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\begin{document}

\title{Anemia, nutrition and ambulatory oxygen weaning in a cohort of
oxygen-dependent premature infants.}



\author[1]{Adriana Montealegre}%
\author[2]{Nathalie Charpak}%
\affil[1]{Pontifical Xavierian University}%
\affil[2]{Kangaroo Foundation}%


\vspace{-1em}



  
  \date{May 05, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Background: In Bogot\selectlanguage{ngerman}á, Colombia, oxygen-dependent (OD) preterm infants
are home discharged in Kangaroo Position, to a Kangaroo Mother Care
program (KMCP) with ambulatory oxygen, strict follow-up and oxygen
weaning protocols. Objectives: 1) to describe growth and morbimortality
up to 6 months of an OD preterm infants' cohort. 2) to explore the
association between oxygen requirement, perinatal history, Hb levels,
transfusions, feeding patterns and growth. Methods: Prospective cohort
study. Descriptive and multivariate analysis. Results: 445 patients were
recruited with 33 weeks median gestational age (GA). 21\% of mothers had
preeclampsia, 50\% infections and 77\% received antenatal
corticosteroids. Upon KMCP admission, median GA, chronological age and
hospital stay were 36 weeks, 19 and 17 days, respectively; 55.6\% of
patients had neonatal sepsis and 66.6\% were admitted to Neonatal
Intensive Care Unit. Patients had on average 52 days with oxygen, a
median of 3200g and 42 weeks GA at oxygen weaning. Median follow-up
oxygen saturation was 94\% with 0.016-0.5 l/min of oxygen. One-year
mortality was 0.2\% and attrition 20\%. At 6 months, all patients had
appropriate growth and 66\% were breastfeeding. Multiple regression
analysis showed that higher GA, Hb levels, weight gain, and exclusive
breastfeeding decreased oxygen requirement whilst invasive ventilation
and transfusions had the opposite effect (R2=0.48). Conclusions: In OD
preterm infants, there is a close relationship between days of oxygen
requirement and GA, mechanical ventilation, Hb levels at discharge,
transfusions, exclusive breastfeeding and weight gain. Strict monitoring
with established protocols in an ambulatory KMCP allows adequate growth
and safe oxygen weaning.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{Title:} Anemia, nutrition and ambulatory oxygen weaning in a
cohort of oxygen-dependent premature infants.

\textbf{Authors:} Adriana del Pilar Montealegre-Pomar, MD,
MSc\textsuperscript{a,b,c}, Nathalie Charpak, MD*\textsuperscript{a,b}

\textbf{Affiliations:} \textsuperscript{a}Kangaroo Foundation, Bogot\selectlanguage{ngerman}á,
Colombia, \textsuperscript{b}Pontificia Universidad
Javeriana,\textsuperscript{c}Hospital Universitario San Ignacio.

*Contributed equally as co-first author.

\textbf{Correspondent author:} Adriana Montealegre-Pomar, Hospital
Universitario San Ignacio, Carrera 7 No 40-62, Bogotá, Colombia. Tel:
+57 1 594-6161 Ext 2491. Cell Phone: +57 315-670-1641,
e-mail:\emph{montealegre.a@javeriana.edu.co}The authors do not need
reprints.

\textbf{Key words:} Kangaroo-Mother Care Method; Bronchopulmonary
Dysplasia; oxygen inhalation therapy; oximetry.

\textbf{Sources of Funding:} this project was supported by the Kangaroo
Foundation, the Integral Kangaroo Mother Care Program, the Pontificia
Universidad Javeriana in Bogotá, Colombia and the Nestlé Foundation
(grant).

\textbf{Conflict of Interest statement:} the authors have no conflicts
of interest relevant to this article to disclose.

\textbf{Abbreviated title:} Anemia, nutrition and ambulatory oxygen
weaning in BPD.

\subsection*{Structured Abstract
(250/250)}

{\label{structured-abstract-250250}}

\emph{Background:} In Bogotá, Colombia, oxygen-dependent (OD) preterm
infants are home discharged in Kangaroo Position, to a Kangaroo Mother
Care program (KMCP) with ambulatory oxygen, strict follow-up and oxygen
weaning protocols.

