Neuropsychological Outcomes in Extremely Preterm Preschoolers Exposed to Tiered Low Oxygen Targets: An Observational Study.

An observational study of neuropsychological outcomes at preschool age of tiered lowered oxygen (O2) saturation targets in extremely preterm neonates. We studied 111 three-year-olds born <28 weeks' gestational age. Fifty-nine participants born in 2009-2010 during a time-limited quality improvement initiative each received three-tiered stratification of oxygen rates (83-93% until age 32 weeks, 85-95% until age 35 weeks, and 95% after age 35 weeks), the TieredO2 group. Comparisons were made with 52 participants born in 2007-2008 when pre-initiative saturation targets were non-tiered at 89-100%, the Non-tieredO2 group. Neuropsychological domains included general intellectual, executive, attention, language, visuoperceptual, visual-motor, and fine and gross motor functioning. Descriptive and inferential analyses were conducted. Group comparisons were not statistically significant. Descriptively, the TieredO2 group had better general intellectual, executive function, visual-motor, and motor performance and the Non-tieredO2 group had better language performance. Cohen's d and confidence intervals around d were in similar direction and magnitude across measures. A large effect size was found for recall of digits-forward in participants born at 23 and 24 weeks' gestation, d=0.99 and 1.46, respectively. Better TieredO2 outcomes in all domains except language suggests that the tiered oxygen saturation target method is not harmful and merits further investigation through further studies. Benefit in auditory attention appeared greatest in those born at 23 and 24 weeks. Participants in the tiered oxygen saturation group also had fewer ventilation days and a lower incidence of bronchopulmonary dysplasia, perhaps explanatory for these neuropsychological outcomes at age 3.

Latent mean differences in executive function in at-risk preterm children: the delay-deficit dilemma.

OBJECTIVE: To examine whether a one-factor executive function (EF) model fit data for three groups of children differing in birth criteria (extremely low birth weight [ELBW], late preterm [LPT], and Term) at each of two chronological ages, 3 and 6 years, and whether the latent mean amount of EF differed. METHODS: A retrospective observational cohort study of 1,079 participants; 668 aged 3 years born 2000-2009 (93 ELBW, 398 LPT, and 177 Term) and 411 aged 6 years born 1998-2006 (126 ELBW, 102 LPT, and 183 Term). Latent means analysis was conducted using five indicators for EF: noun fluency, action-verb fluency, similarities reasoning, matrices reasoning, and working memory. RESULTS: A one-factor model had acceptable fit for all groups (RMSEA<.06, CFI >0.95, SRMR <0.08). Statistically significant between-groups differences were found for all comparisons except one; there were no statistically significant differences between LPT-Term at age 6. At age 3, ELBW was 0.98 and 1.70 SD below LPT and Term, respectively; LPT was 0.61 SD below Term. At age 6, ELBW was 0.70 and 0.78 SD below LPT and Term, respectively; LPT was 0.10 SD below Term. CONCLUSIONS: Executive deficit identified early in development after preterm birth could represent a transient developmental delay likely to resolve at older age or a more subtle adverse effect likely to persist over the life span. Study at multiple age points should assist in resolving this dilemma, which has important implications for early age neuropsychological screening and intervention.

Subtle adverse effects of late preterm birth: a cautionary note.

OBJECTIVE: Late preterm birth increases risk of perinatal health complications that typically resolve in the short term. Thus, early elective delivery is thought to have no long-term effects. Whether there is increased risk of adverse psychological outcomes that emerge in early childhood remains uncertain. METHOD: The authors compared intellectual, neuropsychological, and behavioral outcomes in 278 late preterm (35-36 weeks) and 192 term (37-41 weeks) participants at age 3 years recruited from a single center, using analysis of variance, analysis of covariance, and regression analyses. Late-preterm participants were further subgrouped by admission to the neonatal intensive care unit (NICU; n = 202) or a well-baby unit (n = 76). Analyses included 132 additional participants born at 34 weeks. RESULTS: Late preterm participants had lower general conceptual ability (GCA; i.e., IQ); lower verbal, nonverbal, spatial, visuomotor, and dexterity scores; and poorer adaptability than term participants (p < .01; -0.271 to -0.511 SDs). Gestational age was the most important predictor of these subtle outcomes, not neonatal medical variables; no differences were found between NICU admitted and nonadmitted late-preterm groups. A 1-week increase in gestational age resulted in a 1.941 increase in GCA (d = 0.127). CONCLUSION: Gestation is a developmental continuum best not interrupted during its natural course. Our data showing subtle but appreciable effects have important implications for obstetric practice and parental decision making regarding early elective delivery in the absence of maternal or fetal adverse indications.

