S Chandra, M Gupta, T Nain, A Mishra, K Agarwal

Abstract

Introduction: Hypoxic ischaemic encephalopathy (HIE) is a significant cause of mortality and short and long term morbidities. Aim: To study the effect of Kangaroo Mother Care (KMC) on outcomes in babies with mild and moderate HIE. Methods: In this un-blinded randomised controlled trial over a duration of 30 months, all inborn neonates with mild and moderate HIE (defined by Levene's staging), irrespective of gestational age, were included in the study. Neonates were partitioned into an intervention or KMC group (those receiving KMC in addition to the ongoing management) and a control group (receiving only medical and supportive management). The two groups were later analysed for primary (good or poor) and secondary outcomes (including mean duration of Neonatal Intensive Care Unit (NICU) stay, mean duration of hospital stay and progression of stage of HIE). Data were analysed using the Epi-info software version 7.2.0.1. Results: Out of 165 patients with HIE, 35 patients were excluded (due to different reasons) and the remaining were divided into a KMC or intervention (n=65) and control groups (n=65). Primary outcome was good in 56 (86.1%) patients and poor in 9 (13.8%) patients in the KMC group. Mean duration of NICU stay was 3.14 days (1.00-20.00; SD 3.88) in the KMC group which was significantly less than (p=0.005) 5.19 days (1.00-23.00; SD 4.244) in the control group. Mean duration of hospitalisation was not statistically different in the case and control groups (p=0.208). Progression from mild to moderate HIE was seen in 2 (2/65=3.0%) patients in the KMC group and showed marginal statistical significance (p=0.081) compared with the control group where progression was seen in 9 (9/65=13.8%). Conclusion: Patients with mild to moderate HIE in NICU receiving KMC had a significantly shorter duration of NICU stay thus prompting more robust research on this subject.

Introduction

Kangaroo Mother Care (KMC) is a type of newborn care involving skin-to-skin contact with the mother or caregiver, leading to responsive care giving.¹ It has been endorsed by the World Health Organization (WHO) as a low cost, safe and effective intervention in reducing morbidity and mortality among preterm and low birth weight newborns.²

Though traditionally used in preterm and low birth weight babies, skin-to skin contact has also been advocated as a standard of care in healthy term newborns.³ For instance, in a study by Ramani et al⁴ KMC for a duration of either for at least 80% of the time or at least 9 hours during the day of birth was effective in preventing hypothermia in term infants.

Hypoxic Ischaemic Encephalopathy (HIE) in a neonate is of great concern to the neonatologists and paediatricians and is a significant cause of mortality and short and long term morbidities in them.⁵

However, more evidence is still needed for the prevention and management of perinatal asphyxia and neonatal encephalopathy especially in low and middle income countries.^6,7

To the best of our knowledge, the role of KMC has yet not been explored in HIE. Hence, this study aimed at studying the effect of KMC on outcomes in neonates, admitted in Neonatal Intensive Care Unit (NICU), with mild and moderate HIE.

Aim

To study the effect of Kangaroo Mother Care (versus 'no intervention'), in inborn neonates admitted to NICU with mild and moderate HIE, on primary and secondary outcomes (defined in the Methods section).

Patients and Methods

This was an un blinded randomised controlled trial conducted in the NICU of a tertiary care teaching hospital, over a duration of 30 months (July 2021-December 2023), after obtaining ethical clearance from the Institutional Ethics Committee.

HIE was classified as per the Levene's staging⁸ into mild, moderate and severe. Standard definitions⁹ were used to define neonates, gestational age and birth weight.

Neonates delivered in the hospital and getting admitted to NICU, with mild and moderate HIE, were included in the study, after taking a written informed consent from their parents or guardians. Patients with severe HIE, those requiring ventilator support for more than 24 hours, those with congenital malformations, or those whose parents gave a negative consent were excluded from the study. Neonates going Leave against Medical Advice (LAMA) anytime during the NICU stay were also excluded. Neonates who satisfied the inclusion criteria, were randomised into an intervention or KMC group (those receiving KMC along with medical and supportive management) and a control group (receiving only medical and supportive management). Randomisation was done on the basis of computer generated random numbers.

According to the National Neonatal Perinatal Database (NNPD) report from India, incidence of HIE is 1.4% among the institutional deliveries.¹⁰ However, since our study was based in NICU, we took the NICU based prevalence of HIE in our hospital which is around 15% of the total inborn NICU admissions. Number of inborn NICU admissions during the study period was 866. Taking a margin of error of 5%, sample size was calculated to be 160.

