Evaluating current practice and knowledge about antibiotic stewardship principles in paediatric tertiary hospitals to identify target areas for future teaching activities.

PURPOSE: Antibiotic exposure among hospitalized children is very high. With inappropriate antimicrobial use resulting in increased rates of antimicrobial resistance, the implementation of antibiotic stewardship programs is critically needed. This survey study aimed to identify current practice and knowledge about antibiotic stewardship and infection control among paediatricians in tertiary care paediatric hospitals in and around Munich, Germany. METHODS: A prospective cross-sectional study based on an anonymous questionnaire, structured into different sub-sections regarding antibiotic use, antimicrobial resistance, antibiotic stewardship and infection control, was conducted between 1st of May and 30th of June 2016 in five paediatric hospitals. RESULTS: In total, 111 paediatricians across all grades were eligible for participation. The overall proportion of correct answers for all sub-sections of the survey ranged from 54.1% correct answers in the antibiotic handling and bacterial resistance section to 72.9% correct answers in the hospital hygiene/infection control section. In general, knowledge across all categories was similar for junior doctors, middle-grade doctors or consultants. Advocating empiric use of narrow-spectrum instead of broad-spectrum antibiotics was considered to be the most difficult measure to implement in daily practice (36.9%). De-escalation from broad-spectrum empirical therapy to targeted treatment was considered the easiest measure to achieve (43.2%). CONCLUSION: Our results demonstrate that principles of antimicrobial stewardship and aspects of hospital hygiene/infection control are not satisfactorily known among hospital-based paediatricians in and around Munich. We identified four important target areas for future educational interventions that should play a more prominent role in both pre- and postgraduate medical training.

Papilloma of the Fallopian Tube: A Rare Gynecologic Neoplasm Harboring a BRAF (c.1799T>A) Mutation (V600E).

Papillomas of the fallopian tube are exceedingly rare benign tumors, and only very few cases have been reported in the literature. Clinically, they may present as a mass lesion or occur without symptoms. Histomorphologically, they are papillary tumors covered by nonatypical epithelium with occasional ciliated or goblet cells growing in the lumen, and they are most frequently located in the infundibular region of the fallopian tube. They require a number of differential diagnostic evaluations and can be mistaken for either other benign tumors or malignant neoplasms. Because of their rare occurrence, molecular data about this entity have been lacking so far. Herein, a case of a papilloma with a BRAF (c.1799T>A) mutation (V600E) in a 45-yr-old woman with tumor-like dilation of the fallopian tube is presented.

Discordancy for a Villous Maturation Defect in a Dizygotic Twin Placenta.

Background: Dizygotic twin pregnancies with discordant manifestation of abnormalities with unclear etiology are of interest because they arise in the same environment. Case report: We present a dizygotic third trimester twin placenta with discordant villous maturation, one placenta lacking developed syncytiocapillary membranes. The twins were eutrophic with no perinatal or postnatal complications. Conclusions: Discordant manifestation of villous maturation in dizygotic twin placentas could be a hint for a genetic rather than an environmental etiology. Villous maturation defect may be underrecognized and has been associated with perinatal morbidity and stillbirth in the late third trimester. Proper recognition is important because of the increased recurrence risk of villous dysmaturity.

Children's Depression Screener (ChilD-S): development and validation of a depression screening instrument for children in pediatric care.

The aim of the present study was to develop and validate the Children's Depression Screener (ChilD-S) for use in pediatric care. In two pediatric samples, children aged 9-12 (N(I) = 200; N(II) = 246) completed an explorative item pool (subsample I) and a revised item pool (subsample II). Diagnostic accuracy of each of the 22 items from the revised pool was evaluated in order to select the best items for the brief instrument ChilD-S. Areas under the curve (AUCs) of the revised item pool and the ChilD-S were compared. A diagnostic interview, the Kinder-DIPS, served as gold standard. For the purpose of screening for depressive disorders in children, the eight-item ChilD-S (AUC = 0.97) performed just as well as the revised 22-item pool (AUC = 0.94). For the ChilD-S the optimal cut-off point of ≥11 yielded a sensitivity of 0.91 and a specificity of 0.89. The ChilD-S shows high potential for depression screening of children in pediatric care.

Mercury poisoning of a 4-year-old child by indirect contact to a mercury-containing facial cream: A case report.

