Behaviour and development in 24-month-old moderately preterm toddlers

OBJECTIVE: Moderately preterm children (gestational age 32-36+6 weeks) are at risk of cognitive and behaviour problems at school age. The aim of this study was to investigate if these problems are already present at the age of 2 years. STUDY DESIGN: Developmental outcome was assessed at 24-months (corrected age) with the Bayley-III-NL in 116 moderately preterm (M=34.66 ± 1.35 weeks gestation) and 99 term born children (M=39.45 ± 0.98 weeks gestation). Behaviour problems were assessed with the Child Behaviour Checklist. RESULTS: With age corrected for prematurity, moderately preterm children scored below term peers on Receptive Communication skills (11.05 ± 2.58 vs 12.02 ± 2.74, p=0.02). Without correcting age for prematurity, moderately preterm children scored below term born peers on Cognition (8.97 ± 2.11 vs 10.68 ± 2.35, p<0.001), Fine Motor (10.33 ± 2.15 vs 11.96 ± 2.15, p<0.001), Gross Motor (8.47 ± 2.55 vs 9.39±2.80, p=0.05), Receptive Communication (10.09 ± 2.48 vs 12.02 ± 2.74, p<0.001) and Expressive Communication (10.33 ± 2.43 vs 11.49 ± 2.51, p=0.005) skills. Compared with term peers, more moderately preterm children showed a (mild) delay (ie, scaled score <7) in gross motor skills with age uncorrected for prematurity (20.7% vs 11.2%, p=0.04). Moderately preterm children had more internalising behaviour problems than term children (44.76 ± 8.94 vs 41.54 ± 8.56, p=0.03). No group differences were found in percentages of (sub)clinical scores. CONCLUSIONS: At the age of 2 years, uncorrected for prematurity, differences in cognition, communication, and motor development were present in moderately preterm children compared with term born peers. After correcting age for prematurity, a difference was only found for receptive communication skills. In addition, moderately preterm children show more internalising behaviour problems

Behaviour and development in 24-month-old moderately preterm toddlers

OBJECTIVE: Moderately preterm children (gestational age 32-36+6 weeks) are at risk of cognitive and behaviour problems at school age. The aim of this study was to investigate if these problems are already present at the age of 2 years. STUDY DESIGN: Developmental outcome was assessed at 24-months (corrected age) with the Bayley-III-NL in 116 moderately preterm (M=34.66 ± 1.35 weeks gestation) and 99 term born children (M=39.45 ± 0.98 weeks gestation). Behaviour problems were assessed with the Child Behaviour Checklist. RESULTS: With age corrected for prematurity, moderately preterm children scored below term peers on Receptive Communication skills (11.05 ± 2.58 vs 12.02 ± 2.74, p=0.02). Without correcting age for prematurity, moderately preterm children scored below term born peers on Cognition (8.97 ± 2.11 vs 10.68 ± 2.35, p<0.001), Fine Motor (10.33 ± 2.15 vs 11.96 ± 2.15, p<0.001), Gross Motor (8.47 ± 2.55 vs 9.39±2.80, p=0.05), Receptive Communication (10.09 ± 2.48 vs 12.02 ± 2.74, p<0.001) and Expressive Communication (10.33 ± 2.43 vs 11.49 ± 2.51, p=0.005) skills. Compared with term peers, more moderately preterm children showed a (mild) delay (ie, scaled score <7) in gross motor skills with age uncorrected for prematurity (20.7% vs 11.2%, p=0.04). Moderately preterm children had more internalising behaviour problems than term children (44.76 ± 8.94 vs 41.54 ± 8.56, p=0.03). No group differences were found in percentages of (sub)clinical scores. CONCLUSIONS: At the age of 2 years, uncorrected for prematurity, differences in cognition, communication, and motor development were present in moderately preterm children compared with term born peers. After correcting age for prematurity, a difference was only found for receptive communication skills. In addition, moderately preterm children show more internalising behaviour problems

