Intranasal Fresh Mother's Own Milk (iF-MOM) for Prevention of Intraventricular Hemorrhage in Extremely Preterm Infants ≤29 Weeks' Gestational Age: A Prospective, Nonrandomized Interventional Study With Propensity Score-Weighted Historical Controls
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 67
- 主要终点
- Incidence of Any-Grade Intraventricular Hemorrhage (Papile Grades I-IV)
研究概览
简要总结
Babies born very prematurely are at risk of intraventricular hemorrhage (IVH), which is bleeding in or around the fluid-filled spaces of the brain. Most IVH occurs during the first week after birth. Human colostrum and early breast milk contain growth factors, neurotrophic factors, immune-modulating substances, antioxidants, and other biologically active components that may have neuroprotective effects.
This study will evaluate whether giving very small amounts of a baby's own mother's fresh breast milk as nasal drops during the first 7 days of life may help prevent IVH in infants born at 29 weeks' gestation or earlier.
Approximately 67 eligible infants will be enrolled prospectively at Women's Hospital and St. Boniface Hospital in Winnipeg, Manitoba, Canada. At each scheduled study care session, fresh mother's own milk will be administered intranasally at 0.2 mL per nostril (0.4 mL total) before routine nursing care and, if tolerated and the infant remains clinically stable, repeated after care. Thus, a completed care session provides up to 0.8 mL. Study administration will be coordinated with 2-4 routine care sessions per day for 7 consecutive days, corresponding to a planned total daily volume of 1.6-3.2 mL.
The main study outcome is whether IVH of any grade is present on the routine cranial ultrasound performed at 4 to 7 days of life. Other outcomes include severe IVH, progression of IVH, post-hemorrhagic ventricular complications, mortality before hospital discharge, and the safety and tolerability of intranasal mother's own milk.
Outcomes in the prospectively treated infants will be compared with those of eligible infants previously cared for at the same neonatal intensive care units between 2020 and 2025. Statistical methods using propensity score weighting will be used to account for measured differences between the prospectively treated infants and the historical comparison group.
详细描述
Intraventricular hemorrhage (IVH) remains an important complication of extreme prematurity and occurs predominantly during the first postnatal week. The immature germinal matrix vasculature, impaired cerebral autoregulation, hemodynamic instability, inflammation, oxidative stress, and other factors contribute to vulnerability to hemorrhage in extremely preterm infants.
Fresh colostrum and early mother's own milk contain multiple biologically active constituents with potential neuroprotective effects, including growth factors, neurotrophins, anti-inflammatory and immune-modulating mediators, antioxidants, and other bioactive components. Intranasal administration is being evaluated as a non-invasive route that may permit exposure of the central nervous system to milk-derived bioactive factors through proposed olfactory, trigeminal, perineural, and perivascular pathways.
This is a prospective, nonrandomized interventional study conducted at Women's Hospital and St. Boniface Hospital in Winnipeg, Manitoba, Canada. Eligible inborn infants at 29+0 weeks' gestation or less will be prospectively enrolled within 72 hours of birth. Enrolled infants will receive intranasal fresh mother's own milk during the first 7 days of life.
Fresh milk from the infant's own mother or birthing parent will be used. Milk used for study dosing will not be refrigerated or frozen before intranasal administration and will be used within 3 hours of expression. Each study dose consists of 0.2 mL administered into each nostril, for a total of 0.4 mL per dose. Doses will be administered 2 to 4 times daily for 7 consecutive days, coordinated with routine nursing care when possible. Clinical feeding and oral immune therapy needs will take priority over study dosing.
Infants will remain on continuous cardiorespiratory monitoring and pulse oximetry. Safety assessments will be performed during dosing and for at least 60 minutes after each administration. Study dosing may be delayed, withheld, or stopped if prespecified clinical instability or safety concerns occur.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 0 Hours 至 72 Hours（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Gestational age ≤29+0 weeks based on the best obstetric estimate, with first-trimester ultrasound preferred.
- •Inborn at Women's Hospital or St. Boniface Hospital, Winnipeg, Manitoba, Canada.
- •Written informed consent obtained from a parent or legal guardian; antenatal consent may be obtained when preterm delivery is anticipated.
- •Mother/birthing parent intends and is able to provide fresh own milk for study dosing; low initial milk volume is acceptable because of the small intranasal dosing requirements.
- •Enrollment within 72 hours of life.
排除标准
- •Major congenital brain malformation, including holoprosencephaly, lissencephaly, schizencephaly, severe primary hydrocephalus, large arachnoid cyst, or other space-occupying lesion.
- •Airway or nasal anomaly precluding intranasal administration, including choanal atresia/stenosis, severe cleft palate/lip with nasal involvement, or Pierre Robin sequence with severe obstruction.
- •Trisomy 13, Trisomy 18, or another severe chromosomal/genetic disorder.
- •Acute surgical condition requiring immediate intervention, such as esophageal atresia with tracheoesophageal fistula.
- •Life-limiting condition, including comfort-care designation, anticipated survival <72 hours, known lethal diagnosis such as bilateral renal agenesis or anencephaly, or severe birth asphyxia with anticipated poor neurologic outcome.
- •Maternal contraindication to lactation, including HIV, or inability/unwillingness to provide fresh mother's own milk.
- •Evidence of Grade III-IV intraventricular hemorrhage on cranial ultrasound before enrollment.
- •Absence of fresh own-mother/birthing-parent milk for study dosing, including circumstances in which only donor or surrogate-provided milk is available.
研究组 & 干预措施
iF-MOM Intervention
Eligible extremely preterm infants born at ≤29+0 weeks' gestation will receive intranasal fresh mother's own milk (iF-MOM) in addition to standard neonatal intensive care. The initial administration volume is 0.2 mL per nostril (0.4 mL total). If tolerated without a clinically significant administration-related adverse event, the volume may be increased to 0.4 mL per nostril (0.8 mL total) at the discretion of the treating/study clinical team. Intranasal administrations will occur 2-4 times daily, coordinated around routine nursing care, for 7 consecutive days.
干预措施: Intranasal Fresh Mother's Own Milk (iF-MOM) (Other)
结局指标
主要结局
Incidence of Any-Grade Intraventricular Hemorrhage (Papile Grades I-IV)
时间窗: 4 to 7 days of life
Presence of any intraventricular hemorrhage (IVH), Papile Grades I-IV, assessed on the standardized cranial ultrasound performed at 4-7 days of life.
次要结局
- Incidence of Severe Intraventricular Hemorrhage (Papile Grades III-IV)(From the initial cranial ultrasound performed at 4-7 days of life through hospital discharge, up to 6 months of life)
- Progression of Intraventricular Hemorrhage(From the initial cranial ultrasound performed at 4-7 days of life through hospital discharge, up to 6 months of life)
- Post-Hemorrhagic Ventricular Dilatation Requiring Intervention(From the initial cranial ultrasound performed at 4-7 days of life through hospital discharge, up to 6 months of life)
- All-Cause Mortality(From birth until death or hospital discharge, whichever occurs first, assessed up to 6 months of life)
- Incidence and Severity of Adverse Events Associated With Intranasal iF-MOM Administration(During the 7-day intervention period)
研究者
Michael Narvey
Associate Professor, Department of Pediatrics and Child Health
University of Manitoba