ORIGINAL RESEARCH

published: 15 March 2022

doi: 10.3389/fnbeh.2022.860223

Efficacy and Feasibility of an

Osteopathic Intervention for
Neurocognitive and Behavioral
Symptoms Usually Associated With
Fetal Alcohol Spectrum Disorder
Ramon Cases-Solé 1,2 , David Varillas-Delgado 3* , Marta Astals-Vizcaino 4 and
Óscar García-Algar 2,4
1
Centre Osteopatia La Seu, Lleida, Spain, 2 Department of Surgery and Medical-Surgical Specialties, Universitat
de Barcelona, Barcelona, Spain, 3 Faculty of Health Sciences, Universidad Francisco de Vitoria, Madrid, Spain, 4 Department
of Neonatology, Hospital Clínic-Maternitat, ICGON, BCNatal, Barcelona, Spain

The purpose of this study was to evaluate the efficacy and feasibility of a 4-week planned
Edited by: osteopathic manipulative treatment intervention on the improvement of neurocognitive
Lauren A. Fowler,
and behavioral symptoms usually associated with fetal alcohol spectrum disorder. Thirty-
University of South Carolina,
United States two symptomatic children without fetal alcohol spectrum disorder aged 3–6 years with
Reviewed by: low level of attention from two schools and an osteopathic center were recruited
Michael Seffinger, in a prospective randomized pilot study in an osteopathic manipulative treatment
Western University of Health
Sciences, United States
group [osteopathic manipulative treatment (OMT)] or a control group (standard support
James William Hendry Sonne, measures). Neurocognitive maturity test results for attention (A), iconic memory (IM),
University of South Carolina,
spatial structuration (SS), and visual perception (VP) were recorded at baseline and
United States
post-intervention. No adverse effects were communicated and there were no dropouts.
*Correspondence:
David Varillas-Delgado A significant increase in neurocognitive assessments was observed in children in the
david.varillas@ufv.es OMT group at post-treatment. Intergroup post-intervention statistical differences were
found for A, SS, and IM were p = 0.005, p < 0.001, and p < 0.001, respectively; no
Specialty section:
This article was submitted to differences were seen for VP (p = 0.097). This study shows that a 4-week osteopathic
Learning and Memory, manipulative treatment intervention may be a feasible and effective therapeutic approach
a section of the journal
Frontiers in Behavioral Neuroscience
for neurocognitive and behavioral symptoms usually present in fetal alcohol spectrum
Received: 22 January 2022
disorder, justifying more studies on children affected by this condition.
Accepted: 08 February 2022
Keywords: fetal alcohol spectrum disorder (FASD), prenatal alcohol exposure, osteopathic manipulative
Published: 15 March 2022
treatment, neurocognitive disorders, attention
Citation:
Cases-Solé R, Varillas-Delgado D,
Astals-Vizcaino M and García-Algar Ó INTRODUCTION
(2022) Efficacy and Feasibility of an
Osteopathic Intervention
Neurocognitive and behavioral symptoms are high incidence disabilities among children with
for Neurocognitive and Behavioral
Symptoms Usually Associated With
FASD that affect the daily life of the patient, attention deficit being the most frequent (Weyrauch
Fetal Alcohol Spectrum Disorder. et al., 2017). Several systematic reviews underline the need for further research on the effectiveness
Front. Behav. Neurosci. 16:860223. of specific interventions aimed at early and individualized treatments of children with fetal
doi: 10.3389/fnbeh.2022.860223 alcohol spectrum disorders (FASDs), as well as new effective treatment strategies to improve

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Cases-Solé et al. Neurocognitive Behavioral Symptoms in FASD