\emph{Objectives:} 1) to describe growth and morbimortality up to 6
months of an OD preterm infants' cohort. 2) to explore the association
between oxygen requirement, perinatal history, Hb levels, transfusions,
feeding patterns and growth.

\emph{Methods:} Prospective cohort study. Descriptive and multivariate
analysis.

\emph{Results:} 445 patients were recruited with 33 weeks median
gestational age (GA). 21\% of mothers had preeclampsia, 50\% infections
and 77\% received antenatal corticosteroids. Upon KMCP admission, median
GA, chronological age and hospital stay were 36 weeks, 19 and 17 days,
respectively; 55.6\% of patients had neonatal sepsis and 66.6\% were
admitted to Neonatal Intensive Care Unit. Patients had on average 52
days with oxygen, a median of 3200g and 42 weeks GA at oxygen weaning.
Median follow-up oxygen saturation was 94\% with 0.016-0.5 l/min of
oxygen. One-year mortality was 0.2\% and attrition 20\%. At 6 months,
all patients had appropriate growth and 66\% were breastfeeding.
Multiple regression analysis showed that higher GA, Hb levels, weight
gain, and exclusive breastfeeding decreased oxygen requirement whilst
invasive ventilation and transfusions had the opposite effect
(R\textsuperscript{2}=0.48).

\emph{Conclusions:} In OD preterm infants, there is a close relationship
between days of oxygen requirement and GA, mechanical ventilation, Hb
levels at discharge, transfusions, exclusive breastfeeding and weight
gain. Strict monitoring with established protocols in an ambulatory KMCP
allows adequate growth and safe oxygen weaning.

\subsection*{Introduction}

{\label{introduction}}

Currently in Colombia, preterm infants are discharged home once they are
stable and adapted to the Kangaroo Mother Care (KMC) method, without
taking into consideration their weight or gestational age (GA), and are
followed up through high-risk ambulatory programs called Kangaroo Mother
Care Programs (KMCP). Home discharge is carried out in Kangaroo Position
(KP) (permanent skin-to-skin contact) for thermoregulation, with a
feeding strategy based on exclusive breastfeeding (EBF) wherever
possible, and a strict, multidisciplinary ambulatory follow-up.

KMC was created in 1978 at the Instituto Materno Infantil of Bogotá,
Colombia, by Dr. Rey- Sanabria and has gone through multiple
modifications to become a routine tool for the care of premature or low
birth weight (LBW) infants. It is evidence-based and has been partially
or fully implemented, in most neonatal units around the
world\textsuperscript{1--3}.

Starting in 1999, as the survival of preterm infants improved,
ambulatory management of oxygen-dependent (OD) babies began in the KMCPs
of Bogotá (2600m above sea level), mostly due to bronchopulmonary
dysplasia (BPD). These programs seek to fulfill three main goals: 1) to
achieve and maintain a good nutritional status that promotes growth,
based on EBF and eventually supplemented with preterm formula. 2) to
monitor oxygen-therapy (OT), in order to achieve adequate oxygen
saturation (SpO2), correcting anemia in a timely manner, if necessary,
and 3) to carry out a strict multidisciplinary follow-up that reduces
neurodevelopmental as well as morbimortality problems, inherent to this
population.

Currently, although ambulatory OT in premature infants has increased,
little is known about how it should be monitored\textsuperscript{4}.
While SpO2 limits have been extensively investigated during
hospitalization with studies such as SUPPORT, BOOST and
COT\textsuperscript{5}, there is little evidence on monitoring the
minimum acceptable limits of SpO2 after hospital discharge, and optimal
titration of OT at home in children with BPD\textsuperscript{4}.
Furthermore, there is not enough information on the ideal hemoglobin
(Hb) value to guarantee adequate oxygenation and growth in children with
BPD who are followed-up in the KMCPs of Bogotá.

