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AIM: Very preterm (VPT) birth is a known early vulnerability factor, impacting both physical and mental health over the life-span. The additional burden of psychiatric illness in VPT adolescents is likely to adversely affect critical developmental tasks and personal, social and academic/vocational trajectories. Our aim was to examine the magnitude and extent of the risk of psychological burden by determining the prevalence of psychiatric disorders in our prospectively followed-up VPT and full-term (FT) control cohorts, in this period of developmental transition at age 17 years. METHODS: Rates of psychiatric disorder in the VPT and FT control cohorts were ascertained at clinical interview of the adolescents and their care giver(s) by an adolescent psychiatrist. RESULTS: VPT birth was associated with a greater risk of generalised anxiety disorder (VPT vs. FT risk ratio (RR) 2.33; 95% confidence interval (CI): 1.16, 4.67, P = 0.02), as well as attentional problems (VPT vs. FT RR 3.46; 95% CI: 1.01, 11.88, P = 0.03). Although care givers of VPT adolescents reported many social and communication difficulties, and observation at clinical interview supported this, our data did not reach clinical threshold for group differences in autistic spectrum disorder. For all other psychiatric disorders, there was no difference between VPT and FT control adolescents. CONCLUSION: Our longitudinal cohort follow-up study examining the late effects of VPT birth has demonstrated increased rates of clinically significant psychiatric disorder in this period of important developmental transition. Families and health professionals need to be aware of the increased risk so they can monitor for symptoms and seek effective mental health treatments and support.
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AIM: To compare the mental health and neurodevelopmental profiles of school-age children born very preterm, with and without an anxiety disorder, and to identify neonatal medical, psychosocial, and concurrent neurodevelopmental correlates. METHOD: A regional cohort of 102 (51 males, 51 females) children born very preterm (mean [SD] gestation at birth=28wks [2], range=23-31wks) was studied from birth to age 9 years alongside a comparison group of 109 (58 males, 51 females) children born at term (mean [SD] gestation at birth=40wks [1], range=38-41wks). At age 9 years, all children underwent a neurodevelopmental evaluation while parents were interviewed using the Development and Well-Being Assessment to diagnose a range of DSM-IV childhood psychiatric disorders. Detailed information was also available about the children's neonatal medical course and postnatal psychosocial environment, including maternal mental health and parenting. RESULTS: At age 9 years, 21% (n=21) of very preterm and 13% (n=14) of term-born children met diagnostic criteria for an anxiety disorder. Clinically-anxious children born very preterm were characterized by higher rates of comorbid mental health (odds ratio [OR]=11.5, 95% confidence interval [CI]=3.8-34.7), social (OR=6.2, 95% CI=2.1-18.4), motor (OR=4.4, 95% CI=1.6-12.2), and cognitive (OR=2.6, 95% CI=1.0-7.0) problems than those without an anxiety disorder. Concurrent maternal mental health and child social difficulties were the strongest independent correlates of early-onset child anxiety disorders. INTERPRETATION: Children born very preterm who developed an early-onset anxiety disorder were subject to high rates of comorbid problems. Findings highlight the importance of addressing both maternal and child mental health issues to optimize outcomes in this high-risk population. What this paper adds One out of five school-age children born very preterm are likely to meet DSM-IV diagnostic criteria for an anxiety disorder. Half of these children born very preterm with an early-onset anxiety disorder have comorbid attention-deficit/hyperactivity disorder. Other neurodevelopmental correlates of early-onset anxiety disorders include lower cognitive ability, motor problems, and peer social difficulties. Concurrent maternal mental health and child social adjustment problems were the strongest correlates of early-onset anxiety disorder risk among children born very preterm.
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Transtornos de Ansiedade/diagnóstico , Ansiedade/diagnóstico , Família/psicologia , Saúde Mental , Transtornos do Neurodesenvolvimento/diagnóstico , Ansiedade/psicologia , Transtornos de Ansiedade/psicologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Masculino , Transtornos do Neurodesenvolvimento/psicologia , Pais/psicologiaRESUMO
This study aimed to investigate factors affecting N-terminal pro-B-type natriuretic peptide (NTproBNP) in preterm infants and the ability of NTproBNP to predict haemodynamically significant patent ductus arteriosus (HsPDA). Prospective cohort study of 51 infants < 30 weeks gestation. Blood NTproBNP and heart ultrasound were performed on day of life 3, 10, 28 and 36 weeks corrected age. NTproBNP levels analysed for prediction of HsPDA. The effect of gestational age, ventilation, hypoxia, bronchopulmonary dysplasia (BPD), creatinine and haemoglobin levels on NTproBNP levels were investigated. Infants with HsPDA had higher mean (SD) day 3 NTproBNP (1840 pmol/L (1058) versus 178 pmol/L (140) p < 0.001). Receiver operator curves of day 3 NTproBNP for prediction of day 3 and day 10 HsPDA had an area under the curve of 0.98 and 0.94, respectively. A chosen day 3 NTproBNP value of ≥ 287 pmol/L for the prediction of day 3 HsPDA correctly classified 92% (sensitivity 92%, specificity 92%). NTproBNP demonstrated only modest ability to predict severe BPD. Chronological but not gestational age affected NTproBNP. Ventilation, hypoxia and haemoglobin levels did not influence NTproBNP but creatinine level was positively correlated. CONCLUSION: Day 3 NTproBNP is a useful biomarker to predict HsPDA and may be a valuable tool in future trial design. What is Known: ⢠NTproBNP is a cardiac hormone used to diagnose and monitor cardiac dysfunction in adults and has been shown to be higher in premature infants with haemodynamically significant ductus arteriosus (HsPDA). What is new: ⢠NTproBNP is highly predictive of ultrasound-defined HsPDA and may be a useful tool for further triage ⢠Early NTproBNP higher in infants who develop severe BPD and with renal impairment but not affected by gestational age, recent exposure to hypoxia or haemoglobin levels while late levels unexpectedly higher in those without BPD or HsPDA.
