[Epignathus, hypolastic left heart syndrome, and trisomy 18 in a small for gestational age female twin]. / Epignato, sindrome del cuore sinistro ipoplasico e trisomia 18 in una gemella piccola per età gestazionale.

We describe a rare association of hypoplastic left heart syndrome, trismony 18, and epignathus in a 970 g female twin born at 37 weeks of gestational age. She died at 24 hours of age. Neonatologists and obstetricians should be aware of this rare association for a thorough prenatal counselling.

Epoprostenol for very low birth weight (VLBW) infants: a novel dilution protocol.

Epoprostenol has been the first effective treatment for severe pulmonary arterial hypertension. Epoprostenol is provided in vials for adult therapy. To our knowledge there are no reports on specific dilution protocols for epoprostenol in VLBW infants, when very small infusion rates are required. We describe the dilution protocol we applied to a preterm infant who was born at 30 weeks of gestational age with a weight of 1.000 g. Our dilution protocol keeps the recommended dilution ratios, and the required solution pH, for very small dosages of epoprostenol, using the same diluent vial. Our method allows a correct and safe administration of epoprostenol in VLBW infants.

Intrauterine depressed skull fracture with spontaneous resolution.

We describe a full term male infant born by cesarean section, who presented a deep round depression of the left parietal bone at birth. MRI scan showed no signal alteration on cortical and sub-cortical level in correspondence of the depressed skull fracture. At four months of age, a skull X-ray was normal. At 18 months of age growth and neurologic follow-up is normal.

Weaning of epoprostenol in a small infant receiving concomitant bosentan for severe pulmonary arterial hypertension secondary to bronchopulmonary dysplasia.

Endothelin receptor antagonism is an important therapeutic tool of pulmonary arterial hypertension (PAH). Bosentan was the first orally active, dual antagonist of endothelin receptors in human adults, and has been recently considered for children as well. However, little is known about bosentan treatment in children weighing less than 10 kg. We describe the use of bosentan concomitantly to epoprostenol in an infant weighing 3.5 kg and affected with severe bronchopulmonary dysplasia (BPD) and PAH. At 5 months old, when she presented subsystemic PAH secondary to severe BPD, she was treated with oxygen, digoxin and diuretics. At 8 months old, due to severe PAH not responsive to 100% oxygen, high frequency oscillatory ventilation (HFOV) and nitric oxide (NO), we started epoprostenol and bosentan. Bosentan dose was doubled at 9 months old, when HFOV and NO were slowly discontinued due to improved oxygenation index. Regular echocardiographic measurements of systolic right ventricular pressure were recorded by the method of tricuspidal atrio-ventricular gradient. A four-month combined epoprostenol and bosentan treatment decreased systolic right ventricular pressure from 68% to 40% of the systemic level, till its normalization at 11 months old. Later, when bosentan and epoprostenol were discontinued and sildenafil was started, severe PAH was reported again. Our patient died due to septic shock and refractory hypoxia at 14 months old.

[Metabolic compensation and malformations in pregnancy complicated by diabetes]. / Compenso metabolico e malformazioni in gravidanze complicate da diabete.

Congenital malformations are considered the more frequent perinatal complications affecting offsprings of diabetic mothers; they represent the main cause of mortality of these neonates. Since diabetes is strictly controlled, the incidence and the seriousness of its complications are reduced from 8-10% to 2-3%. In this study we followed 56 pregnancies complicated by diabetes. There were 3 case of malformations. We correlate these with the metabolic maternal balance and with the HbA1c values. We could confirm the relationship between malformation and metabolic imbalance and also the absence of fetal malformations in women with metabolic compensation since the beginning of the pregnancy.

[Sepsis caused by Candida in the neonatal period]. / Sepsi da Candida nel periodo neonatale.

