An Exploratory Principal Factor Analysis of Very Low Birth Weight Clinical Data and Development-Behavioral Outcomes at 4 Years of Age

Samia Valeria Ozorio Dutra, PhD, RN; Jessica Gordon, PhD, APRN, CPNP-PC; Emily Shaffer, PhD; Elizabeth Miller, PhD; Cedric Harville, II, PhD; Ji Youn Yoo, PhD, RN; Anujit Sarkar, PhD; Ming Ji, PhD; Amy D'Agata, PhD, RN; Maureen Groer, PhD, RN, FAAN


Pediatr Nurs. 2022;48(1):21-33. 

In This Article

Abstract and Introduction


This exploratory paper describes associations between neonatal clinical data and behavioral outcomes among infants born with very low birth weight (VLBW) at 4 years of age. Statistical analysis of 24 VLBW infants was conducted using principal factor analysis (PFA). Multiple linear regressions were calculated to explore the relationship between identified risk factors (demographic and clinical data) and behavioral measures: the Battelle Developmental Inventory (2nd ed.) Screening Test (BDI-2 ST) and the Achenbach Child Behavior Checklist (CBCL). Gestational age was controlled for in the model. Exploratory PFA results indicated that two factors had greater ability to explain observed variations within the sample. The first factor significantly associated high-level neonatal care with aggressive behaviors (β = -0.7477, p < 0.05). The first factor was also predictive of lower personal-social, communication, and cognitive scores. The second factor significantly associated cardiopulmonary complications with pervasive developmental problems (attention deficit hyperactivity disorder, anxiety, depression, and oppositional defiant disorder) (β = 0.1977, p < 0.05). These results showed that behavioral consequences at 4 years of age were found among children born VLBW due to the severity of illness, the need of high-level care, and cardiopulmonary complications during the neonatal period. These findings suggest VLBW infants experience longer term effects from trauma early in life and warrant further study.


Early childhood neurodevelopment refers to the development of neurological pathways that influence performance or functioning. In the newborn period, genetic factors, novel experiential inputs, and behavioral responses act on a still immature brain substrate to stimulate development of brain circuits (Tau & Peterson, 2010). The brain is sensitive to harmful exposures, such as toxins, drugs, nutritional deficiencies, infection, medical illness, and environmental stressors, throughout the life cycle (Tau & Peterson, 2010). For infants born preterm, a critical period of brain development continues outside the womb in a stimulation-rich environment that starkly contrasts the inutero environment. Physiological instability coupled with neurologic insults (i.e., intraventricular hemorrhage [IVH], pain, stress, oxidative stress) can lead to compromised brain functioning (Altimier & Phillips, 2018; Raffaeli et al., 2020). Ultimately, neural circuit health is demonstrated in cognitive, emotional, and behavioral functioning (Shonkoff et al., 2012; Tau & Peterson, 2010). Thus, it is not surprising that in addition to physical health complications, a wealth of literature demonstrates that preterm infants also have increased rates of executive functioning impairment, learning problems, and behavioral difficulties when compared to infants born full term (Bhutta et al., 2002; McCormick et al., 2011).

Each year, nearly 1% of infants are born with extremely low birth weight (less than 1,000 grams) (Stoll et al., 2010), and 1.38% of infants with very low birth weight (VLBW, or less than 1500 grams) (Centers for Disease Control and Prevention, 2020). These infants are more likely to suffer from comorbidities related to the trauma of premature birth on the developing brain (Robinson, 2012). Although advances in neonatal medicine and technology have reduced mortality rates of preterm neonates delivered as early as 23 weeks gestational age (GA), morbidity rates among very preterm infants remains quite high (Manuck et al., 2016; McCormick et al., 2011). Although the relationship between prematurity and long-term developmental outcomes has been well documented, individual outcomes vary widely. GA and birth weight alone cannot fully predict later development; as such, environmental and individual characteristics play a significant role. Environmental characteristics known to have a moderating effect on developmental outcomes of preterm infants include the home environment, socioeconomic status (SES), maternal age and education level, parenting practices, and parent-infant interaction (Camerota et al., 2015; Delonis et al., 2017). Although research has shown neurodevelopmental outcomes to be influenced by birth GA and the infant's home environment after discharge, understanding how early life experiences in the neonatal intensive care unit (NICU) influences later development warrants investigation (Camerota et al., 2015; ElHassan et al., 2018).

Learning and developmental outcomes not only have an inverse relationship with birth GA, but they also impact those born closer to term (Morse et al., 2009). Compared to term-born controls, even late preterm infants (34 to 36 weeks gestation) show a 36% higher risk for developmental delay and 10% to 13% higher risk of learning and behavioral concerns in kindergarten associated with academic retention, suspension, and need for exceptional student education services (Morse et al., 2009). In a sample of 405 infants, significant cognitive impairment at 18 to 22 months of age was found in nearly 50% of infants with GA less than 25 weeks (Hintz et al., 2011). Preterm birth has also been associated with a higher level of attention deficit hyperactivity disorder (ADHD) symptoms in preschool children after accounting for genetic and environmental factors (Ask et al., 2018; McCormick et al., 2011).

Current research shows preterm infant morbidities have been associated with compromised later-life neurodevelopment (i.e., brain injury, seizures, and sepsis) (Smith et al., 2011). Less known is how factors associated with neonatal clinical experience, such as neonatal illness severity (Richardson et al., 2001), are related to developmental and behavioral neurodevelopment during early childhood. In one study, parent report of infant illness was a significant predictor of one aspect of negative child behavior (i.e., demandingness) at 5 years of age. However, the use of only one-item assessment of infant illness and reliance on parent recall of their child's infancy when their child was 3 years old limits the generalizability of the sample (Brown et al., 2011).

Further research is needed to determine associations between neonatal clinical experiences and longer-term developmental-behavioral outcomes so health professionals and caregivers can assess infants early in life for potential concerns and consider mitigation strategies. NICU factors reported to impact longer term neurodevelopmental outcomes include biologic factors, such as birth gestational age and genotype (Arisanti et al., 2019; Brook, 2008; D'Agata, Walsh et al., 2017); psychosocial factors, such as the parent-child relationship, parental separation, and maternal stress (Chan et al., 2018; Talge et al., 2007); and environmental factors in the NICU (D'Agata, Sanders et al., 2017; D'Agata et al., 2016; Valeri et al., 2015). Understanding how different biologic factors are associated with neonatal clinical experiences and later-life development and behavior would provide important information for those who care for former preterm-born individuals. The purpose of this exploratory study is to describe the association between neonatal clinical data and developmental-behavioral outcomes among VLBW infant at 4 years of age. We hypothesized that negative experiences during the NICU stay, such as illness severity, will be associated with developmental-behavioral outcomes on children at 4 years of age.