Clinical neuropsychology in prematurity and neurodevelopment

In this post, the psychologist and international expert on Alzheimer’s and other dementias, Cristian Francisco Liébanas Vega, talks about prematurity and neuropsychological rehabilitation in premature babies.

Prematurity is a serious problem for both the newborn (NB) and their family, as it is associated with high morbidity at birth and a high risk of future disabilities. The number of children born prematurely and their survival has significantly increased in recent decades due to advances in obstetric and neonatal care. Reducing mortality without increasing morbidity and sequelae is one of the most important challenges of Perinatal Medicine (Rodrigo et al., 2014).

Premature birth or preterm birth is when delivery occurs before 37 weeks of gestation.

Prematurity can be classified into different groups based on the gestational age at which the birth occurs or by the baby’s weight since these parameters are usually related in these children. The lower the gestational age and birth weight, the higher the likelihood of complications arising from prematurity, the higher the risk of death and developmental sequelae.

There are some variables for classifying prematurity, such as gestational age or birth weight achieved. Based on gestational age, premature babies are classified as follows:

• Late preterm: born between weeks 34+0 and 36+6.

• Moderate preterm: born between weeks 32+0 and 33+6.

• Very preterm: born between weeks 28+0 and 31+6.

• Extreme preterm: born before 28 weeks.

Based on birth weight, premature babies are classified as follows:

• Low birth weight: less than 2500 grams.

• Very low birth weight: between 1000 and 1500 grams.

• Extremely low birth weight: between 800 and 1000 grams.

• Very extremely low birth weight: less than 800 grams.

It is also important to highlight the concept of weight in relation to gestational age. A newborn with low birth weight for gestational age is one who has a birth weight <10th percentile for gestational age and sex. Thus, a newborn can be born preterm (<37 weeks), full-term (37 to 41 weeks 6 days), or post-term (>42 weeks) and be underweight (<10th percentile), appropriate weight (10th-90th percentile), or overweight (>90th percentile) for their gestational age.

Newborns with a birth weight of 1500 grams or less, a gestational age of 32 weeks or less, and low birth weight for gestational age are considered at risk for neuro-psychosensory issues and will require neurodevelopmental follow-up at least until 6 years of age in the early intervention setting and also subsequent monitoring of executive functions, school learning rhythm, motor coordination, adaptive skills, and behavior, at least in late childhood and adolescence.

Epidemiology and etiopathogenesis

According to sources from the World Health Organization (WHO) (Liu et al., 2016), around 15 million premature babies are born worldwide each year, with a prematurity rate ranging from 5% to 18%. In Spain and neighboring countries, the prematurity rate is around 7% to 9% of all births. Approximately 10% of this group corresponds to very premature babies born before 32 weeks and weighing less than 1500 grams, who have the highest incidence of mortality, morbidity, and sequelae throughout their development (Ponte et al., 2022). The group of late preterm babies (34 weeks to 36+6) is the largest (70-74% of all very preterm babies) and although a high percentage will not require hospitalization, they still face a higher risk of complications and sequelae during their development compared to full-term babies (Liu et al., 2016).

The etiopathogenesis of premature delivery involves a large number of factors (Rellán et al., 2008):

• Maternal-dependent factors: reproductive factors, diseases, toxic habits, gynecological factors, stress, having been preterm…,

• Fetal factors (congenital abnormalities, intrauterine growth restriction, infections, fetal distress…),

• Multiple pregnancy,

• Complications specific to gestation: preeclampsia, premature rupture of membranes…

However, in 70% of cases, preterm delivery occurs spontaneously, making primary prevention difficult. This is a consequence of a premature onset of labor (45%) or premature rupture of membranes (25%). The remaining 30% corresponds to cases where delivery is medically indicated due to maternal or fetal problems (Rellán et al., 2008). It is important to mention the generalized increase in prematurity rates over the last 10-20 years.

This increase can be attributed, in our setting, to a multitude of factors occurring simultaneously. These factors include advances in perinatal care, improvements in evaluation methods, an increase in the age of pregnant women, and therefore, the prevalence of diseases such as diabetes mellitus or hypertension. There is also a greater demand for and use of assisted reproduction techniques (not only does multiple gestation increase the risk, but also the risk is higher even with a singleton pregnancy). The increasing number of late preterm births has influenced this rise in the prematurity rate, while the percentage of births at a gestational age of 32 weeks or less has remained unchanged (Rellán et al., 2008).

