Premature Birth Clinical Trial
Official title:
Is it Possible to Prolong the Duration of Exclusive Breastfeeding in Premature Infants? a Prospectivt Study
In this project three studies examined two possible explanations and one possible preventive
intervention to early cessation of exclusively breastfeeding in premature infants.
Study 1 The content of protein in the milk of mothers, who delivers prematurely, is about a
third higher than in the milk from the mother who delivers on time. The nutritional
composition changes over time and the content of protein decrease. Therefore the premature
infant is at risk of protein deficiency. While the infant is feeding by tube this decreasing
content of protein can made up by adding, while it is more difficult when the infant is
exclusively breastfeeding. The hypothesis is that reduced protein content in breast milk is
associated to a fewer number of days where the premature infant is exclusively breastfed.
Study 2 The premature infant is characterized with immature muscle with a low tension and
therefore, a low ability to eat its needs by breastfeeding the first period. The transfer of
milk from mother to child is an interaction between the mothers and her milk ejection reflex
that establish a positive pressure on the milk and the child that have to establish a vacuum.
The hypothesis is that the premature infants suction power is too weak to establish
sufficient intraoral vacuum to ensure milk transfer from the breast to the infant and it can
be related to a fewer number of days where the infant is exclusively breastfed.
Study 3 The premature infants low muscle tone and its immaturity also influence on the
organization and the quality of movements, marked as neuro motor processes. These processes
form the oral motor base supporting movement which involves the infant ability to establish
vacuum. The hypothesis is that Oral Stimulation for a specific program in 5 minutes before
the minimum 2 meals per. day for at least 14 days increases the preterm infant's ability to
create intra oral vacuum and thus the power to transfer milk from the breast, thereby
extending the number of days when the infant is exclusively breastfed.
200 infants are included consecutively, as a recurring cohort in all 3 studies. In Study 1
the mothers' milk is analyzed in order to the content of protein. In Study 2 the infant
suction is assessed by vacuum measurement. In study 3 the families are randomized to an
intervention or control group and parents off 100 infants are guided by occupational
therapists in a program of oral stimulation of their child.
The purpose of this project, which consists of three studies, is to investigate whether
insufficient protein in breastmilk and / or inadequate intra oral vacuum of the infant can
explain early breastfeeding cessation in the premature infant. Furthermore to test whether
the breastfeeding period may be extended by oral stimulation.
The rate of breastfeeding in mothers of infants born prematurely is lower than in mothers who
give birth on time. A Danish survey shows that about 70% of premature are on exclusive
breastfeeding at discharge and that this rate is decreasing to about 30% six weeks after
discharge. Breastmilk is the healthiest nutrition for the newborn and based on WHO's strategy
for the feeding of infants Board of Health recommends that newborn infants, including
premature, as far as possible are exclusively breastfed for six months. Exclusively
breastfeeding means that the infant only gets the breastmilk of the mother. Exclusively
breastfeeding has health implications for both mother and infant. Breastfeeding reduces
lactation incidence of infectious diseases, improves cognitive development and visual
function in the infant and reduces the risk of developing later obesity. In addition, the
level of immune protective factors and anti-inflammatory elements is high in the mother's
milk to the preterm infant and therefore reduce the infant's increased risk of early and
severe infections, and death late effects. Furthermore, breastfeeding may reduce the risk of
premature infant's abnormal vessel growth in the eye, and appears to have a protective effect
on the disease being of significant excess mortality primarily attack the intestines of the
preterm infant (necrotizing enterocolitis).