With regards to nutrition, it is known that malnutrition in children
with BPD is an early phenomenon and continues throughout childhood.
Preterm OD patients have a lower caloric reserve in the neonatal period
contrasted to their high energy requirements, due to increased breathing
work, as well as a difficulty in oral nutrition\textsuperscript{6--8}.
It is important to learn about the best nutritional strategy that
promotes adequate growth.

The objectives of this study are 1) to describe the monitoring of SpO2,
feeding pattern, somatic growth and morbimortality during the first 6
months, of a cohort of OD infants followed-up in 2 centers of excellence
in KMC in Bogotá, Colombia. 2) to establish the relationship between
these variables, Hb level upon KMCP admission, and time required to
reach oxygen weaning.

\textbf{Materials and Methods}

445 patients were recruited from a prospective cohort of 452 preterm OD
neonates, cared for in two ambulatory KMCPs in Bogotá, Colombia, between
July 25, 2017 and May 7, 2018, and followed during the first 6 months of
corrected age. Patients with a contraindication to breastfeeding due to
HIV and those with major congenital malformations, genetic problems,
intestinal malabsorption and hemolytic diseases were excluded.

\subsubsection*{Procedures}

{\label{procedures}}

Once eligible patients were identified at the KMCPs admission, informed
consent was requested from parents. Babies' perinatal data and levels of
the last Hb measured within last 7 days were obtained from the
hospitalization clinical history and recorded. In case of no Hb recent
measurement, a capillary blood sample was taken in the KMCP with
Hemocue®.

Children were controlled daily in the first days of follow-up,
monitoring their weight gain until reaching 15-20 g/kg/day. Afterwards,
weekly controls of anthropometric measurements, clinical evaluation and
dynamic oximetry were carried out until oxygen weaning (Figure 1). This
constitutes the ambulatory equivalent of minimal inpatient care. The
objective of OT was to achieve an SpO2 between 90-94\% with an adequate
heart rate. At the time of oxygen weaning, the nurse would take a
capillary Hb sample and record SpO2.

Upon admission to KMCPs, parents were provided with comprehensive
education on OT at home and received an explanatory brochure. Only
infants with OT \textless{} 1 l/min were admitted, because parents are
living in average at one hour of transportation and oxygen tank capacity
is limited.

Medical care of these patients included routine prophylactic treatments
such as oral iron, vitamins and prophylaxis for apnea of prematurity
with xanthine. The follow-up program included detection of
ophthalmological, auditory, cardiovascular and neurological conditions,
including echocardiography and brain ultrasound.

During follow-up, anthropometric data were carefully collected and
adjusted to the Fenton reference charts\textsuperscript{9}, until child
reached term (40 weeks GA) and then, to the WHO corrected age
charts\textsuperscript{10}.

Babies remained in a permanent skin-to-skin contact, 24 hours a day, in
a strict vertical position between mother's breasts and clothing,
supported by an elastic wrap. The baby could be fed at any time, staying
in KP until the child showed clear signs of intolerance (profuse
sweating or discomfort with the position). Nutrition was based on EBF to
the extent possible. If the goal of obtaining a weight gain at least
equal to intrauterine was not achieved despite receiving intensive
breastfeeding counseling and having ruled out pathological conditions
such as anemia, infection or hypothermia related to poor adherence to
KP, supplementation with preterm formula (24 Kcal/30cc) with a dropper
or spoon was initiated. The amount was calculated based on 30\% of the
recommended daily caloric intake, and after at least one week of
adequate growth, a progressive reduction of the supplement was
attempted, so as to reach 40 weeks GA with EBF.

At each follow-up, rehospitalizations, feeding patterns and
administration of iron, vitamins or erythropoietin (EPO) with exact dose
received were recorded, as well as a physical examination by the
pediatrician, and neurosensory and psychomotor development evaluations
using standardized formats. At the end of these multidisciplinary
evaluations, a certified nurse recorded the dynamic oximetry (rest,
sleep, suction), together with the required oxygen flow in liters per
minute.

