Priya Jegatheesan

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.

Increased Indomethacin Dosing for Persistent Patent Ductus Arteriosus in Preterm Infants: A Multicenter, Randomized, Controlled Trial

OBJECTIVE We conducted a multicenter, randomized, controlled trial to determine whether higher doses of indomethacin would improve the rate of patent ductus arteriosus (PDA) closure. STUDY DESIGN Infants (<28 weeks gestation) who received a conventional, prophylactic 3-dose course of indomethacin were eligible if they had continued evidence of persistent ductus patency on an echocardiogram obtained before the third prophylactic indomethacin dose. Infants (n = 105) were randomized to receive an extended 3-day course of either low-dose (0.1 mg/kg/d) or higher-dose (0.2 or 0.5 mg/kg/d) indomethacin. An echocardiogram was obtained 24 hours after the last dose of study drug. RESULTS Despite increasing serum indomethacin concentrations by 2.9-fold in the higher-dose group, we failed to detect a significant decrease in the rate of persistent PDA (low = 52%; higher = 45%, P = .50). The higher-dose group had a significantly higher occurrence of serum creatinine >2 mg/100 mL (low = 6%, higher = 19%, P < .05) and moderate/severe retinopathy of prematurity (ROP) (low = 15%, higher = 36%, P < .025). The incidence of moderate/severe ROP was directly related to the poststudy indomethacin concentrations (odds ratio = 1.75, confidence interval: 1.15-2.68, P < .01). CONCLUSION Increasing indomethacin concentrations above the levels achieved with a conventional dosing regimen had little effect on the rate of PDA closure but was associated with higher rates of moderate/severe ROP and renal compromise.

Oxygen Saturation Nomogram in Newborns Screened for Critical Congenital Heart Disease

OBJECTIVE: To establish simultaneous pre- and postductal oxygen saturation nomograms in asymptomatic newborns when screening for critical congenital heart disease (CCHD) at ∼24 hours after birth. METHODS: Asymptomatic term and late preterm newborns admitted to the newborn nursery were screened with simultaneous pre- and postductal oxygen saturation measurements at ∼24 hours after birth. The screening program was implemented in a stepwise fashion in 3 different affiliated institutions. Data were collected prospectively from July 2009 to March 2012 in all 3 centers. RESULTS: We screened 13 714 healthy newborns at a median age of 25 hours. The mean preductal saturation was 98.29% (95% confidence interval [CI]: 98.27–98.31), median 98%, and mean postductal saturation was 98.57% (95% CI: 98.55–98.60), median 99%. The mean difference between the pre- and postductal saturation was −0.29% (95% CI: −0.31 to −0.27) with P < .00005. Its clinical relevance to CCHD screening remains to be determined. The postductal saturation was equal to preductal saturation in 38% and greater than preductal saturation in 40% of the screens. CONCLUSIONS: We have established simultaneous pre- and postductal oxygen saturation nomograms at ∼24 hours after birth based on >13 000 asymptomatic newborns. Such nomograms are important to optimize screening thresholds and methodology for detecting CCHD.

Duration of Cord Clamping and Neonatal Outcomes in Very Preterm Infants

Background Delayed cord clamping (DCC, ≥30s) increases blood volume in newborns and is associated with fewer blood transfusions and short-term neonatal complications. The optimal timing of cord clamping for very preterm infants should maximize placental transfusion without interfering with stabilization and resuscitation. Aim We compared the effect of different durations of DCC, 30-45s vs. 60-75s, on delivery room (DR) and neonatal outcomes in preterm infants <32 weeks gestational age (GA). Methods This is a single-center prospective observational study. Data were collected prospectively from eligible infants from two groups: 30-45s DCC group (January 2008 to February 2011, n = 187) and 60-75s DCC group (March 2011 to April 2014, n = 166). Results The 60-75s DCC group compared to the 30-45s DCC group had higher hematocrits at <2 hours (49.2% vs. 47.4%, p = 0.02). In infants <28 weeks GA, the 12–36 hours hematocrit was higher in the 60-75s DCC group compared to the 30-45s DCC group (47.9% vs. 42.1%, p = 0.002). The 60-75s DCC group had reductions in DR intubation (11% vs. 22%, p = 0.004), hypothermia on admission (1% vs. 5%, p = 0.01), surfactant therapy (13% vs. 28%, p = 0.001), intubation in the first 24 hours (20% vs. 34%, p = 0.004), any intubation (27% vs. 40%, p = 0.007), and any red blood cell transfusion (20% vs. 33%, p = 0.008) during the hospitalization compared to the 30-45s DCC group. These reductions remained significant after adjusting for GA, gender and >48 hours of antenatal steroid exposure. There was no difference between the two groups in neonatal death, intraventricular hemorrhage, chronic lung disease, late onset sepsis, necrotizing enterocolitis and severe retinopathy of prematurity. Conclusion In this study cohort increasing DCC duration from 30-45s to 60-75s is associated with decreased hypothermia on admission, neonatal respiratory interventions and red blood cell transfusions without increase in neonatal mortality and morbidities.

