METHODS
death, human T-cell lymphotropic virus, gastroschisis, HIV infection, oropharyngeal, perforation, volvulus, NB, necrosis, sepsis, stenosis
SEPSIS, INTESTINAL ATRESIA, GASTROSCHISIS, HIV INFECTION, VOLVULUS, STERILE, ADVERSE EVENT, SECONDARY, NECROSIS, EVENTS, OBSTETRIC COMPLICATION, STENOSIS
A double-blind randomized trial was conducted with newborns at a federal public
children’s hospital in Rio de Janeiro that specializes in preterm NBs and children
with surgical problems. Newborns diagnosed with simple gastroschisis who were born
at the hospital and admitted to the neonatal unit from March 2019 to July 2022 and
followed-up until hospital discharge were included. We excluded those whose delivery
did not occur at the institution and/or NBs with a surgical diagnosis of complex
gastroschisis (presence of stenosis, intestinal atresia, perforation, necrosis or
volvulus according to the eviscerated content), born to mothers with a recent
history of legal drug use (before hospitalization and delivery), HIV infection or
human T-cell lymphotropic virus (HTLV).Each mother of a newborn eligible for the study was approached and given the details
about the research protocol, which included the randomization of the study groups,
the milking procedure and the oropharyngeal colostrum administration. After parental
informed consent was obtained, each newborn was randomly allocated to the
intervention group or the control group. The NBs in the intervention group received
0.2mL of maternal colostrum administered directly into the oral mucosa during the
first 48 hours of life for a period of 3 days with 3-hour intervals between each
treatment. For operational reasons, the protocol of oropharyngeal colostrum
administration at night was not applied.The control group received the “simulated procedure”, which consisted of the
researcher remaining with her hand inside the incubator, with an empty syringe, for
a period similar to that of the intervention group.Patients were randomized in blocks of four and stratified into two groups of
gestational age: < 37 weeks and ≥ 37 weeks. Randomization by gestational
age was possible because adequate prenatal care at the institution allows for the
scheduling of elective surgeries, with follow-up of obstetric complications and
prevention of damage to the intestinal loops. The randomization of patients to both
study groups was performed through the website Randomization.com (Blinding was applied to all health professionals of the neonatal unit involved in the
study, as well as to the statistician responsible for data analysis.Only the research member who performed the colostrum therapy and the lactary member
knew to which group each newborn belonged.All mothers were instructed on manual expression with aseptic techniques at the
bedside. These procedures, information and guidelines on expressing milk are used
for all mothers who do not breastfeed in the first hours of life, as recommended in
the hospital routine.The mothers received a sterile colostrum storage bottle, identified with the date,
time and name of the newborn. The researcher remained by the mother’s side to assist
her in this process. When manual milking was impossible, an electric pump (Pump Mini
Electric-Medela®) was used, and its accessories were duly sterilized before
each use.Colostrum collection in the first 24 to 48 hours occurred in the ward where the
mother was hospitalized (hosting room or pregnant women’s ward). The mothers were
instructed and encouraged to massage and express the milk in the first 24 hours,
every 2 or 3 hours, understanding that the process of stimulation of the breasts,
during hospitalization and after hospital discharge, is essential for the success of
milk production. Only two mothers were unable to express themselves by hand,
requiring the use of an electric pump.For the NBs randomized to the intervention group, the mother’s own colostrum was sent
to the human milk handling site in a biological safety cabinet before being sent to
the neonatal unit. For the NBs randomized to the control group (sham procedure), the
colostrum was stored in refrigerators available in the hospitalization units and
subsequently sent to the Milk Bank. There was no medical prescription for the
intervention, and blinding was respected.The protocol proposed by Rodriguez et al.The syringes were identified with the data of the NB (name, medical record, care unit
and time of distribution), wrapped in autoclave adhesive tape (Missner® 19mm
x 30m autoclave-proof adhesive tape) so that their contents could not be identified,
sealed with a sterile universal colored syringe cap and personalized in a plastic
bag for distribution.A total of 0.2mL was administered every 3 hours during the day, totaling 0.8mL every
24 hours, the therapy was not conducted during the night due to operational reasons.
The oropharyngeal administration of colostrum was only performed for 72 hours
because, after delivery, the mothers remained in the hospital for approximately 2 to
3 days.After the therapy was completed, the NB followed the routine of the neonatal unit,
with a zero diet, until medical release. During the entire procedure, the NB
remained monitored for oxygen saturation, heart rate and respiratory rate. An
adverse event was the occurrence of any change in these parameters: heart rate >
200 or < 80 beats per minute, respiratory rate > 60 breaths per minute or
oxygen saturation < 88%.The following events were considered lost to follow-up: early neonatal death, use of
treatment doses below 75% of the required amount (either due to nonavailability of
maternal colostrum or clinical instability of the newborn) and maternal withdrawal
from the study. Study suspension was considered if, after the interim analyses, the
data revealed clear harms or benefits.The beginning of enteral nutrition was determined by the physician responsible for
the neonatal unit, and human milk was preferred, according to the protocol already
followed in the institution. Breastfeeding was initiated when the NB was clinically
stable, and the volume of orally administered diet by cup or bottle was
approximately 25/30mL of human milk.Data were collected from medical records, including demographic data and medical
history during hospitalization until hospital discharge. The primary outcome measure
was the number of days from birth to oral feeding (first sucking diet). The
secondary clinical outcomes were the number of days without food, number of days on
parenteral feeding, number of days until start of enteral tube feeding, number of
days to reach full enteral feeding (100/120mL/kg/day), sepsis (positive blood
culture) and total length of stay (until hospital discharge).The sample size was calculated considering a significance level of 5% and power of
80% to show clinically relevant differences at the beginning of the oral diet. Based
on the results of previous studies,Data were collected using the research form and the NB medical records. The
Statistical Package for the Social Sciences (SPSS) software for Windows, version
13.0 (SPSS Incorporation, 1998), was used for data analysis with a significance
level of 5%. Analysis of variance was performed for variables with a normal
distribution, and nonparametric tests were performed for variables with a nonnormal
distribution (Kruskal‒Wallis and Wilcoxon tests). Chi-square and Fisher’s exact
tests were used for the analysis of categorical variables. For the comparison
between groups, numerical or qualitative ordinal variables, the
Wilcoxon-Mann‒Whitney U test was applied.The Ethics Committee for Research on Human Beings approved this project under number
2,942,243 (CAAE: 99246718.4.0000.5269) on March 14, 2019. It was included in the
Brazilian Clinical Trials Registry (REBEC - 