Prevalence and independent risk factors for hearing loss in NICU infants

Aim: To determine the prevalence and independent relationship between hearing loss and risk factors in a representative neonatal intensive care unit (NICU) population. Methods: Automated auditory brainstem response (AABR) hearing screening has been introduced since 1998 in the Dutch NICUs. After a second AABR failure, diagnostic ABR was used to establish diagnosis of hearing loss. Newborns who died before the age of 3 months were excluded. In the present study only the NICU infants who were born with a gestational age &lt;30 weeks and/or a birth weight &lt;1000 g between October 1, 1998 and January 1, 2002 were included. Risk factors included in the study were familial hearing loss, in utero infections, craniofacial anomalies, birth weight &lt;1500g, hyperbilirubinemia, ototoxic medications, cerebral complications, severe birth asphyxia, assisted ventilation ≥5 days and syndromes. Results: A nationwide cohort of 2186 newborns were included. Mean gestational age was 28.5 weeks (SD 1.6) and mean birth weight was 1039 g (SD 256). Prevalence of uni- or bilateral hearing loss was 3.2% (71/2186; 95% CI 2.6-4.1). Multivariate analysis revealed that the only independent risk factors for hearing loss were severe birth asphyxia (OR 1.7; 95% CI 1.0-2.7) and assisted ventilation ≥5 days (OR 3.6; 95% CI 2.1-6.0). Conclusion: The prevalence of hearing loss in a representative NICU population was 3.2%. Independent risk factors for hearing loss were severe birth asphyxia and assisted ventilation ≥5 days.</p

Hearing loss by week of gestation and birth weight in very preterm neonates

OBJECTIVE: To gain insight into health and related costs associated with very preterm births, one needs accurate information about the prevalence of the disabling conditions, including neonatal hearing loss (NHL).STUDY DESIGN: We assessed the prevalence of NHL by week of gestation and categories of birth weight in very preterm neonates. Results of the 2-stage Automated Auditory Brainstem Response nationwide Newborn Hearing Screening Program in Dutch Neonatal Intensive Care Units and diagnostic examinations were centrally registered between October 1998 and December 2012 and included in this study. NHL was defined as impaired when the neonate conventional Auditory Brainstem Response level exceeded 35 dB near Hearing Level at diagnostic examination. Birth weight was stratified into &lt;750 g, 750-999 g, 1000-1249 g, 1250-1499 g, and ≥ 1500 g, and by small for gestational age (SGA; &lt;10th percentile) vs appropriate for gestational age. Logistic regression analyses and recursive partitioning were performed.RESULTS: In total, 18,564 very preterm neonates were eligible. The prevalence of NHL consistently increased with decreasing week of gestation (1.2%-7.5% from 31 to 24 weeks) and decreasing birth weight (1.4%-4.8% from ≥ 1500 g to &lt;750 g, all P &lt; .002). Most vulnerable to NHL were girls &lt;28 weeks, boys &lt;30 weeks, and SGA neonates. The SGA effect started at 27 weeks.CONCLUSIONS: Gestational age and birth weight quantify the risk of NHL. This information can be used at the individual level for parent counseling and at the population level for medical decision making.</p

Referral patterns of children with poor growth in primary health care

Background. To promote early diagnosis and treatment of short stature, consensus meetings were held in the mid nineteen nineties in the Netherlands and the UK. This resulted in guidelines for referral. In this study we evaluate the referral pattern of short stature in primary health care using these guidelines, comparing it with cut-off values mentioned by the WHO. Methods. Three sets of referral rules were tested on the

Screening rules for growth to detect celiac disease: A case-control simulation study