In summary, the population of preterm neonates (PTNB) is very heterogeneous regarding its etiology, clinical presentation, complications, and prognosis, requiring a multidisciplinary approach to care.

Brain injury in PTNB

Following Dr. Miranda (2006), premature birth itself, along with all the stimuli the brain is exposed to in the extrauterine environment, affects the normal cerebral development of very preterm newborns to a greater or lesser extent. This impact depends on intrauterine brain development, the age and cause of prematurity, perinatal pathologies (hypoxia, hypotension, hypo/hypercapnia, infections), the intensive treatment the child requires in the first weeks of life, and the type, location, and extent of possible brain injuries. At 40 weeks, the brain of an extremely preterm baby has less complexity in its sulci and gyri, lower volume, and less white matter maturation than that of a full-term newborn (Miranda, 2006).

Neurological/neuropsychological complications are common in very preterm newborns, often involving multiple factors that occur simultaneously or successively to cause more than one type of injury (Cerisola et al., 2019).

In very preterm newborns, the most common central nervous system pathology usually consists of: intracranial hemorrhages (ICH), white matter lesions (WML), and cerebellar lesions.

Intracranial hemorrhage (ICH)

Various types of ICH occur in very preterm newborns, including germinal matrix hemorrhage (GMH), intraventricular hemorrhage (IVH), and parenchymal hemorrhages, with the latter being less common. Both GMH and IVH can be grouped under the term periventricular-intraventricular hemorrhage (P-IVH) and are the main complications leading to brain injury in very preterm newborns.

The most common origin of hemorrhages in the brain of very preterm newborns is the germinal matrix (GM), a highly vascularized structure located in the periventricular subependymal region. When GMH occurs, it can rupture the underlying ependyma and enter the ventricles, leading to IVH (Ballabh, 2014).

P-IVH is classified into different grades defined by the presence or absence of hemorrhage in the ventricles, the percentage of intraventricular hemorrhage, and the presence or absence of periventricular hemorrhagic infarction.

• Grade I: hemorrhage is localized in the subependymal GM,

• Grade II: there is intraventricular blood occupying less than 50% of the ventricle area and no ventricular dilation,

• Grade III: there is intraventricular blood occupying more than 50% of the ventricle area with ventricular dilation,

• Grade IV: intraventricular and intraparenchymal hemorrhage, corresponding to periventricular venous hemorrhagic infarction.

This level of hemorrhage will result in a loss of their cellular progenitors, and due to the pressure from the hemorrhage and oxidative stress resulting from it, the surrounding white matter injury will worsen, contributing to periventricular leukomalacia (PVL) (Cerisola et al., 2019).

GMH occurs in very preterm newborns due to multiple factors. According to studies conducted by Ballabh (2014) on its pathogenesis, “it will be the fragility of blood vessels that prepares the ground and hemodynamic fluctuations, combined with a lack or immaturity of autoregulatory mechanisms, that trigger the hemorrhage.” Hemodynamic fluctuations constitute important risk factors, such as vaginal delivery, low Apgar score, severe respiratory distress, pneumothorax, hypoxia, hypercapnia, seizures, persistent ductus arteriosus, infections… Platelet and coagulation abnormalities act as aggravating factors in this situation (Ballabh, 2014).

Neuropsychological rehabilitation in premature babies

Babies born before 37 weeks are considered premature. They are at risk of developmental problems, both cognitive and motor. Cognitive development refers to thinking and learning abilities. On the other hand, motor development refers to the ability to move, crawl, or walk.

Therefore, premature babies are more likely to develop some neuropsychological disorders. These disorders can vary in severity. Among them, learning difficulties, ADHD, auditory, visual or language impairments, dyslexia, ASD, or cerebral palsy are noteworthy.

Pediatric neuropsychological rehabilitation is aimed at children with neurological disorders that affect their functional capacity. The goal is to maximize their autonomy and help them develop their abilities.

Thus, pediatric neuropsychological rehabilitation begins in the early months of life and often has a preventive nature.