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Biomarcadores/sangue , Permeabilidade do Canal Arterial/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Área Sob a Curva , Displasia Broncopulmonar/sangue , Displasia Broncopulmonar/complicações , Estudos de Coortes , Creatinina/sangue , Permeabilidade do Canal Arterial/fisiopatologia , Ecocardiografia/métodos , Feminino , Idade Gestacional , Hemodinâmica/fisiologia , Hemoglobinas/análise , Humanos , Hipóxia/complicações , Lactente , Recém-Nascido , Recém-Nascido Prematuro/sangue , Masculino , Estudos Prospectivos , Curva ROC , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: To document associations between confirmed and suspected neonatal infection and motor, cognitive, educational, and mental health outcomes of very preterm (VPT)-born children at 9 years of age; to examine the potential intervening role of cerebral white matter abnormalities (WMAs) and structural development on term magnetic resonance imaging. STUDY DESIGN: A regional cohort of 110 infants born VPT in Christchurch, New Zealand were studied from birth to age of 9 years. Confirmed infection was defined as positive blood, cerebrospinal fluid or urine culture, and/or necrotizing enterocolitis ≥ stage 2. Suspected infection was defined as ≥ 5 days of antibiotics with evidence of clinical correlates. At term gestational equivalence, infants underwent structural magnetic resonance imaging. At age 9 years, neuromotor function, IQ, educational achievement, and mental health were assessed. RESULTS: During hospitalization, 25% of VPT infants had confirmed and 23% had suspected infection. Longer-term neurodevelopmental impairments were largely confined to infants with confirmed infection (relative risk 1.4-3.1, vs uninfected). After accounting for other neonatal factors, these infants were at increased risk of severe motor impairment (OR 3.3, 95% CI 1.3-8), attention deficit hyperactivity disorder (ADHD) (OR 3.6, 95% CI 1.6-8), and IQ delay (OR 2.0, 95% CI 1-3.9). Cerebral WMAs contributed to associations between confirmed infection and motor and IQ impairments but not to ADHD (P = .005). CONCLUSIONS: Confirmed neonatal infection heightens VPT infants' risk for neurodevelopmental impairment. WMA appears to be an important intervening factor linking infection and severe motor and IQ impairments. Further analysis of the neurologic mechanism accounting for ADHD in infants with infection is needed.
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Encéfalo/patologia , Deficiências do Desenvolvimento/patologia , Doenças do Prematuro/patologia , Infecções/complicações , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Nova Zelândia , Fatores de RiscoRESUMO
Here, we report a high incidence of PAX5 abnormalities observed in 32/68 (47%) of patients with genetically unclassified childhood precursor B-cell acute lymphoblastic leukaemia (pre-B ALL). Various deletions, gains, mutations and rearrangements of PAX5 comprised 45%, 12%, 29% and 14%, respectively, of the abnormalities found. 28% of patients showed more than one abnormality of the gene, implying bi-allelic impairment of PAX5. Novel PAX5-RHOXF2, PAX5-ELK3 and PAX5-CBFA2T2 rearrangements, which lead to aberrant expression of PAX5, were also identified. PAX5 rearrangements demonstrated a complex mechanism of formation including concurrent duplications/deletions of PAX5 and its partner genes. Finally, the splice variant c.1013-2A>G, seen in two patients with loss of one PAX5 allele, was confirmed to be germ-line in one patient and somatic in the other. PAX5 alterations were also found to be clinically associated with a higher white blood cell count (P = 0·015). These findings contribute to the knowledge of PAX5 alterations and their role in the pathogenesis of pre-B ALL.