Problem Area / factors in milk composition with the importance of breastfeeding Breastmilk
contains the necessary nutritional components and energy that the infant needs. Therefore,
the milk of the mother delivering early have a higher content of fat and protein, and thereby
a higher level of energy comparing with the milk from the mother who have given birth to
term. The content of protein in the milk of the mother who gives birth prematurely is about
12 grams per liter and thus approximately one-third higher than that from the mother who
gives birth on time. The nutritional composition of breastmilk vary considerably over time
and the content of protein is decreasing why the premature infant are at risk of protein
deficiency and thereby insufficient growth. During the hospital stay, and while the infant
are feed by tube this decreasing protein content are made up by adding, while it is more
difficult when the infant breastfeed exclusively. Protein is important for the infant's
growth and strength and a local statement from Hvidovre Hospital found that 18% of all
hospitalized preterm infants in 2014 were added additional protein to breastmilk, because
growth was not sufficient. The question is whether reduced protein content in breastmilk has
a correlation with the number of days where preterm infants are exclusively breastfed?
Problem Area / intra oral vacuum strength of the infant with significance for breastfeeding
The period from birth to the premature infant feed exclusively at the breast without
supplementary tube feeding varies from weeks to months, depending on how early the infant is
born. The premature infant is characterized as being immature and with low muscle tone and
therefore, a decreased ability to breastfeed the first time. The transfer of milk from mother
to infant is an interaction between the mother and her milk ejection reflex creates a
positive pressure on the milk and the infant creates a vacuum. If the infant not create a
vacuum at the back of the mouth, the nipple of the mother is just pushed together and the
infant is not transferred milk from the breast to the oral cavity. The amount of milk is
regulated in relation to demand and a weak or shortage of vacuum will cause a shortage of
milk transfer, which in turn physiologically will lead to less milk production and thereby
decreasing amount. Studies that investigates this process and measured intra oral vacuum,
shows all the importance of the infant's contribution by milk transfer, but does not answer
to the extent the premature infants ability to create vacuum importance of breastfeeding
establishment and maintaining. The question is whether the premature infants sucking strength
is too weak to establish sufficient intraoral vacuum to ensure milk transfer from the breast
to the infant and it can be related to a fewer number of days where the infant is exclusively
breastfed.
In addition to the premature infants muscle tone has its immaturity also affect the
organization and quality of body movements. Organization and quality in the movements may be
referred to neuro motor processes and form among others the oral motor base supporting the
movements involving the infant's ability to create vacuum. The processes preceding the
creation of vacuum and studies have shown that by early intervention with oral stimulation in
the form of stimulation of the nerves and muscles in and around the mouth, it can be oral
motor basis strengthened. Studies where the infant carefully is stimulated with a finger,
showing that the premature infant's muscles and sucking reflex can be influenced so that it
is able to suck a larger volume in a shorter time in the bottle compared to the infant that
is not stimulated orally. This presents an opportunity to influence the premature infant´s
strength and maybe increase the ability to create intra oral vacuum affected by oral
stimulation as a skill the infant preserves. The question is whether oral stimulation can
increase the premature infant's ability to create vacuum and thus increase the power to
transfer milk from the breast and thereby extending the number of days when with exclusively
breastfed? The 3 studies are based on the same cohort. The cohort is identified and recruited
at the Neonatal Intensive Care Unit at Hvidovre Hospital and relevant families where the
mother delivers prematurely are included consecutively in accordance to the inclusion and
exclusion criteria. The cohort will be demographically representative of everyday life in
clinical practice with various family formation, education levels and socio-economic
background conditions.
Power calculations are based primary outcome: exclusively breastfeeding duration and made to
show effect on exclusively breastfeeding duration between the intervention- and the control
group. Requirements for power calculation are a mean value of the vacuum set at 100% with a
standard deviation (SD) of 26%. To detect the smallest clinically relevant difference of 13%,
equivalent to half a SD and with an expected drop out of 20%, which included 200 infants (100
infants in each group) in the study (alpha = 0.05 and beta = 0.1 ). There hospitalized
annually on average 300 preterm infants in the neonatal section. It is expected about 100
infants to meet the criteria for inclusion, thus achieved at approximately 2 year.
