Abstract
Objective:
The study was designed to investigate whether attainment of object permanence, a measure of early working memory used at 18–22 months corrected age, was associated with executive function at 6–7 years in a cohort of children born extremely preterm.
Study Design:
Children enrolled in the Neuroimaging and Neurodevelopmental Outcome (NEURO) study, a secondary study to the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) of the NICHD NRN, were eligible for this longitudinal study. Testing completed at 18 to 22 months corrected age was compared to testing at school age with a specific focus on measures of executive function.
Results:
Children who had achieved object permanence mastery at a corrected age of 18–22 months had higher mean scores on the WISC-IV tests of verbal comprehension and processing speed at age 6–7 years. Regression models indicated that object permanence scores were significant predictors of both verbal comprehension and processing speeds scores, after controlling for other factors. When analyzed by subgroup for sex, these results were significant for girls but not for boys.
Conclusions:
This study found that an early mastery of object permanence was associated with higher scores in areas of verbal comprehension and processing speed in girls. These results have implications for potentially identifying young children born preterm that are at greater risk for difficulties with cognitive and working memory skills at school age.
Keywords: extremely low birth weight, development, executive function
1. INTRODUCTION
Children born preterm frequently have executive function difficulties, which have been linked to cognitive, academic, and behavioral problems [1]. Executive function is a term that encompasses three main areas of processing skills: working memory, inhibition, and cognitive flexibility [2]. Problems of executive function persist through school age in children born preterm, often resulting in poor academic performance [3]. Tests of cognitive skills have been used most frequently to identify early learning problems that result in later behavior, learning, and executive function difficulties [4].
In an earlier study of executive function in young children born preterm, Woodward et al. [5] found that 2 year-old children born preterm had difficulty encoding new information in working memory compared to term-born infants. On MRI these children had bilateral reduction in cerebral tissue volume in areas specifically related to working memory (dorsolateral prefrontal cortex, parieto-occipital, and premotor areas). In another study using a test of object permanence as a measure of early working memory, preterm children who received erythropoiesis-stimulating agents had higher object permanence scores and higher scores on the Bayley III cognitive scale [6].
The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network (NRN) previously reported that at 18–22 months adjusted age, scores on the Bayley-III cognitive and language scales correlated positively with a measure of object permanence [7]. The present study was designed to investigate whether the measure of object permanence used at 18–22 months in that study was associated with executive function at 6–7 years in these children [8].
Measures of fluid cognition ability at school age allow us to better identify children with difficulty in domains of executive function and related abilities, such as working memory, inhibition, perceptual reasoning, or processing skills [9]. We hypothesized that early object permanence mastery score at 18–22 months would correlate with higher scores of executive function at age 6–7 years in this group of children born extremely preterm. As girls did better on tests of object permanence at 18–22 months adjusted age, we hypothesized that they would continue to do better on tests of executive function at school age. We further hypothesized that adverse findings on cranial ultrasound and significant lesions on MRI would correlate with lower scores on early tests of object permanence and lower scores on tests of cognition and executive function at school age.
2. METHODS
2.1. Study Population
The study cohort was originally enrolled at birth in the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) of the NICHD NRN and were eligible if they had also been enrolled in its secondary study, the Neuroimaging and Neurodevelopmental Outcome (NEURO) [8]. The SUPPORT study was a randomized multicenter trial of ventilation and oxygenation management strategies, and enrolled infants at 24–27 6/7 weeks gestation [10]. Children were eligible for the present study if they had been tested between June 2005 and February 2009 in one of the 15 participating centers of the NRN, had object permanence scores at 18 to 22 months adjusted age, and had completed testing at 6 to 7 years. Figure 1 provides a study selection flow chart of the children in the current study. Parent report was used to obtain information on ethnicity/race and maternal education level.
Figure 1.
Sample Selection Flowchart
2.2. Test Measures
The object permanence measure consisted of 3 items from the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) [11] Cognitive Scale. These object permanence items sequentially increase in difficulty and are scored as pass or fail. First, the child is asked to find a toy hidden under one of two washcloths (Finds Hidden Object), then the cloths are reversed after the toy is hidden (Finds Hidden Object – Reversed), and finally the toy is hidden under one cloth, removed and hidden a second time under the second cloth (Finds Hidden Object – Visual Displacement). Object permanency score ranged from 0 to 3 and object permanence mastery (categorical) was scored when the child had correctly answered two or 3 items.
Testing at 6 to7 years included the Wechsler Intelligence Scale for Children – 4th edition (WISC-IV) [12], which was administered individually. Examiners were certified to ensure consistency of administration for all centers. The composite scores used in the analysis included verbal comprehension index, perceptual reasoning index, working memory index, and processing speed index. The standard score had a mean of 100 and standard deviation of 15. Full scale IQ is the summation of the above scales and was therefore not used in the analyses.
