Papers by Ramasubbareddy Dhanireddy
Neonatal Hospital Course and Outcomes of Live-born Infants with Trisomy 18 at Two Tertiary Care Centers in the United States
American Journal of Perinatology, 2016
Objectives Trisomy 18 is presumed to be a lethal chromosomal abnormality; medical management of i... more Objectives Trisomy 18 is presumed to be a lethal chromosomal abnormality; medical management of infants with this aneuploidy is controversial. Our objective was to describe our approach and experience with trisomy 18 infants. Study Design We reviewed the initial hospital course, management, and factors predicting discharge from the hospital from two large tertiary care neonatal intensive care units in the southern United States over 26 years. Results Of the 29 infants with trisomy 18, 21 (72%) died in the hospital and 8 (28%) were discharged home. 19 (66%) infants received mechanical ventilation and 10 (34%) received inotropic medications. Eight infants had critical congenital heart defects; only one survived to discharge. Three infants underwent major surgeries; one cardiac surgery, one tracheoesophageal fistula repair, and one myelomeningocele repair. Median length of hospital stay was 14 days (range, 0-78) for all the infants and 31 days (range, 18-66) for those that were discharged home. Factors associated with discharge from the hospital were female sex, higher gestational age, and absence of critical congenital heart defects. Median survival time was 13 days and was significantly longer for females compared with males. Our 1-month and 1-year survival rates were 31% and 3.9% respectively. Conclusions A significant proportion of infants with trisomy 18 were discharged home. These data are helpful in counseling parents of infants with trisomy 18.
Glycerin Suppositories Use in Very Low Birth Weight Infants
American Journal of Perinatology, 2016
Objective To study the characteristics of very low birth weight (VLBW) infants receiving glycerin... more Objective To study the characteristics of very low birth weight (VLBW) infants receiving glycerin suppositories (GS) and evaluate the association of GS use with outcomes. Study Design This is a retrospective study of VLBW infants admitted to a level III neonatal intensive care unit. Infants with birth weight between 500 and 1,499 g were evaluated. We evaluated the frequency of GS use and compared the characteristics and outcomes of the GS group with the no-GS group. Multivariate analyses controlling for gestational age and small for gestational age status were performed to study the effect of GS on outcomes. Results A total of 1,073 infants were included in the study. Out of those, 527 (49.1%) infants received GS. Incidence of necrotizing enterocolitis was not significantly different between the two groups, while days to reach full enteral feeds and length of hospital stay were significantly longer in the GS group. Conclusion Frequent use of GS warrants further prospective studies to evaluate its safety and efficacy in view of our study showing association with longer time to reach full enteral feeds. We speculate that GS use could be a marker for gastrointestinal dysmotility and hence the association with unfavorable clinical outcomes.
Respiratory Distress Syndrome in the Newborn: Relationship to Serum Prolactin, Thyroxine and Sex
Crit Care Med, 1981
Prolactin and thyroxine levels were measured by radioimmunoassay in cord blood of 61 premature in... more Prolactin and thyroxine levels were measured by radioimmunoassay in cord blood of 61 premature infants of 26-36 weeks gestation. 30 of the infants subsequently developed respiratory distress syndrome (RDS). The infants who developed RDS had a mean cord prolactin level of 174.5 +/- 24.5 ng/ml and a mean cord thyroxine level of 5.9 +/- 0.4 micrograms/dl. In the 31 healthy infants, the mean cord prolactin and thyroxine levels were significantly higher (226.3 +/- 25.8 ng/ml and 7.1 +/- 0.4 micrograms/dl, respectively). The correlation coefficient between prolactin and thyroxine was r = 0.56 in infants with RDS (p less than 0.0008). Both prolactin and thyroxine correlated with gestational age in the RDS group (r = 0.71 and 0.47, respectively). Discriminant analysis shows that the correlation between prolactin and thyroxine is independent of gestational age (r2 = 0.32, p less than 0.05). There was no correlation between the levels of prolactin and thyroxine in infants without RDS. In the healthy group, the cord prolactin levels were significantly higher (p less than 0.01) in female (335.8 +/- 47.7 ng/ml) than in male infants (209 +/- 17.2 ng/ml). Premature infants who develop RDS have significantly lower thyroxine and prolactin levels in cord blood than infants who remain healthy.