Fungal pathogens have become increasingly important as causes of mortality and in newborn infants, especially preterm with very law birth weight, admitted to a neonatal intensive care unit. We report here the cases of 26 neonates (19 VLBW) with systemic fungal infections. Average birth weight and gestational age were 1405 +/- 977 g (range 595-4180 g) and 29 +/- 5 weeks (range 24-41 weeks) respectively. 24 newborn infants required endotracheal intubation and mechanical ventilation and 6 were affected by a severe congenital malformation. An umbilical e/o central intravascular catheter was inserted in all infants and each of them received antibiotics (one or more courses). The Candida species isolated were: C. albicans (n. 23; 88.5%), C. parapsilosis (n. 2; 7.6%) and C. glabrata (n. 1; 3.8%). Frequently encountered symptoms and signs in our neonates included: vasomotor instability with peripheral hypoperfusion (92%), gastro-intestinal disturbances (69%), respiratory distress and increasing ventilatory requirements (65%). Other symptoms were less frequent. 20 newborn infants had leucocytosis, 19 thrombocytopenia, 14 presented both signs. Factors found to be frequently associated with fungal infection included: use of broad-spectrum antibiotic therapy, presence of central venous or umbilical artery catheter, endotracheal intubation and mechanical ventilation, surgical abdominal intervention. After antifungal systemic therapy, clinical cure and microbiological eradication were achieved in 81% of cases, only 1 out of 11 deaths was directly attributed to Candida infection. In our experience the association of amphotericin B+ 5 glucytosine proved to be an effective and well-tolerated therapy for the treatment of severe fungal infections in neonates. A high index of suspicion, especially in premature infants (VLBW), a rapid diagnosis and early initiation of antifungal therapy still remain the essential features in treating neonatal fungal infections.

Evaluation of antibiotic-induced nephrotoxicity in preterm neonates by determining urinary alpha 1-microglobulin.

alpha 1-Microglobulin (alpha 1-m, protein HC), a relatively low molecular weight protein of about 31,000 daltons, was measured in urine of three groups of 34 preterm neonates: group A consisted of 9 healthy preterm neonates; groups B (n = 13) and C (n = 12) consisted of preterm neonates with suspected or confirmed bacterial infections. Immediately after birth, all group B neonates were treated with ampicillin and aztreonam in combination, and all group C neonates were treated with oxacillin and amikacin in combination. To optimize amikacin administration, computerized individually tailored doses were administered. Urine samples were obtained from a short collection in sterile bags on the 1st, 4th, and 7th day after delivery in all infants. Urinary alpha 1-m concentrations were measured by a turbidimetric method (latex agglutination photometric immunoassay) and results were expressed as a ratio to urinary creatinine. In group A, urinary alpha 1-m concentrations were stable after birth. In group C, alpha 1-m excretion increased immediately within the 1st day of treatment, and over the 1st week of life urinary alpha 1-m levels were significantly higher than in group A (P = 0.033). These data support the conclusion that amikacin administration was the most important factor inducing renal tubular dysfunction in the neonates of group C.

[Malformative uropathies: prenatal diagnosis, incidence, and diagnostic protocol]. / Le uropatie malformative: diagnosi prenatale, incidenza e protocollo diagnostico.

With the aim to evaluate the progress in prenatal diagnosis and postnatal management of urinary tract malformations, we report the postnatal incidence of this problem related to prenatal US diagnosis. Contributions from ten neonatologist Groups are included; they are referred to a limited area in the north-west of Italy. During the year 1993, 11.503 pregnant women were tested by US and 90 neonates were further studied in the first week of postnatal age; in 44 of them the urinary tract malformation were confirmed by US. The incidence has varied from 0. 64 to 6.08% (3,8 per 1.000 life birds) confirming the importance of such a screening.

Low molecular mass proteins and urinary enzymes in amniotic fluid of healthy pregnant women at progressive stages of gestation.