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BACKGROUND: Invasive fungal infection is an important cause of mortality and morbidity in very preterm and very low birth weight infants. Early diagnosis is difficult and treatment is often delayed. Systemically absorbed antifungal agents (usually azoles) are increasingly used as prophylaxis against invasive fungal infection in this population. OBJECTIVES: To assess the effect of prophylactic systemic antifungal therapy on mortality and morbidity in very preterm or very low birth weight infants. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 8), MEDLINE, EMBASE, and CINAHL (to May 2015), conference proceedings, and previous reviews. SELECTION CRITERIA: Randomised controlled trials or quasi-randomised controlled trials that compared the effect of prophylactic systemic antifungal therapy versus placebo or no drug or another antifungal agent or dose regimen in very low birth weight infants. DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two review authors. MAIN RESULTS: We identified 15 eligible trials enrolling a total of 1690 infants. Ten trials (1371 infants) compared systemic antifungal prophylaxis versus placebo or no drug. These trials were generally of good methodological quality. Meta-analysis found a statistically significant reduction in the incidence of invasive fungal infection (typical risk ratio (RR) 0.43, 95% confidence interval (CI) 0.31 to 0.59; risk difference (RD) -0.09, 95% CI -0.12 to -0.06). The average incidence of invasive fungal infection in the control groups of the trials (16%) was much higher than that generally reported from large cohort studies. Meta-analysis did not find a statistically significant difference in the risk of death prior to hospital discharge (typical RR 0.79, 95% CI 0.61 to 1.02; typical RD -0.04, 95% CI -0.07 to 0.00). Very limited data on long-term neurodevelopmental outcomes were available. Three trials that compared systemic versus oral or topical non-absorbed antifungal prophylaxis did not detect any statistically significant effects on invasive fungal infection or mortality. Two trials that compared different dose regimens of prophylactic intravenous fluconazole did not detect any significant differences in infection rates or mortality. AUTHORS' CONCLUSIONS: Prophylactic systemic antifungal therapy reduces the incidence of invasive fungal infection in very preterm or very low birth weight infants. This finding should be interpreted and applied cautiously since the incidence of invasive fungal infection was very high in the control groups of many of the included trials. Meta-analysis does not demonstrate a statistically significant effect on mortality. There are currently only limited data on the long-term neurodevelopmental consequences for infants exposed to this intervention. In addition, there is a need for further data on the effect of the intervention on the emergence of organisms with antifungal resistance.
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Antifúngicos/uso terapêutico , Deficiências do Desenvolvimento/prevenção & controle , Doenças do Prematuro/prevenção & controle , Recém-Nascido de muito Baixo Peso , Micoses/prevenção & controle , Deficiências do Desenvolvimento/etiologia , Fluconazol/uso terapêutico , Humanos , Recém-Nascido , Doenças do Prematuro/mortalidade , Micoses/complicações , Micoses/mortalidade , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Invasive fungal infection is an important cause of mortality and morbidity in very preterm or very low birth weight infants. Uncertainty exists about the effect of prophylactic oral/topical non-absorbed antifungals to reduce mucocutaneous colonisation and so limit the risk of invasive fungal infection in this population. OBJECTIVES: To assess the effect of prophylactic oral/topical non-absorbed antifungal therapy on the incidence of invasive fungal infection, mortality and morbidity in very preterm or very low birth weight infants. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL: The Cochrane Library, 2015, Issue 7), MEDLINE, EMBASE, and CINAHL (to May 2015), conference proceedings, and previous reviews. SELECTION CRITERIA: Randomised controlled trials or quasi-randomised controlled trials that compared the effect of prophylactic oral/topical non-absorbed antifungal therapy versus placebo or no drug or another antifungal agent or dose regimen in very preterm or very low birth weight infants. DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of the Cochrane Neonatal Review Group with separate evaluation of trial quality and data extraction by two review authors. MAIN RESULTS: Four trials, in which a total of 1800 infants participated, compared oral/topical non-absorbed antifungal prophylaxis (nystatin or miconazole) with placebo or no drug. These trials had various methodological weaknesses including quasi-randomisation, lack of allocation concealment, and lack of blinding of intervention and outcomes assessment. The incidence of invasive fungal infection was very high in the control groups of three of these trials. Meta-analysis found a statistically significant reduction in the incidence of invasive fungal infection (typical risk ratio 0.20, 95% confidence interval 0.14 to 0.27; risk difference -0.18, -0.21 to -0.15) but substantial statistical heterogeneity was present. We did not find a statistically significant effect on mortality (typical risk ratio 0.87, 0.72 to 1.05; risk difference -0.03, -0.06 to 0.01). None of the trials assessed posthospital discharge outcomes. Three trials (N = 326) assessed the effect of oral/topical non-absorbed versus systemic antifungal prophylaxis. Meta-analyses did not find any statistically significant differences in the incidences of invasive fungal infection or all-cause mortality. AUTHORS' CONCLUSIONS: The finding of a reduction in risk of invasive fungal infection in very low birth weight infants treated with oral/topical non-absorbed antifungal prophylaxis should be interpreted cautiously because of methodological weaknesses in the included trials. Further large randomised controlled trials in current neonatal practice settings are needed to resolve this uncertainty. These trials might compare oral/topical non-absorbed antifungal agents with placebo, with each other, or with systemic antifungal agents and should include an assessment of effect on long-term neurodevelopmental outcomes.