Latent mean comparisons on the BRIEF in preterm children: parent and teacher differences.

Executive function is a heterogeneous construct applied to cognitive capacities that together enable individuals to effectively engage in activities toward a purposive goal. Children born at extremely low birth weight (ELBW) are at risk of executive dysfunction on performance-based measures. In natural contexts, executive function may be described using such parental and teacher questionnaires as the Behavior Rating Inventory of Executive Function (BRIEF). This study examined the factor structure of the BRIEF-parent form in 124 ELBW children and of the BRIEF-teacher form in 90 ELBW children. Although our data showed that the fit of a two-factor structure was adequate for the parent report, a three-factor model provided advantages over the two-factor model across all fit indices and best characterized the data. For teacher report, these data supported a three-factor but not a two-factor model. Using the three-factor model for both groups of informants, we compared parent and teacher reports (n = 90 pairs) between the three identified latent variables. Parents reported significantly more difficulty with Emotional Regulation (p < .05), and teachers reported significantly more difficulty with Behavioral Regulation (p < .05). No significant differences were found between parent and teacher reports for Metacognition.

In vitro fertilization and late preterm preschoolers' neuropsychological outcomes: the PETIT study.

OBJECTIVE: In vitro fertilization (IVF) is considered a generally safe procedure, although associated with a higher incidence of preterm birth. The literature is inconsistent about the psychological impact of IVF, and we found no reports about outcome in late preterm (LPT) children. Our objective was to study neuropsychological and behavioral outcomes in a cohort of preschoolers born LPT between 2004 and 2007. STUDY DESIGN: Participants were 397 LPT children (mean age, 3.8 years) conceived assisted by IVF (n = 105) or non-IVF (n = 292). Standardized performance-based tests of general conceptual ability (intelligence quotient), executive function, focused/selective attention, visual-spatial perception, visual-motor skill, manual dexterity, learning, and memory were administered. Parents completed behavioral and executive function questionnaires. RESULTS: IVF group characteristics included older maternal age (P < .001), lower birthweight (P < .001), and higher maternal education (P < .001). No main-effect significant group differences were found for any variable after controlling for these variables. However, sex differences were demonstrated for the neuropsychological variables in copying (P > .001), nonverbal reasoning (P = .001), manual dexterity (P = .001), and inhibitory capacity (P = .006), all favoring girls. CONCLUSION: Birth following IVF-assisted conception did not increase the risk of intellectual, neuropsychological, or behavioral deficit in LPT preschoolers. As shown in earlier gestational-age participants, girls have selective advantages. These findings should be reassuring for parents who conceive through IVF and deliver infants 1-3 weeks before term gestational age. Future study of these children at elementary school age may detect subtle impairments not yet apparent at age 3 years.

Late preterm birth: a review of medical and neuropsychological childhood outcomes.

Late preterm (LP) birth (34 0/7 - 36 6/7 weeks' gestation) accounts for nearly three-fourths of all preterm births, making this population a sizeable public health concern. The immature fetal development associated with LP delivery increases the risk of mortality and short-term medical complications. Which combination of maternal, fetal, or neonatal risk factors may be most critical has only recently begun to be addressed, and whether LP birth's disruptive impact on brain development will exert adverse effects on neuropsychological functioning in childhood and adolescence has been understudied. Early data have shown a graded response, with LP children often functioning better than very preterm children but worse than term children, and with subtle intellectual and neuropsychological deficits in LP children compared with healthy children born at term gestational age. Further characterization of the neuropsychological profile is required and would be best accomplished through prospective longitudinal studies. Moreover, since moderate and LP births result in disparate medical and psychological outcomes, the common methodology of combining these participants into a single research cohort to assess risk and outcome should be reconsidered. The rapidly growing LP outcomes literature reinforces a critical principle: fetal development occurs along a dynamic maturational continuum from conception to birth, with each successive gestational day likely to improve overall outcome.

