Breast Cancer Screening and BI-RADS Scoring Trends Before and During the COVID-19 Pandemic in an Academic Safety-Net Hospital.

BACKGROUND: Little is known about how the COVID-19 pandemic affected screening mammography rates and Breast Imaging Reporting and Data Systems (BI-RADS) categorizations within populations facing social and economic inequities. Our study seeks to compare trends in breast cancer screening and BI-RADS assessments in an academic safety-net patient population before and during the COVID-19 pandemic. PATIENTS AND METHODS: Our single-center retrospective study evaluated women ≥ 18 years old with no known breast cancer diagnosis who received breast cancer screening from March 2019-September 2020. The screening BI-RADS score, completion of recommended diagnostic imaging, and diagnostic BI-RADS scores were compared between the pre-COVID-19 era (from 1 March 2019 to 19 March 2020) and COVID-19 era (from 20 March 2020 to 30 September 2020). RESULTS: Among the 11,798 patients identified, screened patients were younger (median age 57 versus 59 years, p < 0.001) and more likely covered by private insurance (35.9% versus 32.3%, p < 0.001) during the COVID-19 era compared with the pre-COVID-19 era. During the pandemic, there was an increase in screening mammograms categorized as BI-RADS 0 compared with the pre-COVID-19 era (20% versus 14.5%, p < 0.0001). There was no statistically significant difference in rates of completion of diagnostic imaging (81.6% versus 85.4%, p = 0.764) or assignment of suspicious BI-RADS scores (BI-RADS 4-5; 79.9% versus 80.8%, p = 0.762) between the two eras. CONCLUSIONS: Although more patients were recommended to undergo diagnostic imaging during the pandemic, there were no significant differences in race, completion of diagnostic imaging, or proportions of mammograms categorized as suspicious between the two time periods. These findings likely reflect efforts to maintain equitable care among diverse racial groups served by our safety-net hospital.

A Rheological Study on the Effect of Tethering Pro- and Anti-Inflammatory Cytokines into Hydrogels on Human Mesenchymal Stem Cell Migration, Degradation, and Morphology.

Polymer-peptide hydrogels are being designed as implantable materials that deliver human mesenchymal stem cells (hMSCs) to treat wounds. Most wounds can progress through the healing process without intervention. During the normal healing process, cytokines are released from the wound to create a concentration gradient, which causes directed cell migration from the native niche to the wound site. Our work takes inspiration from this process and uniformly tethers cytokines into the scaffold to measure changes in cell-mediated degradation and motility. This is the first step in designing cytokine concentration gradients into the material to direct cell migration. We measure changes in rheological properties, encapsulated cell-mediated pericellular degradation and migration in a hydrogel scaffold with covalently tethered cytokines, either tumor necrosis factor-α (TNF-α) or transforming growth factor-ß (TGF-ß). TNF-α is expressed in early stages of wound healing causing an inflammatory response. TGF-ß is released in later stages of wound healing causing an anti-inflammatory response in the surrounding tissue. Both cytokines cause directed cell migration. We measure no statistically significant difference in modulus or the critical relaxation exponent when tethering either cytokine in the polymeric network without encapsulated hMSCs. This indicates that the scaffold structure and rheology is unchanged by the addition of tethered cytokines. Increases in hMSC motility, morphology and cell-mediated degradation are measured using a combination of multiple particle tracking microrheology (MPT) and live-cell imaging in hydrogels with tethered cytokines. We measure that tethering TNF-α into the hydrogel increases cellular remodeling on earlier days postencapsulation and tethering TGF-ß into the scaffold increases cellular remodeling on later days. We measure tethering either TGF-ß or TNF-α enhances cell stretching and, subsequently, migration. This work provides rheological characterization that can be used to design new materials that present chemical cues in the pericellular region to direct cell migration.

Infant massage as a stress management technique for parents of hospitalized extremely preterm infants.

