Factors associated with the Dubowitz neurological examination in preterm new-borns

Introduction

The present study investigated factors associated with the Dubowitz neurological examination (DNE) in preterm new-borns (PNB). While there has been an increase in prematurity rates, advances in science have made it possible to guarantee higher survival rates for these infants (Pinto et al., 2019). Nonetheless, prematurity is still the leading cause of mortality in new-borns and is a predictor for perinatal morbidity since it is associated with neurodevelopmental delay and deficiencies in sensory-motor abilities. These deficiencies occur due to the negative impact of prematurity on sensory processing, impairing the central nervous system (CNS) in managing, integrating, and adapting information gathered by sensory organs (Stylanou-Riga et al., 2018; Torchin & Ancel, 2016).

PNB are those born at less than 37 gestational weeks and can be classified as extreme (less than 28 weeks), very (from 28 weeks to 31 weeks and six days), moderate (from 32 weeks to 33 weeks and six days) and late-terms (from 34 weeks to 36 weeks and six days) (American Academy of Pediatrics, 2017). Overall, around 15 million premature births are estimated to occur every year, which translates into approximately one in 10 births (Chawanpaiboon et al., 2018); out of these, 84.7% are usually moderate or late preterm, 10% are very preterm and 5% are classified as extremely premature (Blencowe et al., 2012). Some factors associated with prematurity might be closely related to social inequalities, including low parental education and low family income, which might impede both access and consistency in health care needs (Torchin & Ancel, 2016). Indeed, one in three premature births occurs in women with diabetes or gestational diabetes (Dyck et al., 2020) or among those with super imposed preeclampsia (Rezende et al., 2020), which poses the question of whether these circumstances could have been prevented. Additionally, the most common consequence of premature birth for mothers is vaginal and urinary tract infection, conditions that require consistent care (Aguilera et al., 2019). Premature birth often entails neonatal intensive attention, enhancing the chances for serious complications, including neonatal sepsis (Jiang et al., 2020), retinopathy (Palmer et al., 2020), intraventricular haemorrhage or periventricular leukomalacia (Khazanchi et al., 2020), and neuropsychomotor complications (Bélanger et al., 2018).

Consequently, as cognitive, language, and motor development may be impaired in PNB, comprehensive assessments are necessary to uncover features that might compromise optimal growth and to direct immediate interventions (Fuentefria et al., 2017; de Paula Machado et al., 2017). Although the value of early neurological evaluation is widely accepted, the role of reliable, ecologically-valid measurements has been explored less, particularly in developing countries (do Nascimento et al., 2011). The DNE was created in 1980 with the intention of monitoring the neurological conditions and neuropsychomotor development of PNB and full-term new-borns (Dubowitz et al., 1980). Since its first applications, the DNE has been sensitive to perinatal factors such as anoxia, difficulties in deliveries, infections and other environmental influences (Dubowitz et al., 1980). Moreover, the evaluation is well tolerated by new-borns and has shown a reliability level between judges of above 96% (Dubowitz et al., 1999). In 2003, DNE scores were categorised according to gestational age (GA) (Mercuri et al., 2003).

Although there has been substantial evidence relating premature birth to a myriad of medical, sociodemographic and environmental factors, around two-thirds of these births occur without an evident risk factor, which warrants further research (Vogel et al., 2018). Hence, the current study seeks to advance the understanding of factors associated with infants’ neurological development. One of the hypotheses was that abnormalities in neurological evaluations would be correlated with neonatal, maternal, and sociodemographic factors. In particular, we hypothesised that the DNE score would be altered in babies which required some type of neonatal support (Chaskel et al., 2018) and in the children of mothers with previous illnesses or complications throughout pregnancy (Aguilera et al., 2019; Dyck et al., 2020). Moreover, based on the premise that high income partly explains higher education, which would then supposedly increase protective healthy behaviours (such as strict prenatal care), we hypothesised that both income and education would be inversely associated with the DNE scores.

Methods

Results

Discussion

This study investigated factors associated with the DNE in premature infants, hypothesising that abnormalities in the neurological assessment would be correlated with neonatal, maternal, and sociodemographic factors. Specifically, we predicted low scores in the DNE in infants which required some type of neonatal support (Chaskel et al., 2018) and in the children of mothers with diagnosed illnesses or among those with pregnancy complications (Aguilera et al., 2019; Dyck et al., 2020). Furthermore, based on the premise that elevated income might explain higher educational levels, which, in turn, could increase the adoption of healthy behaviours - including strict prenatal care - we hypothesised that these sociodemographic factors would be inversely associated with the DNE.

Even though premature birth has been associated with various medical, sociodemographic, and environmental factors, nearly 66% of these births occur without a clearly defined risk factor. Indeed, the strongest predictors associated with the DNE in this study were father's age and family income. While specific comparisons with past reports are not fully possible due to the adoption of diverse measures, our findings build upon, expand, and are coherent with the specialised literature. For instance, a strong correlation has been reported between children’s motor development and father’s age (Borba et al., 2017); moreover, there is evidence that younger fathers have increased chances of having underweight and premature children (Goisis et al., 2018). We observed a positive correlation between both paternal and maternal education and family income. In this direction, Delgado et al. (2020) recently reported lower motor development among those receiving governmental benefits, supporting the claim linking low income with neurological deficits in Brazilian children. Another investigation in Brazil showed that economic hardship can have an impact on premature births, particularly among uneducated mothers (Sadovsky et al., 2018). Indeed, maternal instruction has been negatively associated with full-term pregnancies and birthweight (Mattei & Carreno, 2017).