OBJECTIVES: Amniotic fluid alpha1-microglobulin (alpha1-m) and beta2-microglobulin (beta2-m) levels, as well as N-acetyl-beta-D-glucosaminidase (NAG) and alanine aminopeptidase (AAP) activities, were measured in the course of uncomplicated pregnancies to assess their variations as gestation progresses. DESIGN AND METHODS: Samples were obtained from 141 healthy pregnant women divided into three groups on the basis of gestational stage. Quantitative estimation of proteins was performed immunometrically and enzyme activities were determined spectrophotometrically. RESULTS: It was found that, during pregnancy, alpha1-m and beta2-m concentrations as well as AAP activity significantly decrease, although their reduction patterns vary. Controversial results were found for NAG activity: the normalization of values for amniotic fluid creatinine significantly changed the reduction pattern of this enzyme. No statistically significant differences were found between male and female fetuses for amniotic fluid values of the biochemical substances studied. CONCLUSIONS: The behavior observed for alpha1-m, beta2-m, and AAP might be linked to the progressive development and maturation of fetal renal tubular function. Amniotic fluid total NAG activity seems not to depend only on fetal urinary excretion.

[Neonatal ultrasonic screening and follow up of urinary tract malformations]. / Screening ecografico neonatale e follow-up delle uropatie malformative.

1881 consecutive healthy newborn babies underwent abdominal ultrasonography on day 4-6. 228 subjects presented an echographic abnormality. Renal abnormalities were diagnosed in 213 newborn. Of those, 134 had dilatative uropathy with a pelvic diameter greater than 5 mm, 73 renal medulla hyperechogenicity, 3 ectopics, 2 unilateral renal agenesis and one horseshoe kidney. Extrarenal findings were present in 15 neonates: 11 with surrenal gland haemorrhage and 4 with hepatic ultrasonographic alterations. Grignon classification was used for evaluation of the dilatative urinary tract abnormalities. In 173 renal pelvis (134 neonates) the anteroposterior diameter was found > 5 mm: 97 were classified as GI (5-10 mm), 45 as GII (10-15 mm), 13 as GIII ( > 15 mm), 11 as GIV (moderate dilatation of the calyces with easily identified residual renal cortex) and 7 as GV (severe dilatation of the calyces with atrophic cortex). The follow-up of 72.3% of these abnormalities showed a spontaneous normalization in 90% of GI, 73% of GII and 58% of GIII. Only one patient with GIII demonstrated progressive dilatation and he underwent corrective surgery. 15 of the 17 newborn with severe uropathy (GIV-GV), had regular follow-up. 8 underwent surgery and 7 showed a progressive spontaneous recovery and in 4 of these cases a complete resolution. The ultrasound follow-up of all cases of renal medulla hyperechogenicity and surrenal gland haemorrhage shows a spontaneous resolution without any clinical or biochemical complication.

[Neonatal infections caused by group B beta-hemolytic Streptococcus]. / Le infezioni neonatali da streptococco beta-emolitico di gruppo B.

The aim of the Asiago Congress is to illustrate the progress in Group B Streptococcal neonatal disease management. It is of primary importance the obstetricians and neonatologists should think alike and should not allow their interest to develop along separate lines. The themes of the Congress were the incidence, the clinical and diagnostic new features, the old and the new therapeutic trends and the obstetrician's prevention. Contributions from twenty-four Neonatologist Groups are included; they are summarized in four main articles and all together they form a synopsis of modern clinical practice and recent research in neonatal medicine.

Staphylococcus epidermidis isolation and antibiotic resistance in a neonatal intensive care unit.

Bacterial ecology was studied in 1114 newborns (355 at term, 759 preterm) admitted to a neonatal intensive care unit (NICU) during a three year period. Bacterial samples were taken in each newborn from external ear canal, pharynx and eyes in all patients, and from endotracheal tube, umbilical catheter and blood in selected patients. The predominant flora was characterized by gram-positive microorganisms (63.53%), Staphylococcus epidermidis representing 34.68% of all isolated strains. S. epidermidis isolation increased significantly with time (p < 0.002) and was highest in summer. The percentage of S. epidermidis resistant strains to oxacillin (63.8%) and to amikacin (17.8%) was high. This is the antimicrobial combination we commonly employ as empirical treatment of suspected bacterial infection in our NICU. Knowledge of characteristics of local microbial flora seems important in order to optimize preventive and therapeutic policies for neonatal infections.