We report the severe mercury poisoning of a 4-year-old child by a so far unknown route of exposure, namely, by skin-to-skin contact. The child was admitted to the hospital with episodic pain in his extremities, tachycardia, hypertension, increased sweating, behavioral changes and weight loss. Extensive examinations eventually revealed an acute mercury poisoning. The initial mercury levels were 19 µg/L in urine (reference level 0.4 µg/L) and 37 µg/L in blood (reference level 0.8 µg/L). A facial cream bought online, containing approximately 18% mercury, was identified as the primary source of intoxication. The symptoms improved after disposal of the cream and chelation therapy. Further analyses, home visits and interviews suggested that the child was accidently intoxicated by skin-to-skin contact with the mother, although other routes of exposure such as dust ingestion and surface-to-skin contact cannot be excluded. The mercury levels in urine and blood samples of the child and other family members as well as in domestic dust samples decreased considerably over time.

Guidelines for diagnosis and management of congenital central hypoventilation syndrome.

BACKGROUND: Congenital Central Hypoventilation Syndrome (CCHS) is a rare condition characterized by an alveolar hypoventilation due to a deficient autonomic central control of ventilation and a global autonomic dysfunction. Paired-like homeobox 2B (PHOX2B) mutations are found in most of the patients with CCHS. In recent years, the condition has evolved from a life-threatening neonatal onset disorder to include broader and milder clinical presentations, affecting children, adults and families. Genes other than PHOX2B have been found responsible for CCHS in rare cases and there are as yet other unknown genes that may account for the disease. At present, management relies on lifelong ventilatory support and close follow up of dysautonomic progression. BODY: This paper provides a state-of-the-art comprehensive description of CCHS and of the components of diagnostic evaluation and multi-disciplinary management, as well as considerations for future research. CONCLUSION: Awareness and knowledge of the diagnosis and management of this rare disease should be brought to a large health community including adult physicians and health carers.

Rapid fully automatic segmentation of subcortical brain structures by shape-constrained surface adaptation.

This work presents a novel approach for the rapid segmentation of clinically relevant subcortical brain structures in T1-weighted MRI by utilizing a shape-constrained deformable surface model. In contrast to other approaches for segmenting brain structures, its design allows for parallel segmentation of individual brain structures within a flexible and robust hierarchical framework such that accurate adaptation and volume computation can be achieved within a minute of processing time. Furthermore, adaptation is driven by local and not global contrast, potentially relaxing requirements with respect to preprocessing steps such as bias-field correction. Detailed evaluation experiments on more than 1000 subjects, including comparisons to FSL FIRST and FreeSurfer as well as a clinical assessment, demonstrate high accuracy and test-retest consistency of the presented segmentation approach, leading, for example, to an average segmentation error of less than 0.5 mm. The presented approach might be useful in both, research as well as clinical routine, for automated segmentation and volume quantification of subcortical brain structures in order to increase confidence in the diagnosis of neuro-degenerative disorders, such as Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, or clinical applications for other neurologic and psychiatric diseases.

Influence of PCO2 Control on Clinical and Neurodevelopmental Outcomes of Extremely Low Birth Weight Infants.

BACKGROUND: Levels or fluctuations in the partial pressure of CO2 (PCO2) may affect outcomes for extremely low birth weight infants. OBJECTIVES: In an exploratory analysis of a randomized trial, we hypothesized that the PCO2 values achieved could be related to significant outcomes. METHODS: On each treatment day, infants were divided into 4 groups: relative hypocapnia, normocapnia, hypercapnia, or fluctuating PCO2. Ultimate assignment to a group for the purpose of this analysis was made according to the group in which an infant spent the most days. Statistical analyses were performed with analysis of variance (ANOVA), the Kruskal-Wallis test, the χ2 test, and the Fisher exact test as well as by multiple logistic regression. RESULTS: Of the 359 infants, 57 were classified as hypocapnic, 230 as normocapnic, 70 as hypercapnic, and 2 as fluctuating PCO2. Hypercapnic infants had a higher average product of mean airway pressure and fraction of inspired oxygen (MAP × FiO2). For this group, mortality was higher, as was the likelihood of having moderate/severe bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and poorer neurodevelopment. Multiple logistic regression analyses showed an increased risk for BPD or death associated with birth weight (p < 0.001) and MAP × FiO2 (p < 0.01). The incidence of adverse neurodevelopment was associated with birth weight (p < 0.001) and intraventricular hemorrhage (IVH; p < 0.01). CONCLUSIONS: Birth weight and respiratory morbidity, as measured by MAP × FiO2, were the most predictive of death or BPD and NEC, whereas poor neurodevelopmental outcome was associated with low birth weight and IVH. Univariate models also identified PCO2. Thus, hypercapnia seems to reflect greater disease severity, a likely contributor to differences in outcomes.