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Antifúngicos/uso terapêutico , Doenças do Prematuro/prevenção & controle , Recém-Nascido de muito Baixo Peso , Micoses/prevenção & controle , Administração Oral , Administração Tópica , Fluconazol/uso terapêutico , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Miconazol/uso terapêutico , Nistatina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Invasive fungal infection is an important cause of mortality and morbidity in very low birth weight infants. Early diagnosis is difficult and treatment is often delayed. Systemic antifungal agents (usually azoles) are increasingly used as prophylaxis against invasive fungal infection. OBJECTIVES: To assess the effect of prophylactic systemic antifungal therapy on mortality and morbidity in very low birth weight infants. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 3), MEDLINE, EMBASE, and CINAHL (to August 2012), conference proceedings, and previous reviews. SELECTION CRITERIA: Randomised controlled trials or quasi-randomised controlled trials that compared the effect of prophylactic systemic antifungal therapy versus placebo or no drug or another antifungal agent or dose regimen in very low birth weight infants. DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two review authors. MAIN RESULTS: We identified 11 eligible trials enrolling a total of 1136 infants. Seven trials (involving 880 infants) compared systemic antifungal prophylaxis versus placebo or no drug. These trials were generally small but of good methodological quality. Meta-analysis found a statistically significant reduction in the incidence of invasive fungal infection in infants who received systemic antifungal prophylaxis (typical risk ratio (RR) 0.41, 95% confidence interval (CI) 0.27 to 0.61; risk difference (RD) -0.09, 95% CI -0.14 to -0.05). The average incidence of invasive fungal infection in the control groups of the trials (16%) was much higher than that generally reported from large cohort studies (< 5%). Meta-analysis did not find a statistically significant difference in the risk of death prior to hospital discharge (typical RR 0.74, 95% CI 0.52 to 1.05; RD -0.04, 95% CI -0.08 to 0.01). Very limited data on long-term neurodevelopmental outcomes were available. Two trials that compared systemic versus oral or topical non-absorbed antifungal prophylaxis did not detect any statistically significant effects on invasive fungal infection or mortality. Two trials that compared different dose regimens of prophylactic intravenous fluconazole did not detect any significant differences in infection rates or mortality. AUTHORS' CONCLUSIONS: Prophylactic systemic antifungal therapy reduces the incidence of invasive fungal infection in very low birth weight infants. This finding should be interpreted and applied cautiously since the incidence of invasive fungal infection was very high in the control groups of most of the included trials. Meta-analysis does not demonstrate a statistically significant effect on mortality. There are currently only limited data on the long-term neurodevelopmental consequences for infants exposed to this intervention. In addition, there is a need for further data on the effect of the intervention on the emergence of organisms with antifungal resistance.
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Antifúngicos/uso terapêutico , Deficiências do Desenvolvimento/prevenção & controle , Recém-Nascido de muito Baixo Peso , Micoses/prevenção & controle , Deficiências do Desenvolvimento/etiologia , Fluconazol/uso terapêutico , Humanos , Recém-Nascido , Micoses/complicações , Micoses/mortalidade , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Invasive fungal infection is an important cause of mortality and morbidity in very preterm or very low birth weight infants. Uncertainty exists about the effect of prophylactic oral/topical non-absorbed antifungals to reduce mucocutaneous colonisation and so limit the risk of invasive fungal infection in this population. OBJECTIVES: To assess the effect of prophylactic oral/topical non-absorbed antifungal therapy on the incidence of invasive fungal infection, mortality and morbidity in very preterm or very low birth weight infants. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL: The Cochrane Library, 2012, Issue 3), MEDLINE, EMBASE, and CINAHL (to August 2012), conference proceedings, and previous reviews. SELECTION CRITERIA: Randomised controlled trials or quasi-randomised controlled trials that compared the effect of prophylactic oral/topical non-absorbed antifungal therapy versus placebo or no drug or another antifungal agent or dose regimen in very preterm or very low birth weight infants. DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of the Cochrane Neonatal Review Group with separate evaluation of trial quality and data extraction by two review authors. MAIN RESULTS: Four trials, in which a total of 1800 infants participated, compared oral/topical non-absorbed antifungal prophylaxis (nystatin or miconazole) with placebo or no drug. These trials had various methodological weaknesses including quasi-randomisation, lack of allocation concealment, and lack of blinding of intervention and outcomes assessment. The incidence of invasive fungal infection was very high in the control groups of three of these trials. Meta-analysis found a statistically significant reduction in the incidence of invasive fungal infection [typical risk ratio 0.20 (95% confidence interval 0.14 to 0.27); risk difference -0.18 (-0.21 to -0.16)] but substantial statistical heterogeneity was present. We did not find a statistically significant effect on mortality [typical risk ratio 0.87 (0.72 to 1.05); risk difference -0.03 (-0.06 to 0.01)]. None of the trials assessed posthospital discharge outcomes.Two trials (N = 265) assessed the effect of oral/topical non-absorbed versus systemic antifungal prophylaxis. Meta-analyses did not find any statistically significant differences in the incidences of invasive fungal infection or all-cause mortality. AUTHORS' CONCLUSIONS: The finding of a reduction in risk of invasive fungal infection in very low birth weight infants treated with oral/topical non-absorbed antifungal prophylaxis should be interpreted cautiously because of methodological weaknesses in the included trials. Further large randomised controlled trials in current neonatal practice settings are needed to resolve this uncertainty. These trials might compare oral/topical non-absorbed antifungal agents with placebo, with each other, or with systemic antifungal agents and should include an assessment of effect on long-term neurodevelopmental outcomes.
