INA Early Intervention for Babies at Risk

Brain and nervous system development are experience dependent. Indeed, the sequence of development is laid out genetically, but early environmental events are major contributors to the system ’ s development and optimal functioning. Various fetal injuries and birth trauma make babies vulnerable to developmental problems: cerebral palsy, seizures, abnormal muscle tone, delayed developmental milestones, sensory integration, and more. Our goal in the study presented here was to improve the neurodevelopmental track of babies at risk using Infant Neural Aquatic. Parent and baby dyads who met initial criteria were recruited for a 5 – 6 months intervention period through an open invitation, followed by a conversation and signing informed consent. In the beginning and end of intervention period, participants completed questionnaires, and developmental features of the babies were assessed using analysis of neuro-motor and vocal characteristics. Significant neurodevelopmental delta between values at the end and beginning of intervention period, comparing intervention and control, is described, and the strength of INA specific intervention tool is analyzed.


Early intervention
In the old Talmud, an imbecile, deaf-mute, and a minor were included in the same category related to religious obligations (Baba Kama 55 page B). This approach was explained as probably the earliest expression of the significance and power of early intervention-for babies and for disabled people.
In recent decades, we return to this approach and look for suitable and efficient early intervention models in order to successfully cope with developmental insults.
Training with babies in an aquatic setting has been found to benefit and promote infant health and development [1][2][3], being based on the physical properties of water and their physiological outcomes on the neuromotor [4-6], cardiovascular [7,8], and respiratory functions [3]. Specifically, training with babies in an aquatic setting adapted for young babies with developmental risk may strengthen the function of autonomic parasympathetic nervous system and improve the development of neural circuits through better brain perfusion and sensory-motor training [1,2,9,10].
In warm water, increased environmental pressure advances deep lung ventilation and higher lymphatic and venous return from the periphery; higher levels of blood and lymph entering the heart's right atrium cause slight bradycardia, producing a calming effect; most important for these infants, the water buoyant force causes the proprioceptors to cease registration of gravity; and an automatic reduction of muscle tone ensues. The benefits of reduced muscle tone linger for some hours following immersion. In these beneficial conditions, training is most effective both for sensory, emotional, and neuromotor purposes, and active parent role in this process is an additional advantage.
Training with young babies at risk, in an aquatic setting, may not cure severe brain lesions such as cerebral palsy; however, implying specific training approaches in specific developmental time windows may allow early effective intervention [11][12][13][14][15] which may eventually improve brain development.
This was our basic concept when we started our journey into the project, yet our findings showed us that our training protocol may have a deep neuro-power, more than we could foresee.

Early brain development and brain lesions
Neurodevelopmental syndromes are a continuously growing issue. These are impairments in the growth and development of the brain and CNS which appear in a variety of emotional, cognitive, motor, and social skills. One most important question when diagnosing and treating young children concerns the critical developmental time window through which chances for improvement would be strongest. Considering the fragility of young babies who are at developmental risk and the general tendency to postpone definite developmental diagnosis, the consideration of intervention should include neurological background of developmental mile stones.
During fetal development, a temporary assembly progresses in the subcortical future white matter, situated between the intermediate zone and the developing cortical plate, named cortical subplate [16]. As widely described in our recent paper [17], the subplate is thickest around the time of high production of oligodendrocyte father cells (29 weeks PMA), and is absorbed gradually until around 4 months postterm, with relocation of fiber terminals into the cortex [18,19]. Most of its networks run through the (future) periventricular white matter. The size and duration of the subplate visibility correspond with cortical fiber complexity, being considered a recent phylogenetic structure that enables the increasing complexity of cortical circuitry [20].
The cortical subplate is a transmission complex for the neural projections of the developing cortical circuits and a regulating component that orchestrates neural network activity [21,22]. Hence, subplate neurons are important for precise wiring and functionality of the cerebral cortex-they make initial temporary synapses between thalamic axons and their destinations in the early C4 layer [23].
SCP neurons, with their numerous synaptic contacts, are important factors that influence cortical development and ripening [24][25][26]. In the time gap of their presence, the SCP neural circuits are prone to hypoxic insult [27], which may cause long-term influence on brain development and functional deficits in various aspects. The time window of SCP circuits' high action is also the time window when young infants born premature make their first surviving out of utero.

Neurodevelopmental impairments
Neurodevelopmental impairments range from MND (minimal brain deficit) to ASD (autism spectrum disorder) and CP (cerebral palsy) [28-34]. Despite recent technological and scientific advance, there is currently no cure for severe neurodevelopmental impairments. However, various therapies may reduce the traumatic effect of brain lesions when diagnosed and treated during specific time windows in early infancy. Hence, the first weeks of baby's life may be critical for brain development through early and effective intervention.
The babies participating in our study were born premature and participated in this research during cortical subplate activity time window. Average birth percentage of preterm babies is around 10% and it is continuously rising. Prematurity is the global second frequent cause of death among babies. Although new medical tools enable more premature babies to live, many are at high risk for brain damage [29,33,35,36] and neurodevelopmental insults [30,34].
For example, cerebral palsy in premature neonates is caused mainly by developmental brain injury at the white matter of the brain-periventricular leucomalacia (PVL), due to bleeding in the brain (IVH, ICH), oxygen or blood deprivation (hypoxia, anoxia) in the brain [29, 32, 33]. Periventricular leucomalacia may cause severe, long-term damage to brain tissue [37][38][39][40]. Common symptoms of CP include lack of muscle coordination while performing voluntary movements (ataxia), and stiff or tight muscles and exaggerated reflexes (spasticity) with associated cognitive impairments.
There is a remarkable increase in the number of children diagnosed with ASD over the past 30 years, from less than 0.1% [55,56] to $1% [57] and more. Among infants at risk, premature infants have a five times higher risk of developing ASD, and a significantly high incidence of autistic symptoms was identified in premature infants [58,59]. Changes in diagnostic criteria, different assessment tools, and increased public awareness may be only partially responsible for the increase in ASD epidemiology [60]. Studies indicate that genetic, neurological [59,[61][62][63][64][65][66], and environmental [67][68][69][70][71][72] factors are involved in the emergence of autism spectrum disorder (ASD).
Prenatal exposure to particulate matter solid fuels and traffic-related air pollutants, especially in the third trimester of prenatal development [67], link the ambient epigenetic aspects with internal genetic vulnerability due to lower, enzymatically based, removal ability of harmful remnants from infant's body. Indeed, these findings are in agreement with recent neurological understanding about the developmental time window of subcortical plate (SCP) during late prenatal and early postnatal period.
Early and effective intervention, through the important developmental time window of cortical subplate activity, may minimize neurological and functional deficits.