neuropsychological symptoms in this population (Reid et al., (Dockstader et al., 2010; Haegens et al., 2012; Wiesman and
2015; Ordenewitz et al., 2021). According to the experience, Wilson, 2020). Furthermore, other works have demonstrated
osteopathy and its application through osteopathic manipulative effects on cortical plasticity after OMT interventions (Ponzo
treatment (OMT) may be an efficient therapeutic tool as et al., 2018), as well as specific brain connectivity changes in
an adjuvant treatment in FASDs. A systematic literature sensorimotor, locomotor, and postural function networks, which
review was conducted on using PubMed, Medline and the suggests an alteration in the processing of information post-OMT
Cochrane Library with the keywords “Fetal Alcohol Spectrum (Tramontano et al., 2020).
Disorder,” “Fetal Alcohol Syndrome,” “Osteopathic Manipulative Over the past years, there has been an increase in the number
Treatment,” “Neurocognitive Disorders,” and “Attention.” The of publications on pediatric OMT, with additional evidence of
reviewed literature indicates that children with FASDs may its benefits in the field of neurological development disorders
benefit from interventions when appropriately adapted to their (DeMarsh et al., 2021). Nevertheless, further research is needed
neurodevelopmental disabilities (Petrenko, 2015) and may help on the effectiveness of OMT in children (Parnell Prevost et al.,
improve their health-related quality of life (Stade et al., 2006). 2019; DeMarsh et al., 2021).
Similarly, there should be acceptance of the interventions by Improvement of A in children and adolescents with attention
the patients and their families (Petrenko, 2015). This is very deficit hyperactivity disorder (ADHD) has been seen (Accorsi
relevant for sensitive populations, such as the families with FASD et al., 2014), as well as positive effects in learning processes and
members (Domeij et al., 2018; Flannigan et al., 2020; McLachlan infant neurological development (Frymann, 1976; Frymann et al.,
et al., 2020; Pruner et al., 2020), particularly in communities 1992). Social behavior and communication indexes ameliorated
such as ours, were prevalence of FASD of internationally adopted in a sample of children with autism (Bramati-Castellarin et al.,
children is very high (Catalunya, 2019; Palacios et al., 2019). 2016) as well as the mood, sleep, and limb function in children
Despite the global increase in the practice and specialization with cerebral palsy (Duncan et al., 2004). There is convincing
of pediatric osteopathy (International Alliance, 2020; DeMarsh evidence on the positive effect of OMT as adjuvant treatment
et al., 2021; Schwerla et al., 2021), and its low-risk-profile (Hayes in premature infants in neonate intensive care units (ICUs),
and Bezilla, 2006; DeMarsh et al., 2021), further research is e.g., decreased hospital stays and associated costs (Lanaro
needed to gather a body of evidence that could be used to et al., 2017). Therefore, interventions such as an OMT may
recommend pediatric OMT under specific clinical conditions aid in neurocognitive and behavioral pediatric development
(DeMarsh et al., 2021). Thus, following recent recommendations including those to FASDs.
in the literature (DeMarsh et al., 2021), assessment of viability and We hypothesized that standardized OMT aimed to correct
safety of OMT interventions in pediatric osteopathy are required individualized somatic dysfunctions would improve measures
before their use on specific population groups. indicated by the Cumanin measuring test. The main primary
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This preliminary study was designed on the assumption that objective of this pilot study was to evaluate the efficacy and
the FASD population and their families will be receptive to feasibility of a 4-week planned OMT intervention delivered by
experimental interventions (Stade et al., 2006; Domeij et al., 2018) a qualified pediatric osteopath, on Attention (A), iconic memory
and because of the lack of studies assessing the efficacy of OMTs (IM), spatial structuration (SS) and visual perception (VP) in a
on FASD-related neurocognitive and behavioral symptoms (Reid group of children without FASD with low levels of A. The main
et al., 2015; Petrenko and Alto, 2017; Ordenewitz et al., 2021). secondary objective was to validate the intervention to apply it to
Positive effects of therapeutic interventions on FASD population in future studies.
neuropsychological symptoms in people with FASD have
been shown, indicating that gains on attention (A) may be
achieved, and generalize to other areas of functioning (Reid et al., MATERIALS AND METHODS
2015; Petrenko and Alto, 2017; Ordenewitz et al., 2021).
One of the purposes of osteopathy is to detect and Study Design
correct somatic dysfunctions and their potential negative effects Prospective randomized pilot study.
through manual contact by OMT. The results of research
carried out to date suggest that OMT has anti-inflammatory Patients
(Standley and Meltzer, 2008; Licciardone et al., 2012; Degenhardt Children aged 3 to 6 years without a FASD diagnosis
et al., 2017) and parasympathetic effects (Henley et al., 2008; but with symptoms usually present in FASDs (Kodituwakku,
Giles et al., 2013; Ruffini et al., 2015). Although specific 2009; Lange et al., 2017; Weyrauch et al., 2017; Maya-
metabolic and neurological alterations linked to the somatic Enero et al., 2021) identified through a neuropsychological
dysfunction have been identified (Van Buskirk, 1990; Korr, 1991; assessment referred from schools and an osteopathic center,
Snider et al., 2011), the underlying physiological mechanisms were recruited between June 1 and July 17, 2020. Children
remain under study (Tozzi, 2015; Tramontano et al., 2020; with A and behavior problems according to their parents
Roura et al., 2021). Moreover, there is evidence on the and/or teachers, following inattention criteria in the DSM-
relation between the somatosensory system and neurological 5 handbook were pre-selected (Battle, 2013). Reduced levels
development processes, particularly in the areas of perception of A were recognized using the Neuropsychological Maturity
and cognition. Recent research has shown a dynamic interaction Questionnaire for Children (Cumanin ) (Portellano Pérez et al.,
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between the somatosensory system and a-related brain centers 2009) before the intervention during the recruitment process.