By inclusion the family is anonymized by allocating an ID number. When multiple assigned each
infant this ID number and a one of letters a, b or c. All data and all measurements is
obtained / made and recorded as far as possible of the project manager or alternatively the
project nurse.
6 weeks after the date for the expected terminator date either the family are visiting the
Neonatal section or the project manager/project nurse visiting the family in order to a
status of breastfeeding, vacuum measurement and the infant's growth. In addition the family
is contact by telephone the week in which the infant's postnatal age is 6 months. Here is
recorded breastfeeding status, the time of any termination of exclusive breastfeeding and the
infant's weight at GP visit 5 month old. The infant's growth is defined by its naked weight,
Length and head circumference. Previous studies show a number of factors which affect
breastfeeding duration. Features concerning socio-demographic background variables, perinatal
and psychosocial conditions will gathered by the project manager or project nurse using a
questionnaire in an interview with the family and form data in the analyzes. Participation in
the project is safe and not associated with risk or discomfort for either mother or infant.
STUDY 1 / PROTEIN IN BREASTMILK Data are obtained in the human milk section at the hospital.
Volume is obtained in milliliter (ml.) and protein content in gram pr. 100 ml. by using Miris
Human Milk Analyzer according to the usual practice. Miri is the only European equipment that
analyzes human milk. The test sample is 10 milliliters and the result given within a minute
and logged into the machine and then transferred to the project database. When the mother is
exclusively breastfeeding, we ask for 10 ml. Manual hand compressed breast milk. The analyzed
milk can´t be reused and is therefore destroyed.
STUDY 2 / WEEK STRENGTH ASSESSMENT BY VACUUM MEASUREMENT Sucking strength of the premature
infant is defined as the ability to create intra oral vacuum during sucking.
The intra oral vacuum of the premature infant is assessed by measuring the vacuum in the unit
of mBar and are primary made by the project manager which is blinded to know if the infant
has received oral stimulation or not. The measurement is made when the infant is awake and
show readiness to suck. For vacuum measurement is a manometer selected with a bottle
pacifier, which fits a Calmaflaske made by the firm Medela. The pacifier is shaped and is
similar in function a breast and extra small so that it matches the premature mouth of a
premature infant. As in a completely closed system the sucking of the infant is registered on
this connected manometer. In order to obtain a measure of reproducibility of the method all
vacuum measurements is carried out at 3 consecutive measurements. The advantage of the 3
measurements within a short time is to determine the intra-individual variability, but only
if the infant is motivated and show redlines for measurement 3 times. The equipment is
developed in cooperation with the Technical University of Denmark.
STUDY 3 / randomized INTERVENTION STUDY / ORAL STIMULATION Infants whose mothers is included
in the cohort is randomized to receive / not receive oral stimulation when the infant's
postnatal age is at least 32 + 0 weeks, as it is the time when the infant is able to
coordinate sucking and swallowing reflex. In multiple birth all infants is randomized to the
same group. The list is generated block randomized in blocks of 10
Families were randomized to the intervention group granted in total one hour instructions in
a program of oral stimulation by one of two occupational therapists with experience in oral
stimulation of preterm infants. The program is in collaboration with the project team
developed and described by the Department of Physiology and Occupational therapy at Hvidovre
Hospital. The first guidance for parents has duration of approximately half an hour and then
follow-up once or twice, depending on the needs of the family. To maintain consistent
intervention over time is the program of oral stimulation written in a script, where the
family also must record the following variables: date and time of oral stimulation. In
occupational therapy the guidance and in the script examines the signs that the infant
exhibits when it is ready / not ready for stimulation. The family also sees a movie where
these signs and the program of oral stimulation review auditory and visual. Families in the
control group is not seeing the movie, do not receive the script or the supervision of
occupational therapists and these infants do not get oral stimulation. Both groups receive
instructions after usual practice i.e. guidance and elements that promote breastfeeding
example, skin to skin contact and compression.
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