Evaluation of three-year neurodevelopmental outcomes in infants prenatally exposed to substance use

Prenatal substance use is associated with harmful effects on maternal, neonatal, and infant health. This includes prematurity, low birth weight, neonatal withdrawal syndrome, and long-term deficits in the physical, cognitive, behavioral, and emotional development of children (Behnke et al., 2013, Cook et al., 2017, Etemadi-Aleagha and Akhgari, 2022, Ross et al., 2015). Indeed, neonates exposed to substance use during pregnancy have a higher risk of admission to a Neonatal Intensive Care Unit and Neonatal Intermediate Care Unit (NICU and NIMCU) (Avalos et al., 2023, Dumbhare and Taksande, 2023, Sarkar and Donn, 2006) hence, early identification of newborns exposed to substance use guarantees an accurate clinical evaluation, promotes early intervention, and mitigates signs of withdrawal in the neonate if they appear (Jarque et al., 2021, Roca et al., 2021). Meconium has become the “gold standard” for the detection of newborns exposed to substance use during the pregnancy (Jones, 2023). Since its formation starts around the 12th week of gestation and it accumulates until birth, it was considered that it reflected pregnant women with substance use disorder during the second and third trimesters.

Drug and alcohol biomarkers detection in neonatal biological matrices is a useful tool to objectively detect prenatal exposure (Jarque et al., 2021, Roca et al., 2021). Research on the consequences of prenatal substance use has largely focused on short-term obstetric and neonatal outcomes, including low birth weight, stillbirth, and preterm birth. However, knowledge of long-term neurobehavioral consequences is limited, and furthermore, there are other environmental factors associated with substance consumption that can affect the development of children. For example, maternal substance use disorder has been shown to negatively impact mother-child bonding and interaction and increase the risk of childhood exposure to stress, trauma, and/or violence (Guille and Aujla, 2019). Additionally, many studies investigating the relationship between prenatal exposure to substance use and child development do not consider other variables that are often associated with substance use and can affect child development. These variables are prenatal care, childbirth, premature birth, low birth weight, poverty, nutrition, perinatal psychiatric comorbidities, multiple substance use, and the child's family situation (Guille and Aujla, 2019).

Prematurity or low birth weight is associated with poor academic performance, inattention, behavioral problems, and anxiety in school-age children, including a 2.6-fold increased risk of attention-deficit/hyperactivity disorder, independently of the type of substance use (Bhutta et al., 2002, Villar et al., 2012). Therefore, it is important to determine if prenatal drug exposure contributes to any neurodevelopmental impairments linked to prematurity, low birth weight, or other perinatal morbidities.

Although there are different tools and scales, which can lead to different results that are barely comparable to each other (Guille and Aujla, 2019), the Bayley Scales of Infant and Toddler Development (BSID), developed in the United States, is one of the most used tests to evaluate the neurodevelopment of children under three years of age, and, for many, it is considered the reference standard for measuring the development in early childhood (Weiss et al., 2010). Performance of 3-year-old children on the Bayley-III scale might indicate their future cognitive, language and motor function (Nishijima et al., 2022).

The objective of this study was to investigate cognitive, motor, and language development at 3 years of age using BSID-III cut-off scores as a clinical outcome in a cohort of newborns requiring admission to the NICU and NIMCU at birth who were prenatally exposed to substance use, which were detected using biomarkers in neonatal meconium.

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