KMC was initiated within 24 hours of birth after initial stabilisation. Cases were subject to minimum 6 hours/baby/day of KMC; between 6:00 hours-8:00 hours, 11:00 hours-13:00 hours and 16:00 hours-18:00 hours, between two feeds, whilst in NICU; along with continued medical management. These timings were chosen in line with the fact that there was minimal traffic and disturbance in the NICU before and after the morning consultant rounds, and before the evening consultant rounds respectively. The control group on the other hand received continued medical and supportive management only.

KMC was done by placing a naked infant on the bare chest of mother.¹¹ In case the mother was sick or not available, any other guardian available gave skin-to-skin contact. KMC was aborted in case of seizure or any untoward event.

Both the KMC and control groups were analysed for primary and secondary outcomes.

Primary outcome was defined on the basis of in-hospital outcome as:

1. Good (Survival) or
2. Poor (Mortality)

Secondary outcomes included:

1. Mean duration of NICU stay;
2. Mean duration of hospitalisation and
3. Progression of stage of HIE

Patients' demographic and clinical details were recorded on a predesigned standardised data collection proforma. Data was later entered into Microsoft Excel worksheet 2013 and thence analysed using the Epi info software version 7.2.0.1. Frequencies were calculated for categorical data and mean and standard deviation (SD) for continuous variables. A p value of <0.05 was considered to be statistically significant.

Results

We enrolled 165 patients of HIE admitted to NICU during the study period. Of these, 8 patients with severe HIE, 19 patients requiring intubation for more than 24 hours and 3 patients with congenital malformations (1 with congenital diaphragmatic hernia and 2 with congenital cyanotic heart disease) were excluded (Figure 1). Also, 5 patients took LAMA during the course of their NICU stay, due to personal reasons. Thus finally 130 patients were included in the study and randomised to KMC (65 patients) and control (65 patients) groups.

Figure 1 Patient flow chart.

Baseline demographic characteristics were similar in both the groups (Table 1). Majority of newborns were males (77/130=59.2%). Most of them were appropriate for gestational age (AGA) (118/130=90.4%) followed by small for gestational age (SGA) (9/130=7.1%) and large for gestational age (LGA) (3/130=2.4%) respectively. Mean birth weight of the neonates enrolled was 2668 grams (1660-3570 grams; SD 352.94).

Maternal risk factors included hypothyroidism (6/130=4.6%), hypertension (43/130=33.4%), gestational diabetes mellitus (31/130=23.8%), epilepsy (9/130=7.1%) and sepsis (4/130=2.3%). There were no maternal risk factors in 37 (37/130=28.5%) patients.

Most of the newborns were delivered by lower segment caesarean section (65/130=50.0%). Majority of newborns were term (96/130=73.8%). Thirty-four babies (34/130= 26.1%) were born preterm. These included 20 (20/130= 15.4%) late preterm neonates, 7 (7/130=5.4%) moderate and 7 (7/130=5.4%) early preterm neonates each. Mean birth weight was 2668 grams (1660-3370; SD 352.9).

Ninety-three (93/130=71.5%) patients had mild HIE and 37 (37/130=28.6%) patients, had moderate HIE. The KMC group had 45 neonates with mild HIE and 20 with moderate HIE. The control group had 48 neonates with mild HIE and 17 neonates with moderate HIE.

Co-morbidities associated or developed during the hospital stay included neonatal hyper bilirubinaemia (57/130=43.8%), neonatal sepsis (24/130=18.4%), meconium aspiration syndrome (38/130=29.2%) and acute kidney injury (5/130=3.8%), seizures (9/130=6.9%), necrotising enterocolitis (1/130=0.7%) and shock (5/130=3.8%). Some neonates had more than one comorbidity.

Primary outcome was good in 56 (56/65=86.1%) patients and poor in 9 (9/65=13.8%) patients in the KMC group. In the control group, 50 (76.9%) patients survived and 15 (23.0%) succumbed to their illness. This difference in primary outcome was not statistically significant (p=0.139).

Mean duration of NICU stay was 3.14 days (1.00-20.00; SD 3.88) in the KMC group which was significantly less (p=0.005) (Figure 2) compared with that in the control group, 5.19 days (1.00-23.00; SD 4.244).

Figure 2 Mean duration of NICU stay.

Mean duration of hospitalisation was 5.67 days (1.00-24.00; SD 4.25) in the KMC group and 6.61 days (1.00-25.00; SD 4.32) in the control group. This difference in outcome was not statistically significant though (p=0.208) (Figure 3).