Mothers of infants born extremely preterm requiring prolonged medical intervention in the Neonatal Intensive Care Unit (NICU) are at high risk of developing stress. Parent-administered infant massage is a well-established, safe intervention for preterm infants with many developmental benefits, but the published literature has mostly examined its impact on infants and parents through self-reported or observational measures of stress. The aim of this study was to measure salivary cortisol, a biomarker for stress, in extremely preterm infants and their mothers immediately pre and post parent-administered infant massage in order to detect potential changes in physiologic stress. Twenty-two mother-infant dyads completed massage education with a physical or occupational therapist. All dyads provided salivary cortisol samples via buccal swab immediately pre- and post-massage at the second session. Of mothers determined to be "cortisol responders" (15/22), salivary cortisol levels were lower after massage (pre-minus post-level: -26.47 ng/dL, [CI = -4.40, -48.53], p = .016, paired t-test). Our primary findings include a clinically significant decrease (as measured by percent change) in maternal cortisol levels immediately post parent-administered massage, indicating decreased physiological stress. Integration of infant massage into NICU clinical practice may support maternal mental health, but further powered studies are necessary to confirm findings.

Las madres de infantes nacidos extremadamente prematuros en la Unidad de Cuidado Intensivo Neonatal (NICU) se encentran bajo alto riesgo de desarrollar estrés. El masaje que una madre le da al infante es una intervención segura, bien establecida, para infantes prematuros, con muchos beneficios de desarrollo, aunque la información publicada disponible ha examinado por la mayor parte el impacto del masaje en los infantes y progenitores por medio de medidas de estrés auto reportadas o de observación. El propósito de este estudio fue medir el cortisol salival, un biomarcador de estrés, en infantes extremadamente prematuros y sus madres inmediatamente antes y después del masaje que la madre le da, para detectar posibles cambios en el estrés fisiológico. Veintidós díadas madre-infante completaron 2 sesiones educativas de masaje con un terapeuta físico u ocupacional. Todas las díadas aportaron muestras de cortisol salival por medio de hisopado bucal inmediatamente antes y después del masaje en la segunda sesión. Los niveles de cortisol en infantes no fueron suficientes para el análisis. De las madres a quienes se les determinó haber dado "respuesta de cortisol" (15/22), los niveles de cortisol salival fueron más bajos después del masaje (nivel antes menos nivel después: −26.47 ng/dL, [CI = −4.40, −48.53]. p = .016, prueba-t pareada). Entre nuestros resultados primarios se incluye una baja clínicamente significativa (tal como fue medida por el cambio porcentual) en los niveles de cortisol materno inmediatamente después del masaje. Estos resultados sugieren que el masaje dado por la madre a infantes prematuros pudiera reducir el cortisol materno, un marcador fisiológico de estrés.

Prenatal and perinatal factors associated with neonatal neurobehavioral profiles in the ECHO Program.

BACKGROUND: Single-cohort studies have identified distinct neurobehavioral profiles that are associated with prenatal and neonatal factors based on the NICU Network Neurobehavioral Scale (NNNS). We examined socioeconomic, medical, and substance use variables as predictors of NNNS profiles in a multi-cohort study of preterm and term-born infants with different perinatal exposures. METHODS: We studied 1112 infants with a neonatal NNNS exam from the Environmental influences on Child Health Outcomes (ECHO) consortium. We used latent profile analysis to characterize infant neurobehavioral profiles and generalized estimating equations to determine predictors of NNNS profiles. RESULTS: Six distinct neonatal neurobehavioral profiles were identified, including two dysregulated profiles: a hypo-aroused profile (16%) characterized by lethargy, hypotonicity, and nonoptimal reflexes; and a hyper-aroused profile (6%) characterized by high arousal, excitability, and stress, with low regulation and poor movement quality. Infants in the hypo-aroused profile were more likely to be male, have younger mothers, and have mothers who were depressed prenatally. Infants in the hyper-aroused profile were more likely to be Hispanic/Latino and have mothers who were depressed or used tobacco prenatally. CONCLUSIONS: We identified two dysregulated neurobehavioral profiles with distinct perinatal antecedents. Further understanding of their etiology could inform targeted interventions to promote positive developmental outcomes. IMPACT: Prior research on predictors of neonatal neurobehavior have included single-cohort studies, which limits generalizability of findings. In a multi-cohort study of preterm and term-born infants, we found six distinct neonatal neurobehavioral profiles, with two profiles being identified as dysregulated. Hypo- and hyper-aroused neurobehavioral profiles had distinct perinatal antecedents. Understanding perinatal factors associated with dysregulated neurobehavior could help promote positive developmental outcomes.