Clinical and laboratory observations : time of first stool in extremely low birth weight (≤1000 grams) infants
The Journal of Pediatrics, 1993
Preliminary evidence of genetic anticipation in type 2diabetes mellitus
Medical Science Monitor, Jun 1, 2005
The term "anticipation" in genetic diseases refers to earlier age at onset and/... more The term "anticipation" in genetic diseases refers to earlier age at onset and/or increased severity in successive generations. Several diseases with genetic anticipation include rheumatoid arthritis, Crohn's disease, Schizophrenia, Graves' disease and several other neuropsychiatric disorders. The aim of the present study was to investigate whether genetic anticipation may occur in diabetes. The medical records of 485 subjects with type 2 diabetes, seen in the Diabetes Clinic were screened for subjects with a family history of diabetes and also aware of a definite date of diagnosis for both the subject and their family member. Ninety-six parent-child pairs with a known definite date of diagnosis of type 2 diabetes were identified and the age at onset of diabetes between two parent-child generations was compared. The age at diagnosis of the subjects with positive family history of diabetes was lower than those with no family history of diabetes (48.82+/-12 vs. 56.18+/-13; p<0.001). There was a significant difference in the mean age at diagnosis between the 1(st) generation and 2(nd) generation (57.39 vs. 52.03 years p<0.0001). When the age at diagnosis of the subjects with siblings was compared (38 sibling pairs), there was no significant difference noted (52.21 vs. 50.57; p=0.35). Patients in the second affected generation seem to acquire the disease at an earlier time in life, indicating strong evidence of anticipation. We conclude that genetic anticipation might occur in type 2 diabetes.
Early versus Delayed Human Milk Fortification in Very Low Birth Weight Infants-A Randomized Controlled Trial
The Journal of pediatrics, Jan 22, 2016
To compare the effect of initiating human milk fortification at 2 different feeding volumes on fe... more To compare the effect of initiating human milk fortification at 2 different feeding volumes on feeding intolerance and the time to reach full feeding volume. Very low birth weight infants (n = 100) were prospectively randomized to early fortification (EF) (beginning at a feeding volume of 20 mL/kg/d) or delayed fortification (at a feeding volume of 100 mL/kg/d). We employed a standardized feeding protocol and parenteral nutrition guidelines for the nutritional management of all study infants. The median days to reach full feeding volumes were equivalent in the 2 groups (20 vs 20, P = .45). No significant difference was observed in the total number of episodes of feeding intolerance (58 vs 57). Two cases of necrotizing enterocolitis (Bell stage ≥2) and deaths occurred in each group. Median daily protein intake (g/kg/d) was higher in EF group in week 1 (3.3 [3.2, 3.5] vs 3.1 [2.9, 3.3], P < .001), week 2 (3.6 [3.5, 3.8] vs 3.2 [2.9, 3.4], P < .001), and week 3 (3.7 [3.4, 3.9] vs...
The Journal of Clinical Investigation, 1995
Uteroglobin (UG) gene encodes a cytokine-like, multifunctional, antiinflammatory protein, with po... more Uteroglobin (UG) gene encodes a cytokine-like, multifunctional, antiinflammatory protein, with potent phospholipase A2-inhibitory activity. It has been suggested that during implantation this protein protects the embryos from maternal immunological assault, facilitates the maintenance of quiescence in the uterus throughout pregnancy, prevents the onset of premature labor, and helps maintain an inflammationfree respiratory organ. This latter function of UG is suggested to be accomplished by preventing hydrolysis of surfactant phospholipids by a lung-specific phospholipase A2. Using reverse transcription polymerase chain reaction, in situ hybridization, immunofluorescence, and radioimmunoassay, we studied UG gene expression in the rabbit uterus throughout gestation and in the fetal lung. Here, we report that: (a) contrary to previous reports, UG gene expression in the rabbit uterus occurs throughout gestation with a precipitous decline just before parturition; (b) this gene expression is dramatically increased in the fetal lung with increasing gestational age; and (c) while there is an inverse relationship between the levels of UG, PGE2, and PGF2., a positive correlation was found in that of UG and leukotriene C4 in the fetal lung. Our results raise the possibility that dysregulation of UG gene expression, at least in part, may contribute to the onset of premature labor and the development of inflammatory lung disease in premature neonates. (J. Clin. Invest. 1995. 96:343-353.)
