A) At engine level

A recent systematic review conducted by Fuentefria, Silveira and Procianoy in 2017, in which articles related to gross motor development in preterm infants were analyzed using the AIMS (Alberta Infant Motor Scale) scale, reveals how there is a statistically significant lower gross motor performance in the 6 to 18 month corrected age period in relation to developmental outcomes obtained in term born infants⁷. These differences are not only evident in the development of gross motor skills, but also affect the development of fine motor skills and motor functionality, with environmental factors being a conditioner of the evolution and motor development of premature infants in the first two years of corrected age^8,9. In later ages, a meta-analysis carried out in 2009 stands out, in which articles were analysed on follow-up studies evaluating, among others, the motor development of children born prematurely up to the age of 15. After the analysis, the authors concluded that there was a motor delay maintained throughout all the years in comparison with a group of term born, motor deficits that were observed in balance skills, ball skills, manual dexterity and gross and fine motor development¹⁰.

Up to 15 percent of children born less than 30 weeks gestation develop cerebral palsy, and 50 percent have a developmental progression to motor impairment ranging from mild to severe at school age¹¹. The data reflected in a Serbian study carried out in 2016 stands out, where it is shown that more than half (54.4 percent) of the children with cerebral palsy were born prematurely¹².

Cerebral palsy, in addition to having an inseparable motor pathology, can be associated with other difficulties such as sensory alterations, communication and behavioral disorders, and perceptual deficits, such as problems in the proprioceptive establishment of the body schema and spatial orientation, among others¹³. The sum of all or part of it turns out to be a compendium that will lead the child with cerebral palsy to possess or to be at greater risk of developing learning problems.

B) At the sensory-cognitive level:

Through a cohort study, which followed premature children who developed retinopathy up to 5 years of age, it was observed how there is a three to four times greater risk of developing motor, cognitive and auditory impairment compared to premature children who did not develop retinopathy¹⁴.

Likewise, in the first three years of a child's life, any degree of hearing impairment will lead to difficulties in linguistic development, affecting personality, behaviour, school performance and social relations¹⁵.

The sensory disorders that prematurely born children may develop go beyond visual and auditory deficits, as sensory processing also includes tactile, tactile-oral, vestibular and proprioceptive sensations. Gestational age, male gender, white matter lesions and low parental education have been identified as risk factors for developing sensory disorders¹⁶.

In 2014, Chorna and collaborators conducted a prospective cohort study where children born prematurely up to the first 12 months of corrected age were followed, observing that there was a high prevalence of sensory disorders (82 percent of 72 participants), related to abnormal sensory reactivity. They showed that lower gestational age was related to abnormal reactivity to deep pressure and vestibular stimulation, and that an abnormal adaptive motor response to tactile stimuli is related to worse motor and language development scores¹⁶.

Wickremasinghe and colleagues, in 2013, observed how there was a high prevalence of sensory disorders in children born very prematurely, after follow-up until the age of 4 years, observing that the areas most affected were auditory, tactile and vestibular processing. In addition, these authors showed that the most affected quadrant was low registration¹⁷, results coinciding with those obtained in a more recent study, where follow-up was carried out up to two years of age corrected for extreme prematurity (<25 weeks of gestation), also obtaining atypical results in sensory processing, the most common behavior being low registration¹⁸.

Deterioration in the ability to receive and integrate sensory information and to adapt seems to interfere with motor, cognitive and language development, as well as behaviour¹⁶.

Entering the cognitive area, low birth weight has been described as a predisposing factor for developing a low IQ¹⁹.

This difficulty in achieving good academic performance translates into possible learning problems, as reflected through an international meta-analysis, which included the monitoring of a total of 64,000 children who were born prematurely. It was observed how they had lower scores in reading, mathematics and spelling in primary education, keeping the scores low in reading and spelling in secondary education²⁰.

In terms of executive function, significant deficits in verbal fluency, inhibition of response, planning and verbal and spatial work memory were found in a group of 200 children born prematurely at the age of 4 to 12 years, compared with a control group of children born at the same age at the same time²¹.

However, the greatest neurocognitive compromise related to prematurity is considered to be attentional difficulties. Referring again to the meta-analysis carried out in 2017 by Allotey and collaborators, the studies show a higher percentage of behavioral problems in children born prematurely at school age compared to those born at term. It is also estimated that premature babies born less than 32 weeks gestation are three times more likely to be diagnosed with TDAH²⁰.

Language is another major cognitive skill, where prematurity can also become a handicap in neurolinguistic development.

As evidenced by a study carried out in Sweden in 2013, after following 456 children born extremely prematurely (<27 weeks of gestation), at 2 and a half years of life, 9.4% had a moderate language disability, compared to 2.5% for those born at term; 6.6% of the population studied had a severe language disability, the latter being non-existent in the group of those born at term. Significant differences were also found between boys and girls born extremely prematurely, with boys registering lower language scores than girls²². At school, at the age of 6 to 10, Ríos-Flórez and collaborators compared the language skills of 80 children born prematurely with 80 born at term, concluding that language is compromised in the premature group, with the lowest gestational age being related to lower performance in verbal designation, comprehension of spoken speech and semantic verbal fluency²³.

C) Socio-emotional and behavioral alterations:

Already at the early age of 4 and 6 months of corrected age, in those born prematurely, aversion and withdrawal of gaze have been observed in social interactions, remaining attentive in a shorter time than children born at term²⁴. Likewise, at 2 years of corrected age, greater behavior problems are described in boys and girls with less than 30 weeks of gestation at birth, particularly in internalizing and deregulating behaviors, in comparison with those born at term, being these alterations more significant in the female sex, in low birth weight, in alterations of the white substance and treatment with corticoids²⁵.

In older ages, it is worth noting the results found through a British study which assessed behavioural difficulties in premature births at the age of 9 and 10 years. In the same study, in addition to finding a greater proportion of children born prematurely with problems of inattention and hyperactive and compulsive behaviors, was observed in school age, greater problems with parents and among peers, emotional problems and greater antisocial behaviors, compared with children born at term²⁶.

In addition to hyperactivity, a greater risk has been described for other externalizing problems such as passivity and instability; and internalizing problems such as anxiety, depression, somatic complaints, fears and phobias²⁷. Specifically, in a meta-analysis conducted by Bhutta, Cleves, Casey, Cradok and Anand on behavioural problems, it was found that boys and girls with a history of prematurity have a higher risk of presenting them compared to those born at term, and it was also found that, 81 percent of the studies reviewed that included premature infants between the ages of 5 and 14 showed a higher prevalence of so-called internalized disorders such as anxiety, depression and deprivation symptoms, and 69 percent of the studies refer to the presence of sociabilization disorders²⁷. Along the same lines, a large cohort study conducted in the United Kingdom and Ireland, under the name EPICURE, concluded that at 11 years of age, children who were born extremely preterm (<26 weeks of gestation), had a higher risk of developing TDAH, emotional disturbance and TEA²⁸.

Although there are many studies that relate prematurity to an increased risk of developing TEA, Hernandez and colleagues consider this relationship complex, since prematurity and associated problems can lead to false positives in current screening for interferences with the signs of TEA, so they advise monitoring and prospective screening with detection tools adapted and validated to the characteristics of the premature population²⁹. This fact was already mentioned in 2011 by Johnson and Marlow, where they described a "phenotype of premature behavior" that includes symptoms and disorders that can interfere and lead to a greater allocation of psychiatric problems in premature children³⁰.