Context:P450 oxidoreductase deficiency (PORD) is a unique congenital adrenal hyperplasia variant that manifests with glucocorticoid deficiency, disordered sex development (DSD), and skeletal malformations. No comprehensive data on genotype-phenotype correlations in Caucasian patients are available.Objective:The objective of the study was to establish genotype-phenotype correlations in a large PORD cohort.Design:The design of the study was the clinical, biochemical, and genetic assessment including multiplex ligation-dependent probe amplification (MLPA) in 30 PORD patients from 11 countries.Results:We identified 23 P450 oxidoreductase (POR) mutations (14 novel) including an exonic deletion and a partial duplication detected by MLPA. Only 22% of unrelated patients carried homozygous POR mutations. p.A287P was the most common mutation (43% of unrelated alleles); no other hot spot was identified. Urinary steroid profiling showed characteristic PORD metabolomes with variable impairment of 17α-hydroxylase and 21-hydroxylase. Short cosyntropin testing revealed adrenal insufficiency in 89%. DSD was present in 15 of 18 46,XX and seven of 12 46,XY individuals. Homozygosity for p.A287P was invariably associated with 46,XX DSD but normal genitalia in 46,XY individuals. The majority of patients with mild to moderate skeletal malformations, assessed by a novel scoring system, were compound heterozygous for missense mutations, whereas nearly all patients with severe malformations carried a major loss-of-function defect on one of the affected alleles.Conclusions:We report clinical, biochemical, and genetic findings in a large PORD cohort and show that MLPA is a useful addition to POR mutation analysis. Homozygosity for the most frequent mutation in Caucasians, p.A287P, allows for prediction of genital phenotype and moderate malformations. Adrenal insufficiency is frequent, easily overlooked, but readily detected by cosyntropin testing.

The use of ACV in pregnancy is not yet recommended for two main reasons : its safety has not been established and the,lack of studies on pharmacokinetics. In this paper, we have.reviewed data concerning nine pregnant women who was iven ACV in the perinatal period. Route of administration ani doses were as following : orally (0) 350 mg/8 hours (5), lntravenousl (IV) 5-10 mg/kg/8 hours ( 4 ) . Plasm? trough (T) and eak (P) fevels of ACV was deteroinated by radio~mmuno assay. At girth, plasma ACV levels were achieved in the mother and her offspring. P and T after IV were effective to inhiblt viral replication (17-41 pmol/l 1 22-1 36 umol/l) and hi her than in vitro ID 50 for Herpes'vi;adea'viruses (0.1-4 pmoY/l) ; whereas T and P ranged from 0.32 to 0, 59 pmol/l and from 1.79 to 3.78 pmol/l after 10 doses given orally. Furthermore steady state plasma level was not achieved even after 10 doses 0. The maternal foetal ratio of ACV level was approximately 1. No side effects were noted in newborns. Conclnsion : If this drug is felt,to be used in a pregnant.voman, IV administration seems to be advisable regarding it's efficacy. 0 administration requires more data about recommended dosage. Transplacental passa e of ACV occurs. Plasma ACV levels in the mother reflect probagly foetal ACV level. Fifteen very low birth weight I1tLBY1 children, nine appropriate for qeitati;i;al age in6A. aean birth weight 1302tIb4 g, gestational age 30t_1.5 neeksl, and six jrall for gestaticaa! aqe ISSR, aean birth neigih I:b3t117 g, qestatlonal age 35.35.5 weeks), xere studied at the age of 7-12 years, and coapared to trentysix age-, sex-, and height-latched healthy children, who were born at term (lean birth weight 3?2b+ib7 51. !lox of :Ce YLRY rhildren had developed chronic broncopullonary disease, The hab~tua! !ere1 of physical act~vity was not different in the YLBY and control Grcup. Pulronary function tests and progresirre exercise tests on treadlill were perforled. Forced v!tal caoacity, forced expiraiory ?oliiae at one second and forced expiratory flow between 251 and 751 of vital capaclty were in tb: norral range for all the subjects. No difference; were founo in aaxiwda oxyeen con'.um~tion (YO2 aaxl, anaerobic threshold IATI and #axiral heart rate between :he ASR !'lo2 lax - Lidoca~rcis either a convulsant or an anticonvulwnt drug, according to the plasmatic levels. W e used its anticonvulwnt effect in scizures of various etiology. Lidocairtinfusion (L.I.) was efficient in 19/29 full term (FT) and in 10/13 prcmaturc babies (PT) with seizures (confirmed by EEG) resisting to Phenobarbital and Diazepam therapy. L.1. was given at decreasing dosage (4 mg/kg/h, day 1; 3 mg/kg/h, day 2; 2 mg/kg/h,day 3; 1 mg/kg/h,day 4). After L.I. beginning : -seizures were controlled within 30 min. in 23 cases, aftcr 3 to 13 hours in 4 cases; -background EEG changed in some casts, immediatly or after a delay (up to 24 hours) into a very discontinuous pattern. In 2 cases L.I. alone did not control seizures, but an additional bolus (2 mg/Kg) was efficient ...

For the first time a multimodal approach to NEC prophylaxis is reported, consisting of early trophic feeding with human breast milk, and enteral administration of an antibiotic, an antifungal agent, and probiotics. A retrospective analysis of local protocol of NEC prophylaxis is presented. Included were all VLBWI admitted to the NICU, including transfers within the first 28 days of life. These infants were divided into two groups, an "inborn group" (infants admitted within the first 24 h of life) and an "outborn group" (infants admitted after the onset of their second day of life). Prophylaxis of NEC according to protocol was started at the day of admission, and was continued until discharge. Between 1998 and 2004, 405 VLBWI were admitted, including all transfers within the first 28 days of life. A total of 334 (82%) infants were admitted within the first 24 h of life (inborn group), and 71 (18%) were admitted after 24 h of life (outborn group). Five infants developed clinical features of necrotizing enterocolitis. The inborn group showed a NEC incidence of 0.7% (two infants), whereas the outborn group showed a NEC incidence of 4.5% (three infants), respectively. This difference was significant (P=0.049, Fisher's exact test). A surgical treatment with bowel resection was performed in two infants (both from the outborn group). The present study used a combination of different strategies, all having shown to have some beneficial effect, but not having brought a clinical breakthrough in single administration studies. Combinated were the beneficial effects of human breast milk feeding, oral antiobiotics, oral antifungal agents, and the administration of probiotics. In a homogenous group of preterm infants, using this protocol of multimodal NEC prophylaxis, there was a very low incidence of NEC, when started within the first 24 h of life.

We found a moderate rate of proven RSV hospitalizations in infants with CDH, and palivizumab prophylaxis led to a non-significant reduction of proven and hypothesized RSV hospitalizations.

In an international multicenter trial infants with clinical and radiological signs of severe RDS (age 2-15 h, birthweight 700-2,000 g, mechanical ventilation, FiO₂ ≧ 0.6, no complicating disease) were randomized to receive either a single dose (n = 176) or up to three subsequent doses (n = 167) of a natural porcine surfactant (Curosurf). Using a logistic regression model, the effects of therapy, birthweight, sex, hospital and other clinical factors on survival and various outcome parameters were evaluated. Mortality (13 vs. 21 %, p < 0.05) and the incidence of pneumothorax (9 vs. 18%, p < 0.01) were significantly lower in the multiple-dose group. Low birthweight, hospital allocation, low Apgar score and initial disease severity were associated with an increased mortality. Low birthweight, hypothermia (admission temperature < 36°C) and acidosis (pH < 7.25) prior to surfactant treatment could be identified as risk factors for the development of intracranial hemorrhage.