Add-on efficacy of oil massage (Abhyanga) along with standard neonatal care in neonatal hyperbilirubinemia: An open-label Randomized Controlled Clinical Study

Introduction

Perinatal events have a profound impact on the growth, development, and adult life of a child. Insults and injuries in the neonatal period are associated with chronic neurodevelopmental, cognitive, and behavioral complications often lacking complete reversal. Hence preventive neonatology is a domain of public health interest. Kaumarabhritya or Ayurvedic pediatrics begins with neonatal care and has multiple unique practices. They are unresearched by the Ayurvedic fraternity despite their documented benefits. Massage is a multifaceted modality mentioned in Ayurveda and has been researched worldwide. This study aims to compare the add-on efficacy of oil massage using Ayurvedic polyherbal oils in managing neonatal jaundice, stress, oxidative stress, and hypothermia, explore the bilirubin-lowering action of Ayurvedic herbs at the cellular level, and compile the newborn care practices in Ayurvedic hospitals and educational institutes.

Methodology

Participants per group: Sample Size: 70

Study Design: Randomized Active Controlled Trial

Intervention: Oil massage shall be done as per the Ayurveda Neonatal Massage Therapy Protocol (ANMTP) (each session of 15 minutes) twice a day for a week in addition to Neonatal resuscitation, routine care, phototherapy.

Comparator: Neonatal resuscitation, routine care, phototherapy.

Primary Objective

·       To compare the add-on efficacy of oil massage (abhyanga) with Arukaladi taila done using Ayurveda neonatal massage therapy protocol for 15 minutes with moderate pressure twice a day for two to seven days in addition to standard newborn care in reducing the total serum bilirubin levels in neonates compared to those receiving standard newborn care alone.

 Secondary Objective

·       To evaluate the add-on efficacy of oil massage with Bala tailain addition to standard newborn care on perinatal stress indicated by salivary cortisol levels of newborns.

·       To compare thermoregulation in neonates receiving oil massage and SNC against those receiving SNC alone (indicated by mean body temperature).

·       To compare the insulin-like growth factor 1, in neonates receiving oil massage and SNC against those receiving SNC alone.

·       To evaluate the antioxidant efficacy of neonatal massage by comparing Glutathione reduced/oxidized ratio and Malondialdehyde in neonates receiving oil massage and SNC against those receiving SNC alone.

·       To evaluate the efficacy of neonatal massage by comparing the adverse reaction against phototherapy via symptomatic assessment.

·       To evaluate the bilirubin-lowering action of Eclipta alba (Linn.) Hassk (Bhringaraja) hydroalcoholic extract in HepG2 (human liver) cell lines in terms of its effect on uridine diphosphogluconurate glucuronosyltransferase (UGT1A1) expression.

·       To collect information about practices related to neonatal care in Ayurvedic hospitals and educational institutions.

Inclusion Criteria:

1.     Healthy Neonates immediately after birth, irrespective of sex and ethnicity

2.     Gestational age >28 weeks, birth weight > 1500 g

3.     An APGAR Score of more than 7 in the first minute.

4.     Neonates who do not require oxygen support, positive ventilation, or parenteral nutrition.

5.     Neonates fulfilling KA87 (neonatal hyperbilirubinemia) clinical features as per ICD-11.

  Exclusion Criteria:

1.     Extremely preterm neonates (<1500g)

2.     Extremely Low Birth Weight (<28 weeks)

3.     Rhesus and ABO incompatibility, G6PD deficiency.

4.     Birth injuries

5.     Congenital anomalies

6.     Signs of infection, intraventricular or subgaleal hemorrhage,

7.     Signs of gastrointestinal obstruction, or biliary atresia.

8.     Neonates who are on/require oxygen support, positive ventilation, parenteral nutrition, or other intravenous infusions.

9.     Neonates expressing hypersensitivity to oil test dose.

10.  Neonates whose both parents are minors.

11.  Mothers receiving drugs narcotic agents, barbiturates, aspirin, chloral hydrate, reserpine, and phenytoin sodium pre- or post-parturition.

**1.1.1.**Diagnostic Criteria

·       Neonatal hyperbilirubinemia shall be diagnosed based on Total Serum bilirubin levels, i.e., above 95th percentile of TSB distribution.

·       Severe neonatal hyperbilirubinemia shall be considered in case of onset before 24 hours and jaundice necessitating phototherapy.

Visual assessment with Kramer score shall be supplementary evidence of hyperbilirubinemia.

1****Withdrawal Criteria

1.     Neonates with Total Serum Bilirubin levels equal to above 20 mg/dl.

2.     Neonates with features suggestive of bilirubin encephalopathy (characterized by lethargy, Poor feeding, vomiting, high-pitched cry, hypotonia followed by hypertonia, opisthotonos, and seizure) or indicated for exchange transfusion.

3.     Neonates developing fever, signs of sepsis, respiratory distress, necrotizing enterocolitis, seizures, neurological dysfunction, or any other illnesses.

4.     Parents demanding withdrawal from study.

5.     Mothers on narcotic agents, barbiturates, aspirin, chloral hydrate, reserpine, and phenytoin sodium as medications.

1. Outcomes

Primary Outcome

·       Lowering of total serum bilirubin levels below phototherapy thresholds for the day of life and gestational age following oil massage with Arukaladi taila

Secondary Outcome

• Reduction in salivary cortisol level following oil massage with Bala taila.
• Thermoregulation in neonates following oil massage and SNC.
• Reduction in Malondialdehyde and increase in insulin-like growth factor 1 and Glutathione reduced/oxidized ratio (GSH/GSSG ratio) in neonates following oil massage and SNC.
• Reduction in adverse reactions to phototherapy.
• Increase in expression of uridine diphosphogluconurate glucuronosyltransferase (UGT1A1) following administration of aqueous and hydroalcoholic extracts of Eclipta alba (Linn.) Hassk in HepG2 (human liver) cell lines.
• Collection of information about practices related to neonatal care in Ayurvedic hospitals and educational institutions.