Wheezing and infantile colic are associated with neonatal antibiotic treatment

Cohort studies have suggested that early life antibiotic treatment is associated with increased risk of atopy. We determined whether antibiotic treatment already in the first week of life increases the risk for atopic and non-atopic disorders. The INCA study is a prospective observational birth cohort study of 436 term infants, with follow-up of one year. 151 neonates received broad-spectrum antibiotics for suspected neonatal infection (AB+), versus a healthy untreated control group (N=285) (AB-). In the first year, parents recorded daily (non-) allergic symptoms. At 1 year, doctors-diagnoses were registered and a blood sample was taken (n=205). Incidence of wheezing in the first year was higher in AB+ than AB- (41.0% vs. 30.5%, p=0.026; aOR 1.56 (95%CI 0.99-2.46, p=0.06). Infantile colics were more prevalent in AB+ compared to AB- (21.9% and 14.4% p=0.048), antibiotic treatment was an independent risk factor for infantile colics (aOR 1.66 (95%CI 1.00-2.77) p=0.05). Allergic sensitization (Phadiatop >0.70kUA/L) showed a trend towards a higher risk in AB+ (aOR 3.26 (95%CI 0.95-11.13) p=0.06). Incidence of eczema, infections, and GP visits in the first year were similar in AB+ and AB-. Antibiotic treatment in the first week of life is associated with an increased risk for wheezing and infantile colics. This study may provide a rationale for early cessation of antibiotics in neonates without proven or probable infection. This article is protected by copyright. All rights reserve

Neonatal microbiota development and the effect of early life antibiotics are determined by two distinct settler types

The neonatal period, during which the initial gut microbiota is acquired, is a critical phase. The healthy development of the infant's microbiome can be interrupted by external perturbations, like antibiotics, which are associated with profound effects on the gut microbiome and various disorders later in life. The aim of this study was to investigate the development of intestinal microbiota and the effect of antibiotic exposure during the first three months of life in term infants. Fecal samples were collected from healthy infants and infants who received antibiotics in the first week of life at one week, one month, and three months after birth. Microbial composition was analyzed using IS-pro and compared between antibiotics-treated and untreated infants. In total, 98 infants, divided into four groups based on feeding type and delivery mode, were analyzed. At one week of age, samples clustered into two distinct groups, which were termed “settler types”, based on their Bacteroidetes abundance. Caesarean-born infants belonged to the low-Bacteroidetes settler type, but vaginally-born infants were divided between the two groups. The antibiotics effect was assessed within a subgroup of 45 infants, vaginally-born and exclusively breastfed, to minimize the effect of other confounders. Antibiotics administration resulted in lower Bacteroidetes diversity and/ or a delay in Bacteroidetes colonization, which persisted for three months, and in a differential development of the microbiota. Antibiotics resulted in pronounced effects on the Bacteroidetes composition and dynamics. Finally, we hypothesize that stratification of children's cohorts based on settler types may reveal group effects that might otherwise be masked

A host-protein based assay to differentiate between bacterial and viral infections in preschool children (OPPORTUNITY) : A double-blind, multicentre, validation study

BACKGROUND: A physician is frequently unable to distinguish bacterial from viral infections. ImmunoXpert is a novel assay combining three proteins: tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma induced protein-10 (IP-10), and C-reactive protein (CRP). We aimed to externally validate the diagnostic accuracy of this assay in differentiating between bacterial and viral infections and to compare this test with commonly used biomarkers. METHODS: In this prospective, double-blind, international, multicentre study, we recruited children aged 2-60 months with lower respiratory tract infection or clinical presentation of fever without source at four hospitals in the Netherlands and two hospitals in Israel. A panel of three experienced paediatricians adjudicated a reference standard diagnosis for all patients (ie, bacterial or viral infection) using all available clinical and laboratory information, including a 28-day follow-up assessment. The panel was masked to the assay results. We identified majority diagnosis when two of three panel members agreed on a diagnosis and unanimous diagnosis when all three panel members agreed on the diagnosis. We calculated the diagnostic performance (ie, sensitivity, specificity, positive predictive value, and negative predictive value) of the index test in differentiating between bacterial (index test positive) and viral (index test negative) infection by comparing the test classification with the reference standard outcome. FINDINGS: Between Oct 16, 2013 and March 1, 2015, we recruited 777 children, of whom 577 (mean age 21 months, 56% male) were assessed. The majority of the panel diagnosed 71 cases as bacterial infections and 435 as viral infections. In another 71 patients there was an inconclusive panel diagnosis. The assay distinguished bacterial from viral infections with a sensitivity of 86·7% (95% CI 75·8-93·1), a specificity of 91·1% (87·9-93·6), a positive predictive value of 60·5% (49·9-70·1), and a negative predictive value of 97·8% (95·6-98·9). In the more clear cases with unanimous panel diagnosis (n=354), sensitivity was 87·8% (74·5-94·7), specificity 93·0% (89·6-95·3), positive predictive value 62·1% (49·2-73·4), and negative predictive value 98·3% (96·1-99·3). INTERPRETATION: This external validation study shows the diagnostic value of a three-host protein-based assay to differentiate between bacterial and viral infections in children with lower respiratory tract infection or fever without source. This diagnostic based on CRP, TRAIL, and IP-10 has the potential to reduce antibiotic misuse in young children. FUNDING: MeMed Diagnostics

Antibiotic Overuse in Children with Respiratory Syncytial Virus Lower Respiratory Tract Infection

