Correlation Between Cerebral Oxygenation and Neurodevelopment in VLBW Preterm Infants.
Condition: Psychomotor Impairment
MeSH terms: Psychomotor Disorders
Study type: Observational

Summary: 
      The recent improvements in neonatal intensive care have led to a substantial increase in the
      survival rate of preterm infants; nevertheless, this population is still at high risk for
      long-term neurodevelopmental disabilities. Significant anatomical changes in brain structures
      and abnormal patterns of neuronal myelination and brain connectivity have been associated
      with preterm birth, with possible long-term effects on cognitive, motor and social skills.

      The validation of clinical tools able to predict neurodevelopmental outcomes in the preterm
      population might help at identifying infants at greatest risk of impairment, who would
      benefit most from early supportive interventions exploiting brain neuroplasticity.

      Near infrared reflected spectroscopy (NIRS) provides a bedside, non-invasive, continuous
      monitoring of cerebral oxygen saturation (CrSO2), which has been proposed as a predictive
      marker for later neurodevelopment in neonates undergone cardiac surgery; to date, however,
      evidence on the correlation between CrSO2 and later neurodevelopment in preterm infants is
      almost lacking.

      This study aims to evaluate whether CrSO2 monitoring, performed before NICU discharge in
      clinically stable very low birth weight (VLBW) preterm infants, can predict psychomotor
      outcomes during the first 24 months of corrected age (ca).
    

Detailed description: 
      The improvements in neonatal intensive care occurred over the last decades have led to a
      substantial increase in the survival rate of preterm infants, especially of extremely low
      birth weight. Nevertheless, the delicate maturation of central nervous system (CNS) in the
      extrauterine environment, together with the possible development of prematurity-related
      clinical complications that could result in brain injury, place this population at high risk
      for long-term neurodevelopmental disabilities.

      Significant anatomical changes in brain structures have been associated with preterm birth;
      among these, enlarged ventricles and subarachnoid spaces, reduced subcortical white matter
      and decreased cortical and deep nuclear grey matter are the most common. Additionally, there
      is increasing evidence of abnormal patterns of neuronal myelination and brain connectivity in
      preterm infants, with possible concerning long-term effects on language, motor and social
      skills. As for cognitive abilities, a direct correlation with gestational age (GA) has been
      previously shown in a large cohort of preterm born children at school age.

      In its early phases, the developmental of CNS is characterized by an intrinsic
      neuroplasticity, according which repeated experiences could influence the arrangement of
      synaptic connections and neural circuitries, thus resulting in structural and functional
      changes. By exploiting this feature, an early establishment of supportive interventions¬
      might aid to compensate the anatomical and functional constraints connected to preterm birth
      and to improve preterm infants' neurodevelopment.

      The validation of clinical tools able to predict neurodevelopmental outcomes in the preterm
      population might help at identifying infants at greatest risk of impairment, who would
      benefit most from early rehabilitative interventions. Near infrared reflected spectroscopy
      (NIRS) provides a bedside, non-invasive, continuous monitoring of cerebral oxygen saturation
      (CrSO2) and has been largely adopted to assess neonatal brain oxygenation and perfusion in
      intensive care settings. Perioperative CrSO2 has been recently proposed as a possible
      predictor of later neurodevelopmental outcomes in neonates undergone cardiac surgery; data
      evaluating the correlation between CrSO2 and later neurodevelopment in preterm infants,
      however, are very scarce and limited to the first days of life; at this time, CrSO2 can be
      widely influenced by the occurrence of systemic haemodynamic instability and is blind to
      several clinical complications, known as potential causes of brain damage, that can occur
      later on during hospital stay and thus are not necessarily directly related to changes in
      cerebral oxygenation within the first days of life (e.g. necrotizing enterocolitis [NEC],
      late onset sepsis).

      Hence, the aim of this study was to evaluate whether CrSO2 monitoring, performed before NICU
      discharge in clinically stable very low birth weight (VLBW) preterm infants, can predict
      psychomotor outcomes during the first 24 months of corrected age (ca).

      Infants meeting eligibility criteria (for details see specific section) undergo a 3-hour
      continuous monitoring of CrSO2 by means of the INVOS 5100 oximeter when satisfying the
      following condition: stable clinical condition, no need for oxygen supplementation, full
      enteral feeding (defined as 160 ml/kg/day) After discharge, the enrolled infants are included
      in a long-term neurodevelopmental follow-up, which is part of the normal routine care for
      preterm-born infants and aims at the early identification and treatment of neurocognitive
      sequelae possibly related to preterm birth.

      In this context, psychomotor outcome (PSO) is assessed at 6, 12, 18 and 24 months ca by means
      of the Griffiths Mental Development Scales 0-2 years [26]. These scales investigate five main
      areas (locomotor, personal and social skills, hearing and language, eye and hand
      coordination, performance), providing a general developmental quotient (DQ) of infant's
      abilities and five sub-scale quotients (SQ) for each of the developmental areas.

      The Griffiths Scales are administered individually, over a 45-min period, by the same
      professional trained psychologist for the whole study period and are implemented in the
      presence of the infant's parent.

      A correlation analysis between mean CrSO2 values and GQ/SQ scores at each follow-up
      appointment will be performed. In order to evaluate the effect of possible confounding
      variables on the observed results, a mixed model including a number of risk factors known to
      affect preterm infants' neurodevelopment will be built for hierarchical multiple regression
      analysis. Significance level will be set at p<0.05.
    

Intervention name(s): Griffiths Mental Development Scales
Intervention type(s): Diagnostic Test
Intervention description(s): Griffiths Mental Development Scales investigate 5 main areas (locomotor, personal and social skills, hearing and language, eye and hand coordination, performance), providing a general developmental quotient (DQ) of infant's abilities and five sub-scale quotients (SQ) for each developmental area.
The assessments are performed individually in a quiet room, over a 45-min period, by the same professional trained psychologist for the whole study period and are implemented in the presence of the infant's parent. The obtained results are adjusted for corrected age, in order to consider the neurobiological maturation of the enrolled infants.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Preterm infants admitted to the Neonatal Intensive Care Unit (NICU) of St. Orsola-Malpighi
        Hospital, Bologna (Italy) fulfilling the eligibility criteria.
      
Keywords: NIRS; Griffiths Mental Development Scales; prematurity