After oxygen weaning, monthly controls were carried out during the first
6 months of life with nutritional and multidisciplinary
assessment\emph{.}

\subsubsection*{Ethical Considerations}

{\label{ethical-considerations}}

This study was adjusted to comply with the national and international
standards for research in human beings, in accordance with the
provisions of the Declaration of Helsinki and the resolution of good
clinical practices in the country\textsuperscript{11,12}. Informed
consent was requested from parents. The study had approval by the
scientific and ethics committees of the institutions.

\textbf{Analysis}

The STATA14 program was used for statistical analysis. To characterize
the population, descriptive analysis with means and standard deviations
(SD) or medians and range, according to the variable distribution, were
done; subsequently, a multiple linear regression analysis was performed
to establish variables that could be associated with OT time.

\subsubsection*{Results}

{\label{results}}

452 patients were eligible, of which parental consent was not given in 7
cases. 445 patients were recruited. With regards to the
socio-demographic background, most of the parents had jobs, were stable
couples, and had a secondary education, with a monthly income
corresponding to the Colombian minimum wage (229 USD). Between mothers,
more than 50\% had a history of urinary tract or gynecological
infection, 21\% had toxemia and 77\% received prenatal corticosteroids
(Table 1).

Patients' average GA at birth was 33 weeks, 58.4\% were male and 25\%
had Intrauterine Growth Restriction (IUGR). The average GA at
recruitment was 36.5 weeks, with a median of 19 days. The median total
hospital and Neonatal Intensive Care Unit (NICU) stay were 17 days and 3
days, respectively; 49\% of patients required invasive ventilation
(median 2 days) and 16\% CPAP only (median 2 days); 56\% had early or
late sepsis (Table 2).

Median oxygen requirement was 51 days. Mean SpO2 during follow-up was
94\% (SD 2.1). Oxygen volume upon admission had a median of 0.06 (1/16)
l/min with a range between 0.02-0.5 (1/64-1/2) l/min. Median weight at
oxygen weaning was 3200g with a mean GA of 42 weeks (Table 3). At the
time of weaning, 99.8\% of patients were \selectlanguage{english}[?]36 weeks GA, 66.3\% \selectlanguage{english}[?]40 weeks,
94.3\% had \textgreater{} 28 days with oxygen, and 84.9\% were \selectlanguage{english}[?]36 weeks
and had \textgreater{}28 days with oxygen.

Concerning hematological parameters, 20\% of patients had been
transfused at least once prior to entering the study (1-8 transfusions).
Between KMCP admission and 40 weeks, only 4.5\% required additional
transfusions, being minimal after oxygen weaning (0.5\%). During
follow-up, a very low proportion of patients received EPO (0.5-1\%).

Iron replacement was 51.7\% at 40 weeks, 82.8\% at 3 months, and 80.6\%
at 6 months. The mean Hb value upon entering the study was 14.1 g/dl (SD
3.2) and at weaning 11.4 g/dl (SD 1.9).

Regarding growth and feeding pattern, Table 3 shows how at 6 months, all
patients had adequate anthropometric measurements and 66\% of patients
received some breast milk at 6 months, while only 34\% received
exclusive formula.

With respect to neuromotor examination at follow-up (INFANIB), 19.5\%
and 20.8\% reported a non-normal examination at 3 months and at 6
months, respectively; 20.2\% had a Griffiths scale score\textless{}85 at
6 months. Additionally, refractive errors were found in 82\% of the
patients, (68\% with hypermetropic astigmatism), Retinopathy of
Prematurity (ROP) in 7.9\% (1.2\% required surgery) and hearing problems
in 1.2\%.

Rehospitalizations between KMCP admission and 40 weeks occurred in 9.6\%
of the cohort (17.4\% of them were for transfusions), 4.8\% of patients
were rehospitalized between 40 weeks and 3 months and after 3 months
there were no rehospitalizations.

At 40 weeks, 442 patients were followed up (99.3\%), at 3 months 395
(88.8\%) and at 6 months 356 (80\%), with an attrition up to 20\%, due
mostly to problems with the health insurer. Only one patient out of the
total cohort died (0.2\%).