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Cases-Solé et al. Neurocognitive Behavioral Symptoms in FASD

Decreased levels of A were considered with scorings below the A qualified pediatric osteopath, with a master’s degree in
50th percentile (p > 50) in the attention scale (Portellano Pérez Osteopathy, following the recommendations of the European
et al., 2009). Due to the absence of previous studies, it was not Standard UNE-EN 16686 (16686:2015), and a postgraduate
possible to perform the estimated calculation of the sample size specialization in Pediatric Osteopathy, carried out the
for this pilot study. OMT interventions. A qualified psychologist performed the
Children diagnosed with ADHD, or other neurological, neuropsychological pre-/post-tests to all participants at baseline
genetic, and/or metabolic pathology, or receiving and at conclusion of the intervention (the day after the last
pharmacological treatment at the beginning of the intervention OMT session). Specific and general recommendations of each
or had undergone OMT over the 12 months prior to the questionnaire were followed. Pre- and post-tests took between 20
intervention, were excluded. and 30 min each (Portellano Pérez et al., 2009).
Informed consent to participate in the study was obtained
from the parents/legal tutors, who also received written and Outcome Variables
verbal information on the design of the study and protocol. The primary outcome for validating and assessing the OMT was
The Ethical Committee for Clinical Research Parc de Salut MAR the percentage of patients who completed the intervention and
(Barcelona, Spain) approved the study protocol (2016/7052/I), showed statistically significant differences in the individually
conducted according to the guidelines of the Declaration of administered Cumanin measuring test, which includes
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Helsinki for Human Research of 1964 (last modified in 2013). neuropsychological maturity scales that allow to determine the
centile values for A, IM, SS, and VP (Portellano Pérez et al.,
Interventions 2009). Investigators who performed and assessed the OMT were
Two groups of children were defined: the OMT group (n = 16) blinded to patient random allocation.
children who received three OMT sessions over a 4-week period
(one session every 2 weeks). Permuted-block randomization was Description and Neurofunctional Significance of the
used for treatment allocation. A research associate generated Neurocognitive Scales
the random sequence using the Excel software. The control Attention (A): 20 items – the aim was to identify and mark
group (n = 16) were children who received standard support 20 geometrical figures identical to the proposed model (a
measures. Participants from both groups got the same tailored square) shown among 100 figures, 80 of which were distractors
standard support learning measures at their schools, following and 20 squares identical to the model. The test was carried
the standard guidelines of educational intervention based on out for 30 sec and the correct answers (correctly crossed-
the creation of enabling environments and individualized out squares) and errors (other incorrectly crossed-out figures)
support adapted to children with neurocognitive and behavioral were noted, although only the number of correctly crossed-
symptoms, e.g., low level of A (Battle, 2013; Catalunya, out figures was taken into account. Maximum score = 20;
2019). Support measures received by the participants at school minimum = 0. This assesses structures that are involved with
throughout the study period were not modified. A processes, particularly reticular formation and prefrontal
At the first intervention, each participant underwent a cortex. The right cerebral hemisphere is dominant in A control
protocolized anamnesis and an osteopathic physical examination (Portellano Pérez et al., 2009).
based on SOAP (Subjective, Objective, Plan, Assessment) notes Iconic memory (IM): 10 items – the child had to memorize
and exam forms (Sleszynski et al., 1999; Sleszynski and 10 simple drawings of objects for 1 min. Then, the child had
Glonek, 2005). Somatic dysfunctions were detected by physical to say the name of the drawings he remembered, in a period
examination, based on tissue texture changes, asymmetry, of 90 sec. The child got 1 point for each well-remembered
limitation in normal range of motion, and tissue tenderness object. It was not considered if child said an incorrect object.
parameters (TART), which guided the osteopathic evaluation Maximum score = 10; minimum = 0. Immediate memory is
and OMT intervention. The parameters of somatic dysfunctions related to structures such as the hippocampus, parietal cortex,
were described by the position and motion of a body part as and amygdala. This scale evaluates right hemisphere function
determined by palpation. (Portellano Pérez et al., 2009).
Using OMT techniques, the identified somatic dysfunctions Spatial structuration (SS): 15 items – the child had to
were corrected one by one in the whole body (Tramontano perform increasingly difficult spatial orientation activities via
et al., 2020). The following approaches were used: psychomotor (11 items) and graphomotor responses (4 items).
balanced ligamentous techniques, balanced membranous Maximum score = 15; minimum = 0). Essentially, this is related
techniques/osteopathy in the cranial field, and facilitated with association centers at the parietal-temporal-occipital cortex,
positional release techniques (Johnson and Kurtz, 2003). An in charge of spatial representation on the Penfield sensory
osteopathic physical examination and an OMT intervention homunculus at the parietal cortex (Portellano Pérez et al., 2009).
were performed in each session to assess and correct somatic Visual perception (VP): the child had to reproduce 15
dysfunctions. The time allocated for the first session was 50 min, items geometrical designs of increasing difficulty. Each correctly
and the next two 30 min each. drawn figure was valued with 1 point. The test ended if
To improve adherence and reduce performance bias, the child made 4 consecutive drawings wrong. Maximum
participants were assigned the OMT the same day every week. score = 15; minimum = 0. Secondary visual areas and
Reminder and confirmation calls were made to families 24 h associative areas on the occipital lobe mediate this, as well
before each scheduled intervention and before the pre-/post-tests. as the mnemonic function, which is mediated by deeper