Selective deficit in spatial location memory in extremely low birth weight children at age six: the PETIT study.

Spatial location memory has rarely been assessed in young children due to a scarcity of developmentally appropriate tests. This study sought to compare nonverbal learning and recall in children born extremely low birth weight (ELBW; <1000 g) and less than 33 gestational weeks (GW) with term-born children at early school age using a recently developed and adapted test. We administered a modification of the Hopkins Board to 210 children at age six; 84 born ELBW (35 born < 26 GW; 49 born 26-33 GW) and 126 term-born. Six measures were obtained: naming, trials-to-criterion, errors-to-criterion, delayed item recall, delayed location recall, and percent retention. After age correction, ELBW children had worse general cognition, item naming, delayed item recall, delayed location recall, and percent retention than term-born children. Delayed item recall and percent retention performances of ELBW children remained worse after correction for general cognition. ELBW groups (< 26 GW and 26-33 GW) groups performed worse than term-born children in naming and delayed item recall with chronological age as covariate. Those born before 26 GW, but not 26-33 GW, performed worse than term-born children in delayed location recall and percent retention. Differences remained significant after controlling for gender, maternal education, and delivery type. All three groups' performance declined from final learning trial to delayed location recall, with a decline greater for less than 26 GW than term-born children. Extreme prematurity (< 26 GW) and ELBW are significant risk factors for spatial location memory deficit. The modified Hopkins Board discriminated high-risk preterm and term-born children at early school age and appears to be a useful test to measure this rarely studied cognitive capacity.

Executive functions in extremely low birth weight and late-preterm preschoolers: effects on working memory and response inhibition.

Executive function (EF) refers to fundamental capacities that underlie more complex cognition and have ecological relevance across the individual's lifespan. However, emerging executive functions have rarely been studied in young preterm children (age 3) whose critical final stages of fetal development are interrupted by their early birth. We administered four novel touch-screen computerized measures of working memory and inhibition to 369 participants born between 2004 and 2006 (52 Extremely Low Birth Weight [ELBW]; 196 late preterm; 121 term-born). ELBW performed worse than term-born on simple and complex working memory and inhibition tasks and had the highest percentage of incomplete performance on a continuous performance test. The latter finding indicates developmental immaturity and the ELBW group's most at-risk preterm status. Additionally, late-preterm participants performed worse compared with term-born on measures of complex working memory but did not differ from those term-born on response inhibition measures. These results are consistent with a recent literature that identifies often subtle but detectable neurocognitive deficits in late-preterm children. Our results support the development and standardization of computerized touch-screen measures to assess EF subcomponent abilities during the formative preschool period. Such measures may be useful to monitor the developmental trajectory of critical executive function abilities in preterm children, and their use is necessary for timely recognition of deficit and application of appropriate interventional strategies.

Neuropsychological and behavioral outcomes of extremely low birth weight at age three.

Preterm (PT) birth is an established risk factor for high mortality and morbidity rates. Infants and school-aged children have been well-studied, but few have described neuropsychological and behavioral outcomes at preschool age. We compared a 2004-2006 preterm/extremely low birth weight (ELBW) cohort (PT/ELBW; N = 60) born ≤ 33 weeks gestation and <1,000 g with term-born participants (N = 90) at age 3. PT/ELBW subgroups (<26 weeks; 26-33 weeks) performed more poorly than the term-born group on verbal, nonverbal, fine motor, visual-motor, visual attention, noun fluency, early number concepts, and functional communication measures prior to age correction; PT/ELBW children born <26 weeks additionally performed more poorly on action-verb fluency. Those born 26-33 weeks had executive and adaptive deficits on parental behavioral report. Age correction significantly improved preterm scores without masking relative verbal, nonverbal, motor, and behavioral weaknesses that may require early intervention. In conclusion, subtle delays in emergent neuropsychological and behavioral functions are measurable at age 3, and neurobiological immaturity remains a prepotent influence on outcome in the preschool years. Further study should enhance our understanding of the trajectory of brain development and the limits of neuroplasticity in these highly at-risk children.