Figure 3 Mean duration of hospital stay.

Progression from mild to moderate HIE was seen in 2 (2/65=3.0%) patients in the KMC group and 9 (9/65=13.8%) patients in the control group. This difference showed marginal statistical significance (p=0.081). None of the patients with moderate HIE showed progression to severe HIE in the KMC group and 3 (3/65=4.6%) patients progressed to severe HIE in the control group (p=0.161) (Figure 4).

Figure 4 Progression from mild to moderate stage.

Discussion

Patients with HIE, receiving KMC had a significantly shorter duration of NICU stay and showed less significant progression from mild to moderate HIE, in this study. None of the patients with moderate HIE showed progression to severe HIE in those receiving KMC.

To the best of our knowledge, this is the first study to evaluate the effects of KMC in babies with mild and moderate HIE. Hence there is a paucity of literature on this particular aspect of neonatal care.

Birth asphyxia accounts for the majority of neonatal deaths¹² and interventions aimed at improving its management can have marked impact on outcomes especially in resource limited settings.⁶

KMC as an intervention has been studied in various maternal and neonatal conditions. Beneficial effects of KMC for mothers have been reported in maternal attachment,¹³ early resolution of maternal pain,3 alleviation of postpartum maternal depression¹⁴ and improvement in parents' sleep quality, mood, parent-infant interaction and serum cortisol concentrations in parents.¹⁵

Beneficial effects of KMC for neonates, have already been reported in the management of neonatal hypothermia,^4,16 neonatal pain management,¹⁷ improvement in physiological stress parameters¹⁸ and non-pathological jaundice¹⁹ in newborns, as also providing morbidity and mortality²⁰ benefit to them. It has also been shown to improve the rates of exclusive breastfeeding,²¹ development of oral skills²² and increased weight gain²³ in neonates.

A recent randomised controlled trial has revealed that infants receiving KMC, show left frontal brain activation patterns (asymmetry and coherence)²⁴ KMC also leads to moderate to large increases in oxytocin and moderate decreases in cortisol activity which may garner favourable neuro maturational and neurological outcomes for such mother-infant dyads.²⁵

KMC is also shown to be associated with improved neuro-developmental outcomes in preterm infants.^25,26

A qualitative study done in 11 NICUs in British Columbia also stressed that KMC is an evidence based developmental strategy associated with improved short and long term outcomes in preterm infants.²⁷

In a study by Jegannathan et al,²⁸ the average duration of KMC was 4.6 hours/baby/day which was increased to 16.6 hours/baby/day as a quality improvement initiative. Another study has reported that KMC for duration of at least 9 hours/baby/day on the day of birth was effective in preventing hypothermia in term infants.4 However, we could provide KMC for only 6 hours/baby/day as the study was conducted in the NICU.

In the current study there was a statistically significant reduction in the length of NICU stay in babies receiving KMC compared with the controls. However, this did not translate into a statistically significant difference in the total duration of hospitalisation. Such an impact on the length of hospital stay was also not seen by Guo.²⁹

In contrast, in a systematic review on the effectiveness of Kangaroo Mother Care on the hospitalisation period of preterm and low birth weight infants, there was a statistically significant reduction in the length of hospital stay (in days) in the KMC group compared with the group receiving only conventional care (MD -4.66, 95% CI -7.15 to -2.17).³⁰ A meta-analysis including 17 randomised controlled trials and 17, 668 participants also concluded that KMC had a favourable effectiveness on secondary clinical outcomes such as mean duration of hospital stay, hypothermia and sepsis.³¹

In a multi-year analysis of KMC outcomes in rural Tanzania, KMC was associated with 70% survival overall and 92% survival after the first 24 hours of life. In our study the survival rate in the KMC group was 86.1%, which is comparable to the study aforesaid.³²

Conclusion

Neonates with mild and moderate HIE receiving in-NICU KMC had a significantly shorter duration of NICU stay compared with those not receiving the same.

Limitations

This study has the following limitations. First, the neuro-developmental outcomes of babies with HIE were not studied. Second, weight gain as an outcome was not compared between the two groups as this was not the objective of our study. Third, majority of newborns in this study were term, were AGA, had mild HIE and had a normal birth weight. These factors could be confounding.

Future Directions

More studies with a larger sample size and long term follow-up are required to address these limitations.

Acknowledgement

My patients and their parents.

Funding

None

Declaration of Interest

None

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