Breast Milk vs Sucrose in Relieving Procedural Pain in Preterm Neonates During Blood Draw by Automated Heel Lance
Condition: Pain
MeSH terms: Pain, Procedural
Study type: Interventional
Phase: Phase 4

Summary: 
      Skin breaking procedure through an automated heel lancet for blood draws is a common painful
      procedure in the Neonatal Intensive care unit (NICU). Recurrent pain in preterm neonates is
      associated with long-term complications. The primary objective of the study is to compare
      pain scores between two groups (24% sucrose and breast milk) during blood draw using an
      automated heel lancet in preterm neonates. The investigator conducted a prospective
      randomized controlled trial in preterm neonates, to compare the pain scores in infants
      receiving either breast milk or sucrose. Premature Infant pain profile- Revised pain profile
      is used to assign pain scores. The primary outcome measure is the comparison of pain scores
      between the two groups.
    

Detailed description: 
      Blood draw by automated heel lancet is a common painful procedure in the Neonatal Intensive
      care units (NICU). The cutaneous sensory receptors on all mucosal and cutaneous surfaces are
      developed by 20 weeks gestational age (GA) and the neuronal circuits that carry pain stimuli
      from skin to cerebral cortex are developed by around 26 weeks of GA. Recurrent pain in
      preterm neonates impacts their postnatal growth, development, is associated with altered pain
      perception, and increased behavioral responses for future painful procedures.

      Oral sucrose is a commonly administered and effective non-pharmacologic intervention used in
      the NICU for pain relief. There is insufficient evidence on its mechanism of action, minimum
      effective dose, the effect of repeated doses on long-term neurodevelopmental outcomes, and
      the consistency in providing pain relief with repeated doses over time. Moreover, the
      analgesic effect of sucrose is a developmentally transient phenomenon. Another
      non-pharmacologic intervention studied for pain relief in neonates is breast milk. The
      analgesic property of breast milk is presumed to be from its sweet taste from lactose,
      flavor, and odor. Breast milk has high levels of tryptophan, a melatonin precursor which may
      increase secretion of beta-endorphin, an endogenous opioid.

      There is a paucity of data comparing analgesic properties of breast milk and sucrose in
      preterm neonates, along with insufficient evidence of sucrose as mentioned earlier, The
      investigator conducted this prospective randomized controlled trial (RCT) comparing sucrose
      with breast milk for pain relief in preterm neonates.

      The primary objective of the study is to compare pain scores between two groups (24% sucrose
      and breast milk) during blood draw by automated heel lancet, in preterm neonates. The pain
      scores between the two groups will also be compared at 30 seconds intervals until two minutes
      post-procedure.

      The current study is conducted at Hutzel Women's Hospital and Children's Hospital of Michigan
      NICU. Institutional Review Board approval was obtained from Wayne State University prior to
      study initiation. Before the study was initiated, physicians were trained in assessing the
      PIPP-R pain scale. The pain scores were given by two physicians who were blinded to the
      treatment arm, at baseline, during, 30-, 60-, 90-, and 120 seconds post-procedure. These
      scores were given either at the time of the procedure or a video is recorded to be scored
      later.

      Eligible participants were identified and written informed consent was obtained from the
      parents. The timing and need for a blood draw are decided by the clinical team and are
      performed by the nurse taking care of the participant. Randomization was done by the
      pharmacist through a computer-generated program. Participants were randomly assigned to
      receive either 0.5 ml 24 % sucrose or 2 ml breastmilk, 2 minutes prior to the procedure. On
      the day of the procedure, the pharmacist sent a closed sealed envelope with a randomization
      group to the nurse taking care of the participant. Pain scores are given by two physicians
      during and post-procedure.

      Te Investigators collected maternal characteristics of participants like age, prenatal care,
      race, history of diabetes and hypertension, receipt of antenatal steroids, magnesium,
      histological diagnosis of chorioamnionitis, mode of delivery, and duration of rupture of
      membranes. Neonatal characteristics collected include sex, APGAR score at 1 and 5 minutes,
      birth weight, gestational age, weight on the day of the procedure, postmenstrual age, number
      of skin pricks prior to the day of the procedure, and adverse events pre-defined as heart
      rate >240beats/minute or heart rate <80 beats/minute for >20 seconds, oxygen saturation <80
      for >20 seconds, no spontaneous respiration for >20 seconds, choking, gagging were collected.

      For this non-inferiority trial, the investigators chose the clinically significant difference
      to be 2 between the median PIPP-R scores during the procedure The investigators required 88
      patients (44 in each group) to show that the lower limit of one-sided 95 % CI will be above
      the non-inferiority limit of -2 for an alpha error of 5% and power of 90 %.
    

Intervention name(s): Breast Human Milk; 24 % Sucrose
Intervention type(s): Other; Other
Intervention description(s): Interventional drug is given to the neonates 2 minutes before the heel lance; 0.5 ml of sucrose given once 2 minutes prior to procedure
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Pain management in preterm neonates