Amino Acid-based Formula Versus Extensively Hydrolyzed Formula in the Treatment of Feeding Intolerance in Preterm Infants: Study Protocol for a Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 190
- 试验地点
- 1
- 主要终点
- Time (days) to reach full enteral feeding
研究概览
简要总结
Background: Feeding intolerance is a common problem in preterm infants, which is associated with increased risk of infections, prolonged hospitalization, and increased economic costs. When human milk is not available, formula feeding is required. Amino acid-based formula and extensively hydrolyzed formula could be considered to use for severe feeding intolerance. A recent Cochrane meta-analysis found that preterm infants fed extensively hydrolyzed formula compared with standard formula could not reduce the risk of feeding intolerance and necrotizing enterocolitis, and weight gain was slower. Some studies reported that preterm infants fed amino acid-based formula could reduce the gastric residual volume. Investigators hypothesize that amino acid-based formula can improve feeding intolerance and establish full enteral feeding more rapidly in preterm infants compared with extensively hydrolyzed formula.
Method: The randomized, prospective, controlled trial is to be conducted in Children's Hospital of Chongqing Medical University (Chongqing, China). A total of 190 preterm infants with gestational age < 32 weeks or birth weight < 1500g and with a diagnosis of feeding intolerance will be included. Patients will be randomized to an amino acid-based formula-fed group and an extensively hydrolyzed formula-fed group. The primary outcome is the time (days) to reach full enteral feedings. Secondary outcomes include duration of vomiting and abdominal distension, gastric residual volume, body weight, length and head circumference during hospitalization, length of hospital stay (days), cost of hospitalization, time (days) of parenteral nutrition, change of abdomen circumference, main serum parameters and incidence of adverse events.
Discussion: The successful implementation of the study will provide robust evidence for formula alternatives in preterm infants with feeding intolerance.
详细描述
Globally, approximately 15 million premature infants are born every year, with this number increasing progressively. Due to the immature digestive, absorptive, and immunologic functions, preterm infants are particularly susceptible to mucosal inflammation and bacterial overgrowth, which can lead to feeding intolerance (FI). FI frequently occurs in premature infants, especially in those with a gestational age of <32 weeks or a birth weight of <1500 g. FI is defined as the inability to digest enteral feeding, and is characterized by increased gastric residuals, abdominal distension, vomiting, or both. This delays the establishment of full enteral nutrition and extends the duration of parenteral nutrition, thus increasing the risk of infections, prolonging the length of hospital stay, and increasing economic costs At present, there are some prevention and treatment measures for FI including optimization of enteral nutrition, modification of feeding methods, use of probiotics or medicine, and nursing interventions, but these measures are not fully effective. Feeding strategy for FI is an important clinical challenge for neonatologists. Associated with less feeding intolerance, human milk (HM) is recommended by The World Health Organization (WHO) as the first-choice milk for preterm. However, HM is not always available because of the lack of breast milk banks, diseases of mother and geographic factors, and therefore, formula feeding is required.
Currently, the alternative formulas include Preterm Formula (PF), Partially Hydrolyzed Formula (PHF), Extensively Hydrolyzed Formula (EHF) and Amino Acid-Based Formula (AAF), et al. PF is used in preterm infants when human milk is not available. Clinically, PHF, EHF and AAF are commonly used in treatment for moderate to severe cow's milk protein allergy and prevention for patients at high risk for allergy. PF containing intact protein may not be appropriate for infants with FI. Recently, a guideline mentioned that PHF, EHF and AAF could be considered for use in severe feeding intolerance.
Mihatsch et al. reported that EHF improved the feeding tolerance and enabled a more rapid establishment of full enteral feeding compared with standard PF in preterm infants. The use of EHF could reduce acid gastro-esophageal reflux in preterm infants with FI. A recent Cochrane meta-analysis found that existing data did not support conclusions that feeding PHF or EHF affected the risk of FI or necrotizing enterocolitis (NEC), but the data that could be abstracted from published studies for analysis were limited. Raimondi et al. reported that preterm infants with severe feeding intolerance significantly and rapidly reduced the gastric residual volume after AAF introduction. Jang et al. found the fecal calprotectin levels in AAF-fed infants with FI were significantly lower than those in the HM- or PF-fed infants with FI and showed improvement in the symptoms and signs of FI. However, these studies have some defects, such as small sample sizes, and no randomization. Which formula is more suitable for preterm infants with FI? No scientific evidence is available at present.