Multiple linear regression analysis showed that, adjusting for control
variables, for each week of gestational age, 2.9 fewer days of
supplemental oxygen are required; for each additional gram of Hb on
admission at KMCP, 1.8 fewer days of oxygen are needed; for each day of
invasive ventilation, 1.4 more days of oxygen are required; for each
g/k/d of weight gain until oxygen weaning, 1.6 less days of oxygen are
required; for each transfusion received, 4.8 more days of oxygen are
required. Moreover, with EBF, the oxygen requirement tends to decrease
by up to 10 days (Table 4).

\subsubsection*{Discussion}

{\label{discussion}}

On account of the availability of the ambulatory KMCP in Bogota,
Colombia (2600m), the OT at home is frequent due to two main reasons: 1.
The early discharge of these OD infants has made it possible to reduce
hospital stay with a low mortality during the first year of
follow-up\textsuperscript{13} and, 2. The cost of one month of
ambulatory care in babies who receive oxygen is as low as a single day
of hospitalization in the neonatal unit, reducing the burden on the
health system, as well as on the families.

The Kangaroo Foundation developed a care protocol for these OD children
which has made it possible to have follow-up data on 10,452 children
between 1999 and 2019. In the 2003-2007 period, more than 40\% of
children cared for were OD, decreasing progressively to 17\% between
2018 and 2019.

The history of the OD preterm cohort in this study is similar to that
found in the literature, with predominance of male patients and a
history of maternal infection in more than 50\% of the cases, followed
by toxemia (21\%) and premature rupture of membranes
(6.7\%)\textsuperscript{14--17}.

Regarding postnatal history, almost half of our patients received
invasive ventilation (49\%), although with a low median duration (2
days). This highlights the need to avoid this type of ventilatory
support as much as possible, favoring strategies such as CPAP and/or
nasal ventilation from the delivery room\textsuperscript{8,18,19}.

Additionally, in this cohort, 56\% of patients had a history of early or
late sepsis, that can be acquired from the prenatal stage, as mentioned
above, or during hospitalization, and is associated with
BPD\textsuperscript{20}.

It is noteworthy that all patients in this study met the diagnostic
criteria for BPD defined as the requirement of respiratory support at 36
weeks of GA, which better predicts morbimortality at 18-26 months of
corrected age in this population\textsuperscript{21}. They required OT
for a median of 51 days and at the time of weaning, they had a mean
corrected GA of 42 weeks (SD 5.3).

The two ambulatory KMCPs where the study was carried out, have performed
strict and multidisciplinary follow-up of OD children in KMC, with the
possibility of ambulatory OT for the past 21 years, following technical
guidelines updated in 2017 by the Ministry of Health of the
country\textsuperscript{22}. There is evidence in the literature on the
OT at home for OD children, a practice still scarce worldwide, but that
has increased in recent years\textsuperscript{23}. With this method,
prolonged separation from parents is avoided, improving the probability
of exclusive breastfeeding and reducing morbimortality from infections
due to prolonged hospitalizations, all widely cited benefits of the KMC
method\textsuperscript{13}.

All of our OD patients had adequate anthropometric measurements at 6
months, and 66\% of the cohort received some breast milk. Moreover, when
assessing neurodevelopment, approximately 21\% had a non-normal
neuromotor examination (INFANIB), which coincides with the frequency of
patients with a Griffiths scale \textless{}85 at 6 months (20.2\%), a
relatively low percentage. By having a strict follow-up by a
multidisciplinary team, we allow for the timely treatment of
neurodevelopment and neurosensory problems, reducing alterations that
occur long term\textsuperscript{17}. Another outstanding fact is the low
frequency of ROP in our cohort; 6.7\% (28/421) of patients had
autoregressive ROP and only 1.2\% (5/421) required surgery. Furthermore,
only 1.2\% of the patients assessed presented hearing problems (5/409).

