Effectiveness of Oral Immunotherapy Among Preterm Babies

Study Overview
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Brief Summary
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The aim of the study is to assess the effectiveness of OIT with colostrum on the feeding behavior and Clinical Outcome of Late-onset sepsis and Necrotizing enterocolitis

Detailed Description
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A randomized placebo-controlled double-blinded study in preterm infants < 32+6 weeks' gestation or Birth weight < 1500 g who are admitted to NICU. Exclusion criteria include infants with congenital anomalies, out born infants, infants of single mothers with unknown partners (mother is separated from preterm infants based on the state law) and infants admitted beyond 48 hours of age, confirmed immunodeficiency disorder, Inborn Error of Metabolism, parental refusal to participate. The infants who have overt bleeding, thrombocytopenia < 50,000/mm3 or are critically ill requiring multiple inotropes in high doses, on High frequency ventilation and inhaled nitric oxide and infants with congenital surgical abdomen are excluded from the study. An informed parental consent is obtained at the initial post-natal visit. Each neonate is then randomly assigned to the placebo or intervention group per the block randomization generated using a computer-generated allocation sequence. Allocation is concealed from all involved investigators, bedside nurses, doctors, parents and outcome assessors except the International Board Certified Lactation Consultant (IBCLC) assigned to allocate the intervention. The IBCLC is not an investigator in the study. Intervention group: Colostrum that is fresh or refrigerated is collected by the IBCLC and prepared using 1cc syringes which are labeled with patient identification data, date and time of milk expression. These syringes are concealed using adhesive silk tapes and handed over to the bedside nurse. The tip of the syringe is placed towards the posterior end of the buccal cavity, colostrum/breastmilk is slowly squirted in aliquots of 0.1 ml of the milk into the area . This is to be done slowly drop by drop over a 30 s period. The milk should not pool in the buccal cavity. If it pools, give a few seconds to get absorbed and the rest may be manually rubbed using a swab along the gums and the inner surface of the buccal cavity for 10 seconds with two strokes in each area. Repeat the procedure on the opposite side. If the colostrum was refrigerated the syringe may be kept in the warm incubator for five minutes before administering. OIT will be initiated as soon after birth as colostrum is available no earlier than six hours of age and continued every 4 hours as available. OIT may be provided in babies who are kept nil per oral and is to be continued even when enteral feeding has been ordered to get a minimum of 20 doses and can be continued until the baby reaches full oral feeding. Control group: The control group will receive 0.2 ml of sterile water that will be prepared and applied in an identical manner and frequency to that among the intervention group. This will be started at six hours of age to avoid disclosure of intervention and control group. However, as soon as Mother's milk is available it will be initiated enterally.

Official Title
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Effectiveness of Mother's Own Colostrum and Breast Milk as Oral Immunotherapy and on the Feeding Behaviors and Clinical Outcome Among Preterm Infants

Conditions
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Feeding Behavior, Late-Onset Neonatal Sepsis

Intervention / Treatment
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* Other: Sterile water
* Biological: Breastmilk


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Preterm babies below 33 weeks (32+6) weeks of gestation Birth weight <1500 g Exclusion Criteria: Preterm babies with congenital anomalies Preterm babies with congenital infection like pneumonia. Babies born in other hospitals Babies of single mothers with unknown partners Confirmed immunodeficiency disorder, Inborn Error of Metabolism, Parental refusal to participate. Preterm babies who have overt bleeding

Ages Eligible for Study
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Maximum Age: 4 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: the intervention is carried out among preterm babies below 33 weeks of gestation or weight less than 1500gm
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Sterile water<br>Sterile water: Started by six hours of age, In the control arm, 0.2 ml of sterile water is instilled into the posterior buccal cavity in aliquots of 0.1 ml over a 30 second period. The liquid is given time to get absorbed, any pooled liquid is swabbed in the infants' cheek and gum. This is performed every 4 hours until independent safe cup feeds, breastfeed or bottle feed is established consistently for 48 hours. | Other: Sterile water<br>* Placebo Comparator: Sterile water: 0.2 ml of sterile water is instilled into the posterior buccal cavity in aliquots of 0.1 ml over a 30 second period. The liquid is given time to get absorbed, any pooled liquid is swabbed in the infants' cheek and gum. This is performed every 4 hours until independent safe cup feeds, breastfeed or bottle feed is established consistently for 48 hours.<br>* Other names: Placebo;|
| Experimental: Breastmilk<br>Breastmilk. This is started at 6 hours of age at the earliest; breast milk: 0.2 ml of mothers' own colostrum/ breast milk is instilled into the posterior buccal cavity in aliquots of 0.1 ml over a 30 second period. The colostrum is given time to get absorbed, any pooled milk is swabbed in the infants' cheek and gum. This is performed every 4 hours until independent safe cup feeds, breastfeed or bottle feed is established consistently for 48 hours. | Biological: Breastmilk<br>* Experimental: Breastmilk: 0.2 ml of mothers' own colostrum/ breast milk is instilled into the posterior buccal cavity in aliquots of 0.1 ml over a 30 second period. The colostrum is given time to get absorbed, any pooled milk is swabbed in the infants' cheek and gum. This is performed every 4 hours until independent safe cup feeds, breastfeed or bottle feed is established consistently for 48 hours. independently sucks at breast, bottle or cup feed<br>* Other names: experimental;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feeding Behaviors | feeding behaviour is assessed using a questionaire on feeding behaviour. it consist of feed interruptions due to intolerance, time to reach full enteral feeding, time to independent oral feeds via direct breastfeed, cup or syringe feed or bottle feed consistently for 48 hours safely. | Birth to 45 weeks post menstrual age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Late onset sepsis | late onset sepsis is measured using questionnaire on clinical outcome . it consist of culture proven sepsis and number of episodes. | Birth to 45 weeks post menstrual age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colostrum, Oral immune therapy, Preterm, Oral feeding, Sepsis