Bonioli E

Etiology of nonimmune hydrops fetalis: A systematic review†

Hydrops fetalis (HF) indicates excessive fluid accumulation within the fetal extravascular compartments and body cavities. HF is not a diagnosis in itself but a symptom, and the end‐stage of a wide variety of disorders. In the era before routine immunization of Rhesus (Rh) negative mothers, most cases of hydrops were due to erythroblastosis from Rh alloimmunization, but nowadays, nonimmune hydrops fetalis (NIHF) is more frequent, representing 76–87% of all described HF cases. We performed a systematic review of the pertinent literature based on the QUality Of Reporting Of Meta‐analyses (QUOROM) recommendations, using a QUOROM flowchart and QUOROM checklist. At initial screening 33,345 articles were retrieved. The various inclusion and exclusion criteria aimed at obtaining data that were as unbiased yet as complete as possible decreased the numbers dramatically, and eventually a total of 225 relevant NIHF articles were identified, describing 6,361 individuals. We established 14 different diagnostic categories and provide the pathophysiologic background of each, if known. All 6,361 patients were subclassified into one of the following diagnostic categories: Cardiovascular (21.7%), hematologic (10.4%), chromosomal (13.4%), syndromic (4.4%), lymphatic dysplasia (5.7%), inborn errors of metabolism (1.1%), infections (6.7%), thoracic (6.0%), urinary tract malformations (2.3%), extra thoracic tumors (0.7%), TTTF‐placental (5.6%), gastrointestinal (0.5%), miscellaneous (3.7%), and idiopathic (17.8%).

Congenital pulmonary lymphangiectasia

Congenital pulmonary lymphangiectasia (PL) is a rare developmental disorder involving the lung, and characterized by pulmonary subpleural, interlobar, perivascular and peribronchial lymphatic dilatation. The prevalence is unknown. PL presents at birth with severe respiratory distress, tachypnea and cyanosis, with a very high mortality rate at or within a few hours of birth. Most reported cases are sporadic and the etiology is not completely understood. It has been suggested that PL lymphatic channels of the fetal lung do not undergo the normal regression process at 20 weeks of gestation. Secondary PL may be caused by a cardiac lesion. The diagnostic approach includes complete family and obstetric history, conventional radiologic studies, ultrasound and magnetic resonance studies, lymphoscintigraphy, lung functionality tests, lung biopsy, bronchoscopy, and pleural effusion examination. During the prenatal period, all causes leading to hydrops fetalis should be considered in the diagnosis of PL. Fetal ultrasound evaluation plays a key role in the antenatal diagnosis of PL. At birth, mechanical ventilation and pleural drainage are nearly always necessary to obtain a favorable outcome of respiratory distress. Home supplemental oxygen therapy and symptomatic treatment of recurrent cough and wheeze are often necessary during childhood, sometimes associated with prolonged pleural drainage. Recent advances in intensive neonatal care have changed the previously nearly fatal outcome of PL at birth. Patients affected by PL who survive infancy, present medical problems which are characteristic of chronic lung disease.

Lymphatic Dysplasias in Newborns and Children: The Role of Lymphoscintigraphy

We performed lymphoscintigraphy in 15 patients (newborns and children) affected by congenital lymphatic dysplasia. We suggest that lymphoscintigraphy is mandatory in all patients with signs of lymphatic dysplasia, including those with minimal and initial signs of lymphatic impairment, to obtain very early diagnosis and begin treatment.

Reliability assessment of glucose measurement by HemoCue analyser in a neonatal intensive care unit.