The question now arises: Is there scientific evidence of the benefits of this early intervention?

Is early intervention beneficial?

According to a study by Alicia Spittle, Jane Orton, and others, early intervention programs for premature babies have a positive influence on cognitive and motor development during childhood. Furthermore, the cognitive benefits persist into the preschool age.

However, there was no evidence found of a long-term positive effect in adulthood regarding these cognitive or motor benefits.

Therefore, the aim of this rehabilitation is to enhance cognitive development, reducing the likelihood of cognitive and motor problems in the short and medium term.

References

• Abbott, A. (2015). Neuroscience: The brain, interrupted. Nature, 518(7537), 24-26.https://dor.org/10.1038/518024ª
• Abiramalatha, T., Bandyopadhyay, T., Ramaswamy, V. V., Shaik, N. B., Thanigainathan, S., Pullattayil, A. K., & Amboiram, P. (2021). Risk Factors for Periventricular Leukomalacia in Preterm Infants: A Systematic Review, Meta-analysis, and GRADE-Based Assessment of Certainty of Evidence. Pediatric Neurology, 124, 51-71. https://doi.org/10.1016/j.pediatrneurol.2021.08.003
• Ancel, P.-Y., Goffinet, F., EPIPAGE-2 Writing Group, Kuhn, P., Langer, B., Matis, J.. Hernandorena, X., Chabanier, P., Joly-Pedespan, L., Lecomte, B., Vendittelli, F., Dreyfus, M., Guillois, B., Burguet, A., Sagot, P., Sizun, J., Beuchée, A., Rouget, F., Favreau, A., … Kaminski, M. (2015).
• Survival and morbidity of preterm children born at 22 through 34 weeks’ gestation in France in 2011: Results of the EPIPAGE- Conor study. JAMA1693), https://doi.org/10.1001/jamapediatrics.2014.3351
• Anderson, V., Northam, E., & Wrennall, J. (2018). Developmental Neuropsychology: A Clinical Approach. Psychology Press.
• Ballabh, P. (2014). Pathogenesis and prevention of intraventricular hemorrhage. Clinics in Perinatology, 41(1), 47-67. https://doi.org/10.1016/j.clp.2013.09.007
• Baron, I. S. (2018). Neuropsvchological Evaluation of the Child: Domains, Methods, and Case Studies. Oxford University Press.
• Bax, M., Goldstein, M., Rosenbaum, P., Leviton, A., Paneth, N., Dan, B., Jacobsson, B. Damiano, D., & Executive Committee for the Definition of Cerebral Palsy. (2005). Proposed definition and classification of cerebral palsy, April 2005. Developmental Medicine Child Neurology, 478),571-576. https://doi.org/10.1017/s001216220500112x
• Beaino, G., Khoshnood, B., Kaminski, M., Marret, S., Pierrat, V., Vieux, R., mThiriez, G., Matis, J., Picaud, J.-C., Rozé, J.-C., Alberge, C., Larroque, B., Bréart, G., Ancel, P.- Y., & EPIPAGE Study Group. (2011). Predictors of the risk of cognitive deficiency in very preterm infants: The EPIPAGE prospective cohort. Acta Paediatrica (Oslo, Norway: 1992), 100(3), 370-378. https://doi.org/10.1111/j.1651-2227.2010.02064.x
• Beauchamp, M. H., Peterson, R. L., Ris, M. D., ‘Taylor, H. G., & Yeates, K. O. (2022). Pediatric Neuropsychology: Research, Theory, and Practice. Guilford Publications.
• Burstein, O., Zevin, Z., & Geva, R. (2021). Preterm Birth and the Development of Visual Attention During the First 2 Years of Life: A Systematic Review and Meta-analysis. JAMA Network Open 43), e213687.https://doi.org/10.1001/jamanetworkopen.2021.3687
• Cantallops, A. E., & Rovira, T. R. (2015). Neuropsicologia pediátrica. Editorial Sintesis.
• Castro-Caldas, A., Petersson, K. M., Reis, A., Stone-Elander, S., & Ingvar, M. (1998). The illiterate brain. Learning to read and write during childhood influences the functional organization of the adult brain. Brain: A Journal of Neurology, 121 (Pt 6), 1053-1063. https://doi.org/10.1093/brain/121.6.1053
