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1.
J Am Chem Soc ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32009401

RESUMO

We report that (TMP)Ru(NH3)2 (TMP = tetramesitylporphryin) is a molecular catalyst for oxidation of ammonia to dinitrogen. An aryloxy radical, tri-tert-butylphenoxyl (ArO·), abstracts H atoms from a bound ammonia ligand of (TMP)Ru(NH3)2, leading to the discovery of a new catalytic C-N coupling to the para position of ArO· to form 4-amino-2,4,6-tri-tert-butylcyclohexa-2,5-dien-1-one. Modification of the aryloxy radical to 2,6-di-tert-butyl-4-tritylphenoxyl radical, which contains a trityl group at the para position, prevents C-N coupling and diverts the reaction to catalytic oxidation of NH3 to give N2. We achieved 125 ± 5 turnovers at 22 °C for oxidation of NH3, the highest turnover number (TON) reported to date for a molecular catalyst.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32029530

RESUMO

OBJECTIVES: To develop research priorities on the consequences of very preterm (VPT) birth for the RECAP Preterm platform which brings together data from 23 European VPT birth cohorts. DESIGN AND SETTING: This study used a two-round modified Delphi consensus process. Round 1 was based on 28 research themes related to childhood outcomes (<12 years) derived from consultations with cohort researchers. An external panel of multidisciplinary stakeholders then ranked their top 10 themes and provided comments. In round 2, panel members provided feedback on rankings and on new themes suggested in round 1. RESULTS: Of 71 individuals contacted, 64 (90%) participated as panel members comprising obstetricians, neonatologists, nurses, general and specialist paediatricians, psychologists, physiotherapists, parents, adults born preterm, policy makers and epidemiologists from 17 countries. All 28 initial themes were ranked in the top 10 by at least six panel members. Highest ranking themes were: education (73% of panel members' top 10 choices); care and outcomes of extremely preterm births, including ethical decisions (63%); growth and nutrition (60%); emotional well-being and social inclusion (55%); parental stress (55%) and impact of social circumstances on outcomes (52%). Highest ranking themes were robust across panel members classified by background. 15 new themes had at least 6 top 10 endorsements in round 2. CONCLUSIONS: This study elicited a broad range of research priorities on the consequences of VPT birth, with good consensus on highest ranks between stakeholder groups. Several highly ranked themes focused on the socioemotional needs of children and parents, which have been less studied.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31996408

RESUMO

BACKGROUND: Socioeconomic factors influence language development in the general population, but the association remains poorly documented in children born very preterm (VPT). We assessed the impact of maternal education on language development in children born VPT and effect modification by perinatal risk. METHODS: Data were from the Effective Perinatal Intensive Care in Europe (EPICE) population-based cohort of children born <32 weeks' gestational age (GA) in 2011/2012. Regions from six countries (Estonia, France, Germany, Italy, Sweden and UK) used a validated short form MacArthur Developmental Communicative Inventories Checklist to assess language at 2 years corrected age. Perinatal variables were collected from clinical records. We assessed expressive language delay (ELD), defined as (a) not combining words; and (b) expressive vocabulary <10th percentile of norms for age and sex. Perinatal risk (low, moderate and high) was determined using GA, small for GA and neonatal morbidities. We estimated adjusted risk ratios (aRR) of ELD by maternal education with inverse weighting to account for non-response bias. RESULTS: Of 2741 children, 24.6% were not combining words and 39.7% had a low expressive vocabulary. Low maternal education (lower secondary or less compared with a bachelor's degree or more) increased risks of ELD: not combining words: aRR=1.52 (95% CI 1.36 to 1.69); low expressive vocabulary: aRR=1.25 (1.04 to 1.51). For children with low perinatal risk, the aRR were 1.88 (1.26 to 2.80) and 1.44 (1.06 to 1.95), respectively, compared with those with high perinatal risks: 1.36 (1.10 to 1.67) and 1.11 (0.97 to 1.27), respectively. CONCLUSION: Low maternal education affects ELD for children born VPT, although the association appears attenuated among those with highest perinatal risk.