Risk Factors for Postpartum Depression and Severe Distress among Mothers of Very Preterm Infants at NICU Discharge.

OBJECTIVE: To identify psychological, medical, and socioenvironmental risk factors for maternal postpartum depression (PPD) and severe psychological distress (SPD) at intensive care nursery discharge among mothers of very preterm infants. STUDY DESIGN: We studied 562 self-identified mothers of 641 infants born <30 weeks who were enrolled in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants Study (NOVI) conducted in nine university-affiliated intensive care nurseries. Enrollment interviews collected socioenvironmental data, depression, and anxiety diagnoses prior to and during the study pregnancy. Standardized medical record reviews ascertained prenatal substance use, maternal and neonatal medical complications. The Edinburgh Postnatal Depression Scale and Brief Symptom Inventory were administered at nursery discharge to screen for PPD and SPD symptoms, respectively. RESULTS: Unadjusted analyses indicated mothers with positive screens for depression (n = 76, 13.5%) or severe distress (n = 102, 18.1%) had more prevalent prepregnancy/prenatal depression/anxiety, and their infants were born at younger gestational ages, with more prevalent bronchopulmonary dysplasia, and discharge after 40 weeks postmenstrual age. In multivariable analyses, prior depression or anxiety was associated with positive screens for PPD (risk ratio [RR]: 1.6, 95% confidence interval [CI]: 1.1-2.2) and severe distress (RR: 1.6, 95% CI: 1.1-2.2). Mothers of male infants had more prevalent depression risk (RR: 1.7, 95% CI: 1.1-2.4), and prenatal marijuana use was associated with severe distress risk (RR: 1.9, 95% CI: 1.1-2.9). Socioenvironmental and obstetric adversities were not significant after accounting for prior depression/anxiety, marijuana use, and infant medical complications. CONCLUSION: Among mothers of very preterm newborns, these multicenter findings extend others' previous work by identifying additional indicators of risk for PPD and SPD associated with a history of depression, anxiety, prenatal marijuana use, and severe neonatal illness. Findings could inform designs for continuous screening and targeted interventions for PPD and distress risk indicators from the preconception period onward. KEY POINTS: · Preconceptional and prenatal screening for postpartum depression and severe distress may inform care.. · Prior depression, anxiety, and neonatal complications predicted severe distress and depression symptoms at NICU discharge.. · Readily identifiable risk factors warrant continuous NICU screening and targeted interventions to improve outcomes..

Prenatal Metal Exposure Alters the Placental Proteome in a Sex-Dependent Manner in Extremely Low Gestational Age Newborns: Links to Gestational Age.

Prenatal exposure to toxic metals is associated with altered placental function and adverse infant and child health outcomes. Adverse outcomes include those that are observed at the time of birth, such as low birthweight, as well as those that arise later in life, such as neurological impairment. It is often the case that these adverse outcomes show sex-specific responses in relation to toxicant exposures. While the precise molecular mechanisms linking in utero toxic metal exposures with later-in-life health are unknown, placental inflammation is posited to play a critical role. Here, we sought to understand whether in utero metal exposure is associated with alterations in the expression of the placental proteome by identifying metal associated proteins (MAPs). Within the Extremely Low Gestational Age Newborns (ELGAN) cohort (n = 230), placental and umbilical cord tissue samples were collected at birth. Arsenic (As), cadmium (Cd), lead (Pb), selenium (Se), and manganese (Mn) concentrations were measured in umbilical cord tissue samples via ICP-MS/MS. Protein expression was examined in placental samples using an LC-MS/MS-based, global, untargeted proteomics analysis measuring more than 3400 proteins. MAPs were then evaluated for associations with pregnancy and neonatal outcomes, including placental weight and gestational age. We hypothesized that metal levels would be positively associated with the altered expression of inflammation/immune-associated pathways and that sex-specific patterns of metal-associated placental protein expression would be observed. Sex-specific analyses identified 89 unique MAPs expressed in female placentas and 41 unique MAPs expressed in male placentas. Notably, many of the female-associated MAPs are known to be involved in immune-related processes, while the male-associated MAPs are associated with intracellular transport and cell localization. Further, several MAPs were significantly associated with gestational age in males and females and placental weight in males. These data highlight the linkage between prenatal metal exposure and an altered placental proteome, with implications for altering the trajectory of fetal development.