Selected subtests of the Developmental NEuroPSYchological Assessment −2nd edition (NEPSY-II) [13], were used as measures of executive function and other domains of fluid intelligence. The Memory for Names scale included an immediate recall and 30-minute delayed recall scale. The Inhibition scale combined scores for speed and accuracy of responses into a total score, which was converted into a standardized scaled score for analyses. Standardized scaled scores were calculated with a mean of 10 and standard deviation of 3.
2.3. Cranial ultrasound and MRI
A conventional, qualitative brain MRI was obtained at 35–42 weeks postmenstrual age, and a cranial ultrasound within 2 weeks of the MRI. Central reader interpretations were used for study analyses, and a masked central reader reviewed all brain MRIs utilizing white matter abnormality scoring according to a widely used classification system [14]. Inter-rater agreement for moderate or severe white matter abnormalities was reported to be 96% to 98%, using this classification system [14]. Adverse findings on brain MRI were defined as significant cerebellar lesions (defined as lesions that were bilateral, cystic, and/or ≥4 mm in size) or moderate or severe white matter abnormalities.
2.4. Statistical Methods
First, we computed bivariate analyses to examine the relationship between object permanence at 18–22 months adjusted age and cognitive outcomes at 6–7 years of age. T-tests were conducted to compare mean scores on the WISC-IV and NEPSY-II subscales based on object permanence mastery. Then we fit linear mixed effect regression models of the WISC-IV and NEPSY-II subscales by object permanence mastery, including center as a random effect and controlling for the following background variables: moderate/severe white matter abnormality on MRI, significant cerebellar lesions on MRI, late cranial ultrasound (CUS) adverse finding, early CUS adverse finding, gestational age, sex, severe retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), age at assessment, maternal education, and race/ethnicity. We then tested for a sex by object permanence mastery interaction within the regression models to determine whether the relationship between object permanence and executive functioning differs between boys and girls.
We also examined the relationship between neonatal neuroimaging findings and object permanence at 18–22 months corrected age. We fit mixed effect regression models predicting object permanence by each type of neuroimaging finding, including center as a random effect and controlling for variables collected during the newborn period (i.e., gestational age, sex, severe ROP, BPD, maternal education, and race/ethnicity). A linear model was used for object permanence scores and a generalized linear model for object permanence mastery.
3. RESULTS
Among our sample, birth weights ranged from 370 to 1410 grams with a mean of 844 grams. The mean gestational age was 26 weeks with a range of 24 to 27 weeks. A total of 247 (64%) of the 383 children exhibited object permanence mastery at 18–22 months corrected age. Significantly more girls (124/175 = 71%) than boys (123/208 = 59%) had object permanence mastery (χ2(1) = 5.70, p = 0.017). Table 1 displays demographic characteristics and scale scores.
Table 1.
Demographic and Medical Characteristics and Scale Scores (N=383)
| Characteristic | All (N=383) | Boys (N=208) | Girls (N=175) | Boys vs. Girls |
|---|---|---|---|---|
| N (%) or mean ± SD |
N (%) or mean ± SD |
N (%) or mean ± SD |
p-value | |
| Birth weight | 863.7 ± 191.8 | 887.6 ± 196.1 | 835.4 ± 182.9 | 0.008 |
| Gestational age | 25.9 ± 1.0 | 25.9 ± 1.0 | 26.0 ± 1.0 | 0.269 |
| Multiple gestation | 87 (23) | 50 (24) | 37 (21) | 0.501 |