4.
Pediatrics ; 145(2)2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31924688

RESUMO

BACKGROUND AND OBJECTIVES: Children born extremely preterm (EP) (<26 weeks' gestation) have lower cognitive scores and an increased rate of cognitive impairment compared with their term-born peers. However, the neuropsychological presentation of these EP individuals in adulthood has not been described. The aim of this study was to examine neuropsychological outcomes in early adulthood after EP birth in the 1995 EPICure cohort and to investigate if the rate of intellectual impairment changed longitudinally. METHODS: A total of 127 young adults born EP and 64 term-born controls had a neuropsychological assessment at 19 years of age examining general cognitive abilities (IQ), visuomotor abilities, prospective memory, and aspects of executive functions and language. RESULTS: Adults born EP scored significantly lower than term-born controls across all neuropsychological tests with effect sizes (Cohen's d) of 0.7 to 1.2. Sixty percent of adults born EP had impairment in at least 1 neuropsychological domain; deficits in general cognitive functioning and visuomotor abilities were most frequent. The proportion of EP participants with an intellectual impairment (IQ <70) increased by 6.7% between 11 and 19 years of age (P = .02). Visuospatial functioning in childhood predicted visuomotor functioning at 19 years. CONCLUSIONS: Adults born EP continue to perform lower than their term-born peers in general cognitive abilities as well as across a range of neuropsychological functions, indicating that these young adults do not show improvement overtime. The prevalence of intellectual impairment increased from 11 years into adulthood.

5.
BMJ Open ; 10(1): e031955, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31980507

RESUMO

INTRODUCTION: The aim of the protocol is to present the methodology of a scoping review that aims to synthesise up-to-date evidence on adolescent undernutrition in South Asia. METHODS AND ANALYSIS: The proposed scoping review will be guided by Arksey and O'Malley's framework and the Joanna Briggs Institute Reviewers' Manual. The scoping review question, eligibility criteria and search strategy will be based on the Population, Concept and Context strategy. We will conduct the search in electronic bibliographic databases (Medline (OVID), Embase, Cochrane Library, Web of Science, CINAHL, PsycInfo, Scopus) as well as various grey literature sources in order to synthesise and present the findings with descriptive statistics and a narrative description of both quantitative and qualitative evidence. ETHICS AND DISSEMINATION: This study protocol does not require ethical approval. This protocol will accurately describe the proposed scoping review that will map the evidence on adolescent undernutrition in South Asia. The proposed review aims to gather published and unpublished literature to inform policy and healthcare organisations as well as identify future research priorities in South Asia.

6.
Neuropsychology ; 34(1): 77-87, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31580086

RESUMO

OBJECTIVE: Children born very preterm are at increased risk of inattention, but it remains unclear whether the underlying processes are the same as in their term-born peers. Drift diffusion modeling (DDM) may better characterize the cognitive processes underlying inattention than standard reaction time (RT) measures. This study used DDM to compare the processes related to inattentive behavior in preterm and term-born children. METHOD: Performance on a cued continuous performance task was compared between 33 children born very preterm (VP; ≤ 32 weeks' gestation) and 32 term-born peers (≥ 37 weeks' gestation), aged 8-11 years. Both groups included children with a wide spectrum of parent-rated inattention (above average attention to severe inattention). Performance was defined using standard measures (RT, RT variability and accuracy) and modeled using a DDM. A hierarchical regression assessed the extent to which standard or DDM measures explained variance in parent-rated inattention and whether these relationships differed between VP and term-born children. RESULTS: There were no group differences in performance on standard or DDM measures of task performance. Parent-rated inattention correlated significantly with hit rate, RT variability, and drift rate (a DDM estimate of processing efficiency) in one or both groups. Regression analysis revealed that drift rate was the best predictor of parent-rated inattention. This relationship did not differ significantly between groups. CONCLUSIONS: Findings suggest that less efficient information processing is a common mechanism underlying inattention in both VP and term-born children. This study demonstrates the benefits of using DDM to better characterize atypical cognitive processing in clinical samples. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