CFD- and Bernoulli-based pressure drop estimates: A comparison using patient anatomies from heart and aortic valve segmentation of CT images.

PURPOSE: An aortic valve stenosis is an abnormal narrowing of the aortic valve (AV). It impedes blood flow and is often quantified by the geometric orifice area of the AV (AVA) and the pressure drop (PD). Using the Bernoulli equation, a relation between the PD and the effective orifice area (EOA) represented by the area of the vena contracta (VC) downstream of the AV can be derived. We investigate the relation between the AVA and the EOA using patient anatomies derived from cardiac computed tomography (CT) angiography images and computational fluid dynamic (CFD) simulations. METHODS: We developed a shape-constrained deformable model for segmenting the AV, the ascending aorta (AA), and the left ventricle (LV) in cardiac CT images. In particular, we designed a structured AV mesh model, trained the model on CT scans, and integrated it with an available model for heart segmentation. The planimetric AVA was determined from the cross-sectional slice with minimum AV opening area. In addition, the AVA was determined as the nonobstructed area along the AV axis by projecting the AV leaflet rims on a plane perpendicular to the AV axis. The flow rate was derived from the LV volume change. Steady-state CFD simulations were performed on the patient anatomies resulting from segmentation. RESULTS: Heart and valve segmentation was used to retrospectively analyze 22 cardiac CT angiography image sequences of patients with noncalcified and (partially) severely calcified tricuspid AVs. Resulting AVAs were in the range of 1-4.5 cm2 and ejection fractions (EFs) between 20 and 75%. AVA values computed by projection were smaller than those computed by planimetry, and both were strongly correlated (R2 = 0.995). EOA values computed via the Bernoulli equation from CFD-based PD results were strongly correlated with both AVA values (R2 = 0.97). EOA values were ∼10% smaller than planimetric AVA values. For EOA values < 2.0 cm2 , the EOA was up to ∼15% larger than the projected AVA. CONCLUSIONS: The presented segmentation algorithm allowed to construct detailed AV models for 22 patient cases. Because of the crown-like 3D structure of the AV, the planimetric AVA is larger than the projected AVA formed by the free edges of the AV leaflets. The AVA formed by the free edges of the AV leaflets was smaller than the EOA for EOA values <2.0cm2. This contradiction with respect to previous studies that reported the EOA to be always smaller or equal to the geometric AVA is explained by the more detailed AV models used within this study.

Neurodevelopmental outcomes of extremely low birthweight infants randomised to different PCO2 targets: the PHELBI follow-up study.

BACKGROUND: Tolerating higher partial pressures of carbon dioxide (PCO2) in mechanically ventilated extremely low birthweight infants to reduce ventilator-induced lung injury may have long-term neurodevelopmental side effects. This study analyses the results of neurodevelopmental follow-up of infants enrolled in a randomised multicentre trial. METHODS: Infants (n=359) between 400 and 1000 g birth weight and 23 0/7-28 6/7 weeks gestational age who required endotracheal intubation and mechanical ventilation within 24 hours of birth were randomly assigned to high PCO2 or to a control group with mildly elevated PCO2 targets. Neurodevelopmental follow-up examinations were available for 85% of enrolled infants using the Bayley Scales of Infant Development II, the Gross Motor Function Classification System (GMFCS) and the Child Development Inventory (CDI). RESULTS: There were no differences in body weight, length and head circumference between the two PCO2 target groups. Median Mental Developmental Index (MDI) values were 82 (60-96, high target) and 84 (58-96, p=0.79). Psychomotor Developmental Index (PDI) values were 84 (57-100) and 84 (65-96, p=0.73), respectively. Moreover, there was no difference in the number of infants with MDI or PDI <70 or <85 and the number of infants with a combined outcome of death or MDI<70 and death or PDI<70. No differences were found between results for GMFCS and CDI. The risk factors for MDI<70 or PDI<70 were intracranial haemorrhage, bronchopulmonary dysplasia, periventricular leukomalacia, necrotising enterocolitis and hydrocortisone treatment. CONCLUSIONS: A higher PCO2 target did not influence neurodevelopmental outcomes in mechanically ventilated extremely preterm infants. Adjusting PCO2 targets to optimise short-term outcomes is a safe option. TRIAL REGISTRATION NUMBER: ISRCTN56143743.