Neuromotor outcomes at school age after extremely low birth weight: early detection of subtle signs.

OBJECTIVE: Motor impairments are prevalent in children born at extremely low birth weight (ELBW; <1,000 g). Rarely studied are subtle motor deficits that indicate dysfunction or delay in neural systems critical for optimal cognitive, academic, and behavioral function. We aimed to examine quantifiable signs of subtle neuromotor dysfunction in an early school-aged ELBW cohort that coincidentally had age-appropriate cognition and design copying. METHOD: We studied 97 participants born between 1998 and 2001; 74 ELBW (6.7 years ± 0.75) compared with 23 term-born (6.6 years ± 0.29). Neuromotor outcomes were assessed using the Physical and Neurological Examination of Subtle Signs-Revised, and measures of dexterity/coordination and visual-motor integration. RESULTS: ELBW participants performed worse than term-born on design-copying and dexterity, were age-appropriate compared to normative data, and had slower timed movements and more subtle overflow movements. Those ELBW born <26 weeks performed most poorly compared with those born 26-34 weeks and term-born. CONCLUSION: Subtle motor dysfunctions are detectable and quantifiable in ELBW children by school age, even in the presence of average cognition. Early age assessment of incoordination, motor speed, and overflow movements should aid initiation of timely therapies to prepare at-risk ELBW children for subsequent school entry and facilitate design of optimal early treatment strategies.

Cognitive deficit in preschoolers born late-preterm.

BACKGROUND: late-preterm (LPT) birth accounts for a majority of preterm deliveries and until recently was considered low risk for poor cognitive outcome. Previously, we reported deficits in complicated LPT (cLPT) preschoolers (neonatal intensive care unit [NICU]-admitted). AIM: to extend our prior study by comparing cognitive outcome in cLPT and uncomplicated LPT (uLPT; NICU non-admitted) preschoolers. STUDY DESIGN: single center retrospective cohort study of 118 LPT children born in 2004-2006 at 35-36 weeks of gestation; 90 cLPT and 28 uLPT, compared with 100 term-born (≥ 37 weeks of gestation and ≥ 2500 g) participants. OUTCOME MEASURE: a well-standardized measure of general conceptual ability (GCA), the Differential Ability Scales, Second Edition. RESULTS: cLPT participants had average mean performances but significantly poorer GCA, Nonverbal Reasoning, and Spatial scores than term-born children, and higher rates of Nonverbal Reasoning and Spatial impairment; uLPT did not differ from TERM. Combined LPT males were at eightfold greater risk than term-born males for nonverbal deficit, and at sevenfold greater risk for GCA impairment than LPT females. CONCLUSIONS: finding greater risk of cognitive deficit in those NICU-admitted due to clinical instability or birth weight < 2 kg compared with non-admitted preschoolers indicates that neonatal morbidities contribute to subtle cognitive deficits detectable at young age, with male gender an additive risk factor. LPT gestational age alone is an insufficient predictor of long-term neurocognitive outcome. Further study should elucidate salient etiologies for early emerging cognitive weaknesses and suggest appropriate interventions to prepare at-risk LPT preschoolers for elementary school entry.

Spatial location memory discriminates children born at extremely low birth weight and late-preterm at age three.

OBJECTIVE: The spatial location memory of preschool-aged children born preterm has rarely been studied primarily due to an absence of developmentally sensitive measures. This study aimed to address this gap in the literature. METHOD: We administered a modification of the Hopkins Board to 135 children at age 3 who were born extremely low birth weight (ELBW) (n = 20), late-preterm (LPT) (n = 75), or at term (TERM) (n = 40). Five measures were obtained: naming, trials-to-criterion, errors-to-criterion, delayed item recall, and delayed location recall. RESULTS: ANCOVA indicated that the groups differed in naming (p = .019), errors-to-criterion (p = .002), and delayed item recall (p = .025). For these measures, ELBW performed worse than TERM and LPT, but LPT did not differ from TERM. Corrected age and sociodemographic factors did not eliminate the deficit in spatial location learning for ELBW participants. A MANCOVA found a significant difference in learning, with post hoc tests indicating significant learning across trials in the LPT and TERM groups, but not in the ELBW group. CONCLUSIONS: ELBW is a significant risk factor for developmental delay or impairment of spatial location learning. These findings suggest that the modified Hopkins Board identifies at-risk premature children. This modification may be more broadly useful to assess preschoolers' neurodevelopmental maturation.

