management of newborn suspected with neonatal sepsis.

Sample Size

As this was part of the main study focused on POX detecting CCHD, formal sample size calculations were not employed. The primary outcomes were the detection rates of CCHD and other abnormalities, and the secondary outcomes included the treatment strategies employed, the length of hospital stay, and survival at the age of six months. In another manuscript we have described the type of CCHD detected in this study. Here, we will concentrate on the results of secondary pathologies detected on POX.

Statistical Analysis

All questionnaires underwent thorough quality checks, coding, processing, and cleaning before being entered into Redcap version 16 for analysis using SPSS version 29.0.1. Descriptive statistics were used to summarise the data. Median and interquartile ranges (IQR) were used for continuous variables, while frequencies and percentages were used for categorical variables. A one-way ANOVA was conducted to determine whether the mode of delivery caesarean section (C-section) vs. spontaneous vertex delivery (SVD) had a significant effect on the number of days spent in the hospital, and a multiple linear regression evaluated the influence of gestational age, birth weight, and number of days spent in the hospital on the likelihood of survival at six months. A p-value of less than 0.05 was considered significant for the final model.

Results

Screening and Echocardiogram Findings

Between October 2020 and June 2023. A total of 10, 630 newborns were screened for CCHD using POX; the characteristics of screened newborns are shown in Table 1. Out of those screened, 51 newborns (0.5%) tested positive based on the POX results, and 49 were referred for echocardiography. Among the 49 neonates who underwent echocardiography, 15 (25%) were diagnosed with CCHD, while 5 (6.25%) were found to have other CHD. The remaining 29 neonates (59.2%) were determined to have normal echocardiograms or other non-CHD-related abnormalities and were subsequently referred to pediatricians for further evaluation (see Figure 1).

Characteristics of Referrals

Table 2 shows characteristics of children sent for paediatrician review with abnormal POX results. Among the 29 children reviewed, the mean gestational age was 38.2 weeks (± 3.2 weeks), and the mean birth weight was 3.3 kg (± 0.7 kg). The majority of the newborns, 21 (72.0%), were male, and 18 (66.7%) were delivered via cesarean section. The median time for POX screening was 40.7 (IQR: 28 – 72) hours (see Supplementary 1 and Supplementary 2).

Referral Outcomes

Figure 2 shows the distribution of diagnoses made on paediatrician reviews. Ten newborns (34.5%) were diagnosed with transient tachypnea of the newborn (TTN) and were discharged after their symptoms resolved without further intervention. Eight newborns (27.5%) were diagnosed with pulmonary hypertension, of which four (13.8%) were treated with sildenafil. Both cases responded well to treatment, with symptoms resolving before discharge. Another four (13.8%) were treated with supplemental oxygen, and all showed improvement in oxygenation levels. Additionally, ten newborns (34.5%) were diagnosed with an infection, including neonatal sepsis (n=7, 24.1%) and respiratory infections (n=3,10.3%), and received appropriate antibiotic therapy. One newborn was diagnosed with low gestational age [MS1] and received treatment according to protocol (Table 2).

Outcome analysis

All 29 babies completed their six-month follow-up. The overall survival rate at six months was 86%. The study revealed high survival rates for newborns diagnosed with TTN (100%), Pulmonary hypertension (100%), and Neonatal Sepsis (71%). There were 4 deaths, resulting in an overall mortality rate of 13.8%. One of the deaths was a 1.8 kg baby at 37 weeks gestational age who passed away 14 days after birth due to low birth weight-related issues. The other three deaths were due to sepsis, with one occurring at seven days old and the other two at two months and four months of age. The six months median survival time for those who died was 24 days Figure 3.

Associated factors

Survival at six months was positively correlated with the number of days spent in the hospital (β = 0.70). In contrast, both gestational age and birth weight showed negative correlations with hospital stays, with coefficients of β = -0.35 and β = -0.39, respectively (Supplementary 4).

We also analyzed factors associated with survival at six months, including gestational age, birth weight, length of hospital stays, type of condition, and the presence of neonatal sepsis. Our findings indicated a trend suggesting that the presence of neonatal sepsis was linked to prolonged hospital stays and survival rates at six months; however, this trend did not reach statistical significance (Supplementary 5).

