AI Tool for Early Prediction of

Neonatal Sepsis

Feature and Model Selection Draft

Scope
This document provides an introduction to an AI use case that can be used for early prediction
of Neonatal Sepsis. This document provides a background for introduction to neonatal sepsis
with disease features, current detection techniques along with their shortcomings and a
proposal for an AI based early prediction model.

Background

The World Health Organization estimates that one in ten deaths associated with pregnancy and
childbirth is due to maternal sepsis with over 95% of deaths due to maternal sepsis occurring in
low and middle-income countries. In India, the incidence of clinical sepsis is particularly high,
with an estimated 17,000 cases per 100,000 live births. Unfortunately, the case fatality rates in
India are also concerning, ranging from 25% to 65%, and it's likely that these figures are
underestimated.
Neonatal sepsis is a serious bacterial infection that occurs in newborn infants within the first 28
days of life. It can be caused by bacteria, viruses, or fungi, and can be acquired before or after
birth. The infection can spread throughout the newborn's body and cause severe health
complications such as pneumonia, meningitis, septicemia, organ failure and results in
substantial morbidity and mortality.
The infection may be acquired in utero, from the mother’s genital tract or postnatally from the
community or hospital environment and personnel. Factors including the time of exposure, size
of the inoculum, immunity in the host, and virulence of the infectious agent affect the severity
and course of illness.

Current Detection techniques

There are several techniques and procedures used to detect neonatal sepsis, including:

1. Blood cultures: This is the gold standard for diagnosing neonatal sepsis. Blood samples are
taken from the baby and cultured in a lab to detect the presence of bacterial or fungi
infestations.
2. Complete blood count (CBC): This test measures the number of red blood cells, white blood
cells, and platelets in the baby's blood. A high white blood cell count can indicate an infection.
3. C-reactive protein (CRP) test: CRP is a protein that is produced by the liver in response to
inflammation. Elevated levels of CRP in the baby's blood can indicate an infection.
4. Procalcitonin (PCT) test: PCT is a protein that is produced in response to bacterial infections.
Elevated levels of PCT in the baby's blood can indicate an infection.
5. Lumbar puncture: This is a procedure where a needle is inserted into the baby's lower back to
collect cerebrospinal fluid (CSF) for analysis. CSF analysis can help diagnose meningitis, which
is a type of bacterial infection that can cause neonatal sepsis.
6. Chest X-ray: This can help diagnose pneumonia, which is a common complication of neonatal
sepsis.
7. Urine culture: A urine sample can be collected using a catheter or suprapubic puncture to
detect the presence of bacteria in the baby's urine.

Fig 1. Therapeutic guidelines and treatment model for neonatal infection (2011)

Problem with current detection techniques

1. Non-specific symptoms - Neonatal sepsis, which can manifest as septicaemia,

pneumonia, meningitis, osteomyelitis, arthritis, and urinary tract infections, lacks a
universally accepted definition, particularly in Low- and Middle-Income Countries
(LMICs).
2. Clinical signs are vague and ineffective at detecting early-onset sepsis (EOS).
3. Delayed diagnosis - Culture tests, which can take up to 48 hours to produce results, yield
positive results in only 25% to 45% of cases.
 4. False positive - May produce false-positive or low-yield results after exposure to
antenatal antibiotics.
5. Limited access to diagnostic facilities - Culture-testing facilities are not available in most
district hospitals in India. Consequently, the prediction and diagnosis of neonatal sepsis
rely on culture-independent diagnostic techniques and risk assessment scoring systems.

Proposed Solution
The implementation of an AI-based intervention for the early detection and diagnosis of
neonatal sepsis has the potential to significantly improve clinical outcomes for neonates,
especially in low-resource settings. The AI-powered system utilizes machine learning algorithms
to analyze patient data, including vital signs, laboratory results, and clinical history, to detect the
early signs of neonatal sepsis. This solution would provide real-time alerts to healthcare
providers, allowing for timely intervention and treatment, potentially reducing the incidence of
sepsis-related complications. This intervention will also provide a cost-effective, non-invasive,
and easily accessible solution for neonatal sepsis detection, with the potential to improve health
equity for underserved populations.

● Feature selection
To define features to be selected we need to divide into early onset and late onset
neonatal sepsis. Further, source of data collection is an important parameter to design a
feasible process for data collection and processing.