Maternal Social Risk, Gestational Age at Delivery, and Cognitive Outcomes among Adolescents Born Extremely Preterm.

Background: Children born extremely preterm (EP) are at increased risk of cognitive deficits that persist into adulthood. Few large cohort studies have examined differential impairment of cognitive function in EP-born adolescents in relation to early life risk factors, including maternal social disadvantage, gestational age at delivery, and neonatal morbidities prevalent among EP neonates. Objectives: To assess cognitive abilities in relation to early life risk factors in an EP-born cohort at 15 years of age. Methods: 681 of 1198 surviving participants (57%) enrolled from 2002 to 2004 in the Extremely Low Gestational Age Newborn Study returned at age 15 years for an assessment of cognitive abilities with the Wechsler Abbreviated Scale of Intelligence-II and the NIH Toolbox Cognition Battery (NTCB) verbal cognition and fluid processing composites, the latter of which measured executive functions and processing speed. Three cognitive outcomes, WASI-II IQ, NTCB verbal cognition, and NTCB fluid processing, were analyzed for associations with maternal social disadvantage and gestational age. Mediation of maternal social disadvantage by gestational age and mediation of gestational age by neonatal morbidities were also examined. Results: Test scores were lower for NTCB fluid processing relative to IQ and NTCB verbal abilities. Social disadvantage and gestational age were associated with all three cognitive outcomes. Mediation analyses indicated partial mediation of gestational age associations with all three outcomes by neonatal morbidities but did not support mediation by gestational age of social risk associations with cognitive outcomes. Conclusions: Greater maternal social disadvantage and lower gestational age are associated with less favorable cognitive outcomes among EP-born adolescents at 15 years of age. Neonatal morbidities partially mediate associations between lower gestational age and cognitive outcomes. These findings highlight the need for improved medical and remedial interventions to mitigate risk of poor cognitive outcomes among EP-born adolescents.

Family members' experience of well-being as racial/ethnic minorities raising a child with a neurodevelopmental disorder: A qualitative meta-synthesis.

Raising a child with a neurodevelopmental disorder has often been associated with poorer quality of life and family functioning. Yet, many family members describe themselves as resilient and capable of achieving well-being. Whether and how this occurs in racial/ethnic minority families remains largely unexplored. The aim of this study was to systematically synthesize qualitative studies exploring how families from a racial/ethnic minority background in the United States (1) experienced well-being and (2) responded to challenges they faced while caring for a child diagnosed with three selected neurodevelopmental disorders: autism spectrum disorder, attention deficit hyperactivity disorder, and intellectual disability. A systematic literature search was conducted in November and December of 2019 and updated in October 2021. Three themes were developed based on included studies: "moving toward well-being as a caregiver," "family and culture: impact on well-being," and "community and culture: impact on well-being." The findings in this review indicate that to develop well-being, racial/ethnic minority families faced additional barriers, including racial/ethnic discrimination and stigma within their family and cultural community. The knowledge generated has the potential to identify areas of intervention to promote resilience and well-being in racial/ethnic minority families raising a child with a neurodevelopmental disorder.

Meningitis, urinary tract, and bloodstream infections in very low birth weight infants enrolled in a heart rate characteristics monitoring trial.