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Cases-Solé et al. Neurocognitive Behavioral Symptoms in FASD

areas of the temporal cortex. The frontal cortex is also and treatment, 10.42 min. Average number of somatic
involved, along with various motor-decision centers of the brain dysfunctions (SD) were [most prevalent: cranial (30.0%),
(Portellano Pérez et al., 2009). diaphragm (17.1%), and cervical area (12.8%)] per participant
Each scale allows scores to be recorded, the interpretation at baseline was 4, dropping to 1.5 at the last OMT session.
of which is made by converting these raw scores into centile Percentages of the used approaches were as follows: balanced
scales, which are differentiated into five age groups in months. ligamentous techniques (61.4%), balanced membranous
Scores below normal are considered to be centiles from 20 to techniques/osteopathy in the cranial field (30%), and facilitated
40, with scores below the 20th centile being considered very low positional release (8.6%).
(Portellano Pérez et al., 2009).
Participant Flow
Statistical Analysis Forty-three (n = 43) children were pre-selected; eight were
All statistical analyses were carried out using the Statistical excluded because of a percentile above 50 in the A scale. Thirty-
Package for the Social Sciences (SPSS) v.21.0 for Windows (IBM five candidates (n = 35) were enrolled, of whom three were
Corp. Released 2012. IBM SPSS Statistics for Windows, Version excluded for not meeting the inclusion criteria, i.e., had received
21.0. Armonk, NY, United States: IBM Corp). Categorical OMT treatment over the past 12 months (n = 2) and undergoing
variables were evaluated using frequencies and percentages and pharmacological treatment (n = 1). Thirty-two participants were
quantitative variables with means and standard deviations that finally included in the study, 16 randomly allocated to the OMT
included maximum and minimum values (range). Distribution group and 16 to the control group. One osteopath from a
of the data was evaluated using Shapiro-Wilk test. Comparisons single osteopathic center delivered the OMTs. Standard support
at various time intervals within each group were analyzed measures were applied at school (n = 12). Statistical analyses
using Friedman’s test and, if statistical significance was detected, were performed including the 32 participants. All completed the
multiple comparisons were carried out using Wilcoxon’s sign treatment and there were no dropouts.
rank test. Categorical variables were analyzed using the Pearson’s Statistically significant differences were observed for A in
chi-square (χ2 ) test. Groups were compared with Kruskal-Wallis the control group (p = 0.027) and in the OMT group
test complemented by the Bonferroni correction. Cohen’s d was (p = 0.031) (Table 2) following Friedman’s test; similarly,
calculated to evaluate effect sizes. P values < 0.05 were considered differences (p < 0.001) were found for SS in the control and
statistically significant. OMT groups (Table 3). Statistically significant differences were
seen for VP only in OMT group (p = 0.019) (Table 4); no
statistically significant pre-post results were seen for IM in the
RESULTS control group, contrary to what was observed in the treatment
group (p < 0.001) (Table 5).
Thirty-two participants (n = 32) without FASD were included
Post-treatment statistically significant differences were found
in this study, 16 in the OMT group and 16 in the control
for A, SS, and IM between the treatment and control groups
group. Gender ratio (male: female) was 17:15; 10:6 for the
(p = 0.005, p < 0.001, and p < 0.001, respectively). This was not
OMT group and 7:9 for control group. No adverse effects
the case for VP, for which no statistical differences (p = 0.097)
were communicated and none of the participants dropped out.
Demographic characteristics of children from both groups are
shown in Table 1. TABLE 2 | Neuropsychological maturity test average centile scores for attention.
Average duration of the interventions was as follows:
anamnesis -1st session- 16.25 min, exploration, 10.83 min, Attention