| Antenatal steroids | 365 (95) | 198 (95) | 167 (95) | 0.913 |
| Late sepsis | 119 (31) | 65 (31) | 54 (31) | 0.934 |
| NEC | ||||
| No NEC | 352 (93) | 191 (92) | 161 (92) | 0.242 |
| Medical NEC | 17 (4) | 7 (3) | 10 (6) | |
| Surgical NEC | 14 (4) | 10 (5) | 4 (2) | |
| Severe ROP* | 37 (10) | 18 (9) | 19 (12) | 0.477 |
| Surgery for PDA, NEC or ROP* | 65 (18) | 32 (17) | 33 (20) | 0.400 |
| Postnatal steroids | 26 (7) | 17 (8) | 9 (5) | 0.247 |
| BPD | 139 (36) | 87 (42) | 52 (30) | 0.014 |
| Maternal Education | ||||
| Less than high school | 96 (25) | 51 (25) | 45 (26) | 0.706 |
| High school graduate | 108 (29) | 56 (27) | 52 (30) | |
| Some college or more | 173 (46) | 98 (48) | 75 (44) | |
| Maternal race/ethnicity | ||||
| Black | 122 (32) | 62 (30) | 60 (34) | 0.754 |
| White | 161 (42) | 92 (44) | 69 (39) | |
| Hispanic | 90 (24) | 49 (24) | 41 (23) | |
| Other/unknown | 10 (3) | 5 (2) | 5 (3) | |
| Neonatal neuroimaging | ||||
| Early CUS adverse finding (Grade III/IV ICH or cPVL) | 34 (9) | 19 (9) | 15 (9) | 0.847 |
| Late CUS adverse finding (Moderate/severe VE, cPVL, Porencephalic cyst, shunt) | 22 (6) | 13 (6) | 9 (5) | 0.643 |
| Moderate/severe white matter abnormality on MRI | 72 (19) | 44 (21) | 28 (16) | 0.198 |
| Any cerebellar lesion on MRI | 53 (14) | 34 (16) | 19 (11) | 0.121 |
| Significant cerebellar lesion on MRI | 36 (9) | 22 (11) | 14 (8) | 0.389 |
| Adjusted age at 18–22 month assessment (months) | 19.7 ± 2.1 | 19.9 ± 2.3 | 19.5 ± 1.8 | 0.101 |
| Object Permanence at 18 – 22 months | ||||
| Score | 1.9 ± 1.1 | 1.8 ± 1.1 | 2.0 ± 1.1 | 0.035 |
| Mastery (number (%)) | 247 (64) | 123 (59) | 124 (71) | 0.017 |
| Age at school age follow-up (years) | 6.3 ± 0.5 | 6.3 ± 0.5 | 6.3 ± 0.5 | 0.881 |
| WISC-IV | ||||
| Verbal Comprehension Index (VCI) | 87.5 ± 15.3 | 86.0 ± 15.6 | 89.3 ± 14.8 | 0.040 |
| Perceptual Reasoning Index (PRI) | 91.7 ± 16.4 | 90.6 ± 16.7 | 92.9 ± 15.9 | 0.180 |
| Working Memory Index (WMI) | 88.9 ± 13.7 | 88.1 ± 13.1 | 89.9 ± 14.4 | 0.214 |
| Processing Speed Index (PSI) | 89.2 ± 15.5 | 86.8 ± 16.2 | 91.9 ± 14.2 | 0.001 |
| NEPSY-II | ||||
| Memory for Names | ||||
| MN and MND | 8.3 ± 3.3 | 8.1 ± 3.3 | 8.5 ± 3.4 | 0.286 |
| Inhibition | ||||
| INN combined | 7.2 ± 3.6 | 7.1 ± 3.7 | 7.4 ± 3.5 | 0.369 |
| INI combined | 7.1 ± 3.3 | 6.7 ± 3.3 | 7.4 ± 3.3 | 0.065 |
Number of participants with missing data: ROP (N=23), surgery for ROP, NEC, or PDA (N=27), postnatal steroids (N=3), and education (N=6). Percentages are computed out of those with data for the corresponding variable.
Bivariate comparisons of the executive functioning scales by object permanence mastery are shown in Table 2. Children with object permanence mastery exhibited significantly greater mean WISC-IV verbal comprehension scores than those with no mastery (89.1 vs. 84.6, p = 0.006). Similarly, those with object permanence mastery had significantly higher mean WISC-IV processing speed scores (90.4 vs. 86.8, p = 0.032). No significant differences were found for the WISC-IV perceptual reasoning or working memory indices or for any of the NEPSY-II measures. These findings remained when controlling for other factors using regression models. Children with object permanence mastery continued to have significantly higher adjusted mean scores for the verbal comprehension (p = 0.039) and processing speed (p = 0.034) indices than those without mastery (Table 2). Using Cohen’s d (i.e., standardized mean difference) as a measure of effect size, the size of the difference in mean scores between those with vs. without object permanence mastery was a d value of −0.24 which is equivalent to 0.24 SDs lower for verbal comprehension and a d value of −0.30 equivalent to 0.30 SDs lower for processing speed.
Table 2.