7.
Psychol Med ; : 1-10, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31813397

RESUMO

BACKGROUND: The neurodevelopmental and trauma theories are two widely cited models of psychosis. A third - the developmental risk factor model (DRFM) - recognises the combined role of neurodevelopmental risks and trauma. Our objective was to test these theories using preterm populations as a natural experiment, given the high prevalence of neurodevelopmental deficits and exposure to trauma. METHODS: Two population-based preterm birth cohorts, the Bavarian Longitudinal Study (BLS; N = 399) and EPICure Study (N = 184), were included with term-born controls. Peer victimisation in childhood was assessed by parent and child report and psychotic experiences (PE) were assessed in early adulthood. Different models of psychosis were tested using regression and mediation analyses. RESULTS: There was support for the trauma and DRFM in the BLS. Peer victimisation increased the risk of PE for preterm and term-born participants equally [odds ratio = 4.87, 95% confidence interval (CI) 1.96-12.08]. There was an indirect effect where preterm children were more likely to be victimised, which subsequently increased risk of PE [ß = 1.12 (s.e. = 0.61), 95% CI 0.11-2.48]. The results were replicated in EPICure. CONCLUSIONS: Exposure to trauma which is experienced more often by neurodevelopmental risk children rather than neurodevelopmental risk per se increases the risk of PE. The findings are consistent with the trauma model and DRFM. Interventions focused on reducing trauma may reduce the development of PE.

8.
Prenat Diagn ; 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31834626

RESUMO

OBJECTIVE: To evaluate the test accuracy of non-invasive prenatal testing (NIPT) for fetal trisomy 21, 18, and 13 using cell-free (cf) DNA analysis in maternal plasma with microarray quantitation. METHOD: Systematic review and meta-analysis. Searches in MEDLINE, Pre-MEDLINE, EMBASE, Web of Science, and the Cochrane Library to 09.07.2018. RESULTS: Five studies analyzing 3074 samples, including 187 trisomy 21, 43 trisomy 18, and 19 trisomy 13 cases, were identified. Risk of bias was high in all studies, introduced particularly by exclusions from analysis and by the role of the sponsor. Sensitivity of microarray-based cfDNA testing was 99.5% (95%CI 96.3%-99.9%) for trisomy 21, 97.7% (95%CI 87.9%-99.6%) for trisomy 18, and 100% (95%CI 83.2%-100%) for trisomy 13. Specificity was 100% (95% CI 99.87%-100%) for trisomy 21, 99.97% (95%CI 99.81%-99.99%) for trisomy 18, and 99.97% (95%CI 99.81%-99.99%) for trisomy 13. Pooled test failure rate was 1.1%. A direct comparison of microarray- and sequencing-based cfDNA found equivalent test accuracy. CONCLUSION: Included studies suggest that NIPT using microarray-based cfDNA testing has high sensitivity and specificity for detecting fetal trisomy 21, 18, and 13. However, the evidence base is small and at high risk of bias.

9.
Nucleic Acid Ther ; 29(6): 323-334, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31670606

RESUMO

The trinucleotide repeat containing 6 (TNRC6) family of proteins are core components of RNA interference (RNAi) and consist of three paralogs (TNRC6A, TNRC6B, and TNRC6C). The TNRC6 paralogs associate with argonaute (AGO) protein, the core RNAi factor, and bridge its interactions with other proteins. We obtained TNRC6A and TNRC6B single and double knockout cell lines to investigate how the TNRC6 paralogs contribute to RNAi. We found that TNRC6 proteins are not required for gene silencing when duplex RNAs are fully complementary. TNRC6 expression was necessary for regulation by a microRNA. TNRC6A, but not TNRC6B, expression was necessary for transcriptional activation by a duplex RNA targeting a gene promoter. By contrast, AGO2 is required for all three gene expression pathways. TNRC6A can affect the Dicer localization in cytoplasm versus the nucleus, but none of the three TNRC6 paralogs was necessary for nuclear localization of AGO2. Our data suggest that the roles of the TNRC6 paralogs differ in some details and that TNRC6 is not required for clinical therapeutic silencing mechanisms that involve fully complementary duplex RNAs.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31690558

