Cognitive deficit in preschoolers born late-preterm☆
Introduction
Infants delivered late-preterm (LPT; 34–36 weeks gestation) account for approximately 70% of all preterm births [1]. While birth anywhere along the preterm continuum may be associated with medical complications, LPT infants typically are at less risk for severe immediate medical morbidity compared with infants born ≤ 33 weeks gestation but at greater risk than those term-born [2], [3], [4]. Besides having an increased risk of death [5], [6], LPT infants may suffer less severe complications that necessitate admission to a neonatal intensive care unit (NICU). Among these are respiratory distress due to pneumonia, transient tachypnea of the newborn and respiratory distress syndrome; hyperbilirubinemia; hypoglycemia; pulmonary hypertension; sepsis; and feeding problems [4], [5], [7], [8]. Late-preterm infants are also more likely than those term-born to be re-admitted after hospital discharge [9]. Throughout childhood, those born LPT may experience subtle to extreme motor impairment [10], [11], [12], failure to thrive [13], or neurological impairment [14]. While immediate and short-term medical morbidities are reported [15], [16], [17], [18], the nature and degree of consequent neurocognitive effects have not been well-described. Absence of study is partly due to a long-held presumption that LPT birth signifies sufficient physiological maturation relative to a full-term gestation, such that any complication will be mild, of short duration, and unlikely to significantly influence the later developmental course.
Studies of those infants born at 30–36 weeks gestation provide evidence to counter the assumption of transient morbidity. Psychiatric, social, developmental, and behavioral deficits are reported in these children [19], [20], [21], [22], [23], [24]. For example, healthy LPT children in pre-kindergarten or kindergarten had a higher likelihood of early school related difficulties than term-born children [24]. Children who were born at 30–34 weeks gestation and who had no major neurological problems nonetheless demonstrated poorer intellectual and neuropsychological performances than term-born children at preschool age, with a profile of deficit predicted likely to extend into adolescence [20]. In our earlier study, preschool-aged LPT children had average general conceptual ability (GCA) but performed significantly poorer than term-born participants on tests of visuospatial function, visual-motor integration, and verbal fluency (executive function) [19]. Problems appear to persist throughout the lifespan. For example, LPT adolescents had an increased incidence of academic problems and antisocial behavior [25], and in adults, LPT birth was an important risk factor for medical and social disabilities, with incidence rates inversely related to gestational week at birth [26]. Moreover, NICU-admitted LPT infants had the same risk of requiring interventional therapies as infants born very preterm, indicating that the neonatal morbidities of LPT birth negatively affected neurodevelopment [27]. Such findings contradict long-held opinion that LPT birth is an innocuous and transient condition that is unlikely to negatively influence functioning over an individual's lifespan, and support the impression that LPT and term-born children may not necessarily achieve equivalent outcomes [2]. However, further study is required to better understand how neurocognition may specifically differ between LPT and term-born children, and which distinguishable factors within the LPT definitional category of 34–36 weeks will enhance prediction of outcome.
Our aim in this study was to extend our earlier investigation of complicated (NICU-admitted) LPT children at age 3 [19]. We specifically sought to examine cognitive outcome in those born at 35–36 weeks of gestation by assigning LPT participants to one of two subgroups: 1) NICU-admitted due to clinical instability and/or birth weight < 2 kg (i.e., complicated late-preterm; cLPT), and 2) clinically stable and not NICU-admitted (i.e., uncomplicated late-preterm; uLPT), comparing these two subgroups with term-born preschoolers on a multi-component cognitive measure that provides four main composite scores (General Conceptual Ability, Verbal Cluster, Nonverbal Reasoning Cluster, and Spatial Cluster). We hypothesized that cLPT participants would perform poorer than uLPT and term-born participants on each composite measure. We further hypothesized that cLPT impairment rates would be significantly higher than for either the uLPT or term-born groups. A further aim was to examine whether male gender was an additional risk factor.
Section snippets
Subjects
We conducted a retrospective descriptive cohort single center study of 218 children born in 2004–2006. The Inova Fairfax Hospital for Children Institutional Review Board (IRB) approved the protocol and procedures described below. Admission to the NICU is protocol for all born ≤ 34 weeks gestation or with birth weight < 2 kg, or clinically unstable at any gestational age. Participants in this single center study were recruited by mailing IRB-approved letters to families who then had to assent to be
Results
As expected, the study groups differed in gestational weeks at birth (p < 0.001) and birth weight (p < 0.001). The cLPT and uLPT subgroups were born at a significantly shorter gestational age and with lower birth weight compared with TERM (p < 0.001 in all instances); cLPT and uLPT subgroups did not differ significantly from one another. Fewer TERM than cLPT or uLPT participants were delivered by Cesarean section (p = 0.003). No significant group differences were found for race/ethnicity, gender,
Discussion
With few exceptions, outcomes of LPT birth have been reported as if 34–36 gestational weeks define a single homogeneous group. Hypothesizing within-group differences related to the presence or absence of neonatal medical morbidities, we administered a general cognitive measure to LPT NICU-admitted and NICU non-admitted subgroups, and a term-born comparison group. We found the mean DAS-II GCA, Nonverbal Reasoning Cluster, and Spatial Cluster scores of the complicated LPT, but not of the
Ethical statement
In compliance with the principles laid down in the Declaration of Helsinki; Recommendations guiding physicians in biomedical research involving human subjects, adopted by the 18th World Medical Assembly, Helsinki, Finland, June 1964, amended by the 29th World Medical Assembly, Tokyo, Japan, October 1975, the 35th World Medical Assembly, Venice, Italy, October 1983, and the 41st World Medical Assembly, Hong Kong, September 1989, this manuscript contains a statement that the work has been
Acknowledgments
This research was supported by an Inova Health Systems Faculty Grant awarded to the senior author (ISB), and by the Maggie Snyder Foundation for the Premature and Pediatric Pulmonary Patient of Falls Church, VA. We wish to acknowledge the invaluable assistance of Donna Long, Rebecca Q. Beck, Elyssa Scharaga, and Sarah Doyle.
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2018, Early Human DevelopmentCitation Excerpt :Baron IS et al. showed that the subgroup of LPI with neonatal complications have subtle cognitive deficits at 3.8 years old [16], while McGowan JE et al. found no differences in performance at 3 years of age between cLPI and uLPI [17,18]. Different studies use NU admission or the presence of perinatal morbidity in an equivalent way to determine whether there is a relationship with DD, and researchers obtain conflicting results [11,15–18,22]. The differences may be explained in part by the fact that the evaluation of the LPI are not done in the same way, and it is important to consider that the admission to a NU is not itself a criterion to consider a birth as complicated, given that the admission criteria of LPI in different neonatal units are not uniform.
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None of the authors had financial or other relationships that could be interpreted as conflicts of interests relevant to the content of this manuscript. The information is original and has not been published previously in any form. Portions were presented as an Invited Platform Address at the 2010 Pediatric Academic Societies’ Annual Meeting in Vancouver, BC, Canada.