WISC-IV and NEPSY-II Scores at 6–7 Years by Object Permanence Mastery (OPM) at 18–22 Months
| Scale | Unadjusted |
Adjusted |
||||
|---|---|---|---|---|---|---|
| OP* Mastery Mean (95% CI) |
No Mastery Mean (95% CI) |
p | OP Mastery Mean (95% CI) |
No Mastery Mean (95% CI) |
p | |
| WISC-IV | ||||||
| Verbal Comprehension | 89.1 (87.2, 91.0) | 84.6 (81.9, 87.3) | 0.006 | 88.1 (86.1, 90.2) | 84.8 (82.1, 87.5) | 0.039 |
| Perceptual Reasoning | 92.6 (90.8, 94.5) | 89.9 (86.7, 93.2) | 0.127 | 93.1 (89.9, 96.2) | 91.3 (87.5, 95.0) | 0.311 |
| Working Memory | 89.5 (87.7, 91.2) | 88.0 (85.6, 90.3) | 0.312 | 89.3 (86.9, 91.7) | 88.3 (85.3, 91.2) | 0.507 |
| Processing Speed | 90.4 (88.5, 92.3) | 86.8 (84.0, 89.6) | 0.032 | 90.2 (87.6, 92.7) | 86.3 (83.0, 89.6) | 0.034 |
| NEPSY-II# | ||||||
| Memory for Names | ||||||
| MN and MND | 8.3 (7.9, 8.7) | 8.3 (7.7, 8.8) | 0.909 | 8.2 (7.6, 8.8) | 8.1 (7.4, 8.9) | 0.781 |
| Inhibition | ||||||
| INN combined | 7.4 (6.9, 7.8) | 7.0 (6.3, 7.7) | 0.382 | 7.5 (6.9, 8.2) | 7.0 (6.2, 7.9) | 0.267 |
| INI combined | 7.1 (6.6, 7.5) | 7.1 (6.4, 7.7) | 0.928 | 7.1 (6.6, 7.6) | 7.0 (6.2, 7.7) | 0.769 |
Note: Adjusted means control for center, moderate/severe white matter abnormality on MRI, significant cerebellar lesions on MRI, late cranial ultrasound adverse finding, gestational age, sex, severe ROP, BPD, age at assessment, maternal education, and white race.
OP = object permanence
scale means 10, SD 3
A sex by object permanence interaction was then tested for each model to determine whether the relationship between object permanence and executive functioning differs for boys vs. girls. This interaction was statistically significant for the WISC-IV working memory (F(1,318) = 9.06, p = 0.003) and processing speed (F(1,313) = 7.92, p = 0.005) indices. Figure 2 shows the differences in mean scores on NEPSY-II and WISC-IV for children with vs. without object permanence mastery, after controlling for other factors. Higher values indicate that those with mastery scored higher on the assessments than those without mastery. As shown in the figure, girls with object permanence mastery had significantly higher working memory scores (p = 0.009) and higher processing speed (p < 0.001) than girls without object permanence mastery; however, these differences were not observed among boys (p = 0.159; p = 0.924). While the sex by object permanence mastery interaction was not statistically significant for verbal comprehension (F(1,318) = 2.83, p = 0.094), a similar pattern was evident in examining the sex differences in the associations of object permanence mastery with other cognitive outcomes. Object permanence mastery was significantly associated with higher scores among girls (p = 0.010), but not boys (p = 0.587). Among boys, the effect sizes for the differences in scores on these two scales between those with vs. without object permanence mastery were: verbal comprehension (d=0.13) and processing speed (d=0.07). Data were substantially more robust for girls with effect sizes for those with and without object permanence mastery of (d=0.49) for verbal comprehension and (d=0.63) for processing speed, respectively. No significant sex by object permanence mastery interactions were found for the NEPSY-II scales.
Figure 2.
Adjusted Mean Differences of WISC-IV and NEPSY-II Scores for Object Permanence Mastery vs. No Object Permanence Mastery by Sex
Note: Adjusted mean differences control for object permanence mastery, sex, object permanence mastery x sex interaction, center, moderate/severe white matter abnormality on MRI, significant cerebellar lesions on MRI, late cranial ultrasound adverse finding, gestational age, severe ROP, BPD, age at assessment, maternal education, and white race.
There was no significant relationship between object permanence scores and either early or late CUS findings (Table 3). In contrast, on univariate analysis, lower object permanence scores were significantly associated with cerebellar lesions, (p = 0.016) and moderate/severe white matter abnormality on MRI scans (p = 0.048) (Table 3). When controlling for other neonatal factors, only the association with cerebellar lesions remained significant (p = 0.029).
Table 3.