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Antifúngicos/uso terapêutico , Doenças do Prematuro/prevenção & controle , Recém-Nascido de muito Baixo Peso , Micoses/prevenção & controle , Administração Oral , Administração Tópica , Fluconazol/uso terapêutico , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Miconazol/uso terapêutico , Nistatina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: To determine if very low dose (VLD, 0.5% phenylephrine, 0.1% cyclopentolate) mydriatic microdrop (approximately 7 µL) administration (up to three doses) is non-inferior to low dose (LD, 1% phenylephrine, 0.2% cyclopentolate) mydriatic microdrop administration for ophthalmologist-determined successful retinopathy of prematurity eye examination (ROPEE). DESIGN: Multicentre, prospective, randomised controlled, non-inferiority clinical trial. SETTING: Four neonatal intensive care units in Aotearoa, New Zealand from October 2019 to September 2021. PATIENTS: Infants with a birth weight less than 1250 g or gestational age less than 30+6 weeks and who required a ROPEE. INTERVENTIONS: The intervention: microdrop (approximately 7 µL) of VLD (0.5% phenylephrine and 0.1% cyclopentolate) to both eyes, or the comparison: microdrop of LD (1% phenylephrine and 0.2% cyclopentolate) to both eyes. Up to three doses could be administered. MAIN OUTCOME MEASURES: The primary outcome measure was an ophthalmologist-determined successful ROPEE. RESULTS: One hundred and fifty preterm infants (LD mean GA=27.4±1.8 weeks, mean birth weight=1011±290 g, VLD mean GA=27.5±1.9 weeks, mean birth weight=1049±281 g,) were randomised. Non-inferiority for successful ROPEE was demonstrated for the VLD group compared with the LD group (VLD successful ROPEE=100%, LD successful ROPEE=100%, 95% CI no continuity correction -0.05 to 0.05) and for Maori (95% CI no continuity correction -0.02 to 0.19). CONCLUSION: VLD microdrops enable safe and effective screening for ROPEE in both Maori and non-Maori preterm infants. TRIAL REGISTRATION NUMBER: ACTRN12619000795190.
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Ciclopentolato , Retinopatia da Prematuridade , Lactente , Recém-Nascido , Humanos , Ciclopentolato/farmacologia , Midriáticos/farmacologia , Fenilefrina/farmacologia , Recém-Nascido Prematuro , Retinopatia da Prematuridade/diagnóstico , Retinopatia da Prematuridade/tratamento farmacológico , Peso ao Nascer , Soluções Oftálmicas/farmacologia , Estudos Prospectivos , Pupila , Recém-Nascido de muito Baixo PesoRESUMO
OBJECTIVE: To evaluate the epidemiology and population trends of early-onset sepsis in very preterm neonates admitted to neonatal intensive care units (NICU) in Australia and New Zealand. DESIGN: Retrospective observational cohort study using a dual-nation registry database. SETTING: 29 NICUs that have contributed to the Australian and New Zealand Neonatal Network. PARTICIPANTS: Neonates born at <32 weeks' gestation born between 2007 and 2018 and then admitted to a NICU. MAIN OUTCOME MEASURES: Microorganism profiles, incidence, mortality and morbidity. RESULTS: Over the 12-year period, 614 early-onset sepsis cases from 43 178 very preterm admissions (14.2/1000 admissions) were identified. The trends of early-onset sepsis incidence remained stable, varying between 9.8 and 19.4/1000 admissions (linear trend, p=0.56). The leading causative organisms were Escherichia coli (E. coli) (33.7%) followed by group B Streptococcus (GBS) (16.1%). The incidence of E. coli increased between 2007 (3.2/1000 admissions) and 2018 (8.3/1000 admissions; p=0.02). Neonates with E. coli had higher odds of mortality compared with those with GBS (OR=2.8, 95% CI 1.2 to 6.1). Mortality due to GBS decreased over the same period (2007: 0.6/1000 admissions, 2018: 0.0/1000 admissions; p=0.01). Early-onset sepsis tripled the odds of mortality (OR=3.0, 95% CI 2.4 to 3.7) and halved the odds of survival without morbidity (OR=0.5, 95% CI 0.4 to 0.6). CONCLUSION: Early-onset sepsis remains an important condition among very preterm populations. Furthermore, E. coli is a dominant microorganism of very preterm early-onset sepsis in Australia and New Zealand. Rates of E. coli have been increasing in recent years, while GBS-associated mortality has decreased.
