Developmental milestones in early childhood and genetic liability to neurodevelopmental disorders

Background Timing of developmental milestones, such as age at first walking, is associated with later diagnoses of neurodevelopmental disorders. However, its relationship to genetic risk for neurodevelopmental disorders in the general population is unknown. Here, we investigate associations between attainment of early-life language and motor development milestones and genetic liability to autism, attention deficit hyperactivity disorder (ADHD), and schizophrenia. Methods We use data from a genotyped sub-set (N = 25699) of children in the Norwegian Mother, Father and Child Cohort Study (MoBa). We calculate polygenic scores (PGS) for autism, ADHD, and schizophrenia and predict maternal reports of children's age at first walking, first words, and first sentences, motor delays (18 months), and language delays and a generalised measure of concerns about development (3 years). We use linear and probit regression models in a multi-group framework to test for sex differences. Results We found that ADHD PGS were associated with earlier walking age (β = −0.033, padj < 0.001) in both males and females. Additionally, autism PGS were associated with later walking (β = 0.039, padj = 0.006) in females only. No robust associations were observed for schizophrenia PGS or between any neurodevelopmental PGS and measures of language developmental milestone attainment. Conclusions Genetic liabilities for neurodevelopmental disorders show some specific associations with the age at which children first walk unsupported. Associations are small but robust and, in the case of autism PGS, differentiated by sex. These findings suggest that early-life motor developmental milestone attainment is associated with genetic liability to ADHD and autism in the general population.

Identity (Re)Construction of Female Adolescents with Substance Use Disorders

Identity formation is a developmental milestone for adolescents, and their identities are constructed and re-constructed through their interactions with others and contextual factors in their environment. When considering adolescents with substance use disorders (SUD), often this developmental milestone is misappropriated, misunderstood, and misrepresented. The purpose of this article was to explore how adolescents with substance use disorders form identity and construct a sense of self. Firstly, we explored the identity formation and reconstruction of 20 female adolescents with SUDs based on an in-depth grounded theory methodology (GTM) which included a situational analysis (SA). Secondly, we offered a theoretical model to explain identity construction and reconstruction of adolescents with SUDs that emerged from this research. We conclude this article with practical implications for treatment, and care of adolescents with SUDs.

Is the Age of Developmental Milestones a Predictor for Future Development in Down Syndrome?

Down Syndrome (DS) is the most common genetic alteration responsible for intellectual disability, which refers to deficits in both intellectual and adaptive functioning. According to this, individuals with Down Syndrome (DS) reach developmental milestones (e.g., sitting, walking, and babbling) in the same order as their typically developing peers, but later in life. Since developmental milestones are the first blocks on which development builds, the aims of the current study are to: (i) expand the knowledge of developmental milestone acquisition; and (ii) explore the relationship between developmental milestone acquisition and later development. For this purpose 105 children/adolescents with DS were involved in this study, divided in two groups, Preschoolers (n = 39) and School-age participants (n = 66). Information on the age of acquisition of Sitting, Walking, Babbling, and Sphincter Control was collected, together with cognitive, motor, and adaptive functioning. Sitting predicted later motor development, but, with age, it became less important in predicting motor development in everyday life. Babbling predicted later language development in older children. Finally, Sphincter Control emerged as the strongest predictor of motor, cognitive, language, and adaptive skills, with its role being more evident with increasing age. Our data suggest that the age of reaching the milestones considered in the study has an influence on successive development, a role that can be due to common neural substrates, the environment, and the developmental cascade effect.

Children’s accuracy in answering Why and How Come questions

Children’s developing understanding of language may influence their ability to accurately respond to questions inquiring about their event knowledge (i.e., Why and How Come questions), potentially creating misinterpretations in adult–child communication. The present study examined 120 5-, 7-, and 9-year-old’s accuracy in responding to Why and How Come questions about the cause of their behaviors. Children’s accuracy improved with age, highlighting a developmental milestone whereby children become highly accurate by 7 years of age. Further, the semantic differences in question type did not influence children’s responses, as there were no differences in children’s accuracy when answering Why or How Come questions. The findings from this study highlight the developmental shift in children’s abilities to answer Why and How Come questions, and thus the importance of considering the age and linguistic abilities of the child when inquiring about their event knowledge.

In utero exposure to protease inhibitor-based antiretroviral regimens delays growth and developmental milestones in mice

Antiretroviral therapy (ART) in pregnancy has dramatically reduced HIV vertical transmission rates. Consequently, there is a growing number of children that are HIV exposed uninfected (CHEUs). Studies suggest that CHEUs exposed in utero to ART may experience developmental delays compared to their peers. We investigated the effects of in utero ART exposure on perinatal neurodevelopment in mice, through assessment of developmental milestones. Developmental milestone tests (parallel to reflex testing in human infants) are reflective of brain maturity and useful in predicting later behavioral outcomes. We hypothesized that ART in pregnancy alters the in utero environment and thereby alters developmental milestone outcomes in pups. Throughout pregnancy, dams were treated with boosted-atazanavir combined with either abacavir/lamivudine (ATV/r/ABC/3TC), or tenofovir/emtricitabine (ATV/r/TDF/FTC), or water as control. Pups were assessed daily for general somatic growth and on a battery of tests for primitive reflexes including surface-righting, negative-geotaxis, cliff-aversion, rooting, ear-twitch, auditory-reflex, forelimb-grasp, air-righting, behaviors in the neonatal open field, and olfactory test. In utero exposure to either ART regimen delayed somatic growth in offspring and evoked significant delays in the development of negative geotaxis, cliff-aversion, and ear-twitch reflexes. Exposure to ATV/r/ABC/3TC was also associated with olfactory deficits in male and forelimb grasp deficits in female pups. To explore whether delays persisted into adulthood we assessed performance in the open field test. We observed no significant differences between treatment arm for males. In females, ATV/r/TDF/FTC exposure was associated with lower total distance travelled and less ambulatory time in the centre, while ATV/r/ABC/3TC exposure was associated with higher resting times compared to controls. In utero PI-based ART exposure delays the appearance of primitive reflexes that involve vestibular and sensory-motor pathways in a mouse model. Our findings suggest that ART could be disrupting the normal progress/maturation of the underlying neurocircuits and encourage further investigation for underlying mechanisms.

Child development

The expectation of the growing child is to develop the skills to mature into an individual that can eventually survive to cope independently in their environment. To do this, the child must develop skills in the key functional areas of gross motor, fine motor, and vision, speech–language, and social. The acquisition of these skills is sequential with age. There is variability in the time it takes to acquire skills and their acquisition is affected by factors that are intrinsic (e.g. genetic) and extrinsic (e.g. antenatal factors, postnatal insults, exposure to stimulation, nutrition, etc.) to the child. Achieving an expected developmental skill is known as a developmental ‘milestone’. A delay in achieving a key milestone in a functional area by a certain limit of time that most children would be expected to have reached is called ‘developmental delay’. Delay in all key functional areas of development is known as ‘global developmental delay’. The paediatrician must have a good grasp of what degree of skill acquisition should be expected for the child’s chronological age, know when to watch and wait, and when to refer and investigate further. This is in order to identify problems early, treat any underlying cause, and instigate timely interventions to support the child to maximize their developmental potential.