Evaluation of critical congenital heart defects screening using pulse oximetry in the neonatal intensive care unit.

OBJECTIVE: To evaluate the implementation of early screening for critical congenital heart defects (CCHDs) in the neonatal intensive care unit (NICU) and potential exclusion of sub-populations from universal screening. STUDY DESIGN: Prospective evaluation of CCHD screening at multiple time intervals was conducted in 21 NICUs across five states (n=4556 infants). RESULTS: Of the 4120 infants with complete screens, 92% did not have prenatal CHD diagnosis or echocardiography before screening, 72% were not receiving oxygen at 24 to 48 h and 56% were born ⩾2500 g. Thirty-seven infants failed screening (0.9%); none with an unsuspected CCHD. False positive rates were low for infants not receiving oxygen (0.5%) and those screened after weaning (0.6%), yet higher among infants born at <28 weeks (3.8%). Unnecessary echocardiograms were minimal (0.2%). CONCLUSION: Given the majority of NICU infants were ⩾2500 g, not on oxygen and not preidentified for CCHD, systematic screening at 24 to 48 h may be of benefit for early detection of CCHD with minimal burden.

Amplitude-integrated EEG and range-EEG modulation associated with pneumatic orocutaneous stimulation in preterm infants.

OBJECTIVE: Controlled somatosensory stimulation strategies have demonstrated merit in developing oral feeding skills in premature infants who lack a functional suck, however, the effects of orosensory entrainment stimulation on electrocortical dynamics is unknown. The objective of the study was to determine the effects of servo-controlled pneumatic orocutaneous stimulation presented during gavage feedings on the modulation of amplitude-integrated electroencephalogram (aEEG) and range electroencephalogram (rEEG) activity. STUDY DESIGN: Two-channel EEG recordings were collected during 180 sessions that included orocutaneous stimulation and non-stimulation epochs among 22 preterm infants (mean gestational age=28.56 weeks) who were randomized to treatment and control 'sham' conditions. The study was initiated at around 32 weeks post-menstrual age. The raw EEG was transformed into aEEG margins, and rEEG amplitude bands measured at 1-min intervals and subjected to a mixed models statistical analysis. RESULT: Multiple significant effects were observed in the processed EEG during and immediately following 3-min periods of orocutaneous stimulation, including modulation of the upper and lower margins of the aEEG, and a reorganization of rEEG with an apparent shift from amplitude bands D and E to band C throughout the 23-min recording period that followed the first stimulus block when compared with the sham condition. Cortical asymmetry also was apparent in both EEG measures. CONCLUSION: Orocutaneous stimulation represents a salient trigeminal input, which has both short- and long-term effects in modulating electrocortical activity, and thus is hypothesized to represent a form of neural adaptation or plasticity that may benefit the preterm infant during this critical period of brain maturation.

Early variable-flow nasal continuous positive airway pressure in infants < or =1000 grams at birth.

OBJECTIVE: To compare the incidence of chronic lung disease (CLD) in extremely low birth weight (ELBW, < or =1000 g) infants before and after the introduction of early, preferential application of nasal continuous airway pressure (NCPAP) utilizing a variable flow delivery system. STUDY DESIGN: A retrospective cohort study of ELBW infants 2 years prior to (Pre-early NCPAP, n=96) and 2 years following (Early NCPAP, n=75) the initiation of an early NCPAP policy. RESULTS: There were no significant changes (Pre-early NCPAP vs Early NCPAP) in the incidences of CLD (35 vs 33%, P=0.81) or CLD or death (50 vs 43%, P=0.34). Infants in the Early NCPAP group weaned off mechanical ventilation and supplemental oxygen more rapidly than infants in the Pre-early NCPAP group (hazard ratio (HR) 1.80, P=0.002 and HR 1.69, P=0.01). CONCLUSION: A policy of early NCPAP has not decreased the incidence of CLD despite a decrease in time to successful tracheal extubation.

Urethral seam formation and hypospadias.

Knowledge of the formation of the normal male urethra may elucidate the etiology of hypospadias. We describe urethral formation in the mouse, show the similarities and relevance to human urethral development, and introduce the concept of the epithelial seam formation and remodeling during urethral formation. Three mechanisms may account for epithelial seam formation: (1) epithelial-mesenchymal transformation similar to that described in the fusion of the palatal shelves, (2) apoptosis, and/or (3) tissue remodeling via cellular migration. Urethral development in the embryonic mouse (14-21 days of gestation) was compared with urethral formation in embryonic human specimens (8-16 weeks of gestation) by using histology, immunohistochemistry, and three-dimensional reconstruction. The urethra forms by fusion of the epithelial edges of the urethral folds, giving a midline epithelial seam. The epithelial seam is remodeled via cellular migration into a centrally located urethra and ventrally displaced remnant of epithelial cells. The epithelial seam is remodeled by narrowing approximately at its midpoint, with subsequent epithelial migration into the urethra or penile skin. The epithelial cells are replaced by mesenchymal cells. This remodeling seam displays a narrow band (approximately 30 microns wide) of apoptotic activity corresponding to the mesenchymal cells and not to epithelial cells. No evidence was seen of the co-expression of cytokeratin and mesenchymal markers (actin or vimentin). Urethral seam formation occurs in both the mouse and the human. Our data in the mouse support the hypothesis that seam transformation occurs via cellular migration and not by epithelial mesenchymal transformation or epithelial apoptosis. We postulate that disruption of epithelial fusion remodeling, and cellular migration leads to hypospadias.

Urethral development in the fetal rabbit and induction of hypospadias: a model for human development.

PURPOSE: To determine whether the development of the rabbit phallus would be an appropriate model of human phallic development, we evaluated the formation of the fetal rabbit phallus and attempted to induce hypospadias pharmacologically. MATERIALS AND METHODS: New Zealand rabbit fetuses were obtained on gestational days 20 to 24, 26, 28 and 31. Sex was determined by gonadal morphology, and 6 fetuses were obtained at each age. The perineum was dissected, fixed, sectioned and stained with hematoxylin and eosin, and monoclonal antibodies against neuronal specific enolase. Two pregnant rabbits were treated with 10 mg./kg. finasteride orally daily between gestational days 19 and 28. The development of the external genitalia was compared in treated and untreated control rabbits. RESULTS: The rabbit phallus contains 2 corpora cavernosa and dorsolateral nerves similar to the human. In male and female fetuses fusion of the urethral folds progressed in a proximal to distal sequence forming a seam at the point of ventromedial fusion. In male fetuses urethral fold and ventral preputial fusion continued more distally toward the glans compared to females. Thus, in mature males the urethral meatus and ventral prepuce extended to the tip of the phallus, whereas in females the urethral meatus opened on the proximal phallus and the prepuce was deficient ventrally forming a dorsal hood. Male offspring had a significantly larger anogenital distance postnatally than female offspring. In male fetuses exposed to finasteride urethral fusion did not extend distally and the prepuce was deficient ventrally. Also, male offspring exposed to finasteride in utero had a significantly shorter anogenital distance than females and untreated control males at all ages (p <0.05). CONCLUSIONS: Fetal development of the rabbit phallus and urethra is homologous to the human. Although the gestational period is significantly shorter, the temporospatial pattern of external genitalia development is analogous in these species. Feminization of the rabbit urethra, hypospadias, can be induced by inhibiting 5alpha-reductase. Use of this animal model will allow further study of molecular mechanisms involved in urethral fusion and the evaluation of the pathophysiological processes of hypospadias.