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Sepse , Infecções Estreptocócicas , Recém-Nascido , Humanos , Austrália/epidemiologia , Escherichia coli , Estudos Retrospectivos , Nova Zelândia/epidemiologia , Lactente Extremamente Prematuro , Streptococcus agalactiae , Sepse/epidemiologia , Incidência , Infecções Estreptocócicas/epidemiologiaRESUMO
Caring for a child born preterm places significant emotional and financial burdens on family relationships. This paper examines (a) the extent to which children born very and extremely preterm are more likely to experience parental change/caregiver instability than children born full term, (b) predictors of parental change/s for preterm infants, and (c) whether exposure to parental change/caregiver instability increases child neurodevelopmental risk. Data were collected as part of a prospective longitudinal study of 110 very preterm and 113 full-term born infants and their parents studied from birth to corrected age 12 years. At ages 2, 4, 6, 9 and 12 years, detailed information was collected about the frequency and nature of all parent/caregiver changes for 3-6 monthly intervals of each child's life. At age 12, all children completed a comprehensive neurodevelopmental evaluation of their emotional and behavioural adjustment, cognition, and educational achievement. Results showed that children born very preterm were at increased risk of experiencing parental/caregiver changes, with this risk being greatest for those born extremely preterm. Neonatal medical complexity, family socioeconomic disadvantage, maternal psychological wellbeing, and child neurodevelopmental impairment were associated with a higher risk of parental change. Preterm birth and exposure to parental change/instability contributed additively to poorer child outcomes. Findings support the need for family-focused neonatal and postnatal care strategies for high-risk infants, to support parents as well as their infants to optimize child health and developmental outcomes.
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AIMS: This paper describes the emotional and behavioural adjustment of children born very preterm (VPT) at early school age. Of particular interest was the degree of agreement between parents and teachers, and the extent of situational (parent or teacher) and pervasive (parent and teacher reported) adjustment problems. METHODS: A regionally representative cohort of 104 VPT (≤33 weeks gestation) and 108 full-term (FT) children born during 1998-2000 was studied prospectively to age six. At corrected age six, child emotional and behavioural adjustment was assessed using the parent and teacher rated strengths and difficulties questionnaires. RESULTS: According to parents, 6-year-old VPT children had odds of emotional, inattention/hyperactivity and peer problems that were 2.7 to 3.8 times higher than their FT peers. Similar difficulties were identified by teachers, but odds were much lower and nonsignificant (1.1-1.8). Agreement between parents and teachers was lower in the VPT than the FT group (mean alternative chance-correlated coefficient , AC(1) = 0.63 vs. 0.80). Examination of the extent of pervasively identified adjustment problems showed that VPT children had higher rates of emotional (6% vs. 1%) and inattention/hyperactivity problems (12% vs. 6%) than FT children. CONCLUSIONS: Early school age, VPT children are at increased risk of pervasive emotional problems and inattention/hyperactivity, although these risks are relatively modest. The use of multiple informants to assess VPT children's well-being is important to minimise the effects of report source bias and the over-identification of adjustment problems in children born VPT.
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Adaptação Psicológica , Comportamento Infantil/psicologia , Deficiências do Desenvolvimento/psicologia , Emoções Manifestas , Nascimento Prematuro , Criança , Deficiências do Desenvolvimento/epidemiologia , Feminino , Humanos , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Masculino , Nova Zelândia/epidemiologia , Variações Dependentes do Observador , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: There is emerging evidence of differences in cardiac structure and function in preterm-born adults and increased risk of heart failure. However, there is a paucity of data in populations who have been exposed to modern intensive care and the impact of perinatal factors is unclear. AIMS: To compare echocardiographic measures of cardiac structure and function in a regional cohort of 17-year-olds born very preterm compared to term-born peers and the influence of perinatal factors. STUDY DESIGN: Observational longitudinal cohort study. SUBJECTS: A regional cohort of ninety-one 17-year-olds born at <32 weeks gestation compared to sixty-two term-born controls. OUTCOME MEASURES: Echocardiographic measures of cardiac structure and function. RESULTS: Left ventricular and right atrial volume and left ventricular mass, indexed to body surface area, were significantly smaller in preterm-born adolescents compared to term-born controls even when adjusted for sex. There were no between group differences in cardiac function. Within those born preterm we found a significant association between gestational age and birthweight z-score and measures of cardiac function at 17 years. Within the preterm group, those with a diagnosis of bronchopulmonary dysplasia had higher left ventricular posterior wall thickness, higher mitral deceleration time and lower left atrial area and tricuspid annular plane of systolic excursion. CONCLUSIONS: Adolescents born very prematurely, who have received modern intensive care, have measurable differences in heart structure compared to their term-born peers but heart function is preserved. For those born preterm, gestational age, birthweight and bronchopulmonary dysplasia are associated with differences in cardiac function.