Chapter-24 Parenteral Nutrition in the Newborn
Recent Advances in Neonatology, 2004
Antimicrobial Agents and Chemotherapy, 2008
Fluconazole is being increasingly used to prevent and treat invasive candidiasis in neonates, yet... more Fluconazole is being increasingly used to prevent and treat invasive candidiasis in neonates, yet dosing is largely empirical due to the lack of adequate pharmacokinetic (PK) data. We performed a multicenter population PK study of fluconazole in 23-to 40-week-gestation infants less than 120 days of age. We developed a population PK model using nonlinear mixed effect modeling (NONMEM) with the NONMEM algorithm. Covariate effects were predefined and evaluated based on estimation precision and clinical significance. We studied fluconazole PK in 55 infants who at enrollment had a median (range) weight of 1.02 (0.440 to 7.125) kg, a gestational age at birth (BGA) of 26 (23 to 40) weeks, and a postnatal age (PNA) of 2.3 (0.14 to 12.6) weeks. The final data set contained 357 samples; 217/357 (61%) were collected prospectively at prespecified time intervals, and 140/357 (39%) were scavenged from discarded clinical specimens. Fluconazole population PK was best described by a one-compartment model with covariates normalized to median values. The population mean clearance (CL) can be derived for this population by the equation CL (liter/h) equals 0.015 · (weight/1) 0.75 · (BGA/26) 1.739 · (PNA/2) 0.237 · serum creatinine (SCRT) ؊4.896 (when SCRT is >1.0 mg/dl), and using a volume of distribution (V) (liter) of 1.024 · (weight/1). The relative standard error around the fixed effects point estimates ranged from 3 to 24%. CL doubles between birth and 28 days of age from 0.008 to 0.016 and from 0.010 to 0.022 liter/kg/h for typical 24-and 32-week-gestation infants, respectively. This population PK model of fluconazole discriminated the impact of BGA, PNA, and creatinine on drug CL. Our data suggest that dosing in young infants will require adjustment for BGA and PNA to achieve targeted systemic drug exposures.
Biochemical and Biophysical Research Communications, May 16, 1988
Uteroglobin is a steroid hormone dependent, low molecular weight, secretory protein with many imm... more Uteroglobin is a steroid hormone dependent, low molecular weight, secretory protein with many immunomodulatory properties. Immunomodulation by this protein may, at least in part, be related to its inhibitory effects on phospholipase A 2 activity. Although uteroglobin is conclusively found in the rabbit, its presence in the human is controversial. Here, we present biochemical and immunological evidence for the detection of a uteroglobin-like protein in the wet epithelial living of the respiratory tract of human neonates. Because inhibition of phospholipase A 2 may modulate tissue eicosanoid levels and since many eicosanoids (i.e. prostaglandins and leukotrienes etc.) are well known regulators of smooth muscle contractility, cellular migration and inflammatory processes, the discovery of this protein in the human respiratory tract may have important physiological implications.
Randomized Trial of Late Surfactant Treatment in Ventilated Preterm Infants Receiving Inhaled Nitric Oxide
The Journal of pediatrics, Jan 20, 2015
To assess whether late surfactant treatment in extremely low gestational age (GA) newborn infants... more To assess whether late surfactant treatment in extremely low gestational age (GA) newborn infants requiring ventilation at 7-14 days, who often have surfactant deficiency and dysfunction, safely improves survival without bronchopulmonary dysplasia (BPD). Extremely low GA newborn infants (GA ≤28 0/7 weeks) who required mechanical ventilation at 7-14 days were enrolled in a randomized, masked controlled trial at 25 US centers. All infants received inhaled nitric oxide and either surfactant (calfactant/Infasurf) or sham instillation every 1-3 days to a maximum of 5 doses while intubated. The primary outcome was survival at 36 weeks postmenstrual age (PMA) without BPD, as evaluated by physiological oxygen/flow reduction. A total of 511 infants were enrolled between January 2010 and September 2013. There were no differences between the treated and control groups in mean birth weight (701 ± 164 g), GA (25.2 ± 1.2 weeks), percentage born at GA <26 weeks (70.6%), race, sex, severity of l...
Effects of saline instillation during tracheal suction on lung mechanics in newborn infants
Journal of Perinatology
To evaluate the effect of saline instillation prior to tracheal suction on lung mechanics in mech... more To evaluate the effect of saline instillation prior to tracheal suction on lung mechanics in mechanically ventilated newborn infants, we studied pulmonary mechanics in nine infants with respiratory distress syndrome (RDS) and nine infants with meconium-aspiration syndrome (MAS) at a mean postnatal age of 3 days. Pulmonary mechanics were measured at 10 minutes prior to, and at 10, 20, and 30 minutes after tracheal suction with saline instillation. Suction and study protocol were repeated within 12 hours without saline instillation. The sequence of the study with and without saline instillation was randomly assigned. In infants with RDS, tracheal suction had no effect on pulmonary compliance or airway resistance with and without saline instillation. In infants with MAS, there was no change in compliance after tracheal suction with and without saline instillation. Airway resistance decreased by 35% after tracheal suction with saline instillation in infants with MAS; tracheal suction without saline instillation had no effect on airway resistance. We conclude that saline instillation into trachea as commonly done during tracheal suction has no deleterious effects on lung mechanics in newborn infants.
