Effects of oral stimulation and oral support on non-nutritive sucking and feeding performance in preterm infants.

This study compared the effects of oral stimulation with those of oral support on non-nutritive sucking and feeding parameters in preterm infants. Preterm infants (23 males, 20 females) born between 29 and less than 34 weeks' gestational age (GA; mean GA 31.2wks [standard error of mean{SEM} 0.39]; mean birth-weight 1580g [SEM 120]) were allocated to one of three experimental groups: (Stimulation+support [five males, four females]; Stimulation [four males, seven females]; and Support [seven males, five females]) or a control group. Non-nutritive sucking pressure and sucking activity were quantified in the gavage and transition periods. Oral support minimizes fluid loss, stabilizes the jaw, and organizes deglutition. The time of transition, the quantity of milk ingested per day, and the number of bottle feeds per day were recorded. Variables were analyzed by repeated-measures analysis of variance, with birth-weight as covariate (ANCOVA). Transition time was reduced (p<0.0001) for the Stimulation+support and Support groups. ANCOVA computed during gavage showed increased non-nutritive sucking pressure and sucking activity (p<0.001) for the Stimulation and Stimulation+support groups. ANCOVA computed during transition revealed increases in non-nutritive sucking pressure and daily bottle feeds (p<0.001) for the three experimental groups and in daily milk ingested (p=0.002) for the Stimulation+support and Support groups. We demonstrated that oral support is the result of both the action of chin and cheek support, and the aid to deglutition. An analysis of the organization of sucking patterns should be undertaken to provide better understanding of the mechanisms involved in oral support.

The safety and efficacy of nitric oxide therapy in premature infants.

OBJECTIVES: To assess the safety-efficacy balance of low-dose inhaled nitric oxide (iNO) in hypoxemic premature infants because no sustained beneficial effect has been demonstrated clearly and there are concerns about side effects. STUDY DESIGN: Eight hundred and sixty infants <32 weeks were randomized at birth to receive 5 ppm iNO or placebo when they presented with hypoxemic respiratory failure (HRF) defined by a requirement for mechanical ventilation, fraction of inspired oxygen (FIO 2 ) >40%, and arterio-alveolar ratio in oxygen (aAO 2 ) <0.22. The primary end point was intact survival at 28 days of age. RESULTS: Sixty-one of 415 infants presented with HRF and were compared with 84 of 445 controls who presented with HRF. There was no difference in the primary end point (61.4% in infants [23% with HRF who were treated with iNO] vs 61.1% in controls [21.4% in controls with HRF]; P = .943). For the infants with HRF who were treated with iNO, there was no significant difference from controls for intraventricular hemorrhage (IVH) (6% vs 7%), necrotizing enterocolitis (8% vs 6 %), or patent ductus arteriosus (PDA) (34% vs 37%). Compared with nonhypoxemic infants, the risk of bronchopulmonary displasia (BPD) increased significantly in HRF controls (OR = 3.264 [CI 1.461-7.292]) but not in infants with HRF who were treated with iNO (OR = 1.626 [CI 0.633-4.178]). CONCLUSIONS: iNO appears to be safe in premature infants but did not lead to a significant improvement in intact survival on day 28.

[Necrotizing enterocolitis and apnoeas-bradycardias of the preterm newborn]. / Entérocolite ulcéro-nécrosante et apnées-bradycardies du nouveau-né prématuré

UNLABELLED: We conducted a case control study during six and a half years with the objective to analyse the risk factors for NEC. POPULATION AND METHODS: All cases of confirmed NEC matched to controls for identical gestational age and period of hospitalization; apnoeas-bradycardias prospectively counted. RESULTS: Forty-five cases were compared to 89 controls. The isolated risk factors were: an intra-uterine growth retardation (OR = 3,65, 95% confidence interval [CI] 95%: 1,54-8,63); a birth weight < 1000 g (OR = 8,16, CI 95%: 1,17-56,62), compared to a weight >/= 1500 g; a triple antibiotherapy (OR = 6,15, CI 95%: 1,16-32,45); an umbilical venous catheterization (OR = 2,64, CI 95%: 1,09-6,44); a number of simple apnoeas-bradycardias >/= 3rd tercile (n = 27) (OR = 4,54, CI 95%: 1,29-15,93), or severe (stimulated or with hypoxia) apnoeas-bradycardias >/= 3rd tercile (n = 8) (OR = 6,15, CI 95%: 1,59-23,75); an haemoglobin level lower than the 1(st) tercile (95 g/L) (OR = 5,90, CI 95%: 1,20-20,13); and milk thickening by Gumilk (OR = 2,78, CI 95%: 1,11-6,90). CONCLUSION: In the present practices, anoxo-ischemic factors during the first week of life do not represent an important risk of NEC; a great vigilance must be exercised for indications of the triple antibiotherapy and the treatment of apnoeas-bradycardias.

Population pharmacokinetics of cisapride in neonates.