RESUMO

OBJECTIVE: To determine whether the variation in neurodevelopmental disability rates between populations persists after adjustment for demographic, maternal and infant characteristics for an international very preterm (VPT) birth cohort using a standardised approach to neurodevelopmental assessment at 2 years of age. DESIGN: Prospective standardised cohort study. SETTING: 15 regions in 10 European countries. PATIENTS: VPT births: 22+0-31+6 weeks of gestation. DATA COLLECTION: Standardised data collection tools relating to pregnancy, birth and neonatal care and developmental outcomes at 2 years corrected age using a validated parent completed questionnaire. MAIN OUTCOME MEASURES: Crude and standardised prevalence ratios calculated to compare rates of moderate to severe neurodevelopmental impairment between regions grouped by country using fixed effects models. RESULTS: Parent reported rates of moderate or severe neurodevelopmental impairment for the cohort were: 17.3% (ranging 10.2%-26.1% between regions grouped by country) with crude standardised prevalence ratios ranging from 0.60 to 1.53. Adjustment for population, maternal and infant factors resulted in a small reduction in the overall variation (ranging from 0.65 to 1.30). CONCLUSION: There is wide variation in the rates of moderate to severe neurodevelopmental impairment for VPT cohorts across Europe, much of which persists following adjustment for known population, maternal and infant factors. Further work is needed to investigate whether other factors including quality of care and evidence-based practice have an effect on neurodevelopmental outcomes for these children.

11.
Chem Commun (Camb) ; 55(93): 14058-14061, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31691686

RESUMO

All hydrogen atoms of the NH3 in [Mn(depe)2(CO)(NH3)]+ are abstracted by 2,4,6-tri-tert-butylphenoxyl radical, resulting in the isolation of a rare cyclophosphazenium cation, [(Et2P(CH2)2PEt2)N]+, in 76% yield. An analogous reaction is observed for [Mn(dppe)2(CO)(NH3)]+. Computations suggest insertion of NHx into a Mn-P bond provides the thermodynamic driving force. Contextualization of this reaction provides insights on catalyst design and breaking strong N-H bonds.

12.
Orphanet J Rare Dis ; 14(1): 258, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31730477

RESUMO

BACKGROUND: Mitochondrial trifunctional protein (MTP) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiencies are rare fatty acid ß-oxidation disorders. Without dietary management the conditions are life-threatening. We conducted a systematic review to investigate whether pre-symptomatic dietary management following newborn screening provides better outcomes than treatment following symptomatic detection. METHODS: We searched Web of Science, Medline, Pre-Medline, Embase and the Cochrane Library up to 23rd April 2018. Two reviewers independently screened titles, abstracts and full texts for eligibility and quality appraised the studies. Data extraction was performed by one reviewer and checked by another. RESULTS: We included 13 articles out of 7483 unique records. The 13 articles reported on 11 patient groups, including 174 people with LCHAD deficiency, 18 people with MTP deficiency and 12 people with undifferentiated LCHAD/MTP deficiency. Study quality was moderate to weak in all studies. Included studies suggested fewer heart and liver problems in screen-detected patients, but inconsistent results for mortality. Follow up analyses compared long-term outcomes of (1) pre-symptomatically versus symptomatically treated patients, (2) screened versus unscreened patients, and (3) asymptomatic screen-detected, symptomatic screen-detected, and clinically diagnosed patients in each study. For follow up analyses 1 and 2, we found few statistically significant differences in the long-term outcomes. For follow up analysis 3 we found a significant difference for only one comparison, in the incidence of cardiomyopathy between the three groups. CONCLUSIONS: There is some evidence that dietary management following screen-detection might be associated with a lower incidence of some LCHAD and MTP deficiency-related complications. However, the evidence base is limited by small study sizes, quality issues and risk of confounding. An internationally collaborative research effort is needed to fully examine the risks and the benefits to pre-emptive dietary management with particular attention paid to disease severity and treatment group.