Object Permanence Scores at 18–22 Months by Neonatal Neuroimaging Findings
| Neuroimaging Finding | Unadjusted |
Adjusted |
||
|---|---|---|---|---|
| Mean (95% CI) | p | Mean (95% CI) | p | |
| Early CUS adverse finding (Grade III/IV ICH or cPVL) | ||||
| Yes | 1.6 (1.2, 2.0) | 0.166 | 1.8 (1.3, 2.2) | 0.214 |
| No | 1.9 (1.8, 2.1) | 2.0 (1.8, 2.3) | ||
| Late CUS adverse finding (Moderate/severe VE, cPVL, porencephalic cyst, shunt) | ||||
| Yes | 1.5 (0.9, 2.0) | 0.056 | 1.7 (1.1, 2.2) | 0.184 |
| No | 1.9 (1.8, 2.1) | 2.0 (1.7, 2.3) | ||
| Significant cerebellar lesions on MRI | ||||
| Yes | 1.5 (1.1, 1.9) | 0.016 | 1.6 (1.1, 2.0) | 0.029 |
| No | 2.0 (1.8, 2.1) | 2.0 (1.8, 2.3) | ||
| Moderate/severe white matter abnormality on MRI | ||||
| Yes | 1.7 (1.4, 2.0) | 0.048 | 1.8 (1.5, 2.2) | 0.130 |
| No | 2.0 (1.8, 2.1) | 2.0 (1.8, 2.3) | ||
Note: Adjusted means control for center, gestational age, sex, severe ROP, BPD, maternal education, and white race.
4. DISCUSSION
In this study, we found that girls who had achieved object permanence mastery at a corrected age of 18–22 months had higher mean scores on the WISC-IV tests of verbal comprehension and processing speed at age 6, after controlling for other factors. In our previous study at 18–22 months, we found that boys had significantly lower object permanence scores and Bayley-III language scale scores than girls [7].
Although we had hypothesized that the object permanence scores also would be associated with tests of executive function, we found no relationship of object permanence score with NEPSY-II scores. Few studies have looked at measures of early executive function, although several studies have assessed the relationship of early tests of overall cognitive function with later behavioral and executive function outcomes. Gould and associates [4] found that in a cohort of Australian children born preterm and tested at 18–22 months, lower Bayley-II mental developmental index scores were associated with difficulties in measures of behavior and executive function at 7 years. In another longitudinal study, a group of Swedish children born preterm were assessed at 10 months, 5 ½ years, and 18 years. Those authors also found Bayley-II mental developmental index scores, together with parental education level, were related to scores of cognitive flexibility and working memory at 5 ½ years. Further findings in this study indicated that working memory scores at 5 ½ years were related to working memory scores at 18 years [15]. Many studies continue to confirm that behavior problems and difficulty with executive function are greater in preterm children compared to those born full term [9], and that these problems persist overtime [16].
Studies of preterm children have consistently shown that boys do less well on developmental tests at young ages [17]. Although some studies have indicated that they catch up at later school age [18], others have found that boys born preterm continue to have more problems in areas of cognition, behavior, and neurologic status when tested at 10 years of age [19].
After adjusting for other variables, white matter injury on MRI scans in the newborn period was not significantly associated with object permanence scores at 18 – 22 months; however, cerebellar lesions remained significantly associated with lower object permanence scores at age 18 – 22 months. In the same cohort of children, Hintz et al. found that significant cerebellar lesions were also associated with severe disability at school age [8]. Others have reported that cerebral white matter abnormalities on newborn MRI scan were related to lower scores on tests of cognition and working memory in 4 and 6 year olds born preterm [20]. In a group of preterm-born 7 year-old children, cerebral white matter and deep gray matter injury on neonatal MRI scan were associated with lower cognitive scores, while cerebellar injury was associated with math and motor function problems [21].
Our study did not find an association between either early or late CUS and object permanence scores. It is important to note that very few children had significant early or late CUS abnormalities (9% and 6% respectively), defined as grade III or IV intracranial hemorrhage or cystic periventricular leukomalacia. Ongoing controversy exists regarding the value of either MRI or CUS in the newborn period in identifying later disability, due to the variable positive predictive value of these tests [22].
Identifying early markers of future learning difficulty would be beneficial, allowing early intervention services to target the most vulnerable children. The lack of inclusion of measures other than cognition or intelligence has been noted as a weakness in many studies of both preterm and term children [23]. Though measures of early executive function are limited [24], more test measures are being used that can assess these constructs in young children [25]. Including a measure such as object permanence in a test battery could potentially assist in both research and early intervention as a means of identifying young children at greater risk for later learning problems. More intervention programs are being developed to target methods of enhancing cognitive skills that may best benefit preterm children [21,26].
This study has both limitations and strengths. Testing of young children is difficult and only represents their behaviors at one point in time. In addition, tests can be racially and ethnically biased, although we did include both ethnicity and maternal education as factors in our statistical analyses. Strengths of this research included that our sample size was robust, we used a longitudinal design, and all examiners were certified in the test measures.