Visuospatial and verbal fluency relative deficits in 'complicated' late-preterm preschool children.

BACKGROUND: Late-preterm children constitute a majority of all preterm deliveries (75%). Their immature brain development at birth has been associated with an increased risk for morbidities. Data have been sparse regarding neuropsychological outcomes in the preschool years. AIM: To examine general cognition, attention/working memory, language, manual coordination/motor dexterity, visuomotor, visuospatial, and executive functions in preschoolers born late-preterm (LPT; 34-36 gestational weeks) who required NICU admission compared to term-born participants. DESIGN: Single-center retrospective cohort study of 95 three-year-old children; 60 born LPT in 2004-2005 and admitted to the NICU compared to 35 healthy term-born participants born > or =37 gestational weeks and > or =2500 g. RESULTS: LPT birth was associated with visuospatial (p=.005), visuomotor (p=.012), and executive function (noun [p=.018] and action-verb [p=.026] fluency) relative deficits, but not attention/working memory, receptive or expressive language, nonverbal reasoning, or manual coordination/dexterity deficit. CONCLUSIONS: Late-preterm birth is likely to be associated with negative neuropsychological sequelae, although subtle and selective compared to effects reported for children born at an earlier gestational age. Visuospatial function appears to be especially vulnerable to disruption even at preschool age, and verbal fluency may be useful as an early predictor of executive dysfunction in childhood. Routine preschool neuropsychological evaluation is recommended to identify delay or deficit in LPT children preparing for school entry, and may highlight underlying vulnerable neural networks in LPT children.

Age-appropriate early school age neurobehavioral outcomes of extremely preterm birth without severe intraventricular hemorrhage: a single center experience.

BACKGROUND: Extremely low birth weight (ELBW) is an established risk factor for poor neurocognitive outcome, particularly when severe intraventricular hemorrhage (IVH) complicates the neonatal course. Those born <26 weeks gestational age (GA) are at greatest risk, their outcomes poorer than later born ELBW children. Outcomes of GA subgroups of ELBW uncomplicated by severe IVH have not been well described. AIM: To compare neurocognitive and behavioral outcomes of those born < and >or=26 weeks for an ELBW cohort treated in a single center with extremely low IVH incidence. DESIGN: Single center retrospective observational cohort study of or=26 weeks (102.97+/-13.21) subgroups. No neurocognitive, achievement, or behavioral score was impaired (>or=2 SDs below the normative mean). Subgroup comparisons were nonsignificant after controlling for BW and maternal education, except for >or=26 week advantage for phoneme analysis. Poorer, but low average, performances were found for motor dexterity/coordination, spatial working memory, and selective attention. CONCLUSIONS: Age-appropriate neurocognitive and behavioral function of ELBW survivors suggests outcome may be predicted based on IVH incidence as opposed to birth weight or GA. Factors leading to decreased IVH incidence deserve further study, via single- and cross-center methodologies, to enhance decision-making regarding resuscitation and care of these highly at-risk neonates.

Neuropsychological outcomes of preterm triplets discordant for birthweight: a case report.

Multiple gestation is associated with a higher incidence of preterm birth and preterm birth often results in later neurocognitive and behavioral problems that persist into adulthood. The medical, neurobiological, familial, and socio-environmental factors determinant for an individual are unpredictable. We present neuropsychological data for fraternal triplets discordant for birthweight whose school-age outcome was inconsistent with the low birthweight literature and for whom neurobiological variables appeared especially pertinent. Preterm infants may achieve optimal outcomes, although etiological factors leading to such outcomes may depend heavily on care center variables that limit or avoid intracerebral and other medical complications of prematurity.