Effect of intrauterine cocaine exposure on respiratory distress syndrome in very low birthweight infants
Journal of the National Medical Association
To evaluate the effect of intrauterine cocaine exposure on lung maturity of very low birthweight ... more To evaluate the effect of intrauterine cocaine exposure on lung maturity of very low birthweight infants, the medical records of all infants with birthweight &lt; 1500 g born between January 1989 and December 1990 at DC General Hospital were reviewed. Infants with conditions known to cause lung maturity, severe congenital anomalies, proven early sepsis, and birthweight &gt; or = 500 g were excluded. A total of 69 infants were included in the study. Chest roentgenograms of these infants were evaluated by a pediatric radiologist, who was unaware of the infant&#39;s medical course, for evidence of respiratory distress syndrome (RDS), and radiological findings were correlated with clinical signs. Forty infants were exposed to cocaine in utero (cocaine group) and 29 were not exposed (noncocaine group). African-American ethnicity, pregnancy-induced hypertension, prolonged rupture of membranes, and alcohol use were similar in both groups. Tobacco use among cocaine group mothers was higher (42.5% versus 13.8%; P = .01). Gestational age (28.3 +/- 2.8 versus 28.3 +/- 3 weeks), birthweight (966 +/- 282 versus 1059 +/- 295 g), male gender, and Apgar scores were similar in both groups. Thirty (75%) infants in the cocaine group developed RDS compared with 19 (66%) in the noncocaine group (P &gt; .05). Using multiple logistic regression analysis and controlling for smoking, alcohol use, and prolonged rupture of membranes (24 to 72 hours), the incidence of RDS between the groups remained statistically insignificant. We conclude that intrauterine cocaine exposure does not alter the incidence of RDS in very low birthweight infants.
Trends in Medication Use in Very Low-Birth-Weight Infants in a Level 3 NICU over 2 Decades
American journal of perinatology, Jan 15, 2015
Objective This study aims to study the association between trends in medication utilization and s... more Objective This study aims to study the association between trends in medication utilization and survival in very low-birth-weight (VLBW) infants over a 22-year period. Study Design Medications received by VLBW infants were extracted retrospectively for the four periods 1990 to 1994, 1995 to 2000, 2001 to 2005, and 2006 to 2011 from our perinatal database and stratified by two birth weight groups: ≤ 1,000 g and 1,001 to 1,500 g. Result A total of 5,529 VLBW infants were reviewed. The majority of them were African American (78%), with an increasing proportion over time. The median number of medications per patient in all VLBW infants remained similar over time, 9 (5, 15). A cardiovascular group of medications was most commonly used, with a significant increase in the use of dobutamine and indomethacin. A significant trend toward an increasing number of infants without any antibiotic exposure was also noted. Survival steadily and significantly increased from 83 to 87%. Conclusion The t...
Surfactant replacement therapy for neonatal respiratory distress syndrome
The Indian Journal of Pediatrics, 1990
Conclusions Surfactant treatment of RDS improves oxygcnation and ventilation whether given immed... more Conclusions Surfactant treatment of RDS improves oxygcnation and ventilation whether given immediately after birth or after the onset of the disease. There is also a decrease in associated morbidity (air leak), and improved survival with no significant short term side effects. Information about long term follow-up is limited, but encouraging. The future should bring better surfactants (recombinant DNA human surfactant) and
Ontogeny of Prolactin Receptors in Fetal Rat Lung
Pediatric Research, 1987
Comparison of Two Different Doses of Nebulized Furosemide on Pulmonary Function in Infants With Chronic Lung Disease. 2060
Pediatric Research, 1996
Gut Transit Time (GT) in Very Low Birth Weight Infants 499
Pediatric Research, 1997
In Situ Immortalized Alveolar Type II Cells Produce Uteroglobin, an Antiinflammatory, Cytokine-Like Protein ♦ 55
Pediatric Research, 1997
CANDIDA SEPSIS INCREASES THE SEVERITYOF RETINOPATHY OF PREMATURITY IN EXTREMELY LOW BIRTH WEIGHT (≤1000 grams) INFANTS ♦ 976
Pediatric Research, 1997
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Papers by Ramasubbareddy Dhanireddy