5. CONCLUSION
In conclusion, our study found that early attainment of object permanence was associated with higher scores at school age in areas of cognition in girls, but not boys. These results have implications for potentially identifying young children born preterm who are at greater risk for difficulties with cognitive and working memory skills at school age. In comparison to more cumbersome and expensive tools, such as MRI or CUS, a simple test of object permanence could possibly help identify children as young as 18 months who may have greater risk for learning difficulties.
Highlights.
Object permanence at 18 months was associated with testing of preterm 7-year olds
Object permanence score was associated with cerebellar lesions on MRI at birth
Object permanence score was associated with WISC-IV verbal comprehension score
Object permanence was associated with working memory scores in girls born preterm
Acknowledgements
The National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Heart, Lung, and Blood Institute (NHLBI) provided grant support for the Neonatal Research Network’s Extended Follow-up at School Age for the SUPPORT Neuroimaging and Neurodevelopmental Outcomes (NEURO) Cohort through cooperative agreements. While NICHD staff had input into the study design, conduct, analysis, and manuscript drafting, the comments and views of the authors do not necessarily represent the views of NICHD, NHLBI, the National Institutes of Health, the Department of Health and Human Services, or the U.S. Government.
Data collected at participating sites of the NICHD Neonatal Research Network (NRN) were transmitted to RTI International, the data coordinating center (DCC) for the network, which stored, managed and analyzed the data for this study. On behalf of the NRN, RTI International had full access to all the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis.
We are indebted to our medical and nursing colleagues and the infants and their parents who agreed to take part in this study. The following investigators, in addition to those listed as authors, participated in this study:
NRN Steering Committee Chairs: Alan H. Jobe, MD PhD, University of Cincinnati (2003–2006); Michael S. Caplan, MD, University of Chicago, Pritzker School of Medicine (2006–2011); Richard A. Polin, MD, Division of Neonatology, College of Physicians and Surgeons, Columbia University, (2011-present).
Alpert Medical School of Brown University and Women & Infants Hospital of Rhode Island (U10 HD27904) – Abbot R. Laptook, MD; William Oh, MD; Angelita M. Hensman, PhD RNC-NIC; Barbara Alksninis, PNP; Susan Barnett, RRT; Bill Cashore, MD; Melinda Caskey, MD; Kim Francis, RN; Dan Gingras, RRT; Katharine Johnson, MD; Mary Lenore Keszler, MD; Andrea M. Knoll; Theresa M. Leach, MEd CAES; Elisabeth C. McGowan, MD; Bonnie E. Stephens, MD; Victoria E. Watson, MS CAS.
Case Western Reserve University, Rainbow Babies & Children’s Hospital (U10 HD21364, M01 RR80) – Michele C. Walsh, MD MS; Deanne E. Wilson-Costello, MD; Allison Payne, MD MSCR; Nancy S. Newman, RN; Monika Bhola, MD; Julie DiFiore, BS; Harriet G. Friedman, MA; Maureen Hack, MD (deceased); Bonnie S. Siner, RN; Arlene Zadell, RN; H. Gerry Taylor, PhD; Gulgun Yalcinkaya, MD.
Cincinnati Children’s Hospital Medical Center (UG1 HD27853) – Kimberly Yolton, PhD.
Department of Diagnostic Imaging and Radiology, Children’s National Medical Center, Washington DC – Dorothy Bulas, MD.
Duke University School of Medicine, University Hospital, and Duke Regional Hospital (U10 HD40492, M01 RR30) – Ronald N. Goldberg, MD; C. Michael Cotten, MD MHS; Ricki F. Goldstein, MD; Patricia Ashley, MD; Kathy J. Auten, MSHS; Kimberley A. Fisher, PhD FNP-BC IBCLC; Katherine A. Foy, RN; Sharon F. Freedman, MD; Kathryn E. Gustafson, PhD; Melody B. Lohmeyer, RN MSN; William F. Malcolm, MD; David K. Wallace, MD MPH.
Emory University, Children’s Healthcare of Atlanta, Grady Memorial Hospital, and Emory Crawford Long Hospital (U10 HD27851, RR25008, M01 RR39) – David P. Carlton, MD; Barbara J. Stoll, MD; Ira Adams-Chapman, MD; Diane Bottcher, RN; Susie Buchter, MD; Sheena Carter, PhD; Sobha Fritz, PhD; Ellen C. Hale, RN BS CCRC; Amy K. Hutchinson, MD; Yvonne Loggins, RN; Maureen Mulligan LaRossa, RN; Anthony J. Piazza, MD.
Eunice Kennedy Shriver National Institute of Child Health and Human Development – Stephanie Wilson Archer, MA.