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.

Hospital-wide breastfeeding rates vs. breastmilk provision for very-low-birth-weight infants

To investigate the relationship between breastmilk feeding in very‐low‐birth‐weight infants in the neonatal intensive care unit and breastmilk feeding rates for all newborns by hospital.

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.

Superior mesenteric artery blood flow velocities following medical treatment of a patent ductus arteriosus

We examined superior mesenteric artery blood flow velocity in response to feeding in infants randomized to trophic feeds (n = 16) or nil per os (n = 18) during previous treatment for patent ductus arteriosus. Blood flow velocity increased earlier in the fed infants, but was similar in the 2 groups at 30 minutes after feeding.

Modulation of EEG spectral edge frequency during patterned pneumatic oral stimulation in preterm infants

Background:Stimulation of the nervous system plays a central role in brain development and neurodevelopmental outcomes. Thalamocortical and corticocortical development is diminished in premature infants and correlated to electroencephalography (EEG) progression. The purpose of this study was to determine the effects of orocutaneous stimulation on the modulation of spectral edge frequency fc = 90% (SEF-90), which is derived from EEG recordings in preterm infants.Methods:A total of 22 preterm infants were randomized to experimental and control conditions. Pulsed orocutaneous stimulation was presented during gavage feedings begun at ~32 wk postmenstrual age. The SEF-90 was derived from two-channel EEG recordings.Results:Compared with the control condition, the pulsed orocutaneous stimulation produced a significant reorganization of SEF-90 in the left (P = 0.005) and right (P < 0.0001) hemispheres. Notably, the left and right hemispheres showed a reversal in the polarity of frequency shift, demonstrating hemispheric asymmetry in the frequency domain. Pulsed orocutaneous stimulation also produced a significant pattern of short-term cortical adaptation and a long-term neural adaptation manifested as a 0.5 Hz elevation in SEF-90 after repeated stimulation sessions.Conclusion:This is the first study to demonstrate the modulating effects of a servo-controlled oral somatosensory input on the spectral features of EEG activity in preterm infants.

Perfusion index in healthy newborns during critical congenital heart disease screening at 24 hours: retrospective observational study from the USA

Objective To describe the distribution of perfusion index (PI) in asymptomatic newborns at 24 hours of life when screening for critical congenital heart disease (CCHD) using an automated data selection method. Design This is a retrospective observational study. Setting Newborn nursery in a California public hospital with ~3500 deliveries annually. Methods We developed an automated programme to select the PI values from CCHD screens. Included were term and late preterm infants who were screened for CCHD from November 2013 to January 2014 and from May 2015 to July 2015. PI measurements were downloaded every 2 s from the pulse oximeter and median PI were calculated for each oxygen saturation screen in our cohort. Results We included data from 2768 oxygen saturation screens. Each screen had a median of 29 data points (IQR 17 to 49). The median PI in our study cohort was 1.8 (95% CI 1.8 to 1.9) with IQR 1.2 to 2.7. The median preductal PI was significantly higher than the median postductal (1.9 vs 1.8, p=0.03) although this difference may not be clinically significant. Conclusion Using an automated data selection method, the median PI in asymptomatic newborns at 24 hours of life is 1.8 with a narrow IQR of 1.2 to 2.7. This automated data selection method may improve accuracy and precision compared with manual data collection method. Further studies are needed to establish external validity of this automated data selection method and its clinical application for CCHD screening.