13.
N Engl J Med ; 381(15): 1434-1443, 2019 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-31597020

RESUMO

BACKGROUND: Observational data have shown that slow advancement of enteral feeding volumes in preterm infants is associated with a reduced risk of necrotizing enterocolitis but an increased risk of late-onset sepsis. However, data from randomized trials are limited. METHODS: We randomly assigned very preterm or very-low-birth-weight infants to daily milk increments of 30 ml per kilogram of body weight (faster increment) or 18 ml per kilogram (slower increment) until reaching full feeding volumes. The primary outcome was survival without moderate or severe neurodevelopmental disability at 24 months. Secondary outcomes included components of the primary outcome, confirmed or suspected late-onset sepsis, necrotizing enterocolitis, and cerebral palsy. RESULTS: Among 2804 infants who underwent randomization, the primary outcome could be assessed in 1224 (87.4%) assigned to the faster increment and 1246 (88.7%) assigned to the slower increment. Survival without moderate or severe neurodevelopmental disability at 24 months occurred in 802 of 1224 infants (65.5%) assigned to the faster increment and 848 of 1246 (68.1%) assigned to the slower increment (adjusted risk ratio, 0.96; 95% confidence interval [CI], 0.92 to 1.01; P = 0.16). Late-onset sepsis occurred in 414 of 1389 infants (29.8%) in the faster-increment group and 434 of 1397 (31.1%) in the slower-increment group (adjusted risk ratio, 0.96; 95% CI, 0.86 to 1.07). Necrotizing enterocolitis occurred in 70 of 1394 infants (5.0%) in the faster-increment group and 78 of 1399 (5.6%) in the slower-increment group (adjusted risk ratio, 0.88; 95% CI, 0.68 to 1.16). CONCLUSIONS: There was no significant difference in survival without moderate or severe neurodevelopmental disability at 24 months in very preterm or very-low-birth-weight infants with a strategy of advancing milk feeding volumes in daily increments of 30 ml per kilogram as compared with 18 ml per kilogram. (Funded by the Health Technology Assessment Programme of the National Institute for Health Research; SIFT Current Controlled Trials number, ISRCTN76463425.).


Assuntos
Deficiências do Desenvolvimento/prevenção & controle , Nutrição Enteral/métodos , Fórmulas Infantis , Doenças do Prematuro/prevenção & controle , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Leite Humano , Pré-Escolar , Nutrição Enteral/efeitos adversos , Enterocolite Necrosante/prevenção & controle , Seguimentos , Humanos , Recém-Nascido , Recém-Nascido Prematuro/crescimento & desenvolvimento , Recém-Nascido de muito Baixo Peso/crescimento & desenvolvimento , Unidades de Terapia Intensiva Neonatal , Tempo de Internação , Sepse/prevenção & controle
14.
Nat Commun ; 10(1): 4215, 2019 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527595

RESUMO

A major constraint for developing new anti-tuberculosis drugs is the limited number of validated targets that allow eradication of persistent infections. Here, we uncover a vulnerable component of Mycobacterium tuberculosis (Mtb) persistence metabolism, the aspartate pathway. Rapid death of threonine and homoserine auxotrophs points to a distinct susceptibility of Mtb to inhibition of this pathway. Combinatorial metabolomic and transcriptomic analysis reveals that inability to produce threonine leads to deregulation of aspartate kinase, causing flux imbalance and lysine and DAP accumulation. Mtb's adaptive response to this metabolic stress involves a relief valve-like mechanism combining lysine export and catabolism via aminoadipate. We present evidence that inhibition of the aspartate pathway at different branch-point enzymes leads to clearance of chronic infections. Together these findings demonstrate that the aspartate pathway in Mtb relies on a combination of metabolic control mechanisms, is required for persistence, and represents a target space for anti-tuberculosis drug development.