OBJECTIVES: We conducted a population pharmacokinetic analysis of cisapride in neonates to study whether metabolic immaturity in this population may lead to increased concentrations. METHODS: Cisapride was administered orally in 91 neonates at the dose of 0.2 mg/kg four times a day. Plasma concentrations were measured using a validated HPLC method. A one-compartment model with first-order absorption was fitted to the data using NONMEM software. RESULTS: One to seven plasma samples were obtained from neonates aged 7-123 days. Cisapride concentrations ranged from 5.5 ng/mL to 172 ng/mL and were not higher than those reported in adults. The absorption constant rate was fixed to 2.5 h-1. Clearance (CL/F) and volume of distribution (V/F) both significantly correlated to weight (WT), but addition of this covariate in V/F did not improve the objective function after it was added in the CL/F covariate model. Prematurity, postnatal age, or coadministered drugs did not affect cisapride clearance. Final population pharmacokinetic parameters (interindividual variability) were: V/F=17,200 mL (90.4%) and CL/F=3.91 x WT(3/4) mL/h (36.3%). CONCLUSIONS: Our finding that cisapride clearance is primarily influenced by weight is in agreement with current recommendations of weight-adjusted doses. This study indicates that no clinically relevant maturational changes in cisapride clearance have to be considered during the first quadrimester of life.

[Mother-infant and indirect transmission of HSV infection: treatment and prevention]. / Transmission materno-foetale et indirecte de l'infection HSV, traitement et prévention.

INTRODUCTION: Neonatal herpes is a serious condition. The objectives of this critical review of the literature are to: 1) define the modes of mother-infant and indirect transmission of HSV infection; 2) determine current treatments and perspectives for the future. METHOD: We searched for articles published since 1980 in databases using a series of key words. The articles were classed into three categories by level of scientific proof: good (level 1), fair (level 2), poor (level 3, 4 or 5). General reviews were excluded. RESULTS: We selected 153 articles and retained 96. Man to woman contamination was generally reported: 10p.100 of the couples were serodiscordant. Presence of anti-HSV1 antibodies was partially protective against HSV2 infection. Neonates can be contaminated in utero via transplacental hematogenic transmission, at delivery (the most frequent route), or during the postnatal period (indirect transmission). The risk of neonatal contamination is greatest for primary infection (PI) or non-primary infection occurring the last month of pregnancy (50p.100), but transmission is low for maternal recurrence during the week before delivery (5p.100). Cesarean section is mandatory in case of genital PI or non-primary maternal infection during the last month of pregnancy, especially in case of membrane rupture<6 hr, but does not protect the infant in two-thirds of the cases. The decision for cesarean is controversial in case of recurrence. Antiviral treatment of the mother using aciclovir (ACV) is well tolerated. ACV-cesarean combination provides maximal protection for the neonate. A neonate with proven or suspected HSV infection should be isolated from other neonates but not from the mother. Breastfeeding is contraindicated in case of breast lesions. Parenteral ACV 60 g/kg/d is preferred over vidarabine. It should be started immediately after the first virology samples. The risk of recurrence is estimated at 7p.100 for all neonates and warrants treatment using a high oral dose (90-100mg/kg/d) due to the low bioavailability, if the number of recurrences is>3 in 6 months. Antiviral treatment is formally indicated if: 1) neonate viral cultures are positive at day 1 and day 3, 2) clinical lesions suggest herpes, 3) neurological disorders or signs of sepsis with negative bacteriology are present and the mother has a history of herpes or contact with labial herpes; and can be discussed if: 4) PI is proven at delivery or during the last month of pregnancy (irrespective of the delivery route, even if the mother is treated or if the membranes are intact), 5) late cesarean (membrane rupture>4 h) with clinical herpes at delivery, 6) vaginal delivery and recurrent herpes within the last month with associated clinical risk factor(s). CONCLUSION: Many points remain to be clarified concerning optimal management of the mother-infant couple in case of maternal herpes during pregnancy or at delivery. New perspectives concerning diagnosis and prevention of neonatal contamination include: identification of asymptomatic primary infections using rapid identification of genital viral antigen during delivery, identification of women with a risk of asymptomatic excretion using specific serology tests for the pregnant woman and her partner, antiviral treatment for men, topical genital treatments, vaccination of women at risk, monoclonal antibodies, new antiviral agents with mechanisms of action independent of viral thymidine kinase.

Inflammatory mediators and neonatal brain damage.

Inflammatory mediators are multifunctional cytokines that play important roles both in normal central nervous system (CNS) development and in the response of the brain to diverse forms of injury. Interleukin (IL)-1beta, tumor necrosis factor-alpha and IL-6 are among the best-characterized early-response cytokines. Recent data suggest that they may be synthesized and secreted by several CNS cell types, including microglia, astrocytes and neurons. Biological effects of these cytokines that could influence the progression of injury in the brain include stimulating the synthesis of other cytokines and neuronal injury mediators such as nitric oxide synthase, inducing leukocyte infiltration and the expression of adhesion molecules, influencing glial gene expression and damaging oligodendrocytes. In the immature brain, proinflammatory cytokines might lead to white matter damage during prenatal intrauterine infection and contribute to progressive neuronal damage in acute brain injury evoked by cerebral hypoxia-ischemia. Interrupting the proinflammatory cascade might limit the extent of irreversible injury.