Rehospitalizations were low: 9.6\% between KMCP admission and 40 weeks,
and 4.8\% between 40 weeks and 3 months, as opposed to 40-50\% of
rehospitalizations reported in other studies\textsuperscript{8,17}.
There was no record of hospitalizations occurring between 3 and 6 months
and the mortality was of only 1 patient (0.2\%).

It is important to take into account that we had 20\% attrition, mostly
due to problems with the health insurers. All patients who did not
continue the program were contacted by the KMCP social worker to verify
their health status and the reason for leaving the program.

As to the monitoring of home OT, the KMCP has an ambulatory monitoring
protocol that guarantees maintaining an adequate SpO2 until weaning. In
order to do this, a progressive, stress-free and dynamic weaning is
carried out with the baby asleep, awake and during feeding, with a
gradual decrease in oxygen flow, and a monitoring of both weight gain
and other causes of weaning failure such as anemia or infections. The
average saturation at follow-up was 94\% (SD 2.1). There are other
oxygen weaning techniques reported, such as that described by Hussain et
al. in Connecticut, USA, where stress oximetry is performed while
monitoring heart rate and dynamic oximetry with total suspension of
supplemental oxygen. The authors report that the test has a specificity
of 97.4\% and a predictive positive value of 99.6\% in determining
oxygen weaning success\textsuperscript{24}. We prefer a staggered
weaning, to reduce stress and safety issues caused by total oxygen
suspension. Various guidelines from USA, England and Australia have been
published on ambulatory management of OD preterm infants, and how to
reach a low-risk weaning in these past 10 years\textsuperscript{25--27},
all of them are in agreement with our guidelines implemented since 1999.

Multivariate analysis showed that the risk factors for a longer OT are
low GA at birth, invasive ventilation, low Hb levels at KMCP admission,
number of transfusions received, and the protective factors, weight gain
and exclusive breastfeeding up to weaning. Concerning risk factors, the
relation between prematurity, invasive ventilation and BPD is widely
known\textsuperscript{17,20,28,29}. In recent years invasive ventilation
has been reduced; yet, even a relatively low median duration of
ventilation in our cohort, two days, was associated with a higher risk
of BPD.

Another interesting aspect to keep in mind is the link between anemia,
transfusions and a higher frequency of BPD. In our study, for each
additional gram of Hb upon KMCP admission, oxygen dependency would
decrease by 1.8 days and for each transfusion received, 4.8 more days of
oxygen would be required. In this regard, Hellstrom et al., in a
retrospective cohort study with records of 149 extremely premature
babies born in Sweden between 2013 and 2018, found that blood sampling
produced a 58\% depletion of blood volume between days 1-14, which was
correlated with the number of adult blood transfusions (r=0.87); blood
loss from sampling during the first 7 days of life was related to higher
BPD (adjusted OR 2.4; 95\% CI 1.1-5.4)\textsuperscript{30}. Similarly,
Duan et al. in a prospective cohort with 243 children \textless{}32
weeks GA in China, found early anemia significantly associated with the
development of BPD (adjusted OR 4.89; 95\% CI 1.57
-15.26)\textsuperscript{31}. This leads us to think that laboratory
methods that minimize blood sampling during hospitalization in the NICU
should be implemented, hopefully using the micro method technique, which
would allow for better Hb levels at discharge and minimize transfusions.
Subsequently, in ambulatory management, transfusions should depend on
established protocols where the oxygen requirement, weight gain and
hemodynamic status of the patient are assessed, rather than an isolated
Hb level.

