Pasteurised Donor Human Milk Supplementation for Term Babies

Official title

A Randomised Controlled Trial of Pasteurised Donor Human Milk as Supplementary Nutrition for Infants Born to Women With Diabetes in Pregnancy.

Overview

PRESENT is a multi-center randomised controlled trial that aims to assess whether access to pasteurized donor human milk as supplementary nutrition in the first five days of life for term infants born to women with diabetes in pregnancy reduces the proportion of infants who are admitted to a neonatal unit for management of hypoglycemia compared with current standard hospital care. The trial will also assess other important outcomes including breastfeeding rates, maternal mental health, and infant cow's milk allergy. There will be two treatment arms. In the intervention arm, PDHM will be made available to infants from randomisation until day 5 of life. Infants allocated to the control arm will receive care as per local unit policy, including supplemental nutrition as recommended by the treating clinician. After hospital discharge, participants will be asked to complete an electronic questionnaire at 2 \& 6 weeks and 6 \& 12 months after birth. Questionnaires will assess infant feeding practices, maternal quality of life \[including anxiety and depression symptoms and health-related quality of life\] along with infant cow's milk allergy symptoms.

Detailed description

Diabetes in pregnancy is becoming increasingly common globally, with more than 40 000 infants born to women with gestational diabetes alone in Australia each year. These infants are at a high risk of hypoglycaemia and often require admission to the neonatal intensive care unit (NICU) and frequent blood tests for glucose monitoring. Many lack access to sufficient maternal milk partly due to delayed lactogenesis, leading to reliance on cow's milk formula, which may increase risks of cow's milk allergy, early breastfeeding cessation, and long-term metabolic complications.

Pasteurized Donor Human milk (PDHM) supplementation represents an alternative to infant formula when sufficient mother's own milk is not available. In Australia, donor milk is already in use for more vulnerable populations (those born very preterm or of a very low birth weight). However, PDHM is not currently available for term infants, despite strong clinician and community demand.

Expanding the availability of PDHM to term infants has the potential to improve health outcomes for a much larger proportion of the population, with potential benefits for mothers and infants including a reduction in admissions to neonatal intensive care units, a reduction in cow's milk allergy in infants, and improved maternal mental health and breastfeeding outcomes.

Our project will assess the provision of PDHM as in-hospital supplementation for term infants who would otherwise be given cow's milk formula. This trial will address a significant gap in neonatal care and provide evidence to determine whether broader PDHM use could improve both mothers' and infants' and long-term health outcomes.

Interventions

• Other Standard care Cow's milk based formula
  Standard hospital care would be given as as per local unit policy at the site.
• Dietary supplement Dietary Supplement: PDHM Pasteurised Donor Human Milk
  PDHM will be given to infants randomised to the intervention group

Primary outcome measures

• Proportion of infants admitted to neonatal unit for management of hypoglycaemia [Time frame: From birth to 120 hours of life]

Secondary outcome measures (12)

• Duration of hypoglycaemia (<2.6 mmol/L) [Time frame: From birth upto 120 hours of life]
• Proportion of infants requiring IV access for dextrose [Time frame: From birth to 30 days after hospital discharge]
• Episodes of phlebotomy [Time frame: From birth up to 120 hours of life]
• Hospital length of stay (infant) [Time frame: From birth up to initial hospital discharge, up to 90 days of life]
• Hospital re-admission within 30 days [Time frame: From birth to 30 days after discharge]
• Neonatal unit admission and length of stay (infant) [Time frame: From birth to initial hospital discharge, up to 90 days of life]
• Breast milk feeding [Time frame: Breast milk feeding at 120 hours of age (this means received any breast milk in previous 24 hours) and at 2 & 6 weeks and 6 months of age]
• Use of Formula feeding [Time frame: Infant formula feeding at 120 hours of age (received any infant formula in previous 24 hours), and at 2 & 6 weeks and 6 &12 months of age]
• Maternal mental health in the post-partum period GAD-7 [Time frame: At 6 weeks and 6 months post delivery]
• Maternal mental health in the post-partum period using PHQ-9 survey [Time frame: At 6 weeks and 6 months post delivery]
• Maternal & Infant Health-related quality of life using AQoL-4D [Time frame: At 6 weeks and 6 months post delivery]
• Maternal & Infant Health-related quality of life using TANDI [Time frame: At 6 weeks and 6 months post delivery]

Eligibility criteria

Inclusion criteria

Each participant must meet all the following criteria to be enrolled in this trial:

• Mother is >18 years at the time of consent
• Mother has diabetes in pregnancy (type 1, type 2 or gestational diabetes)
• Mother intends to breastfeed for at least 6 weeks at the time of consent.
• Infant is born at ≥ 37 weeks and weighs > 2.5kg
• Clinician caring for infant decides that supplementary nutrition (in addition to maternal breast milk) is required within the first 48 hours after birth.
• Parent/s provide/s a signed and dated informed consent form and has a legally acceptable representative capable of understanding the informed consent document and providing consent on the participant's behalf.