• Cerisola, A., Baltar, F., Ferrán, C., & Turcatti, E. (2019). Mecanismos de lesión cerebral en niños prematuros. Medicina (Buenos Aires), 79, 10-14. Chakraborty, R., Vijay Kumar, M. J., & Clement, J. P. (2021). Critical aspects of neurodevelopment. Neurobiology of Learning and Memory, 180, 107415. https://doi.org/10.1016/j.nlm.2021.107415
• Dennis, M. (1988). Language and the young damaged brain. En Clinical neuropsychology and brain function: Research, measurement, and practice (pp. 89-123). American Psychological Association. https://doi.org/10.1037/10063-003
• Díez-Cirarda, M., Yus, M., Gómez-Ruiz, N., Polidura, C., Gil-Martínez, L., Delgado-Alonso, C., Jorquera, M., Gómez-Pinedo, U., Matias-Guiu, J., Arrazola, J., & Matias-Guiu, J. A. (2022). Multimodal neuroimaging in post- COVID syndrome and Correlation with cognition. Brain, awac384. https://doi.org/10.1093/brain/awac384
• Federación Estatal de Asociaciones de Profesionales de Atención Temprana. (2005). Libro Blanco de la Atención Temprana. Real Patronato sobre Discapacidad.
• Fuentefria, R. do N., Silveira, R. C., & Procianoy, R. S. (2017). Motor development of preterm infants assessed by the Alberta Infant Motor Scale: Systematic review article. Jornal De Pediatría, 934),328-342. https://doi.org/10.1016/j.jped.2017.03.003
• García, P., San Feliciano, L., Benito, F., García, R., Guzmán, J., Salas, S., Fernandez, C., del Prado, N., Ciprián, D., & Figueras, J. (2013). Evolución a los 2 años de edad corregida de una cohorte de recién nacidos con peso inferior o igual a 1.500 g de los hospitales pertenecientes a la red neonatal SEN1500. Anales de Pediatria, 795), 279-287. https://doi.org/10.1016/j.anpedi.2013.03.017
• García Reymundo, M., Hurtado Suazo, J. A., Calvo Aguilar, M. J., Soriano Faura, F. J., Ginovart Galiana, G., Martin Peinador, Y., Jiménez Moya, A., & Demestre Guasch, X. (2019). Recomendaciones de seguimiento del prematuro tardio. Anales de Pediatria, 905), 318.el-318.8. https://doi.org/10.1016/j.anpedi.2019.01.008
• Garrido, A., Alfonso, M., Gómez, M., Niño, G., Patiño, M., & Luque, Y. (2014). Edad motora versus dad corregida en infantes prematuros y con bajo peso al nacer. Revista de Facultad de Medicina, 62, 205-211. https://doi.org/10.15446/revfacmed.v62n2.45376
• GAT. (s. f.). Libro Blanco de la Atención Temprana. Recuperado 6 de noviembre de2022, De https://www.observatonodelainfancia.es/ora/esp/documentos_ficha.aspx?id=807
• GERRARD-MORRIS, A., TAYLOR, H. G., YEATES, K. O., WALZ, N. C., STANCIN, T., MINICH, N., & WADE, S. L. (2010). Cognitive development after traumatic brain injury in young children. Journal of the International Neuropsvchological Society:JINS, 161), 157-168. https://doi.org/10.1017/S1355617709991135
• Gerrard-Morris, A., Taylor, H. G., Yeates, K. O., Walz, N. C., Stancin, T., Minich, N., & Wade, S. L. (2010). Cognitive development after traumatic brain injurv in voung children. Journal of the International Neuropsychological Society: JINS, 16(1), 157-168. https://doi.org/10.1017/S1355617709991135
• Gotardo, J. W., Volkmer, N. de F. V., Stangler, G. P., Dornelles, A. D., Bohrer, B. B. de A., & Carvalho, C. G. (2019). Impact of peri-intraventricular haemorrhage and periventricular leukomalacia in the neurodevelopment of preterms: A svstematic review and meta-analvsis. PloS One, 1410), e0223427. https://doi.org/10.1371/journal.pone.0223427

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