Differences in Regional Brain Volumes Two Months and One Year after Mild Traumatic Brain Injury.

Conventional structural imaging is often normal after mild traumatic brain injury (mTBI). There is a need for structural neuroimaging biomarkers that facilitate detection of milder injuries, allow recovery trajectory monitoring, and identify those at risk for poor functional outcome and disability. We present a novel approach to quantifying volumes of candidate brain regions at risk for injury. Compared to controls, patients with mTBI had significantly smaller volumes in several regions including the caudate, putamen, and thalamus when assessed 2 months after injury. These differences persisted but were reduced in magnitude 1 year after injury, suggesting the possibility of normalization over time in the affected regions. More pronounced differences, however, were found in the amygdala and hippocampus, suggesting the possibility of regionally specific responses to injury.

Automatic determination of differential coronary artery motion minima for cardiac computed tomography optimal phase selection.

RATIONALE AND OBJECTIVES: Selecting the optimal phase for coronary artery evaluation can be challenging, especially at higher heart rates, given that the optimal phase may differ for each of the coronary arteries. This study aimed to evaluate a novel vessel-specific algorithm which automatically outputs the minimum motion phase per coronary artery. MATERIALS AND METHODS: The study included 44 patients who underwent 256-slice cardiac computed tomography for evaluation of chest pain. End-systolic and mid-diastolic minimal motion phases were automatically calculated by a previously validated global motion algorithm and by a new vessel-specific algorithm which calculates the minimum motion for each of the three main coronary arteries, separately. Two readers blindly evaluated all coronary segments for image quality. Median scores per coronary artery were compared by the Wilcoxon signed rank test. RESULTS: The variation, per patient, between the optimal phases of the three coronary arteries was 5.0 ± 4.5% (1%-22%) for end systole and 4.8 ± 4.1% (0%-19%) for mid diastole. The mean image quality scores per coronary artery were 4.0 ± 0.61 for the vessel-specific approach and 3.80 ± 0.69 for the global phase selection (P < .001). Overall, 46 of 122 arteries had a better score with the vessel-specific approach and five with the standard global approach. Interreader agreement was substantial (k = 0.72). CONCLUSIONS: This study has shown that multiple phases are required to ensure optimal image quality for all three coronary arteries and that a vessel-specific phase selection algorithm achieves superior results to the standard global approach.

Permissive hypercapnia in extremely low birthweight infants (PHELBI): a randomised controlled multicentre trial.

BACKGROUND: Tolerating higher partial pressure of carbon dioxide (pCO2) in mechanically ventilated, extremely low birthweight infants might reduce ventilator-induced lung injury and bronchopulmonary dysplasia. We aimed to test the hypothesis that higher target ranges for pCO2 decrease the rate of bronchopulmonary dysplasia or death. METHODS: In this randomised multicentre trial, we recruited infants from 16 tertiary care perinatal centres in Germany with birthweight between 400 g and 1000 g and gestational age 23-28 weeks plus 6 days, who needed endotracheal intubation and mechanical ventilation within 24 h of birth. Infants were randomly assigned to either a high target or control group. The high target group aimed at pCO2 values of 55-65 mm Hg on postnatal days 1-3, 60-70 mm Hg on days 4-6, and 65-75 mm Hg on days 7-14, and the control target at pCO2 40-50 mmHg on days 1-3, 45-55 mm Hg on days 4-6, and 50-60 mm Hg on days 7-14. The primary outcome was death or moderate to severe bronchopulmonary dysplasia, defined as need for mechanical pressure support or supplemental oxygen at 36 weeks postmenstrual age. Cranial ultrasonograms were assessed centrally by a masked paediatric radiologist. This trial is registered with the ISRCTN registry, number ISRCTN56143743. RESULTS: Between March 1, 2008, and July 31, 2012, we recruited 362 patients of whom three dropped out, leaving 179 patients in the high target and 180 in the control group. The trial was stopped after an interim analysis (n=359). The rate of bronchopulmonary dysplasia or death in the high target group (65/179 [36%]) did not differ significantly from the control group (54/180 [30%]; p=0·18). Mortality was 25 (14%) in the high target group and 19 (11%; p=0·32) in the control group, grade 3-4 intraventricular haemorrhage was 26 (15%) and 21 (12%; p=0·30), and the rate of severe retinopathy recorded was 20 (11%) and 26 (14%; p=0·36). INTERPRETATION: Targeting a higher pCO2 did not decrease the rate of bronchopulmonary dysplasia or death in ventilated preterm infants. The rates of mortality, intraventricular haemorrhage, and retinopathy did not differ between groups. These results suggest that higher pCO2 targets than in the slightly hypercapnic control group do not confer increased benefits such as lung protection. FUNDING: Deutsche Forschungsgemeinschaft.