BACKGROUND Rapid and reliable bed-side determination of blood glucose concentration is very important in the management of acutely ill infants and especially in premature newborns. HemoCue is an easy-to-use glucose analyser. The aim of the present study was to examine the usefulness of the HemoCue glucose analyser compared to a reference plasma glucose method (SYS, BM/Hitachi 747/737) in a neonatal intensive care unit (NICU). METHODS Seventy-eight consecutive neonates admitted to our NICU were enrolled in the study. At the time of the study all patients were grouped according to nutritional management (parenteral or enteral nutrition), haematocrit values and birth weight. The effects of feeding management, haematocrit values, and birth weight on accuracy and precision of the device were evaluated. RESULTS Overall data linear regression analysis yielded an r-value of 0.905 and the Bland-Altman method demonstrated that HemoCue overestimates plasma glucose by 0.932 mmol/L. Evaluation of our data by receiver operating characteristic curve demonstrated 100% sensitivity cutoff at 4.1 mmol/L. CONCLUSIONS HemoCue cannot be used satisfactorily in the management of glycaemia in the NICU. In the preterm population, birth weight had a dramatic influence on HemoCue accuracy. Low haematocrit and parenteral feeding further contributed to a decrease in the accuracy of this device.

A diagnostic flow chart for non‐immune hydrops fetalis

A Diagnostic Flow Chart for Non-Immune Hydrops Fetalis Carlo Bellini,* Raoul C.M. Hennekam, and Eugenio Bonioli Department of Pediatrics, University of Genoa, Gaslini Institute, Genova, Italy Institute of Child Health, Great Ormond Street Hospital for Children, University College London, London, UK and Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

X-linked creatine transporter deficiency: clinical description of a patient with a novel SLC6A8 gene mutation.

Creatine transporter deficiency is an X-linked disorder characterized by mental retardation and language delay. The authors report a patient affected by creatine transport deficiency caused by a novel mutation in the SLC6A8 gene. Impairment in social interaction represents a consistent clinical finding in the few cases described to date and may be a diagnostic clue for creatine transporter deficiency in males affected by mental retardation, seizures, and language impairment.

Nonimmune idiopathic hydrops fetalis and congenital lymphatic dysplasia

Six newborns that presented at birth with nonimmune hydrops fetalis and for whom no cause could be found were investigated for the presence of lymphatic dysplasia. Careful analysis led to findings of some degree of lymphatic dysplasia in all patients. This suggests that lymphatic dysplasia may represent at least part of the causes that are responsible for the “idiopathic” form of nonimmune hydrops fetalis. Carefully searching for lymphatic dysplasia in these patients, and if indicated in their relatives, as well as establishing the exact nature of the lymphatic dysplasia must be carried out so as to provide proper genetic counseling to families with nonimmune hydrops.

Slipped capital femoral epiphysis associated with Rubinstein‐Taybi syndrome

Bonioli E, Bellini C, Sénès FM, Palmieri A, Di Stadio M, Pinelli G. Slipped capital femoral epiphysis associated with Rubinstein‐Taybi syndrome.

The Weaver-Smith syndrome

border l ine low IQ, and hypergonad0t rop ic hypogonadism. Pat ient B, however, did not have gynecomastia , and his testicular volume was greater than 4 cc, which is reported to be the max i m um reached in individuals with Klinefel ter syndrome. TM In keeping with more no rma l testicular volumes, he had no rma l serum testosterone concentra t ions on two of three measurement s in the absence of abnormal ly elevated serum gonadot rop in values. The positive H-Y ant igen measurement s confirm the presence of occult Y chromosomal mater ia l in our two pat ients with the 46XX male syndromes, and this appeared to produce increased testicular size and no rma l p i tu i tary-gonadal relat ionships in one patient , in contras t to individuals with Klinefel ter syndrome. Thus, one cannot always assume tha t 46XX males will be similar to individuals with Klinefel ter syndrome.

Fumarate hydratase deficiency

Fumarate hydratase deÐciency E. Bonioli1*, A. Di Stefano1, V . Peri1, U. Caruso1, R. Cerone1, E. L amantea3, F. Taroni3 and C. Bellini2 1 Istituto di Clinica Pediatrica, 2 Istituto di Puericultura e Medicina Neonatale, University of Genoa ; 3 Laboratorio di Patologia Cellulare, Dipartimento di Biochimica e Genetica, Istituto Neurologico Besta, Milan, Italy * Correspondence : Istituto di Clinica Pediatrica dellÏUniversità, Largo G. Gaslini, 5, 16147 Genova, Italy