Assuntos
Ácido Aspártico/metabolismo , Mycobacterium tuberculosis/metabolismo , Antituberculosos/farmacologia , Humanos , Lisina/metabolismo , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Treonina/metabolismo , Tuberculose/microbiologia
15.
Sports Health ; 11(6): 492-497, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31486715

RESUMO

BACKGROUND: The Buffalo Concussion Treadmill Test (BCTT) is a graded exertion test for assessing exercise tolerance after concussion, but its utility is limited for certain populations. HYPOTHESIS: We developed the Buffalo Concussion Bike Test (BCBT) and tested its comparability with the BCTT. We hypothesize that heart rate (HR) at symptom exacerbation on the BCBT will be equivalent to the BCTT. STUDY DESIGN: Case-control study. LEVEL OF EVIDENCE: Level 3. METHODS: Adolescents with acute concussion (AC) (n = 20; mean age, 15.9 ± 1.1 years; 60% male) presenting to a concussion clinic within 10 days of injury and age- and sex-matched healthy controls (n = 20; mean age, 15.9 ± 1.1 years; 60% male) performed the BCTT at first visit and returned within 3 days to perform the BCBT. Test duration, HR, symptom severity (measured using a visual analog scale), and exertion (measured using the Borg Rating of Perceived Exertion) were collected during each test. RESULTS: Adolescents with AC who were exercise intolerant on the BCTT were also intolerant on the BCBT, with symptom exacerbation occurring at a mean 8.1 ± 2.8 minutes on the BCTT versus 14.6 ± 6.0 minutes on the BCBT (P < 0.01). Two 1-sided t tests showed that the HR at symptom exacerbation in AC patients (137 ± 28 bpm on BCTT vs 135 ± 25 bpm on BCBT; 95% CI, <0.01-0.03) and at voluntary exhaustion for controls (175 ± 13 bpm on BCTT vs 175 ± 13 bpm on BCBT; 95% CI, 0.03-0.03) on each test were statistically equivalent. CONCLUSION: The HR at symptom exacerbation on BCBT is equivalent to the BCTT for the assessment of exercise tolerance after concussion in adolescents. CLINICAL RELEVANCE: The BCBT can be used in patients with limited mobility or for research interventions that require limited participant motion.


Assuntos
Traumatismos em Atletas/diagnóstico , Concussão Encefálica/diagnóstico , Teste de Esforço/métodos , Adolescente , Estudos de Casos e Controles , Tolerância ao Exercício/fisiologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino
16.
Lancet Child Adolesc Health ; 3(10): 705-712, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31402196

