Ethics statement
Written informed consent was obtained for all subjects during study enrollment and the study was approved by the institutional review board of Pescara’s hospital. This trial has been registered at http://clinicaltrials.gov/ (identifier NCT01544257).
Objectives
A single blinded randomized control trial was carried out in the NICU of Santo Spirito Hospital in Pescara, Italy, in the period between August 2008 and December 2009. The primary objective of the study was to evaluate the effectiveness of OMT in reducing LOS in a sample of premature infants. The secondary outcomes of the study were the difference in daily weight gain and NICU cost analysis.
Osteopathic care
Osteopathic medicine is a form of drug-free non-invasive manual medicine, designated as complementary and alternative medicine (CAM). It relies on manual contact for diagnosis and treatment. It respects the relationship between body, mind and spirit in health and disease; it lays emphasis on the structural and functional integrity of the body and the body's intrinsic tendency for self-healing. Osteopathic practitioners use a wide variety of therapeutic manual techniques to improve physiological function and restore homeostasis that has been altered by somatic (body framework) dysfunction (ICD-10-CM Diagnosis Code M99.00-09). Related components of the somatic system include: skeletal; arthrodial and myofascial structures; vascular; lymphatic and neural elements, which can become impaired or altered.
Osteopathic practitioners use their understanding of the relationship between structure and function to optimize the body’s self-regulation and self-healing capabilities. This holistic approach to patient care and healing is based on the concept that a human being is a dynamic functional unit, in which all parts are interrelated and possesses its own self-regulatory and self-healing mechanisms.
Two essential components of osteopathic health care are the structural evaluation of the patient for diagnosis and an array of manipulative techniques for treatment.
The aim of the structural examination is to locate the somatic disfunction. In newborns the structural exam is usually performed with the infant lying down on the table. Diagnostic criteria for somatic disfunction are focused on tissue texture abnormalities and tone. Areas of asymmetry and misalignment of bony landmarks are evaluated. The quality of motion, its balance and organization are noted.
In treating children during the very first days of life osteopaths use a wide variety of therapeutic manual techniques to increase range of motion, to improve physiological function and/or support homeostasis that has been altered by somatic dysfunction.
The term osteopathic manipulative treatment (OMT) currently encompasses more than twenty types of osteopath-performed manual treatments [14]. The OMT techniques of choice in treating preterm infants are myofascial release, balanced ligamentous/membranous tension, indirect fluidic and v-spread [13, 15].
In the present study, 8 osteopathic practitioners were involved and randomly divided in two groups: 4 osteopaths performing the evaluation (group A), and 4 osteopaths performing the evaluation and the treatment (group B). Osteopaths from group A and B entered to the NICU in different hours of the schedule days, to provide blinding and to avoid possible confounding. None of the osteopathic practitioners were involved in the study design, data entry or statistical analysis. In addition all practitioners, except for the treating osteopath, were unaware of patients allocation. Osteopathic service was provided twice a week, on Tuesdays and Fridays.
Study population
All newborns who met the following inclusion criteria were considered eligible for the trial: male and female preterm infants entering the NICU in the period between August 2008 and October 2009, subjects born in the Pescara’s hospital and are free from medical complications with written informed consent from parents or legal guardians. Out of N=559 newborns entering the NICU, N= 220 met the inclusion criteria. The exclusion criteria were applied at entry and during the entire newborn’s LOS. At entry the application of the supplementary exclusion the criteria (list of exclusion criteria) further reduced the number of preterm infants to N=110.
List of exclusion criteria:
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gestational age <29, >37 weeks;
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osteopathic treatment performed >14 days after birth;
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newborn transferred to/from other hospital;
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newborn from to HIV seropositive and/or drug addict mother;
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newborn with genetic disorders, congenital abnormalities, cardiovascular abnormalities, neurological disorders, proven or suspected abdominal obstruction, pre- and/or post-surgery patients, pneumoperitoneum and/or atelectasis;
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newborn with respiratory distress syndrome.
Using a permuted-block randomization procedure (1:1 ratio), patients were sequentially allocated to the experimental and control arms using R software (version 2.11.0) as computer random number generator [16].
N=55 preterm infants were randomly assigned to the experimental group, while N=55 infants to the control group (Figure 1). During the trial, 9 subjects dropped out transferred to another hospitals. At the end of the study N=47 preterms were allocated to the experimental group and N=54 to the control group.
Experimental group: patients under standard medical care plus OMT.