Assuntos
Coração , Lactente Extremamente Prematuro , Adolescente , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Estudos Longitudinais , GravidezRESUMO
BACKGROUND: Data on psychiatric disorders in survivors born very preterm (VP; <32 weeks) or very low birthweight (VLBW; <1500 g) are sparse. We compared rates of psychiatric diagnoses between VP/VLBW and term-born, normal birthweight (term/NBW) control participants. METHODS: This individual participant data (IPD) meta-analysis pooled data from eligible groups in the Adults born Preterm International Collaboration (APIC). Inclusion criteria included: 1) VP/VLBW group (birth weight <1500 g and/or gestational age <32 weeks), 2) normal birth weight/term-born control group (birth weight >2499 g and/or gestational age ≥37 weeks), and 3) structured measure of psychiatric diagnoses using DSM or ICD criteria. Diagnoses of interest were Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), Anxiety Disorder, Mood Disorder, Disruptive Behaviour Disorder (DBD), Eating Disorder, and Psychotic Disorder. A systematic search for eligible studies was conducted (PROSPERO Registration Number 47555). FINDINGS: Data were obtained from 10 studies (1385 VP/VLBW participants, 1780 controls), using a range of instruments and approaches to assigning diagnoses. Those born VP/VLBW had ten times higher odds of meeting criteria for ASD (odds ratio [OR] 10·6, 95% confidence interval [CI] 2·50, 44·7), five times higher odds of meeting criteria for ADHD (OR 5·42, 95% CI 3·10, 9·46), twice the odds of meeting criteria for Anxiety Disorder (OR 1·91, 95% CI 1·36, 2·69), and 1·5 times the odds of meeting criteria for Mood Disorder (OR 1·51, 95% CI 1·08, 2·12) than controls. This pattern of findings was consistent within age (<18 years vs. ≥18 years) and sex subgroups. INTERPRETATION: Our data suggests that individuals born VP/VLBW might have higher odds of meeting criteria for certain psychiatric disorders through childhood and into adulthood than term/NBW controls. Further research is needed to corroborate our results and identify factors associated with psychiatric disorders in individuals born VP/VLBW. FUNDING: Australia's National Health & Medical Research Council; CAPES (Coordenação de Aperfeiçoamento de Pessoal deNível Superior) - International Cooperation General Program; Canadian Institutes of Health Research Team Grant; National Council for Scientific and Technological Development (CNPq); Academy of Finland; Sigrid Juselius Foundation; Signe and Ane Gyllenberg Foundation; European Union's Horizon 2020 research and innovation programme: Project RECAP-Preterm; European Commission Dynamics of Inequality Across the Life-course: structures and processes (DIAL); Neurologic Foundation of New Zealand; MRC programme grant; Health Research Council of New Zealand; National Institutes of Health, USA; The Research Council of Norway; Joint Research Committee between St. Olavs Hospital and Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU); Liaison Committee between Central Norway Regional Health Authority and NTNU.
Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Proteínas Cromossômicas não Histona/genética , Proteínas de Ligação a DNA/genética , Heterogeneidade Genética , Histonas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Fatores de Transcrição/genética , Adolescente , Evolução Fatal , Feminino , Humanos , Mutação , Proteína SMARCB1RESUMO
BACKGROUND AND OBJECTIVES: Children born very preterm (VPT) are at high risk of cognitive impairment that impacts their educational and social opportunities. This study examined the predictive accuracy of assessments at 2, 4, 6, and 9 years in identifying preterm children with cognitive impairment by 12 years. METHODS: We prospectively studied a regional cohort of 103 children born VPT (≤32 weeks' gestation) and 109 children born term from birth to corrected age 12 years. Cognitive functioning was assessed by using age-appropriate, standardized measures: Bayley Scales of Infant Development, Second Edition (age 2); Wechsler Preschool and Primary Scale of Intelligence (ages 4 and 6); and Wechsler Intelligence Scale for Children, Fourth Edition (ages 9 and 12). RESULTS: By 12 years, children born VPT were more likely to have severe (odds ratio 3.9; 95% confidence interval 1.1-13.5) or any (odds ratio 3.2; 95% confidence interval 1.8-5.6) cognitive impairment compared with children born term. Adopting a severe cognitive impairment criterion at age 2 under-identified 44% of children born VPT with later severe impairment, whereas a more inclusive earlier criterion identified all severely affected children at 12 years. Prediction improved with age, with any delay at age 6 having the highest sensitivity (85%) and positive predictive value (66%) relative to earlier age assessments. Inclusion of family-social circumstances further improved diagnostic accuracy. CONCLUSIONS: Cognitive risk prediction improves with age, with assessments at 6 years offering optimal diagnostic accuracy. Intervention for children with early mild delay may be beneficial, especially for those raised in socially disadvantaged family contexts.