RESUMO

BACKGROUND: The Parent Report of Children's Abilities-Revised (PARCA-R) can be used to identify preterm born children at risk for developmental delay at age 24 months. However, standardised scores for assessing all children in the general population and quantifying development relative to the norm are unavailable, thus limiting the use of the questionnaire. We aimed to develop scores that are standardised by age and sex for the PARCA-R to assess children's cognitive and language development at age 24-27 months. METHODS: Anonymised data from PARCA-R questionnaires that were completed by parents of 2-year-old children in three previous studies were obtained to form a standardisation sample that was representative of the UK general population. Anonymised data were obtained from three further studies to assess the external validity and clinical validity of the standardised scores. We used the lambda-mu-sigma (lambda for skewness, mu for median, sigma for the coefficient of variation) method to develop scores that are standardised by age and sex for three scales (non-verbal cognitive development, language development, and total parent report composite [PRC]) for children in four 1-month age bands, spanning age 23·5-27·5 months. FINDINGS: We included 6402 children (mean age 25 months and 1 day [range 23 months and 16 days to 27 months and 15 days]) in the standardisation sample and 709 (mean age 24 months and 19 days [23 months and 16 days to 27 months and 15 days]) to test the external validity and 1456 (mean age 24 months and 8·5 days [23 months and 16 days to 27 months and 15 days]) to test the clinical validity of the standardised scores. For all PARCA-R scales, mean standardised scores approximated 100 (SD 15) in both sexes and all age groups. These scores were independent of socioeconomic status. Standardised scores were close to 100 (15) in the external validation sample, showing the validity of the scores. Standardised scores for the total PRC scale for children born very preterm (<32 weeks' gestation) were 0·47 SD lower on average than the normative mean, and for children with neonatal sepsis were 0·73 SD lower on average than the normative mean. These scores were equivalent to a standardised score of 93 (95% CI 91-94) for children born very preterm and 89 (88-91) for children with neonatal sepsis, thus showing clinical validity. INTERPRETATION: The PARCA-R provides a norm-referenced, standardised assessment of cognitive and language development at 24-27 months of age. The questionnaire is available non-commercially in English with translations available in 14 other languages, thus providing clinicians and researchers with a cost-effective tool for assessing development and identifying children with delay. FUNDING: Action Medical Research (Ref: GN2580).

17.
J Dev Behav Pediatr ; 40(9): 706-715, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31415306

RESUMO

OBJECTIVE: Feeding concerns are common in the first 2 years of life and typically reflect maternal perceptions occurring within the larger context of the parent-child relationship. We aimed to determine whether (1) maternal depressive systems predicted perceived picky eating, mediated by maternal negative perceptions; (2) receipt of the Video Interaction Project (VIP) parenting intervention impacted perceived picky eating through this pathway; and (3) perceived picky eating was associated with child growth or subsequent dietary patterns. METHODS: We performed a partial longitudinal analysis of 187 low-income, predominantly Hispanic mother-child dyads enrolled in a randomized controlled trial of the VIP. Mother-infant dyads were enrolled postpartum in an urban public hospital. Participants randomized to the VIP met with an interventionist on days of well-child visits; sessions were designed to facilitate interactions in play and shared reading through provision of learning materials and review of videotaped parent-child interaction; the curriculum did not contain feeding-specific elements. We used structural equation modeling to determine direct, indirect, and total effects of maternal depressive symptoms, maternal negative perceptions, and the VIP on perceived picky eating. We then tested associations between perceived picky eating and (1) child growth, using multivariable linear regression and multilevel modeling; and (2) subsequent child dietary consumption, using multivariable multinomial logistic regression. RESULTS: Maternal depressive symptoms had significant total effects on negative maternal perceptions (ß = 0.32, p < 0.001) and perceived picky eating (ß = 0.21, p < 0.01) after controlling for potential confounders. This effect was partially mediated by maternal negative perceptions (indirect effect: ß = 0.06, p = 0.04). When used in the model as the predictor, the VIP had a significant total effect on perceived picky eating (ß = -0.16, p = 0.02), which was partially mediated by maternal depressive symptoms and negative perceptions (indirect effect: ß = -0.05, p = 0.02). Perceived picky eating was not associated with child diet at age 2 years or adiposity from 6 months to 3 years. CONCLUSION: Maternal concerns about picky eating may reflect deeper depressive symptoms and negative perceptions of her child's behavior. Interventions designed to facilitate positive parenting in general may lessen feeding-specific concerns, such as picky eating. Although reassurance about growth and nutritional outcomes for children perceived as picky eaters is appropriate, clinicians should also consider probing for underlying symptoms of depression that could lead to eating concerns.