BACKGROUND: Displaying heart rate characteristic (HRC) scores was associated with lower sepsis-associated mortality in very low birth weight (VLBW) infants in a multicenter randomized controlled trial (HeRO trial). The aim of this study was to test whether HRC indices rise before diagnosis of urinary tract infection (UTI) or meningitis, with and without concomitant BSI. METHODS: Blood, urine, and cerebrospinal fluid (CSF) culture data after 3 days of age and within 120 days of study enrollment were analyzed from 2989 VLBW infants. The HRC index was analyzed 12 h prior to positive cultures compared to 36 h prior, using paired signed-rank tests. RESULTS: UTI, meningitis, and BSI were diagnosed in 10%, 2%, and 24% of infants, respectively. The mean hourly HRC index was significantly higher 12 h prior to diagnosis of UTI and BSI compared to 36 h prior (UTI 2.07 versus 1.81; BSI 2.62 versus 2.25, both p < 0.0001). The baseline HRC index was higher for meningitis, compared to UTI or BSI, but without a statistically significant rise in the day prior to meningitis diagnosis. CONCLUSIONS: In a large cohort of VLBW infants enrolled in the HeRO trial, the HRC index increased in the 24-h period prior to diagnosis of UTI and BSI but not meningitis.

Early life antecedents of positive child health among 10-year-old children born extremely preterm.

BACKGROUND: To identify modifiable antecedents during pre-pregnancy and pregnancy windows associated with a positive child health at 10 years of age. METHODS: Data on 889 children enrolled in the Extremely Low Gestational Age Newborn (ELGAN) study in 2002-2004 were analyzed for associations between potentially modifiable maternal antecedents during pre-pregnancy and pregnancy time windows and a previously described positive child health index (PCHI) score at 10 years of age. Stratification by race was also investigated for associations with investigated antecedents. RESULTS: Factors associated with higher PCHI (more positive health) included greater gestational age, birth weight, multiple gestation, and medical interventions, including assisted reproduction and cervical cerclage. Factors associated with lower PCHI included correlates of lower socioeconomic status, pre-pregnancy chronic medical disorders in the mother such as pre-pregnancy body mass index (BMI), and maternal asthma. When stratified by race, variation in significant results was observed. CONCLUSIONS: Among children born extremely preterm, medical interventions and higher socioeconomic status were associated with improved PCHI, while chronic illness and high BMI in the mother is associated with lower PCHI at 10 years of age. Knowledge of such antecedent factors could inform efforts to develop interventions that promote positive child health outcomes in future pregnancies.

Assessing Positive Child Health among Individuals Born Extremely Preterm.

OBJECTIVE: To assess the development of a Positive Child Health Index (PCHI) based on 11 adverse outcomes and evaluate the association of PCHI with quality of life (QoL) scores in a preterm cohort. STUDY DESIGN: A total of 889 children enrolled in the Extremely Low Gestational Age Newborn (ELGAN) study in 2002-2004 were followed up at 10 years of age. A parent/caregiver completed questionnaires for child QoL, asthma, visual or hearing impairment, gross motor function impairment, epilepsy, attention deficit/hyperactivity disorder, anxiety, and depression. The child was assessed for cognitive impairment, autism, and obesity. PCHI scores were computed and linear regression models were used to evaluate the relationship between QoL categories (psychosocial, physical, emotional, social, school, and total) and the PCHI (dichotomized and coded as a multilevel categorical predictor) and to assess sex differences. RESULTS: Among ELGAN children, higher PCHI scores were associated with higher reported QoL scores for all QoL categories. Children with no disorders and a PCHI of 100% had Pediatric Quality of Life Inventory total scores that were 11 points higher than children with 1 or more adverse outcomes (PCHI of <100%). Boys had lower QoL scores for the total, psychosocial, social, and school categories. CONCLUSIONS: Positive child health assessed using a quantitative PCHI was associated with QoL across the ELGAN cohort at school age. In the current study, the PCHI encompassed 11 outcomes assessed in ELGANs. Future research could include an enhanced panel of child health outcomes to support the use of PCHI as an indicator of positive child health.

Maternal educational status at birth, maternal educational advancement, and neurocognitive outcomes at age 10 years among children born extremely preterm.