Basics of INA intervention approach
We have developed a unique training model for water-INA (Infant Neural Aquatics). The model consists of repetitive bilateral motor training and sustained moderate aerobic activity and their influence on desensitization and reprocessing of adverse events in utero and after birth.
After parents signed informed consent, INA was conducted in the hydrotherapy pool-babies were placed in warm water in vertical and horizontal positions, supported by the buoyancy of water and the caring hands of parent or therapist. Training started with a set of pre-structured movements through which parents practice handling of the infant in the water, in a way that enables free and integrated movement, eye contact, vocal communication, and increased confidence.   Working technique employed was modified for young and prematurely born Infants, including: passive mobilization, various rotations, relaxed floating, 8 shape delicate mobilization when the infant is supported under occiput and rib cage. Infants were video recorded during water sessions, under water and above water, once a week along 14 consecutive weeks (Figures 1-4).

Developmental track of babies
Developmental track of the babies with early intervention employing the INA approach was conducted at fixed time points using the non-intrusive General Movements (GM) tool [73][74][75]. The babies showed about 70% delta in developmental improvement comparing w/wo INA when the babies were around 55 wPMA.
Using the developmental tool ABAS (Adaptive Behavioral Assessment Scale) [76], the children showed about 40% delta in developmental improvement comparing w/wo INA, when the babies were around 1.5 years old (Graphs 1, 2).
Intervention group. 78.27% of the subjects got the same results in delta1 and delta2 (for 8.70% both delta are equal 0 and for 69.57% both delta were equal 1), 21.74% of the subjects did not get the same results in delta1 and delta2-delta1 = 1 and delta2 = 0 (no opposite cases). We calculated the kappa coefficient (system consistency) = 0.3575 (confidence limit 95% is À0.0242 till 0.7393). We conducted McNemar's Test (significance of results), P = 0.0625.
Control group. 87.50% of the subjects got the same results in delta1 and delta2 (for 66.67% both delta were equal 0 and for 20.83% both delta are equal 1), 12.50% of the subjects did not get the same results in delta1 and delta2-delta1 = 0 and delta2 = 1 (no opposite cases). We calculated kappa coefficient (system consistency) = 0.6897 (confidence limit 95% is 0.3774 till 1.000). We conducted McNemar's Test (significance of results), P = 0.2500.
In order to test if group (w/wo early intervention) and the babies' preliminary grades were dependent, we used Fisher Exact test and got non-significant result (P = 0.5806), which proves no link between group (w/wo early intervention) and babies' developmental grade. In order to test if group (intervention/control) and the babies' grades at 55 wPMA were dependent, we used Fisher Exact test and got In order to test if group's grade (intervention/control) and delta1 were dependent, we used Fisher Exact test and got significant result (P < 0.0001). In the intervention group. 8.70% got delta = 0, and in the control group. 79.17% got delta = 0. In order to test if group's grade (intervention/control) and delta2 were dependent, we used Fisher Exact test and got significant result (P = 0.0199). In the intervention group. 30.43% of delta = 0, and in the control group. 66.67% got delta = 0.

Conclusions, applicative potential, and future aims
Our results show significant improvement in developmental tracks of babies receiving INA compared to babies who did not, that is, delta in developmental tracks, between before and after early intervention, is $40% higher when babies receive INA as observed without INA.
Screening of our videos, recording INA practice with the babies, we interpret that in addition to the significant benefits of the water's physical environment (described above), INA model functions as a therapeutic tool for the babies who experienced a trauma, much like the modern variants of EMDR (Eye Movement Desensitization and Reprocessing) model [77]. The bilateral passive and active stimulation and movement during INA training cause a scheduled activation of both Graph 2. Developmental grades before, immediately after, and 1 year after early intervention period.

Graph 1.
Difference in developmental tracks between before and after early intervention period (delta), in group with INA (blue) compared to group without INA (red), at the age of 55 wPMA (delta1) and at the age of 1.5 years (delta2).
right and left cortical hemispheres, unlock the traumatic experience in the right hemisphere, promote new connections in interhemispheric neural cycles, contributing to the high delta scores in the participants who received INA compared with those who did not.
We assume that longer intervention periods would keep the high delta scores to older age, allowing the brain more training and a longer period of enhanced conditions.
In the next stage of the project, we define the correlation between concentration curves of biomarkers related to brain injury in the participants' body fluids, and neuro-developmental track. Indeed, the research described here directs the light on a certain vulnerable group of babies. However, the scientific and clinical products of this project, when properly tuned, may be successfully applied to various groups who are at developmental risk-children and youth diagnosed with post-trauma, or under extreme/ acute emotional load, etc.