18.
Pediatr Res ; 86(5): 567-572, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31398720

RESUMO

There is significant uncertainty over the role of assessment of long-term neurodevelopmental outcome (LTO) in neonatal clinical trials. A multidisciplinary working group was established to identify key issues in this area and to make recommendations about optimal approaches to evaluate LTO in therapeutic trials in newborns, which can be developed by sponsors and investigators with other key stakeholders. A key consideration for neonatal trials is the potential for the investigational product to cause widespread effects and drives the need to assess outcome in multiple organs. Thus investigators must assess whether the product has an impact on the brain and the potential for it to cause potential effects on LTO. Critically, is assessment of LTO an important direct therapeutic target or a safety outcome? Such decisions and outcomes need to be specific to the product being studied and use published data, only considering expert opinion when prior evidence does not exist. In designing the trial, the balance of benefits, costs, and burdens of assessments to the researcher and families need to be considered. Families and parent advocates should be involved in design and execution of the study. A framework is presented for use by all key stakeholders to determine the need, nature, and duration of LTO assessments in regulatory trials involving newborn infants.

19.
J Pediatr ; 213: 187-195.e1, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31399245

RESUMO

OBJECTIVE: To investigate pathways by which interventions that promote shared reading and play help prevent child behavior problems. We examined whether family processes associated with the family investment pathway (eg, parental cognitive stimulation) and the family stress pathway (eg, mothers' psychosocial functioning) mediated impacts of a pediatric-based preventive intervention on child behavior. STUDY DESIGN: The sample included 362 low-income mothers and their children who participated in a randomized controlled trial of the Video Interaction Project, a pediatrics-based preventive intervention that promotes parent-child interactions in the context of shared reading and play. Parent-child dyads were randomly assigned to group at birth. Three mediators-parental cognitive stimulation, maternal stress about the parent-child relationship, and maternal depressive symptoms-were assessed at child ages 6 and 36 months. The outcome, child externalizing behaviors, was assessed at 36 months. We used a series of path analytic models to examine how these family processes, separately or together, mediated the impacts of the Video Interaction Project on child behavioral outcomes. RESULTS: Intervention impacts on child behavior were mediated by enhancements in cognitive stimulation and by improvements in mothers' psychosocial functioning. A sequential mediation model showed that Video Interaction Project impacts on cognitive stimulation at 6 months were associated with later decreases in mothers' stress about the parent-child relationship and that this pathway mediated intervention impacts on child behavioral outcomes at 3 years of age (P = .023). CONCLUSIONS: Using an experimental design, this study identifies pathways by which parent-child interactions in shared reading and play can improve child behavioral outcomes. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00212576.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31371434

RESUMO

OBJECTIVE: To report outcomes at 2 years corrected age for children of women recruited to a trial comparing alternative policies for timing of cord clamping and immediate neonatal care at very preterm birth. DESIGN: Parallel group randomised (1:1) trial. SETTING: Eight UK tertiary maternity units. PARTICIPANTS: Two hundred and seventy-six babies born to 261 women expected to have a live birth before 32+0 weeks' gestation. INTERVENTIONS: Deferred cord clamping (≥2 min) and immediate neonatal care with cord intact or immediate (≤20 s) clamping and immediate neonatal care after clamping. MAIN OUTCOME MEASURE: Composite of death or adverse neurodevelopmental outcome at 2 years corrected age. RESULTS: Six babies born after 35+6 weeks were excluded. At 2 years corrected age, outcome data were not available for a further 52 children, leaving 218 for analysis (115 deferred clamping, 103 immediate clamping). Overall, 24/115 (21%) children allocated deferred clamping died or had an adverse neurodevelopmental outcome compared with 35/103 (34%) allocated immediate clamping; risk ratio (RR) 0.61 (95% CI 0.39 to 0.96); risk difference (RD) -13% (95% CI -25% to -1%). Multiple imputation for missing data gave an RR 0.69 (95% CI 0.44 to 1.09) and RD -9% (95% CI -21% to 2%). CONCLUSIONS: Deferred clamping and immediate neonatal care with cord intact may reduce the risk of death or adverse neurodevelopmental outcome at 2 years of age for children born very premature. Confirmation in larger studies is needed to determine the real benefits and harms. TRIAL REGISTRATION NUMBER: ISRCTN21456601.

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