Pre-intervention, Post-intervention, Effect size P value

median [IQR] median [IQR] (within group)
TABLE 1 | Baseline characteristics of the study groups.
Control 27.50 [15.00–35.00] 17.50 [15.00–23.75] −0.58 0.027
Control group OMT group P value
OMT 20.00 [5.00–35.00] 30.00 [20.00–43.75] 0.34 0.031
(n = 16) (n = 16)
IQR, interquartile range; OMT, osteopathic manipulative treatment.
Boys/girls 7/9 10/6 0.288
Age at study entry 48.81 (10.001) 54.75 (9.370) 0.093
(months), mean (SD) TABLE 3 | Neuropsychological maturity test average centile scores for spatial
Attention, median [IQR] 27.50 [15.00–35.00] 20.00 [5.00–35.00] 0.152 structuration.

Iconic memory, median 75.00 [61.25–80.00] 75.00 [60.00–80.00] 0.931 Spatial structuration
[IQR]
Spatial structuration, 65.00 [60.00–70.00] 80.00 [35.00–93.75] 0.085 Pre-intervention, Post-intervention, Effect size P value
median [IQR] median [IQR] median [IQR] (within group)
Visual perception, 45.00 [40.00–75.00] 57.50 [40.00–78.75] 0.212
median [IQR] Control 65.00 [60.00–70.00] 30.00 [21.25–50.00] −1.80 <0.001
OMT 80.00 [35.00–93.75] 57.50 [30.00–83.75] −0.68 <0.001
IQR, interquartile range; OMT, osteopathic manipulative treatment; SD,
standard deviation. IQR, interquartile range; OMT, osteopathic manipulative treatment.

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Cases-Solé et al. Neurocognitive Behavioral Symptoms in FASD