Exclusion criteria

Mother/infant pairs meeting any of the following criteria will be excluded from the trial:

• Multiple pregnancy
• Mother has a condition that precludes maternal breast milk consumption e.g. HIV, receiving chemotherapy
• Infant has clinically significant congenital abnormality interfering with effective breastfeeding or breast milk consumption (e.g., cleft lip and palate, metabolic disorder) and/or requiring immediate care in a neonatal unit (e.g., congenital heart disease).
• Infant has received infant formula prior to randomisation.
• Infant admitted to neonatal intensive care prior to randomisation.
• More than 48 hours old at the time of recruitment

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

Australia · 4 centers

• Royal Brisbane and Womens Hospital (QLD) — Brisbane
• Greenslope Hospital (QLD) — Brisbane
• Frances Perry House (VIC) — Melbourne
• Royal Womens Hospital (VIC) — Melbourne

Publications

• Griffith RJ, Harding JE, McKinlay CJD, Wouldes TA, Harris DL, Alsweiler JM; CHYLD Study Team. Maternal glycemic control in diabetic pregnancies and neurodevelopmental outcomes in preschool aged children. A prospective cohort study. Early Hum Dev. 2019 Mar;130:101-108. doi: 10.1016/j.earlhumdev.2019.01.010. Epub 2019 Feb 1. No abstract available. PMID 30716594
• Shah R, Harding J, Brown J, McKinlay C. Neonatal Glycaemia and Neurodevelopmental Outcomes: A Systematic Review and Meta-Analysis. Neonatology. 2019;115(2):116-126. doi: 10.1159/000492859. Epub 2018 Nov 8. PMID 30408811
• Forster DA, Moorhead AM, Jacobs SE, Davis PG, Walker SP, McEgan KM, Opie GF, Donath SM, Gold L, McNamara C, Aylward A, East C, Ford R, Amir LH. Advising women with diabetes in pregnancy to express breastmilk in late pregnancy (Diabetes and Antenatal Milk Expressing [DAME]): a multicentre, unblinded, randomised controlled trial. Lancet. 2017 Jun 3;389(10085):2204-2213. doi: 10.1016/S0140-6736(17)31 PMID 28589894
• Gertz B, DeFranco E. Predictors of breastfeeding non-initiation in the NICU. Matern Child Nutr. 2019 Jul;15(3):e12797. doi: 10.1111/mcn.12797. Epub 2019 Apr 2. PMID 30767426
• De Bortoli J, Amir LH. Is onset of lactation delayed in women with diabetes in pregnancy? A systematic review. Diabet Med. 2016 Jan;33(1):17-24. doi: 10.1111/dme.12846. Epub 2015 Aug 18. PMID 26113051
• Clifford V, Klein LD, Brown R, Sulfaro C, Hoad V, Gosbell IB, Pink J. Donor and recipient safety in human milk banking. J Paediatr Child Health. 2022 Sep;58(9):1629-1634. doi: 10.1111/jpc.16066. Epub 2022 Jul 2. PMID 35779010
• Clifford V, Klein LD, Sulfaro C, Karalis T, Hoad V, Gosbell I, Pink J. What are Optimal Bacteriological Screening Test Cut-Offs for Pasteurized Donor Human Milk Intended for Feeding Preterm Infants? J Hum Lact. 2021 Feb;37(1):43-51. doi: 10.1177/0890334420981013. Epub 2020 Dec 22. PMID 33351688
• Urashima M, Mezawa H, Okuyama M, Urashima T, Hirano D, Gocho N, Tachimoto H. Primary Prevention of Cow's Milk Sensitization and Food Allergy by Avoiding Supplementation With Cow's Milk Formula at Birth: A Randomized Clinical Trial. JAMA Pediatr. 2019 Dec 1;173(12):1137-1145. doi: 10.1001/jamapediatrics.2019.3544. PMID 31633778

Identifiers

NCT: NCT06993103 · 2024-607 · 2024607

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