BackgroundTo determine if a key marker of socioeconomic status, maternal education, is associated with later neurocognitive and academic outcomes among children born extremely preterm (EP).MethodEight hundred and seventy-three children born at 23 to 27 weeks of gestation were assessed for cognitive and academic ability at age 10 years. With adjustments for gestational age (GA) and potential confounders, outcomes of children whose mothers had fewer years of education at the time of delivery and children whose mother advanced in education between birth and 10 years were examined.ResultsChildren of mothers in the lowest education stratum at birth were significantly more likely to score ≥2 SDs below normative expectation on 17 of 18 tests administered. Children of mothers who advanced in education (n=199) were at reduced risk for scoring ≥2 SDs on 15 of 18 measures, but this reduction was statistically significant on only 2 of 18 measures.ConclusionAmong EP children, socioeconomic disadvantage at birth, indexed by maternal education, is associated with significantly poorer neurocognitive and academic outcomes at 10 years of age, independently of GA. Maternal educational advancement during the child's first 10 years of life is associated with modestly improved neurocognitive outcomes.

Behavioural dysfunctions of 10-year-old children born extremely preterm associated with corticotropin-releasing hormone expression in the placenta.

AIM: To evaluate the relationship between corticotropin-releasing hormone (CRH) expression in the placenta and the risk of school-related dysfunctions at the age of 10 years among children born extremely preterm (EP). METHODS: Corticotropin-releasing hormone expression was measured in the placenta of 761 EP children, who had the following assessments at the age of 10 years: Differential Ability Scales, Oral and Written Language Scales, the Wechsler Individual Achievement Test-III, NEPSY-II and the Child Symptom Inventory-4. We evaluated whether lowest and highest quartiles of CRH mRNA were associated with undesirable scores on these assessments. With 272 evaluations, we would expect 14 to be significant at p < 0.05. RESULTS: Only 16 associations were statistically significant. On the other hand, seven of these were social limitations among girls whose placenta CRH mRNA was in the top quartile. Adjusting for delivery indication or restricting the sample to one delivery indication group resulted in few differences. CONCLUSION: Overall, placenta CRH mRNA concentrations in the top or bottom quartiles were not associated with increased risks of dysfunctions 10 years later. Girls whose placenta CRH expression was in the top quartile, however, were at increased risk of seven indicators/correlates of social limitations.

The Relationship of Maternal Prepregnancy Body Mass Index and Pregnancy Weight Gain to Neurocognitive Function at Age 10 Years among Children Born Extremely Preterm.

OBJECTIVE: To assess the association between maternal prepregnancy body mass index and adequacy of pregnancy weight gain in relation to neurocognitive function in school-aged children born extremely preterm. STUDY DESIGN: Study participants were 535 ten-year-old children enrolled previously in the prospective multicenter Extremely Low Gestational Age Newborns cohort study who were products of singleton pregnancies. Soon after delivery, mothers provided information about prepregnancy weight. Prepregnancy body mass index and adequacy of weight gain were characterized based on this information. Children underwent a neurocognitive evaluation at 10 years of age. RESULTS: Maternal prepregnancy obesity was associated with increased odds of a lower score for Differential Ability Scales-II Verbal IQ, for Developmental Neuropsychological Assessment-II measures of processing speed and visual fine motor control, and for Wechsler Individual Achievement Test-III Spelling. Children born to mothers who gained an excessive amount of weight were at increased odds of a low score on the Oral and Written Language Scales Oral Expression assessment. Conversely, children whose mother did not gain an adequate amount of weight were at increased odds of a lower score on the Oral and Written Language Scales Oral Expression and Wechsler Individual Achievement Test-III Word Reading assessments. CONCLUSION: In this cohort of infants born extremely preterm, maternal obesity was associated with poorer performance on some assessments of neurocognitive function. Our findings are consistent with the observational and experimental literature and suggest that opportunities may exist to mitigate risk through education and behavioral intervention before pregnancy.

Circulating Inflammatory-Associated Proteins in the First Month of Life and Cognitive Impairment at Age 10 Years in Children Born Extremely Preterm.