TABLE 4 | Neuropsychological maturity test average centile scores for visual 1992; Accorsi et al., 2014). The sociodemographic profile of
perception.
the FASD population in our community (Catalunya, 2019) is
Visual perception characterized by a high index of FASD children who have
been adopted from countries of Eastern Europe, with high
Pre-intervention, Post-intervention, Effect size P value prevalence of special needs (Palacios et al., 2019) and may
median [IQR] median [IQR] (within group) thus be susceptible to experimental interventions. Thus, in our
Control 45.00 [40.00–75.00] 45.00 [26.25–48.75] −0.31 0.184
opinion, prior validation of any new therapeutic intervention
OMT 57.50 [40.00–78.75] 47.50 [35.00–70.00] −0.42 0.019 aimed at this population should be a priority. Therefore, the
current study evaluates cases with neurocognitive and behavioral
IQR, interquartile range; OMT, osteopathic manipulative treatment.
symptomatology without a FASD diagnosis (Maya-Enero et al.,
2021). The aim was to assess the feasibility of an OMT
TABLE 5 | Neuropsychological maturity test average centile scores for iconic intervention that could be used for FASD individuals. Our results,
memory.
as a preliminary intervention tool, show that OMT can be a valid
Iconic memory approach for treating neurocognitive and behavioral symptoms
usually present in FASDs (Kodituwakku, 2009; Lange et al., 2017;
Pre-intervention, Post-intervention, Effect size P value Weyrauch et al., 2017; Maya-Enero et al., 2021).
median [IQR] median [IQR] (within group) Research evidence indicates that gains in A can be achieved
Control 75.00 [61.25–80.00] 65.00 [60.00–80.00] −0.32 0.117 in FASD populations (Reid et al., 2015; Petrenko and Alto, 2017;
OMT 75.00 [60.00–80.00] 90.00 [80.00–95.00] 1.22 <0.001 Ordenewitz et al., 2021).
In our review of the literature we did not find studies
IQR, interquartile range; OMT, osteopathic manipulative treatment.
evaluating OMT interventions on cases with neurocognitive
and behavioral symptoms usually associated with FASD (Reid
were determined by Kruskal-Wallis test complemented by the et al., 2015; Petrenko and Alto, 2017; Ordenewitz et al., 2021).
Bonferroni correction (Table 6). Moreover, there is lack of relevant studies measuring the efficacy
No relevant adverse events or side effects were communicated. of OMT on neuropsychological development. Accorsi et al.
suggest that OMT may improve selective and sustained A
performances in children and adolescents with ADHD (Accorsi
DISCUSSION et al., 2014), although this should be further investigated.
Absence of adverse effects in our study may be due to the
The objective of this study was to evaluate the efficacy lower incidence of adverse events immediately after the OMT
and feasibility of an OMT intervention on neurocognitive in comparison to other manual medical disciplines (Degenhardt
and behavioral symptoms commonly present in FASD et al., 2018), while the gentle, non-invasive, tailored health care
(Kodituwakku, 2009; Weyrauch et al., 2017; Maya-Enero approach of OMT may have helped maintain patient adherence
et al., 2021), and validate the intervention to apply it to FASD (World Health Organization, 2012). Possibly, protocolized
population in the future. osteopathic anamnesis and examination, the training and
This work shows that a 4-week OMT plan, administered by a experience of the care providers, and supervision of the
qualified pediatric osteopath, is a feasible therapeutic approach procedures, are additional factors that may have contributed to
for children aged 3–6 years who exhibit neurocognitive and the success of the interventions. Families of children affected by
behavioral symptoms usually present in FASD, such as attention FASD show great interest in receiving care and treatment (Lange
deficit (Kodituwakku, 2009; Lange et al., 2017; Weyrauch et al., et al., 2018; Flannigan et al., 2020), which may help maintain a low
2017; Maya-Enero et al., 2021), effectively improving A, SS, dropout rate in future interventions with this population. Further
and IM, but not VP. research is required to assess OMT efficacy and patient’s safety
The development of perception and cognition is linked to (Degenhardt et al., 2018).
the somatosensory system (Dockstader et al., 2010; Haegens In this study, we show positive post-OMT outcomes on a
et al., 2012; Wiesman and Wilson, 2020) and the potential defined population, significant in three of the four assessed
effects of somatic dysfunctions (Frymann, 1976; Frymann et al., variables. These results may be because OMT interventions

TABLE 6 | Post-treatment average score differences in the two study groups.

OMT group, median Control group, median Effect size (between group) P value
difference [IQR] difference [IQR]

Attention 10.00 [7.75–15.00] −10.00 [−11.25−0.00] 0.62 0.005

Iconic memory 15.00 [15.00–20.00] −10.00 [−13.00- −4.00] 0.86 <0.001
Spatial structuration −22.50 [−29.00- −5.00] −35.00 [−38.75- −20.00] 0.79 <0.001
Visual perception −10.00 [−18.75- −5.00] 0.00 [−7.00–5.50] −0.51 0.097

IQR, interquartile range; OMT, osteopathic manipulative treatment.