Table 1. Characteristics of the newborns evaluated for hypoxemia with pulse oximetry to detect early CCHD, (n=10,628)

VARIABLE	CATEGORY	NUMBER (%)
Average Gestational (weeks)	Median (IQR)	38 (37-40)
Birth Weight (kg)	Median (IQR)	3 (2.60-3.40)
Birth Height (cm)	Median (IQR)	47 (45-49
Gender	Male (%)	5721 (54.0%)
Mode of Delivery	Spontaneous vertex Delivery	4400 (41.4)
	Caesarean Section	6201 (58.5)
	Breach Delivery	24 (0.3)
	Undocumented	3 (0.1)
Apgar Score at 5 Minutes	1-4	34 (0.7)
	5-8	3624 (34.5)
	9-10	6864 (64.8)
Maternal age	years; Median (IQR)	30 (25-34)
Residence (Yes)	Dar es Salaam	10004 (95.1)
Parity	Prime gravida	2923 (27.6)
	2-5	7244 (68.5)
	6-10	400 (3.8)
	>10	14 (0.5)
HIV status	Positive	243 (2.3)
	Negative	9996 (95.7)
	Unknown	205 (2.0)
Febrile Illness	Any febrile illnesses during pregnancy (yes)	752 (7.1)
UTI	Urinary tract infections during pregnancy (Yes)	2893 (27.5)
PMTCT-Prevention of Mother to Child Transmission; UTI-Urinary Tract Infection

Table 2: Detailed Breakdown of Non-CCHD [MS2] Conditions Detected at birth (n=29)

Gestational Age (Weeks)	Gender	Mode of delivery	Birth weight	Age at time of test (hrs)	Saturation % (Arm/Foot/diff)	Condition	Treatment given	Number of Days spent in Hospital	Outcome at age 6 months
38	M	C-section	3.6	48	88/92/4	Transient Tachypnoea of the newborn (6)	Supportive Care	2	Alive
37	M	SVD	4.0	27	90/96/6	Transient Tachypnoea of the new born	Supportive Care	1	Alive
48	F	C-section	2.5	48	90/96/6	Transient Tachypnoea of the new born	Supportive Care	1	Alive
48	F	C-section	2.5	48	92/88/4	Transient Tachypnoea of the new born	Supportive Care	2	Alive
36	M	C-section	2.6	72	92/96/4	Transient Tachypnoea of the new born	Supportive Care	2	Alive
39	M	C-section	3.9	42	88/93/5	Transient Tachypnoea of the new born	Supportive Care	2	Alive
38	M	C-section	3.7	48	89/92/4	Transient Tachypnoea of the new born	Supportive Care	2	Alive
36	F	C-section	3.4	49	92/96/4	Transient Tachypnoea of the new born	Supportive Care	2	Alive
39	M	C-section	5.1	46	91/95/4	Transient Tachypnoea of the new born	Supportive Care	2	Alive
38	M	C-section	3.9	42	92/96/4	Transient Tachypnoea of the new born	Supportive Care	1	Alive
37	F	SVD	1.8	16	89/91/2	Low for Gestational age	Supportive care	14	Died in Hospital at age 14 days
38	M	SVD	3.8	28	90/93/3	Pulmonary hypertension	Sildenafil	9	Alive
37	M	C-section	3.8	29	88/90/2	Pulmonary Hypertension	Sildenafil	7	Alive
38	F	C-Section	2.7	67	80/90/10	Pulmonary Hypertension	Sildenafil	18	Alive
36	M	SVD	2.7	24	93/89/4	Pulmonary Hypertension	Sildenafil	8	Alive
40	M	SVD	3.4	24	87/90/3	Pulmonary Hypertension	Oxygen Therapy	3	Alive
39	F	SVD	2.8	26	90/93/3	Pulmonary Hypertension	Oxygen Therapy	2	Alive
38	M	C-section	3.8	56	89/90/9	Pulmonary Hypertension	Oxygen therapy	3	Alive
38	M	SVD	3.7	21	93/89/4	Pulmonary Hypertension	Oxygen Therapy	2	Alive
36	M	C-section	2.6	72	93/94/1 repeat in 1hour 92/94/2	Respiratory Infection	Antibiotics	10	alive
38	M	SVD	3.8	24	88/91/3	Respiratory Infection	Antibiotics	7	Died in hospital at age 7 days
37	F	C-section	2.6	40	89/93/4	Respiratory Infection	Antibiotics	12	Alive
36	M	C-section	2.7	48	83/88/5	Neonatal Sepsis	Antibiotics	8	alive
37	M	C-section	3.4	15	91/83/5	Neonatal Sepsis	Antibiotics	7	Alive
37	M	C-section	3.3	38	92/90/2	Neonatal Sepsis	Antibiotics	8	Alive
38	M	SVD	3.8	28	90/96/6	Neonatal Sepsis	Antibiotics	7	Alive
36	F	C-section	3.2	65	90/94/4	Neonatal Sepsis	Antibiotics	11	Alive
36	M	SVD	3.0	22	86/90/4	Neonatal Sepsis	Antibiotics	29	Died at age of 4 Months
38	M	C-section	2.6	68	92/96/4	Neonatal Sepsis	Antibiotics	10	Died at age of 2 months