When osteopathic treatment was provided, patients from the experimental group received osteopathic evaluations and treatments from group B, plus osteopathic evaluations from group A. Group A was blinded to patients assignment and assessment. The osteopathic evaluation consisted of finding the somatic dysfunctions using a structural examination whilst the treatment was based on the application of indirect techniques as described above. The total time for osteopathic evaluation and treatment was 20 minutes.
Control group: patients under standard medical care plus osteopathic evaluations.
Patients from control group received only osteopathic evaluations from group A. The evaluation took approximately 10 minutes. Once completed, osteopaths from group A remained standing in front of incubators or beds for additional 10 minutes.
NICU discharge criteria
Physiological conditions required for discharge included: maintenance of body heat at room temperature, coordinated sucking, swallowing, and breathing while feeding; sustained pattern of weight gain; and stability of cardiorespiratory function (no episodes of apnea/bradycardia for 2-5 days, free of supplemental oxygen support) [17].
Allocation concealment and blinding
An information technology consultant was responsible for randomization prior to the arrival of the osteopaths to the NICU.
NICU staff was blinded to patients allocations, since all infants were at least touched by osteopaths from group A and B and osteopaths spent the same amount of time in front of incubators and/or beds. Moreover osteopaths were unaware of study design and outcomes.
Data entering and data export
Data collection was performed using an ad hoc locally developed software called EBOM-GCCN.
EBOM-GCCN data set is an informatics tool that improves the efficiency and accuracy of data and developed to assist neonatologists, nurses and osteopaths in daily patient management.
The software consists of three sections:
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Section 1: Intended for use by neonatologists and nurses for recording patients' general details and all clinical information;
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Section 2: Intended for use by osteopaths from group A;
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Section 3: Intended for use by osteopaths from group B.
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Sections 1, 2 and 3 were blinded to all other investigator groups.
Nurses and medical records were collected daily by the NICU staff, from the time the infants were admitted to the NICU to the time of discharge. Each day the osteopathic service was provided, osteopaths from groups A and B recorded data in relation to the structural examination and OMT.
Data export was performed at the end of the study by the statistician from the coordinating center: European Institute for Evidence Based Osteopathic Medicine (EBOM).
Statistical analyses
Sample size calculation used an effect size of 0.6 (mean groups difference of 6 days with a standard deviation of 10), a statistical power of 0.80 and an alfa level equal to 0.05. This produces a sample size of 45 per group. To prevent loss of power, the sample size was increased up to 55 subjects per group.
Statistical analyses are based on intention-to-treat analysis (ITT). Missing data is handled using last observation carried forward (LOCF) imputation technique. Arithmetic means and standard deviation are used for the general characteristics of the study population. Univariate statistical tests are used to compare the experimental group and control group at the baseline. A generalized linear model was also performed to study the independent effect of OMT on LOS and weight gain while taking into account possible confounders. The significance level is set at α=0.05.
The statistical program used for data analyses was R (version 2.11.0) [16].
Cost analyses
A multivariate analysis was performed to study the average hospitalization costs among infants of study and control groups. Hospital discharge data are regularly collected by the Regional Office of the Ministry of Health (ROMH) of Abruzzo, where the NICU of the present study is located. In more detail, the Ministry of Health, besides its central offices, is divided into Regional Offices distributed throughout Italy. In relation to their specific competences, each ROMH carries out activities of control and offers services to the population.
Cost data used in the statistical model were extracted from ROMH 2009 administrative databases. The statistical study of costs and related economic implications were based on discharges of preterm infants with major complications and are explained as following.
The Istituto Superiore di Sanità (ISS, National Healthcare Institute) estimates a precise amount of reimbursement for each DRG (Diagnosis-Related Group). Thus, hospitals receive national and/or regional refunds according to patients DRG. In the case of this study, all infants included were dropped into the DRG category of “preterm with major complications”, which produces a reimbursement of 7.450,09€ adjusted per LOS per newborn [18].
In the statistical analyses, the reference category was given to the control group and the reimbursement value was divided by LOS (mean), producing an estimate cost per newborn per LOS. The latter was used to theoretically compute the exact costs for the study group.
As for the study group, the cost for each OMT session, equal to 20,00€, was conservatively obtained by the charges of insurance companies [19].
Ordinary Least Squares (OLS) regression was used to obtain the effects of OMT on hospitalization costs after adjusting for gender, gestational age, LOS and weight at birth.
All cost estimates were adjusted for inflation to 2012 EUR€ using the Medical Component of the Consumer Price Index [20].