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Cases-Solé et al. Neurocognitive Behavioral Symptoms in FASD

have on somatic dysfunctions, which consequently reduce the early neurodevelopmental difficulties. However, the number
potential negative consequences on perceptual and cognitive and variety of neurocognitive and behavioral evaluation tools
development (Frymann, 1976; Frymann et al., 1992; Tozzi, for children under 6 years is scarce (Portellano Pérez et al.,
2015). More research is needed to assess the effect of OMT 2009; Coles et al., 2021). The short length of the study is
interventions in children younger than 6 years with low a limitation to objectify improvements in neuropsychological
levels of A. Post-treatment results show a favorable effect development. Moreover, the capacity children have for learning
of overall neuropsychological development OMTs toward the and remembering the tests may be a bias in terms of evaluation
negative evolution of these variables over time. Although the (Portellano Pérez et al., 2009). To homogenize our sample
characteristics of this study do not allow to draw additional based on attention deficit, we carried out an assessment of A
conclusions, the results suggest the need of more in-depth studies using the scale of the Cumanin neuropsychological battery
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on the evolution of overall neuropsychological development in throughout 4 weeks before the intervention, a factor that may
pre-school children as stated by Sjöwall et al. (2017) study. increase the recall bias in the variable. The above-mentioned
However, early neuropsychological deficits may be identified and limitations can be reduced by increasing the size of the sample
have predictive value in future development of ADHD symptoms and study duration, as well as an extended follow-up period
and subsequent academic performance (Sjöwall et al., 2017). beyond the post-treatment period (Reid et al., 2015), as this would
Still, the small sample size and duration of the study limit any allow to determine if the achieved results are maintained over
conclusion. More studies with larger samples and longer study time. Moreover, other assessment tools can be used before the
duration are recommended. intervention during the recruitment period to reduce the recall
The average number of somatic dysfunctions per participant bias for this variable.
at baseline was 4 [most prevalent: cranial (30%), diaphragm Cumanin is a neuropsychological assessment instrument
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(17.1%), and cervical area (12.8%)] and 1.5 at the last session. validated in Spain for children between 36 and 78 months of
OMT interventions may explain the observed positive results age, widely used in Spain and other Spanish speaking countries
on somatic dysfunctions. These results seem to corroborate (Urzúa et al., 2010; Ávila Matamoros, 2012; Salvador-Cruz et al.,
data from previous works (Accorsi et al., 2014), although 2019). This means that the results may be not reproducible in
the characteristics of our study limit further comparisons. samples from populations from different countries. The reliability
The different levels of improvement may be explained by the of the questionnaire is considered acceptable and supported by
various development processes and maturation pathways of each a study that includes a sample of 803 participants (Portellano
measured variable (Portellano Pérez et al., 2009), suggesting that Pérez et al., 2009). Thus, four specific scales of the Cumanin R

somatic dysfunctions and OMT interventions may have distinct questionnaire were used. Although the scales have been designed
effects on each process. Additional research is needed to deepen to measure each variable independently, using the scales
into the mechanisms of OMT on somatic dysfunctions (Tozzi, separately may imply a potential bias. This was compensated
2015). Brain plasticity and neurodevelopment mechanisms by strictly following the instructions and steps described for
present during the first stages of life may explain the positive the evaluation (Portellano Pérez et al., 2009). During the
effects observed in our work despite the short duration drafting of this manuscript, a new version of the Cumanin
of the study (Portellano Pérez et al., 2009; Lange et al., questionnaire was published (Cumanin -2) (Portellano-Pérez
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2017). This supports the importance of early interventions et al., 2021), an extended and updated version of Cumanin for R

in neurocognitive and behavioral disorders (Portellano Pérez the neuropsychological assessment of children. Our study did
et al., 2009; Reid et al., 2015; Petrenko and Alto, 2017; not aim to assess and analyze the overall neuropsychological
Ordenewitz et al., 2021). status of the participants, but to evaluate the selected variables
Despite the relevant findings, this study has some limitations. and determine their evolution over time. Therefore, the used
This is a pilot study showing a favorable effect of OMT on assessment tools in this work retain their validity regarding
children between 3 and 6 years of age with attention deficits. pre- and post-intervention assessments. Moreover, in future
More research is needed to assess whether this intervention may interventions involving FASD populations within this age range,
be able to help all children with attention problems, including the use of Cumanin -2 should be considered, because to
R