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections (LRTI) during the first year of life. Antibiotic treatment is recommended in cases suspected of bacterial coinfection. The aim of this prospective study was to estimate the incidence of bacterial coinfections and the amount of antibiotic overuse in children infected with RSV using expert panel diagnosis. METHODS: Children 1 month of age and over with LRTI or fever without source were prospectively recruited in hospitals in the Netherlands and Israel. Children with confirmed RSV infection by Polymerase Chain Reaction (PCR) on nasal swabs were evaluated by an expert panel as reference standard diagnosis. Three experienced pediatricians distinguished bacterial coinfection from simple viral infection using all available clinical information, including all microbiologic evaluations and a 28-day follow-up evaluation. RESULTS: A total of 188 children (24% of all 784 recruited patients) were positive for RSV. From these, 92 (49%) were treated with antibiotics. All 27 children (29%) with bacterial coinfection were treated with antibiotics. Fifty-seven patients (62%) were treated with antibiotics without a diagnosis of bacterial coinfection. In 8 of the 92 (9%), the expert panel could not distinguish simple viral infection from bacterial coinfection. CONCLUSION: This is the first prospective international multicenter RSV study using an expert panel as reference standard to identify children with and without bacterial coinfection. All cases of bacterial coinfections are treated, whereas as many as one-third of all children with RSV LRTI are treated unnecessarily with antibiotics

Antibiotic Overuse in Children with Respiratory Syncytial Virus Lower Respiratory Tract Infection

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections (LRTI) during the first year of life. Antibiotic treatment is recommended in cases suspected of bacterial coinfection. The aim of this prospective study was to estimate the incidence of bacterial coinfections and the amount of antibiotic overuse in children infected with RSV using expert panel diagnosis. METHODS: Children 1 month of age and over with LRTI or fever without source were prospectively recruited in hospitals in the Netherlands and Israel. Children with confirmed RSV infection by Polymerase Chain Reaction (PCR) on nasal swabs were evaluated by an expert panel as reference standard diagnosis. Three experienced pediatricians distinguished bacterial coinfection from simple viral infection using all available clinical information, including all microbiologic evaluations and a 28-day follow-up evaluation. RESULTS: A total of 188 children (24% of all 784 recruited patients) were positive for RSV. From these, 92 (49%) were treated with antibiotics. All 27 children (29%) with bacterial coinfection were treated with antibiotics. Fifty-seven patients (62%) were treated with antibiotics without a diagnosis of bacterial coinfection. In 8 of the 92 (9%), the expert panel could not distinguish simple viral infection from bacterial coinfection. CONCLUSION: This is the first prospective international multicenter RSV study using an expert panel as reference standard to identify children with and without bacterial coinfection. All cases of bacterial coinfections are treated, whereas as many as one-third of all children with RSV LRTI are treated unnecessarily with antibiotics

Risk Factors for Retinopathy of Prematurity in the Netherlands:A Comparison of Two Cohorts

Introduction: Retinopathy of prematurity (ROP) remains an important cause for preventable blindness. Aside from gestational age (GA) and birth weight, risk factor assessment can be important for determination of infants at risk of (severe) ROP. Methods: Prospective, multivariable risk-analysis study (NEDROP-2) was conducted, including all infants born in 2017 in the Netherlands considered eligible for ROP screening by pediatricians. Ophthalmologists provided data of screened infants, which were combined with risk factors from the national perinatal database (Perined). Clinical data and potential risk factors were compared to the first national ROP inventory (NEDROP-1, 2009). During the second period, more strict risk factor-based screening inclusion criteria were applied. Results: Of 1,287 eligible infants, 933 (72.5%) were screened for ROP and matched with the Perined data. Any ROP was found in 264 infants (28.3% of screened population, 2009: 21.9%) and severe ROP (sROP) (stage &gt;= 3) in 41 infants (4.4%, 2009: 2.1%). The risk for any ROP is decreased with a higher GA (odds ratio [OR] 0.59 and 95% confidence interval [CI] 0.54-0.66) and increased for small for GA (SGA) (1.73, 1.11-2.62), mechanical ventilation &gt;7 days (2.13, 1.35-3.37) and postnatal corticosteroids (2.57, 1.44-4.66). For sROP, significant factors were GA (OR 0.37 and CI 0.27-0.50), SGA (OR 5.65 and CI 2.17-14.92), postnatal corticosteroids (OR 3.81 and CI 1.72-8.40), and perforated necrotizing enterocolitis (OR 7.55 and CI 2.29-24.48). Conclusion: In the Netherlands, sROP was diagnosed more frequently since 2009. No new risk factors for ROP were determined in the present study, apart from those already included in the current screening guideline.</p