Based on previous research, investigators design a randomized, prospective, clinical trial of AAF vs EHF in feeding intolerance. investigators hypothesize that AAF can improve feeding intolerance and establish full enteral feeding more rapidly compared with EHF.
The aim of the present study is to investigate whether AAF enables a more rapid establishment of full enteral feeding in preterm infants with FI compared with EHF and help establish improved guidelines and feeding practices.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The study will be double-blinded. A nutritionist who is not directly involved in inpatient care will prepare and label the formula with the participant's randomization number, date and time feeding, then deliver the formula to the nurse caring for the infant. The medical and nursing teams caring for the infants will be unaware of the type of formula used for feeding. The trial statistician will perform data analysis and be kept unaware of treatment group assignment until the results are finalized.
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Admission between December 2021 and December
- •Gestational age (GA) < 32 weeks or birth weight (BW) < 1500g, appropriate for gestational age, admitted to Department of neonatology, Children's Hospital of Chongqing Medical University within the first 24 h after birth, maximal enteral intake < 50 mL/kg/day.
- •Patients are fed with preterm formula when human milk is not available after admission.
- •Meet the diagnostic criteria of feeding intolerance (FI). Currently, a clear and universal definition of FI is lacking, FI is defined as follows with reference to relevant literature：One or two of the criteria below are met: (1) gastric residual volume ≥ 50% of the previous feeding volume (≥ twice within 24 h), with the presentation of vomiting and/or abdominal distension; (2) feeding plans fail: including feeding withheld or decrease > 6h, or not increased > 24h.
- •Parental consent has been obtained.
排除标准
- •Perinatal asphyxia: (1) Apgar score less than four at five minutes; (2) Fetal umbilical artery acidemia: pH less than 7.00 and/or base deficit worse than or equal to minus 12 mmol/L; (3) A significant peripartum or intrapartum hypoxic-ischemic event (e.g., uterine rupture, placental abruption, cord prolapse, amniotic fluid embolism, fetal exsanguination from a vasa previa or massive feto-maternal hemorrhage, etc.).
- •Potential metabolic or chronic disease, congenital abnormality or any other diseases that may affect feeding ability, normal growth, and development before recruitment.
- •Patients who need surgical treatment under general anesthesia (ligation of patent ductus arteriosus is excluded) before or on the date of randomization.
- •Blood pressure is unstable (allowing for dopamine < 5ug/kg/min).
- •Ventilator dependence or FiO2 > 40% on the date of randomization (allowing for nasal intubation, CPAP, and/ or oxygen mask ).
- •Grade III or IV intraventricular hemorrhage is diagnosed before or on the date of randomization.
结局指标
主要结局
Time (days) to reach full enteral feeding
时间窗: through study completion, an average of 3 months
defined as a daily intake of ≥ 150 mL/Kg/day for three days in a row (age at the first day of achieving full enteral feedings as the indicator).
次要结局
- Body length during hospitalization(through study completion, an average of 3 months)
- Gastric residual volume(up to 3 months)
- Hepatic functional markers test(up to 3 months)
- Duration of vomiting and abdominal distension(through study completion, an average of 3 months)
- Body weight during hospitalization(through study completion, an average of 3 months)
- Head circumference during hospitalization(through study completion, an average of 3 months)
- White blood cell count(up to 3 months)
- Length of hospital stay(through study completion, an average of 3 months)
- Cost during hospital stay(through study completion, an average of 3 months)
- Time of parenteral nutrition(through study completion, an average of 3 months)
- Incidence of adverse events(through study completion, an average of 3 months)
- Change in abdomen circumference(up to 3 months)
- Serum electrolytes test(up to 3 months)
研究者
Qin Zhong
doctor
Children's Hospital of Chongqing Medical University