Figure1: Flow chart of screening process and Outcome of Screened newborns

[MS3]

Figure2 : Distribution of Newborn Lesions with positive pulse oximetry at Birth

Figure 3: Kaplan Meir six- months survival functional curve of secondary pathologies

Median Survival time 24 days (95%CI: 0.00-62.8)

Discussion

Pulse oximetry (POX) has become a well-established screening tool for detecting critical congenital heart disease (CCHD) in newborns (35). Recent studies, such as the one by Vaidyanathan et al. (2020), have shown that POX can also be effective in detecting non-cardiac conditions, but its utility remains underexplored especially in LMICs (15,17). Our research has identified cases of serious conditions like neonatal sepsis, and PPHN (persistent pulmonary hypertension of the newborn) through POX screening.

One of the key findings from our analysis was the significant impact of neonatal sepsis on survival. . It showed a negative association with survival (OR = 0.845), [RG4] indicating its role as a major contributor to neonatal mortality. The use of POX

It showed a negative association with survival (OR = 0.845), indicating its role as a major contributor to neonatal mortality. The use of POX screening enabled early detection of sepsis, which might otherwise have gone undiagnosed before discharge. Neonatal sepsis accounts for a third of neonatal deaths worldwide and is recognized by the WHO as a major health concern(8,9,30). It remains one of the leading causes of neonatal mortality, especially in resource-limited settings (9-12). Diagnostic challenges, limited access to antibiotics, antimicrobial resistance, and delayed healthcare leads to its poor outcomes (31-33). Early detection for neonatal sepsis therefore, is imperative. . Our study findings support the growing evidence that POX can be an effective screening tool for sepsis, especially in resource-limited settings, before the onset of severe clinical symptoms and death(15-17,20,21). [RG5]

Our study findings support the growing evidence that POX can be an effective screening tool for sepsis, especially in resource-limited settings, before the onset of severe clinical symptoms and death(15-17,20,21). Moreover, POX is already widely used to monitor oxygen saturation and guide clinical decisions for sick newborns with respiratory or cardiac conditions; its use can be expanded.

Additionally, we were able to identify pulmonary conditions such as Persistent Pulmonary Hypertension of the Newborn (PPHN) in infants who did not exhibit any symptoms at birth. PPHN is a serious acute disorder in newborns that often leads to severe illness and death, and is difficult to diagnose (36-38). While previous research has focused on using echocardiography to diagnose PPHN, many low- and middle-income countries (LMICs) have limited access to such advanced diagnostic tools (36). Our findings show that pulse oximetry (POX) has a potential to detect this condition early, allowing for timely interventions that resulted in the survival of all identified infants. Although we did not look at the number of patients with pulmonary diseases that POX missed, our findings show a glimpse of hope for the potential benefit of early POX-based identification of pulmonary diseases in LMICs, where delayed diagnoses often lead to high mortality rates.

Our findings also suggest that the current approach of supportive care for TTN(transient tachypnoeic of newborns) is largely effective, as most infants recovered within a few days and had positive six-month outcomes. However, for infants with more severe conditions like sepsis, longer hospital stays and more intensive care are necessary. These insights could help improve guidelines for managing at-risk newborns.

Interestingly, we found an unexpected strong correlation between hospital stays and survival at six months. In our view, this finding suggests that prolong hospital stays may play a protective role in improving survival rates for infants detected early, though the small sample size warrants cautions interpretation. However, The lower survival rate in infants with sepsis indicate the burden of this disease and persistent challenges in management of sepsis in newborn, although this study did not look at the mortality of children with neonatal sepsis who died during the time, previous studies from the same hospital showed mortality rate from sepsis was , where as mortality rate from sepsis from this study was…. The early identification in our view may have contributed to this positive results, however the number are small . Future research should aim to confirm these trends in larger cohorts and explore the underlying mechanisms.

Lastly, our research did not find any significant impact of the delivery method on the length of hospital stay or survival rates. Although some studies have suggested that cesarean sections may lead to more complications in newborns, our data did not show any significant differences in outcomes for non-cardiac newborns (42,43). This suggests that the underlying health conditions identified through postnatal care are more important in determining the outcomes for newborns than the delivery method. This finding is particularly relevant in our context, where early identification of at-risk newborns, especially those born preterm and with low birth weights, could lead to more proactive management, such as enhanced respiratory support, nutritional interventions, or even preventive therapies.