Background: It is generally assumed that most patients with celiac disease (CD) have a slowed growth in terms of length (or height) and weight. However, the effectiveness of slowed growth as a tool for identifying children with CD is unknown. Our aim is to study the diagnostic efficiency of several growth criteria used to detect CD children. Methods: A case-control simulation study was carried out. Longitudinal length and weight measurements from birth to 2.5 years of age were used from three groups of CD patients (n = 134) (one group diagnosed by screening, two groups with clinical manifestations), and a reference group obtained from the Social Medical Survey of Children Attending Child Health Clinics (SMOCC) cohort (n = 2,151) in The Netherlands. The main outcome measures were sensitivity, specificity and positive predictive value (PPV) for each criterion. Results: Body mass index (BMI) performed best for the groups with clinical manifestations. Thirty percent of the CD children with clinical manifestations and two percent of the reference children had a BMI Standard Deviation Score (SDS) less than -1.5 and a decrease in BMI SDS of at least -2.5 (PPV = 0.85%). The growth criteria did not discriminate between the screened CD group and the reference group. Conclusion: For the CD children with clinical manifestations, the most sensitive growth parameter is a decrease in BMI SDS. BMI is a better predictor than weight, and much better than length or height. Toddlers with CD detected by screening grow normally at this stage of the disease

Genome-wide identification of directed gene networks using large-scale population genomics data

Identification of causal drivers behind regulatory gene networks is crucial in understanding gene function. Here, we develop a method for the large-scale inference of gene–gene interactions in observational population genomics data that are both directed (using local genetic instruments as causal anchors, akin to Mendelian Randomization) and specific (by controlling for linkage disequilibrium and pleiotropy). Analysis of genotype and whole-blood RNA-sequencing data from 3072 individuals identified 49 genes as drivers of downstream transcriptional changes (Wald P < 7 × 10−10), among which transcription factors were overrepresented (Fisher’s P = 3.3 × 10−7). Our analysis suggests new gene functions and targets, including for SENP7 (zinc-finger genes involved in retroviral repression) and BCL2A1 (target genes possibly involved in auditory dysfunction). Our work highlights the utility of population genomics data in deriving directed gene expression networks. A resource of trans-effects for all 6600 genes with a genetic instrument can be explored individually using a web-based browser

Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility.

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel Na1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on Na1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings

Screening for developmental dysplasia of the hip

The success rates of screening programmes for Developmental Dysplasia of the Hip (DDH) vary widely. Studies on screening programmes for DDH based on a Medline search for the years 1966–1997 are reviewed. The percentage treated in most studies, especially those using ultrasound, are high and suggest substantial over-treatment. Neonatal clinical screening has the best results, but programme effectiveness increases when this is combined with secondary screening of the high-risk population. The extra costs are compensated by reduced treatment costs of late-diagnosed cases

Mortality in children with early-detected congenital central hypothyroidism

Context: Approximately 60% to 80% of patients with congenital central hypothyroidism (CH-C) have multiple pituitary hormone deficiencies (MPHDs), making CH-C a potentially life-threatening disease. Data on mortality in patients with CH-C are lacking. Objective: To study the mortality rate in pediatric patients with early-detected and treated CH-C in the Netherlands and to investigate whether causes of death were related to pituitary hormone deficiencies. Methods: Overall mortality rate, infant mortality rate (IMR), and under-5 mortality rate were calculated in all children with CH-C detected by neonatal screening between 1 January 1995 and 1 January 2013. Medical charts were reviewed to establish causes of death. Results: A total of 139 children with CH-C were identified, of which 138 could be traced (82 with MPHD, 56 with isolated CH-C). Total observation time was 1414 years with a median follow-up duration of 10.2 years. The overall mortality rate was 10.9% (15/138). IMR and under-5 mortality rate were 65.2/1000 (9/138) and 101.4/1000 (14/138), respectively, compared with an IMR of 4.7/1000 and under-5 mortality of 5.4/1000 live-born children in the Netherlands during the same time period (P,0.0001). Main causes of death were severe congenital malformations in six patients, asphyxia in two patients, and congenital or early neonatal infection in two patients. Pituitary hormone deficiency was noted as cause of death in only one infant. Conclusion: We report an increased mortality rate in patients with early-detected CH-C that does not seem to be related to endocrine disease. This suggests that mortality due to pituitary insufficiency is low in patients with early-detected and early-treated CH-C