OBJECTIVES: To evaluate whether in children born extremely preterm, indicators of sustained systemic inflammation in the first month of life are associated with cognitive impairment at school age. STUDY DESIGN: A total of 873 of 966 eligible children previously enrolled in the multicenter Extremely Low Gestational Age Newborn Study from 2002 to 2004 were evaluated at age 10 years. We analyzed the relationship between elevated blood concentrations of inflammation-associated proteins in the first 2 weeks ("early elevations"; n = 812) and the third and fourth week ("late elevations"; n = 532) of life with neurocognition. RESULTS: Early elevations of C-reactive protein, tumor necrosis factor-α, interleukin (IL)-8, intercellular adhesion molecule (ICAM)-1, and erythropoietin were associated with IQ values >2 SD below the expected mean (ORs: 2.0-2.3) and with moderate to severe cognitive impairment on a composite measure of IQ and executive function (ORs: 2.1-3.6). Additionally, severe cognitive impairment was associated with late protein elevations of C-reactive protein (OR: 4.0; 95% CI 1.5, 10), IL-8 (OR: 5.0; 1.9, 13), ICAM-1 (OR: 6.5; 2.6, 16), vascular endothelial growth factor-receptor 2 (OR: 3.2; 1.2, 8.3), and thyroid-stimulating hormone (OR: 3.1; 1.3, 7.3). Moderate cognitive impairment was most strongly associated with elevations of IL-8, ICAM-1, and vascular endothelial growth factor-receptor 2. When 4 or more inflammatory proteins were elevated early, the risk of having an IQ <70 and having overall impaired cognitive ability was more than doubled (ORs: 2.1-2.4); the presence of 4 or more inflammatory protein elevated late was strongly linked to adverse cognitive outcomes (ORs: 2.9-4.8). CONCLUSIONS: Extremely preterm children who had sustained elevations of inflammation-related proteins in the first postnatal month are more likely than extremely preterm peers without such elevations to have cognitive impairment at 10 years.

Cognitive functioning at the age of 10 years among children born extremely preterm: a latent profile approach.

BackgroundSchool-age children born extremely preterm (EP) are more likely than their term peers to have multiple neurocognitive limitations. We identify subgroups of EP children who share similar profiles on measures of intelligence quotient (IQ) and executive function (EF), and describe the nature and prevalence of cognitive impairment in EP children.MethodsOn the basis of measures of IQ and EF, subgroups of EP children with common neurocognitive function are identified using latent profile analysis (LPA). On the basis of these subgroups, we describe the nature and prevalence of impairment in EP children, and examine associations between cognitive function, gestational age, and academic achievement. Classification of neurocognitive function using IQ and EF is compared with a standard classification based on IQ Z-scores.ResultsLPA identified four neurocognitive profiles in EP children, with 34% of EP children classified as normal, 41% low-normal, 17% moderately impaired, and 8% severely impaired. Impaired children exhibited global impairment across cognitive domains, whereas children in the low-normal group tended to have impaired inhibition relative to their reasoning and working memory skills.ConclusionWithin categories of EP children defined in terms of IQ, there is substantial variation in EF; thus, both IQ and EF assessments are needed when describing school-age outcome of EP children.

Antenatal steroid exposure and heart rate variability in adolescents born with very low birth weight.

BACKGROUND: Reduced heart rate variability (HRV) suggests autonomic imbalance in the control of heart rate and is associated with unfavorable cardiometabolic outcomes. We examined whether antenatal corticosteroid (ANCS) exposure had long-term programming effects on HRV in adolescents born with very low birth weight (VLBW). METHODS: Follow-up study of a cohort of VLBW 14-y olds born between 1992 and 1996 with 50% exposed to ANCS. HRV in both the time and frequency domains using Nevrokard Software was determined from a 5-min electrocardiogram tracing. RESULTS: HRV data from 89 (35 male, 53 non-black) exposed (ANCS+) and 77 (28 male, 29 non-black) unexposed (ANCS-) adolescents were analyzed. HRV did not differ between ANCS+ and ANCS- black participants. However, in non-black participants, a significant interaction between ANCS and sex was observed, with ANCS- females having significantly greater HRV than ANCS+ females and males, and ANCS- males for both time and frequency domain variables. CONCLUSION: Among non-black adolescents born with VLBW, ANCS exposure is associated with reduced HRV with apparent sex-specificity. Reduced HRV has been associated with development of adverse cardiometabolic outcomes, thus supporting the need to monitor these outcomes in VLBW adolescents as they mature.