Limitations and Future Directions

While our findings are promising, there are limitations to this study that warrant further exploration. First, the relatively small sample size and the focus on a single LMIC setting may limit the generalizability of the results to other regions. Future studies should aim to replicate these findings in larger and more diverse populations to better understand the potential of POX as a comprehensive neonatal screening tool in different contexts. Additionally, while we demonstrated that prolonged hospital stays were associated with improved survival, this finding requires further investigation to determine the underlying mechanisms and to assess whether this relationship holds across other LMICs or healthcare settings with varying resource levels. Finally, further research is needed to evaluate the long-term outcomes of infants diagnosed through POX screening for non-cardiac conditions, as well as the cost-effectiveness of implementing POX screening on a broader scale in LMICs.

Summary

Our study adds to the growing body of knowledge advocating the widespread implementation of POX screening in LMICs. By demonstrating that POX can detect asymptomatic conditions beyond CCHD, our findings support the argument for integrating POX into national healthcare protocols in LMICs. This is particularly important given the high burden of neonatal mortality in these regions and the limited availability of advanced diagnostic technologies. POX, as a low-cost, non-invasive, and scalable solution, has the potential to fill critical gaps in neonatal care by enabling early detection and timely intervention, ultimately reducing neonatal mortality.

Conclusion

Given the significant burden of sepsis and other undiagnosed pulmonary neonatal conditions in LMICs, routine POX screening could serve as an early warning system. This can prompt early interventions that save lives. In this context, POX offers a scalable solution for both urban and rural hospitals.

Funding: This study was partially funded by Grants from AFAS Foundation, Netherlans, supporting inter-regional collaboration, and grant from East Africa Centre of Excellence in Muhimbili University of Health and Allied Sciences

Availability of data and materials: Data from this study will be made available on request to the corresponding Author.

Competing interests: None declared.

Patient consent: was collected digitally on paper and stored at the Jakaya Kikwete Cardiac Institute.

Ethics approval: The Muhimbili University of Health and Allied Science with Ethics Committee approved this study (application No 0670-03) further permission were obtained from National Institute of Medical Research (NIMR), Muhimbili National Hospital and Jakaya Kiwete Cardiac Institute.

Authors' contributions

NM is a PhD candidate who came up with the research topic, contributed to the study design and data collection, data analysis and provided the first draft of the manuscript. ZK, DN, SM, SK, GS, FS and NL conducted data collection, critically reviewed the manuscript. PC, MS MJ and DG provided critical feedback on the manuscript drafts and mentoring on the data analyses.

Acknowledgements

We would like to express our gratitude to everyone who contributed to this multicenter study, especially the nursery and midwifery staff, medical officers, pediatricians, and the entire administration at both Muhimbili National Hospital and Mwananyamala Regional Hospital. We also want to extend our thanks to the Cardiothoracic team and Cardiologists at Jakaya Kiwete Cardiac Institute, as well as the entire administration and nursing staff at Jakaya Kikwete Cardiac Institute. We would also like to acknowledge the contribution of Lilian Charles, Dr. Jackline Mathew, and Amanda Mnongone for their help with follow-up phone calls and data entry. Lastly, we are grateful to Yutha Nkwera for her outstanding administration throughout the entire study period.

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Supplementary 1: Showing saturation level and differences between different conditions diagnose

Box plots showing Saturations Difference across different conditions

Supplementary 2: Showing average days spent in hospital per conditions

Charts showing Average number of days spent in Hospital per each Conditions

Supplementary 3: Showing the effect of Birth weight and gestation age on 6 month outcome

Figure 7: Scatter Plot showing association of Gestational age, Birth weight and Outcome at six Months.

Infants born closer to full-term (37–42 weeks) with higher birth weights (around 3.5 kg and above) generally have better outcomes. Suggesting, full-term infants with healthy birth weights have fewer complications at six months. prematurity and low birth weight are strong risk factors for poor outcomes

Supplementary 4: Correlation Matrix showing variable correlation to look at factors related to Hospital stay and survival at six months.

NB: Correlation matrix between different variables and time to event: Time to event here means survival at six month. Showing a strong correlations between number spent in hospital and survival at six months.

Supplementary 5: Logistic Regression for factors associated with Survival and Hospital stay.

Predictor	Coëfficiënt (b)	Odds Ratio (OR)	95% CI (Lower)	95% CI (Upper)
Gestational Age (Weeks)	0.024	1.02	0.98	1.07
Birth Weight	-0.222	0.80	0.52	1.24
Number of Days Spent in Hospital	0.224	1.25	0.81	1.94
Condition: Other conditions	0.272	1.31	0.77	2.24
Condition: Neonatal Sepsis	-0.168	0.84	0.61	1.18