those with FASD. Attention deficit in our study population may date, there is no references in the literature that describe the
have a different etiology than that of the FASD population, which clinical significance of the changes in the measurements of
may lead to distinct post-intervention results and conclusions the scales used.
in comparison to those observed in a FASD population (Glass Participants and their families were not blinded to the OMT
et al., 2013; Boseck et al., 2015). In cases of PAE, the impact intervention, and no sham-intervention or placebo treatment
of combined genetic and epigenetic factors throughout pre- was offered due to the lack of standard guidelines for OMT
and postnatal development, makes it difficult to establish a use (Cerritelli et al., 2016). Therefore, a placebo effect should
specific neuropsychological profile (Mattson et al., 2019; Maya- be considered in the current study, which can be overcome by
Enero et al., 2021) or determine its progression over time a homogeneous well-reported sham therapy applied to a third
(Weyrauch et al., 2017). group, using a wait-listed control group or a crossover study
Other limitations are the small sample size, which restricts design in future studies. Due to its importance, the creation of
the assessment of efficacy, and age of participants. In the latter, standard well-reported placebo treatments and their application
OMT on individuals aged 3 to 6 years would enable to intervene in OMT clinical trials should be considered in further works
in early neural development and deliver the intervention during (Cerritelli et al., 2016). In addition, the lack of a predetermined

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Cases-Solé et al. Neurocognitive Behavioral Symptoms in FASD

treatment protocol limits the generalizability of the results. DATA AVAILABILITY STATEMENT
Moreover, this factor allows the intervention on the FASD
population to be tailored to the patient’s profile and symptoms, The original contributions presented in the study are included
as noted in a recent systematic review (Ordenewitz et al., 2021). in the article/supplementary material, further inquiries can be
This is a common obstacle in the field of manual medicine directed to the corresponding author.
that can be minimized by applying standardized procedures
(Alvarez et al., 2016). Following anamnesis and exploration
protocols, discussion and supervision of the procedures among ETHICS STATEMENT
several professionals, and specific training and education of care
providers, were measures adopted to minimize this limitation. The studies involving human participants were reviewed and
Although the characteristics of this study do not allow drawing approved by the Ethical Committee for Clinical Research Parc
further conclusions, our results suggest the need for further de Salut Mar, Barcelona, Spain (2016/7052/I). Written informed
studies on certain clinical presentations characterized by deficits consent to participate in this study was provided by the
in neurocognitive and behavioral development, a field explored participants’ legal guardian/next of kin.
by Frymann et al. (1992) several years ago (Frymann, 1976).

AUTHOR CONTRIBUTIONS
CONCLUSION
RC-S conceived the experiments. RC-S, MA-V, and ÓG-A
Our study provides important data supporting the need for designed and performed the experiments. DV-D analyzed the
more rigorous trials. Statistically significant post-intervention data. RC-S, DV-D, MA-V, and ÓG-A wrote the manuscript.
differences between treatment and control groups were observed All authors contributed to the article and approved the
for A, SS, and IM; no differences were seen for VP. Significative submitted version.
changes in A and IM were observed in the treatment group. No
adverse effects were communicated and none of the participants
dropped out. Our results justify the design of a controlled clinical FUNDING
study to evaluate the feasibility and efficacy of OMT interventions
in FASD populations with larger samples, extended follow-up The authors acknowledged the financial support for this study
periods, and a sham therapy to a third group of participants. from Registro de Osteópatas de España (ROE).

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treatment: a randomized manual placebo-controlled trial. Brain Sci. 10:969. Conflict of Interest: The authors declare that the research was conducted in the
doi: 10.3390/brainsci10120969 absence of any commercial or financial relationships that could be construed as a
Urzúa, A., Ramos, M., Alday, C., and Alquinta, A. (2010). Madurez potential conflict of interest.
neuropsicológica en preescolares: propiedades psicométricas del test
CUMANIN. Ter. Psicol. 28, 13–25. Publisher’s Note: All claims expressed in this article are solely those of the authors
Van Buskirk, R. L. (1990). Nociceptive reflexes and the somatic dysfunction: and do not necessarily represent those of their affiliated organizations, or those of
a model. J. Am. Osteopath. Assoc. 90, 792–794. doi: 10.1515/jom-1990-90 the publisher, the editors and the reviewers. Any product that may be evaluated in
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Weyrauch, D., Schwartz, M., Hart, B., Klug, M. G., and Burd, L. (2017). endorsed by the publisher.
Comorbid mental disorders in fetal alcohol spectrum disorders: a systematic
review. J. Dev. Behav. Pediatr. 38, 283–291. doi: 10.1097/DBP.00000000000 Copyright © 2022 Cases-Solé, Varillas-Delgado, Astals-Vizcaino and García-Algar.
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