Category Factors

Early onset Maternal age, intrapartum temperature, cervicovaginitis, PROM,

Maternal WBC count

Late onset Maternal age, cervicovaginitis, PROM, WBC count

Fever, birth weight, neonatal temperature, fetal

Early onset morbidity(physical appearance into 3 categories), gender,
endotracheal intubation, thyroid hypofunction, umbilical venous
catheter (UVC)
Neonatal Laboratory features - no of bradycardia events,
neutrophil–lymphocyte ratio > 1.5 and C-Reactive Protein > 0.75

Fever, birth weight, fetal morbidity(physical appearance into 3

Late onset categories), gender, gestational age, neonatal temperature,
antibiotics treatment,
Laboratory features - neutrophil–lymphocyte ratio > 1.5 and
C-Reactive Protein > 0.75
Clinical Laboratory factors as a whole which show an overall predictive capability - platelet
count, bradypnea, band cells, heart rate (maximum, minimum), SpO2 minimum, blood pressure
systolic (minimum, mean), thyroid, acyl carnitine, amino acids and adrenal functions

● Model selection
A few categories to help in choosing the type of ML model that can be implemented
include - Performance metrics, dataset size, complexity of model, regularization and
normalization techniques, scalability, etc.
By performing a brief literature review it was observed that most of the research
conducted used Logistic regression for building the model as it had several advantages
in comparison to other approaches. It provided probability prediction of each predictor
unlike only classifying it into different levels. Models generated by this approach, unlike
other models like SVM and Decision Trees, are less likely to be over-fit even with the
smaller datasets.
As data might be from different sources(multi-centre origin study), an external validation
approach has been observed as a recommendation. Though, among internal validations,
bootstrapping has emerged as the most preferred when compared with cross or split
validation as it utilizes the whole dataset thus producing results of low variance.

Early on-set Neonatal Sepsis - Among all the studies conducted, best results were
observed with sepsis neonates classification into clinical-illness, equivocal and well
appearing using a stepwise multinomial logistic regression. Though no external
validation was performed, it has been highly recommended in case of multi-centre origin
studies.
Late on-set Neonatal sepsis - Among different studies conducted, most used logistic
regression, while among the remaining, best results were observed using autoregressive
hidden markov method. Though computationally aggressive and requiring higher seed
sequences to be trained, this methodology showed better results. Depending on features
selected and amount of regularized data present a model can be selected among these.
Bootstrapping or external validation has been recommended.

Potential Impact (Stakeholders)

1. Frontline Health workers: an AI-based solution can reduce the workload of manual
testing and analysis, allowing for faster and more accurate diagnosis of sepsis. It can
also improve the efficiency and quality of lab operations, leading to better patient
outcomes and increased customer satisfaction.
2. Doctors: such a solution can provide an accurate and timely diagnosis of sepsis, leading
to early intervention and treatment, which can reduce the morbidity and mortality
associated with sepsis.
 3. Patients: early detection and treatment of sepsis can improve a patient's chances of
survival and reduce the risk of long-term complications. It can also reduce the need for
invasive diagnostic procedures and the associated risks and discomfort.

References
1. Murthy S, Godinho MA, Guddattu V, Lewis LES, Nair NS. Risk factors of neonatal sepsis
in India: A systematic review and meta-analysis. PLoS One. 2019 Apr 25;14(4):e0215683.
doi: 10.1371/journal.pone.0215683. PMID: 31022223; PMCID: PMC6483350.
2. Sahu P, Raj Stanly EA, Simon Lewis LE, Prabhu K, Rao M, Kunhikatta V. Prediction
modelling in the early detection of neonatal sepsis. World J Pediatr. 2022
Mar;18(3):160-175. doi: 10.1007/s12519-021-00505-1. Epub 2022 Jan 5. PMID:
34984642; PMCID: PMC8898244.
3. Shane AL, Sánchez PJ, Stoll BJ. Neonatal sepsis. Lancet. 2017 Oct
14;390(10104):1770-1780. doi: 10.1016/S0140-6736(17)31002-4. Epub 2017 Apr 20.
PMID: 28434651.

Figures
1. “Therapeutic guidelines in neonatal infection”2011