We also noticed that mothers with higher age had babies with greater vitality (i.e., Apgar 5 min score). Past studies noted that adolescent mothers are more likely to have premature children with a low Apgar score in the fifth minute (Souza et al., 2017), while those aged between 20 and 29 years are more likely to have children with Apgar 5 min scores of greater than eight (Muniz et al., 2016). Moreover, both orotracheal intubation and length of hospitalisation were significantly lower in the group with normal DNE scores. In fact, the literature reports that longer hospitalisations are inversely related to motor development assessments in PNB (Formiga et al., 2017) and that gross motor performance is significantly lower when invasive mechanical ventilation is needed (Nazi & Aliabadi, 2015).

Prematurity and low birthweight are established risk factors for delays in motor and cognitive development (Upadhyay et al., 2019) and these alterations usually occur simultaneously (Oudgenoeg-Paz et al., 2017). Indeed, birthweight was independently associated with the DNE global score in our study; furthermore, it correlated with the tone, type of tone, reflexes, and abnormal signs subdomains. These results resemble data reported by Formiga et al. (2017) who found a positive and moderate correlation at two and four months of life between birthweight and motor development (assessed through the Test of Infant Motor Performance; TIMP).

No studies were located which associated the DNE with maternal, neonatal, and sociodemographic factors, which impedes specific comparisons. However, past investigations have adopted the Hammersmith Infant Neurological Examination (HINE) (Haataja et al., 1999), which is similar to the DNE. In this respect, Romeo et al. (2016) observed associations between gestational age and the HINE’s overall score, whereas Chatziioannidis et al. (2018) reported only one factor associated with a low HINE score, namely being small-for-gestational-age.

In addition to our main findings, the current investigation might have useful data for those involved in maternal and child health. Firstly, 25% of the PNB scored below the ideal cut-off limit of the DNE, albeit these rates range from 57% to 70% when the evaluation is performed at term age (Golin et al., 2009; Grinaboldi et al., 2015). Secondly, readers must consider that the sample of this research was assessed with ages up to six months (chronological age), thus already achieving the term age. In this sense Mercuri et al. (2003) stressed that, although PNB had lower DNE scores when compared to non-pre-terms, all infants evaluated in the study achieved normal scores at 18 months of life. This can be explained by the fact that many components of neurological assessment are age-dependent (Dubowitz et al., 1998), so an increase in maturity is expected to result in better scores in the DNE evaluation (Dubowitz et al., 2005; Romeo et al., 2013). This can also be observed in the first hours of life. Indeed, Romeo et al. (2017) noted significant differences when infants were assessed within 3, 6 and 48 hours. In our research, the domains with least altered scores were movements and reflexes, with 27.5% and 5% of infants scoring below reference values, respectively. These were the only domains that did not show significant differences between the very-, late- and full-term groups in the Romeo et al. study (2016). Additionally, Golin et al. (2009) found that 80% of the PBN scored below cut-off points for tone and 97% had insufficient scores regarding type of tone. These studies validate our findings, as 97.5% of the sample scored below the reference value for tone and 77.5% for type of tone.

Despite the attempts to reduce the incidence of spontaneous premature births, this still stands out as the main cause of perinatal morbidity and mortality, being a complex and multifactorial public health problem (Glover & Manuck, 2018). Over the years, the number of premature infants increased in southern Brazil, with higher proportions of late preterm infants (Sadovsky et al., 2018), accounting for about 74% of the premature population (Chatziioannidis et al., 2018). This is compatible with our research as 70% were late preterm too. Finally, a remarkable percentage (95%) of women from our study reported some sort of complication during pregnancy, with caesarean section accounting for 67.5% of deliveries. This comes with no surprise as it has been noted before that mothers of premature babies have higher rates of complications during pregnancy, especially preeclampsia and haemorrhage, as well as higher rates of caesarean delivery (Cheong et al., 2017). What surprises us is that, even with all the advancements in the field of prenatal care, those rates are still so elevated.

In summary, although our study presents some limitations, especially in the analysis of categorical variables with reduced number of cases per cell - which may have hindered the detection of some risk factors associated with the DNE - this investigation also has some strengths. These include the analyses of factors much less explored in the literature, since we could not locate other studies exploring the relationship between neonatal, maternal, and sociodemographic factors with the DNE in PNB. The measure, created decades ago, has been mostly used in recent studies involving Zika virus (Coutinho et al., 2021), which could explain the scarcity of updated studies utilising this neurological assessment tool among low-risk PNB (Grinaboldi et al., 2015).

An additional limitation concerns the fact that one must not generalise these findings to other realities due to numerous factors already mentioned. Consequently, more research is needed to support early strategies focusing on ameliorating the care dedicated to the child-mother dyad, particularly involving longitudinal and/or interventional designs to translate science into practice and to explore the external validity of the measure. In other words, effectively transforming the taxpayers’ money behind research into better quality of life.

Data availability