Benchmark for Algorithms Segmenting the Left Atrium From 3D CT and MRI Datasets.

Knowledge of left atrial (LA) anatomy is important for atrial fibrillation ablation guidance, fibrosis quantification and biophysical modelling. Segmentation of the LA from Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) images is a complex problem. This manuscript presents a benchmark to evaluate algorithms that address LA segmentation. The datasets, ground truth and evaluation code have been made publicly available through the http://www.cardiacatlas.org website. This manuscript also reports the results of the Left Atrial Segmentation Challenge (LASC) carried out at the STACOM'13 workshop, in conjunction with MICCAI'13. Thirty CT and 30 MRI datasets were provided to participants for segmentation. Each participant segmented the LA including a short part of the LA appendage trunk and proximal sections of the pulmonary veins (PVs). We present results for nine algorithms for CT and eight algorithms for MRI. Results showed that methodologies combining statistical models with region growing approaches were the most appropriate to handle the proposed task. The ground truth and automatic segmentations were standardised to reduce the influence of inconsistently defined regions (e.g., mitral plane, PVs end points, LA appendage). This standardisation framework, which is a contribution of this work, can be used to label and further analyse anatomical regions of the LA. By performing the standardisation directly on the left atrial surface, we can process multiple input data, including meshes exported from different electroanatomical mapping systems.

Change in spontaneous baroreflex control of pulse interval during heat stress in humans.

Spontaneous baroreflex control of pulse interval (PI) was assessed in healthy volunteers under thermoneutral and heat stress conditions. Subjects rested in the supine position with their lower legs in a water bath at 34 degrees C. Heat stress was imposed by increasing the bath temperature to 44 degrees C. Arterial blood pressure (Finapres), PI (ECG), esophageal and skin temperature, and stroke volume were continuously collected during each 5-min experimental stage. Spontaneous baroreflex function was evaluated by multiple techniques, including 1) the mean slope of the linear relationship between PI and systolic blood pressure (SBP) with three or more simultaneous increasing or decreasing sequences, 2) the linear relationship between changes in PI and SBP (deltaPI/DeltaSBP) derived by using the first differential equation, 3) the linear relationship between changes in PI and SBP with simultaneously increasing or decreasing sequences (+deltaPI/+deltaSBP or -deltaPI/-deltaSBP), and 4) transfer function analysis. Heat stress increased esophageal temperature by 0.6 +/- 0.1 degrees C, decreased PI from 1,007 +/- 43 to 776 +/- 37 ms and stroke volume by 16 +/- 5 ml/beat. Heat stress reduced baroreflex sensitivity but increased the incidence of baroreflex slopes from 5.2 +/- 0.8 to 8.6 +/- 0.9 sequences per 100 heartbeats. Baroreflex sensitivity was significantly correlated with PI or vagal power (r2 = 0.45, r2 = 0.71, respectively; P < 0.05). However, the attenuation in baroreflex sensitivity during heat stress appeared related to a shift in autonomic balance (shift in resting PI) rather than heat stress per se.

Prevalence of hepatitis E virus antibodies in children in Germany.

BACKGROUND: Since asymptomatic hepatitis E virus (HEV) infections particularly affect children, there is a need for studies to determine the HEV seroprevalence among infants, children and adolescents. METHODS: The prevalence of anti-HEV IgG antibodies was determined in sera taken in 2008-2010 from 1646 children aged 0-17 years living in Germany. Antibody testing was carried out using the enzyme-linked immunosorbent assay recomWell HEV IgG as well as the recomLine HEV IgG/IgM distributed by Mikrogen. Furthermore, the performance of MP Biomedicals enzyme-linked immunosorbent assay HEV and the HEV-Ab enzyme-linked immunosorbent assay from Axiom was analyzed in comparison with the recomWell/recomLine test system using a defined subset of sera. RESULTS: In children, the overall prevalence of antibodies was 1.0%. Starting with the 5- to 6-year olds, there was a significant increase of HEV seroprevalence to 1.5% in the group of the 15- to 17-year olds. There was no statistically significant difference between seroprevalences of boys (1.2%) and girls (0.7%). Passively transmitted maternal antibodies persisted for about 3 months. The strength of agreement between the recomWell/recomLine system and the ELISAs from MP Biomedicals or Axiom varied between 0.229 and 0.542 and was calculated at 0.111 when the assays from MP Biomedicals and Axiom were compared. CONCLUSIONS: In Germany, only a very small number of HEV infections occur in children. Many infections occur in adults with increasing age. Because of considerable variations in assay accordance, there is an urgent need for standardization of HEV serology.