Gene linkage analysis and DNA based detection of autosomal dominant polycystic kidney disease (ADPKD) in a newborn infant. Case report.

Bilateral polycystic kidneys were detected by ultrasound at 23 weeks gestation in a male fetus. Bilateral renal cysts were subsequently also found in the asymptomatic propositus' mother and grandmother, suggesting the diagnosis of autosomal dominant polycystic kidney disease (ADPKD). The renal ultrasonograms showed cortical cysts with normal or decreased-sized kidneys. Renal function was normal. Seven available members of the family were genotyped for flanking DNA markers tightly linked to the PKD1 gene on chromosome 16p, and for a polymorphism close to a second putative disease gene (PKD2) on chromosome 2. The genetic linkage approach allowed us to detect with a high degree of accuracy the ADPKD1 at risk chromosome in the three patients, as well as in a 28-year-old unaffected female. This report illustrates the feasibility and the usefulness of recent molecular genetic strategies for diagnostic purposes in ADPKD, especially when clinical and radiological data are atypical. Furthermore, it also confirms that early or very early onset forms of the disease are not uncommon, and should be considered in the differential diagnosis of childhood cystic disease.

Tubular proteins and enzyme content in the amniotic fluid.

Amniotic fluid is the product of many substances and fetal urine is considered to be one of the principal components. Only a few reports have been published describing the concentration of microglobulins and urinary enzymes in the amniotic fluid. We determined the levels of alpha 1-m, beta 2-m, AAP and NAG, in 154 samples of amniotic fluid (103 early determinations and 51 late determinations) as a function of gestational age. We observed a statistically significant decrease in concentration of alpha 1-m (P < 0.001), beta 2-m (P < 0.01) and AAP (P < 0.001) when early and late amniotic fluid samples were compared. A statistically significant increase of NAG (P < 0.01) and creatinine (P < 0.01) was also found. A significant correlation was observed between alpha 1-m and beta 2-m, and between AAP and NAG, respectively. The potential role of urinary enzyme and microglobulin determination in amniotic fluid as an index of fetal kidney development, is discussed.

[Staphylococcal infection in the newborn: teicoplanin therapy]. / Sepsi da stafilococco nel neonato: terapia con teicoplanina.

Infections caused by Gram-positive bacteria, particularly in neonatal patients, have increased dramatically over the past 10 years. In the present study 19 newborns (7 at term, 12 preterm) with proven staphylococcal infection were treated with teicoplanin, after a previous ineffective antibiotic treatment (amikacin+oxacillin or third-generation cephalosporin). Bacterial eradication and clinical cure were achieved in all neonates. No adverse events related to the drug occurred. No significant change was observed in serial biochemical and hematological tests. Our results suggest that teicoplanin is highly effective and safe in neonatal staphylococcal infections.

Molecular genetic diagnosis of autosomal dominant polycystic kidney disease in a newborn with bilateral cystic kidneys detected prenatally and multiple skeletal malformations.

We report a case of an unusual prenatal presentation of polycystic kidneys associated with multiple skeletal limb defects, including polydactyly, syndactyly, bilateral agenesis of the tibia, and club foot. The ultrasonographic picture was consistent with a diagnosis of polycystic kidney disease, either the adult onset autosomal dominant type (ADPKD) or the early onset autosomal recessive form (ARPKD). However, there was a positive family history for ADPKD. Linkage analysis was performed in 10 family members, of whom four were affected, using six flanking DNA markers tightly linked to the PKD1 locus on chromosome 16p, and one marker linked to the putative PKD2 locus on chromosome 2p. Lod score determinations indicated that the affected gene in the family is most likely PKD1. The patient inherited the disease linked haplotype from his affected mother.