Need for developing case definitions and guidelines for data collection, analysis, and presentation for neurodevelopmental delay as an adverse event following immunization:
Neurodevelopmental delay (NDD) is a term used to describe delays in skill development of infants and young children. Terminology and definitions of NDD vary broadly in the literature, though all are used to signify a delay in one or more developmental domains compared to typical development. This paper focuses on defining NDD to assist in the identification of developmental delays as potential adverse events following maternal immunization.
1.1.1. Neurodevelopment
Early child neurodevelopment refers to the organization and function of the central nervous system (CNS). The development of the CNS starts early in embryonic life and continues for years after birth. Processes, such as dendritic pruning, myelination, and the growth of an extensive and complex system of connections accelerate during early childhood and persist into adulthood [1]. The early rapid and complex development of the brain underlies the functional or observable performance and abilities in the child.
The pattern and timing of neurodevelopmental skill attainment is similar for most children [1]. For example, during the first three years of life, early development is marked by enormous gains in gross motor abilities (e.g., rolling, standing, walking), fine-motor coordination (e.g., self-feeding, pincer grasp, drawing lines and circles), language abilities (e.g. orienting to familiar voices, babbling, following a simple command, first words, expanding vocabulary), and markedly improved ability to solve increasingly complex problems. The development of each skill influences the development of others. For example, gross motor skill development allows children greater opportunities for exploration and social interaction which promotes language growth [2], [3], [4]. Likewise, increased language capacity promotes the development of cognitive control [5], [6].
Both biological and environmental factors can influence neurodevelopmental trajectories in positive and negative ways throughout the lifespan, beginning as early as the embryonic period, with observable differences in development and functioning notable as early as the antenatal period [7]. For example, genetic disorders, chromosomal abnormalities, infections, perinatal brain injuries, and alterations in neuronal migration may impact brain development and result in NDD. Poverty, insufficient cognitive stimulation, and malnutrition are significant environmental risk factors for atypical neurodevelopment [8]. Ultimately, biological and environmental factors interact. For instance, environmental risk factors can exacerbate existing biological vulnerabilities, or environmental factors can improve neurodevelopmental outcomes despite biological vulnerabilities. Environmental factors such as good nutrition, environmental stimulation, and maternal factors, including maternal education level and responsiveness, are particularly protective and support a positive developmental trajectory [9].
There are specific time periods in which the brain is more sensitive or vulnerable to biological and environmental influences which can affect the long-term trajectory of the developing brain [10], [11]. This is particularly the case during gestation and early life [12], [13]. For example, alterations in neuronal migration in utero have been associated with movement problems, developmental dyslexia, and other developmental delays [14], [15]. Zika virus is a recent example of devastating developmental sequelae to brain development from in utero infection resulting in microcephaly and potentially more subtle effects if the virus is contracted later in life [16]. Similarly, many studies have found an association between responsive caregiving in sensitive periods of early childhood with improved self-regulatory skills later in life [17], [18].