Assuntos
Fatores Etários , Disfunção Cognitiva/diagnóstico , Lactente Extremamente Prematuro , Criança , Pré-Escolar , Intervalos de Confiança , Escolaridade , Família , Feminino , Humanos , Recém-Nascido , Testes de Inteligência , Masculino , Razão de Chances , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Sensibilidade e Especificidade , Meio SocialRESUMO
BACKGROUND: Children born to opioid-dependent mothers are at risk of adverse neurodevelopment. The magnitude of this risk remains inconclusive. OBJECTIVE: To conduct a meta-analysis of studies that assessed neurodevelopmental outcomes of children aged 0 to 12 years born to opioid-dependent mothers, compared with children born to nonopioid-dependent mothers, across general cognitive, language, motor, and social-emotional domains. DATA SOURCES: PubMed, CINAHL, PsycINFO, and Google Scholar databases. STUDY ELIGIBILITY CRITERIA: English-language publications between January 1993 and November 2018, including prenatally opioid-exposed and nonopioid-exposed comparison children, reporting outcomes data on standardized assessments. STUDY APPRAISAL AND SYNTHESIS METHODS: Two reviewers independently extracted data. Pooled standardized mean differences (SMDs) were analyzed using random effects models. Risk of bias was assessed with the Newcastle-Ottawa Quality Assessment Scale. RESULTS: Across 16 studies, individual domain outcomes data were examined for between 93 to 430 opioid-exposed and 75 to 505 nonopioid-exposed infants/children. Opioid-exposed infants and children performed more poorly than their nonopioid-exposed peers across all outcomes examined, demonstrated by lower infant cognitive (SMD = 0.77) and psychomotor scores (SMD = 0.52), lower general cognition/IQ (SMD = 0.76) and language scores (SMD = 0.65-0.74), and higher parent-rated internalizing (SMD = 0.42), externalizing (SMD = 0.66), and attention problems (SMD = 0.72). LIMITATIONS: Most studies examined early neurodevelopment; only 3 reported school-age outcomes thereby limiting the ability to assess longer-term impacts of prenatal opioid exposures. CONCLUSIONS AND IMPLICATIONS OF FINDINGS: Children born to opioid-dependent mothers are at modest- to high-risk of adverse neurodevelopment at least to middle childhood. Future studies should identify specific clinical and social factors underlying these challenges to improve outcomes.
Assuntos
Disfunção Cognitiva/induzido quimicamente , Transtornos Relacionados ao Uso de Opioides/complicações , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Transtornos Psicomotores/induzido quimicamente , Criança , Desenvolvimento Infantil/efeitos dos fármacos , Pré-Escolar , Feminino , Humanos , Transtornos do Desenvolvimento da Linguagem/induzido quimicamente , Masculino , Mães , Transtornos do Neurodesenvolvimento/induzido quimicamente , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologiaRESUMO
BACKGROUND: B-type natriuretic peptide (BNP) is a cardiac hormone released with an N-terminal fragment (NTproBNP) under conditions of ventricular pressure or volume overload. BNP has been proposed for use as a biomarker of cardiac dysfunction in premature infants in the setting of hemodynamically significant patent ductus arteriosus (HsPDA) and bronchopulmonary dysplasia (BPD). In adult settings the presence of proBNP and glycosylated isoforms may affect assay interpretation. However, there are limited data on how immature preterm physiology may affect BNP or NTproBNP levels and no published data on post-translational BNP processing in premature infants. METHODS: Pooled serial plasma samples from preterm infants born at less than 30 weeks gestation were analyzed for BNP congeners using Luminex® assay and high performance liquid chromatography. Samples were grouped according to clinical status: Group 1, no HsPDA and no BPD, Group 2 HsPDA and no/mild BPD, Group 3 HsPDA and moderate/severe BPD. RESULTS: Plasma from 15 infants was analyzed, and across all three groups NTproBNP predominated with minimal amounts of other isoforms; no glycosylation was detected. CONCLUSIONS: NTproBNP appears to be the predominant isoform across each of our clinical groups in our pooled sample analysis with no evidence of significant glycosylation. This suggests NTproBNP is likely to be a robust marker in this clinical setting.