Observer variability identifying attention deficit/hyperactivity disorder in 10-year-old children born extremely preterm.

AIM: A DSM-5 diagnosis of attention deficit/hyperactive disorder (ADHD) requires that symptoms be present in two settings. We wanted to see how teachers and parents compare on their assessments. METHODS: We evaluated how well Child Symptom Inventory-4 (CSI-4) reports from 871 parents and 634 teachers of 10-year-old children born before the 28th week of gestation provided information about indicators of school dysfunction. RESULTS: Kappa values for parent and teacher agreement of any ADHD were at best fair to poor (<0.41). Nevertheless, ADHD identified by each alone provided a moderate amount of information about such indicators of school dysfunction as grade repetition. Only occasionally did agreement provide more information than provided by only one reporter. Mother's social class and intelligence level did not discriminate between parents who did and did not agree with the teacher. CONCLUSION: ADHD identified by a single observer can provide appreciable information about a range of the child's functions needed for success in school and, therefore, should not be discounted when another observer does not consider the child to have ADHD symptoms.

Predictive Validity of the Modified Checklist for Autism in Toddlers (M-CHAT) Born Very Preterm.

OBJECTIVE: To examine the predictive validity of the Modified Checklist for Autism in Toddlers (M-CHAT) administered at age 24 months for autism spectrum disorder (ASD) diagnosed at 10 years of age in a US cohort of 827 extremely low gestational age newborns (ELGANs) followed from birth. STUDY DESIGN: We examined the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the M-CHAT in predicting an ASD diagnosis at age 10 years based on gold standard diagnostic instruments. We then assessed how these predictive parameters were affected by sensorimotor and cognitive impairments, socioeconomic status (SES), and emotional/behavioral dysregulation at age 2 years. RESULTS: Using standard criteria, the M-CHAT had a sensitivity of 52%, a specificity of 84%, a PPV of 20%, and an NPV of 96%. False-positive and false-negative rates were high among children with hearing and vision impairments. High false-positive rates also were associated with lower SES, motor and cognitive impairments, and emotional/behavioral dysregulation at age 2 years. CONCLUSIONS: Among extremely preterm children with ASD, almost one-half were not correctly screened by the M-CHAT at age 2 years. Sensorimotor and cognitive impairments, SES, and emotional/behavioral dysregulation contributed significantly to M-CHAT misclassifications. Clinicians are advised to consider these factors when screening very preterm toddlers for ASD.

Girls and Boys Born before 28 Weeks Gestation: Risks of Cognitive, Behavioral, and Neurologic Outcomes at Age 10 Years.

OBJECTIVES: To compare the prevalence of cognitive, neurologic, and behavioral outcomes at 10 years of age in 428 girls and 446 boys who were born extremely preterm. STUDY DESIGN: A total of 889 of 966 eligible children previously enrolled in the multicenter Extremely Low Gestational Age Newborns Study from 2002-2004 were evaluated at 10 years of age. Children underwent a neuropsychological battery and testing for autism spectrum disorder (ASD), and parents reported on their child's behavior, development, and seizures. RESULTS: Of the children, 28% of boys and 21% of girls exhibited moderate to severe impairment on summary measures of cognitive abilities. Boys had a higher prevalence of impairment than girls in nearly all measures of cognition, were more than twice as likely to have microcephaly (15% in boys, 8% in girls), and require more often assistive devices to ambulate (6% in boys, 4% in girls). In contrast, boys and girls had comparable risk for a history of seizure (identified in 10% of the cohort) or epilepsy (identified in 7% of the cohort). The boy-to-girl ratio of ASD (9% in boys, 5% in girls) was lower than expected compared with the overall US autism population. CONCLUSIONS: In this contemporary cohort of children born extremely premature and evaluated at school age, boys had higher prevalence of cognitive, neurologic, and behavioral deficits than girls. The ratio of boys to girls among those with ASD deserves further study as does the perinatal environmental-genetic interactions that might contribute to male preponderance of deficits in this high-risk sample.