Indiana University, University Hospital, Methodist Hospital, Riley Hospital for Children, and Wishard Health Services (U10 HD27856, M01 RR750) – Brenda B. Poindexter, MD MS; Gregory M. Sokol, MD; Ann B. Cook, MS; Anna M. Dusick, MD (deceased); Faithe Hamer, BS; Heidi M. Harmon, MD MS; Dianne E. Herron, RN CCRC; Abbey C. Hines, PsyD; Carolyn Lytle, MD MPH; Heike M. Minnich, PsyD HSPP; Lu-Ann Papile, MD; Lucy Smiley, CCRC; Leslie D. Wilson, BSN CCRC.
McGovern Medical School at The University of Texas Health Science Center at Houston and Children’s Memorial Hermann Hospital (U10 HD21373) – Kathleen A. Kennedy, MD MPH; Jon E. Tyson, MD MPH; Esther G. Akpa, RN BSN; Nora I. Alaniz, BS; Allison G. Dempsey, PhD; Beverly Foley Harris, RN BSN; Charles Green, PhD; Margarita Jiminez, MD MPH; Janice John, CPNP; Patrick M. Jones, MD MA; M. Layne Lillie, RN BSN; Anna E. Lis, RN BSN; Sarah Martin, RN BSN; Georgia E. McDavid, RN; Brenda H. Morris, MD; Margaret L. Poundstone, RN BSN; Stacy Reddoch, BA; Patti L. Pierce Tate, RCP; Saba Siddiki, MD; Daniel K. Sperry, RN; Sharon L. Wright, MT (ASCP).
National Heart, Lung, and Blood Institute – Mary Anne Berberich, PhD; Carol J. Blaisdell, MD; Dorothy B. Gail, PhD; James P. Kiley, PhD.
RTI International (U10 HD36790) – Dennis Wallace, PhD; Marie G. Gantz, PhD; Jeanette O’Donnell Auman, BS; Jane A. Hammond, PhD; Betty K. Hastings; Elizabeth M. McClure, PhD; Jamie E. Newman, PhD MPH; Jeanette O’Donnell Auman, BS; Carolyn Petrie Huitema, MS; Lindsay Parlberg, BS; James W. Pickett II, BS; W. Kenneth Poole, PhD (deceased); Kristin M. Zaterka-Baxter, RN BSN.
Stanford University and Lucile Packard Children’s Hospital (U10 HD27880, UL1 RR25744, M01 RR70) – Krisa P. Van Meurs, MD; David K. Stevenson, MD; M. Bethany Ball, BS CCRC; Patrick D. Barnes, MD; Barbara Bentley, PsychD MSEd; Elizabeth F. Bruno, PhD; Maria Elena DeAnda, PhD; Anne M. DeBattista, RN PNP; Gabrielle T. Goodlin, BAS; Jean G. Kohn, MD MPH; Melinda S. Proud, RCP; Renee P. Pyle, PhD; Hali E. Weiss, MD.
Tufts Medical Center, Floating Hospital for Children (U10 HD53119, M01 RR54) – Ivan D. Frantz III, MD; Elisabeth C. McGowan, MD; John M. Fiascone, MD; Anne Furey, MPH; Brenda L. MacKinnon, RNC; Ellen Nylen, RN BSN; Ana Brussa, MS OTR/L; Cecelia Sibley, PT MHA.
University of Alabama at Birmingham Health System and Children’s Hospital of Alabama (U10 HD34216, M01 RR32) – Waldemar A. Carlo, MD; Namasivayam Ambalavanan, MD; Monica V. Collins, RN BSN MaEd; Shirley S. Cosby, RN BSN; Myriam Peralta-Carcelen, MD; Vivien A. Phillips, RN BSN; Kirstin J. Bailey, PhD; Fred J. Biasini, PhD; Kristy Domanovich, PhD; Maria Hopkins, PhD; Kristen C. Johnston, MSN CRNP; Carin R. Kiser, MD; Kathleen G. Nelson, MD; Cryshelle S. Patterson, PhD; Richard V. Rector, PhD; Leslie Rodriguez, PhD; Leigh Ann Smith, CRNP; Amanda Soong, MD; Sally Whitley, MA OTR-L FAOTA; Sheree York, PT DPT MS PCS.