In our cohort, adequate weight gain in g/k/d and EBF were associated
with a decrease in OT days, findings supported by studies such as those
carried out by Wemhoner et al., and Ehrenkranz et
al\textsuperscript{32,33}, and that emphasize the fundamental role of
nutrition in reducing the risk of BPD. There are also other studies that
emphasize the benefits of EBM, preferably from the mother, or if this is
not possible, from a donor, to reduce BPD. In a recent meta-analysis by
Villamor et al. in 2016, 31 randomized controlled trials (RCTs) and
observational studies were analyzed, and the results showed that the
administration of donor milk conferred protection against BPD in very
low birth weight preterm infants\textsuperscript{34}. In 2019 another
systematic review published by this author, showed that EBF was
associated with a significant reduction in the risk of BPD (RR 0.74;
95\% CI 0.57-0.96; 5 studies)\textsuperscript{35}; contrastingly, when
comparing children who received mixed feeding and those who received
exclusive formula, there was no significant difference in the risk of
BPD (RR 1.0; 95\% CI 0.78-1.27; 6 studies). The authors hypothesize that
EBF can reduce the incidence of BPD thanks to its bioactive and
nutritional components that counteract oxidative stress, inflammation
and nutritional failures involved in the pathogenesis of BPD. On the
other hand, EBF could also reduce the risk of BPD by reducing the
incidence of Necrotizing Enterocolitis and late sepsis.

Part of the kangaroo care is EBF to the extent possible, supplemented
with liquid formula in case of not achieving the weight gain goals for
GA. Supplement is never administered with a bottle or nipple, but with a
syringe, and the calculated amount is distributed over the intakes that
the child receives in 24 hours. The liquid preterm formula avoids
manipulations. This technique allows for adequate growth by
supplementing without jeopardizing breastfeeding.

It is noteworthy that supplemental iron was administered between
hospital discharge and 40 weeks in only approximately 52\% of our
patients, and in 81\% at 6 months. This may be due in part to the fact
that iron is temporarily suspended when patients have had previous
transfusions; other causes are that the children had not yet reached one
month, when KMCP starts iron by protocol, or received milk formula with
iron.

The results obtained in this cohort of OD preterm infants managed in
ambulatory KMCPs show that it is possible to reduce mother-child
separation and hospital stay and to perform strict ambulatory and
multidisciplinary follow-up. The goals of ambulatory OT would be a safe
oxygen administration and progressive weaning protocol with intense
parents education, SpO2 monitoring, supporting EBF to the extent
possible, supplementing with formula in case of not having an adequate
weight gain, monitoring Hb levels hopefully with a micro-method, having
clear transfusion indication protocols and achieving a multidisciplinary
follow-up to minimize neurodevelopmental problems and morbimortality.

Currently, there are 53 KMCPs in Colombia to care for premature or LBW
children. This ambulatory management of OD children allows to reduce
health system costs, which are a burden for public health in
middle-income countries such as ours. With regards to the latter, there
is evidence which showed how the median hospitalization costs per child
with BPD was \$377,871 USD compared to \$175,836 USD per child without
BPD (adjusted cost ratio 1.54; 95\% CI 1.49-1.59)\textsuperscript{36}.

One weakness of this study is its observational design, without a
comparison to another kind of ambulatory follow-up, which could support
the differences in the outcomes obtained in the KMCPs. However, measures
of effectiveness can be established indirectly, by comparing results
with what is reported in the literature.

On the other hand, selection biases due to mortality prior to hospital
discharge, that could be suspected with average GA at birth of 33 weeks,
and moderate follow-up attrition of 20\%, indicate that the data
obtained should be interpreted with caution.

\textbf{Acknowledgements}

To Drs Andrea Conde, Johana Forero and Claudia Giraldo, Pediatric
residents at the Javeriana University, for their collaboration in data
collection.

To Dr. Maria Calume, who collaborated in coordinating the study, and to
the nurses from the KMCP who helped in the study development.

\textbf{List of abbreviations}

BPD: Bronchopulmonary Dysplasia.

EBF: Exclusive Breastfeeding.

GA: Gestational Age.

Hb: Hemoglobin.

IUGR: Intrauterine Growth Restriction.

KMC: Kangaroo Mother Care.

KMCP: Kangaroo Mother Care Program.

KP: Kangaroo Position.

LBW: Low Birth Weight.

NICU: Neonatal Intensive Care Unit.

OD: Oxygen Dependent.

OT: Oxygen Therapy.

RCT: Randomized Controlled Trial.

ROP: Retinopathy of Prematurity

SpO2: Oxygen saturation.

\subsubsection*{References}

{\label{references}}

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