Optimizing GHT-based heart localization in an automatic segmentation chain.

With automated image analysis tools entering rapidly the clinical practice, the demands regarding reliability, accuracy, and speed are strongly increasing. Systematic testing approaches to determine optimal parameter settings and to select algorithm design variants become essential in this context. We present an approach to optimize organ localization in a complex segmentation chain consisting of organ localization, parametric organ model adaptation, and deformable adaptation. In particular, we consider the Generalized Hough Transformation (GHT) and 3D heart segmentation in Computed Tomography Angiography (CTA) images. We rate the performance of our GHT variant by the initialization error and by computation time. Systematic parameter testing on a compute cluster allows to identify a parametrization with a good tradeoff between reliability and speed. This is achieved with coarse image sampling, a coarse Hough space resolution and a filtering step that we introduced to remove unspecific edges. Finally we show that optimization of the GHT parametrization results in a segmentation chain with reduced failure rates.

Segmentation of the heart and great vessels in CT images using a model-based adaptation framework.

Recently, model-based methods for the automatic segmentation of the heart chambers have been proposed. An important application of these methods is the characterization of the heart function. Heart models are, however, increasingly used for interventional guidance making it necessary to also extract the attached great vessels. It is, for instance, important to extract the left atrium and the proximal part of the pulmonary veins to support guidance of ablation procedures for atrial fibrillation treatment. For cardiac resynchronization therapy, a heart model including the coronary sinus is needed. We present a heart model comprising the four heart chambers and the attached great vessels. By assigning individual linear transformations to the heart chambers and to short tubular segments building the great vessels, variable sizes of the heart chambers and bending of the vessels can be described in a consistent way. A configurable algorithmic framework that we call adaptation engine matches the heart model automatically to cardiac CT angiography images in a multi-stage process. First, the heart is detected using a Generalized Hough Transformation. Subsequently, the heart chambers are adapted. This stage uses parametric as well as deformable mesh adaptation techniques. In the final stage, segments of the large vascular structures are successively activated and adapted. To optimize the computational performance, the adaptation engine can vary the mesh resolution and freeze already adapted mesh parts. The data used for validation were independent from the data used for model-building. Ground truth segmentations were generated for 37 CT data sets reconstructed at several cardiac phases from 17 patients. Segmentation errors were assessed for anatomical sub-structures resulting in a mean surface-to-surface error ranging 0.50-0.82mm for the heart chambers and 0.60-1.32mm for the parts of the great vessels visible in the images.

Fatal neonatal respiratory failure in an infant with congenital hypothyroidism due to haploinsufficiency of the NKX2-1 gene: alteration of pulmonary surfactant homeostasis.

Defects of the NKX2-1 gene, encoding thyroid transcription factor-1, cause brain-thyroid-lung syndrome (MIM 610978), characterised by benign hereditary chorea, congenital hypothyroidism and respiratory disease. The case of a term infant with mild primary congenital hypothyroidism and neonatal persistent respiratory failure with fatal outcome at 10 months of age despite continuous ventilatory support is described. Congenital defects of genes known to disturb surfactant protein and lipid homeostasis (SFTPB, SFTPC, ABCA3) were excluded. Hypothyroidism prompted sequencing of NKX2-1, which revealed a heterozygous 29 bp deletion (c.278_306del29) disrupting the affected allele. Analysis of bronchoalveolar lavage fluid demonstrated an abnormally low amount of surfactant protein C (SP-C) in relation to SP-B, and low levels of surfactant phospholipids, indicating disturbance of SP and lipid homeostasis as a consequence of NKX2-1 haploinsufficiency. NKX2-1 haploinsufficiency may lead to lethal respiratory failure of the newborn due to disruption of pulmonary surfactant homeostasis. NKX2-1 gene analysis should be considered when investigating irreversible respiratory insufficiency of the newborn.