University of California – San Diego Medical Center and Sharp Mary Birch Hospital for Women (U10 HD40461) – Neil N. Finer, MD; Donna Garey, MD MPH; Maynard R. Rasmussen; MD; Paul R. Wozniak, MD; Yvonne E. Vaucher, MD MPH; Wade Rich, BSHS RRT; Martha G. Fuller, PhD RN; Natacha Akshoomoff, PhD; Kathy Arnell, RNC; Rene Barbieri-Welge; Ayala Ben-Tall; Renee Bridge, RN; Clarence Demetrio, RN; Elaine Ito; Meghan Lukasik; Deborah Pontillo; Donna Posin, OTR/L MPA; Cheryl Runyan; James Wilkes; Paul Zlotnik.
University of Iowa (U10 HD53109, UL1 TR442, M01 RR59) – Edward F. Bell, MD; Tarah T. Colaizy, MD; John A. Widness, MD; Jonathan M. Klein, MD; Karen J. Johnson, RN BSN; Michael J. Acarregui, MD; Jane E. Brumbaugh, MD; Diane L. Eastman, RN CPNP MA; Tammy L. V. Wilgenbusch, PhD.
University of New Mexico Health Sciences Center (U10 HD53089, M01 RR997) – Robin K. Ohls, MD; Julie Rohr, MSN RNC CNS; Conra Backstrom Lacy, RN; Rebecca Montman, BSN; Sandra Brown, RN BSN.
University of Texas Southwestern Medical Center at Dallas, Parkland Health & Hospital System, and Children’s Medical Center Dallas (U10 HD40689, M01 RR633) – Pablo J. Sánchez, MD; Charles R. Rosenfeld, MD; Walid A. Salhab, MD; Luc Brion, MD; Roy J. Heyne, MD; Sally S. Adams, MS RN CPNP; James Allen, RRT; Laura Grau, RN; Alicia Guzman; Gaynelle Hensley, RN; Elizabeth T. Heyne, PsyD PA-C; Jackie F. Hickman, RN; Lizette E. Lee, RN; Melissa H. Leps, RN; Linda A. Madden, RN CPNP; Melissa Martin, RN; Nancy A. Miller, RN; Janet S. Morgan, RN; Araceli Solis, RRT; Catherine Twell Boatman, MS CIMI; Diana M Vasil, MSN BSN RNC-NIC.
University of Utah Medical Center, Intermountain Medical Center, LDS Hospital, and Primary Children’s Medical Center (U10 HD53124, M01 RR64) – Bradley A. Yoder, MD; Roger G. Faix, MD; Sarah Winter, MD; Shawna Baker, RN; Karie Bird, RN BSN; Anna E. Bullwinkle, RN; Jill Burnett, RNC BSN; Laura Cole Bledsoe, RN; Sean Cunningham, PhD; Ariel Ford, PhD; Carrie A. Rau, RN BSN CCRC; Cynthia Spencer, RNC BSN; R. Edison Steele, RN; Michael Steffen, PhD; Kimberlee Weaver-Lewis, MS RN.
Wayne State University, Hutzel Women’s Hospital, and Children’s Hospital of Michigan (U10 HD21385) – Seetha Shankaran, MD; Athina Pappas, MD; Beena G. Sood, MD MS; Rebecca Bara, RN BSN; Girija Natarajan MD; Monika Bajaj MD; Elizabeth Billian, RN MBA; Laura A. Goldston, MA; Mary Johnson, RN BSN.
Funding: The National Institutes of Health (M01 RR30, M01 RR32, M01 RR39, M01 RR54, M01 RR59, M01 RR64, M01 RR80, M01 RR70, M01 RR633, M01 RR750, M01 RR997, UL1 RR25008, UL1 RR25744, UL1 TR442), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (U10 HD21364, U10 HD21385, U10 HD21373, U10 HD27851, U10 HD27856, U10 HD27880, U10 HD27904, U10 HD34216, U10 HD36790, U10 HD40461, U10 HD40492, U10 HD40689, U10 HD53089, U10 HD53109, U10 HD53119, U10 HD53124), and the National Heart, Lung, and Blood Institute (NHLBI) (via co-funding) provided grant support for the Neonatal Research Network’s Extended Follow-up at School Age for the SUPPORT Neuroimaging and Neurodevelopmental Outcomes (NEURO) Cohort.
Footnotes
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Conflict of Interest: The authors have no conflicts of interest to disclose.
Financial Disclosure: The authors have no financial relationships relevant to this article to disclose.
ClinicalTrials.gov ID: Extended Follow-up at School Age for the SUPPORT Neuroimaging and Neurodevelopmental Outcomes (NEURO) Cohort: NCT00233324.
Data Sharing: Data reported in this paper may be requested through a data use agreement. Further details are available at https://neonatal.rti.org/index.cfm?fuseaction=DataRequest.Home.
Prior Presentation: This work was presented as a poster at the Pediatric Academic Societies, April 28-May 1, 2019 in Baltimore Maryland.
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