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[NEC--neonatal necrotising enterocolitis--methods of treatment and outcome: a comparative analysis of Scottish (Glasgow) and Polish (Western Pomerania) cases].

The aim of the work was to perform a comparative analysis of medical files of 125 neonates with necrotising enterocolitis treated between 1990 and 1995 in two regional centres: Glasgow (Scotland) and Western Pomerania (Poland), and to search for factors constituting an indication for surgery in NEC. The following data contained in the medical documentation of NEC cases have been analyzed: maternal risk factors, perinatal abnormalities, neonatal risk factors, procedures performed in the neonate, feeding practices, clinical and radiological signs, time of onset of the disease, clinical staging of NEC according to Bell (modified by Walsh and Kliegman), methods of treatment, postoperative course and outcome. The analysis was performed in the whole material and in the subgroup of newborns weighing < 1500 g (low/extremely low birth weight babies). Glasgow neonates with NEC had significantly lower birth weight, gestational age, platelet count, and sodium level when compared to Pomeranian newborns, while the latter had significantly lower leukocyte count and shorter time of onset of the disease. In the subgroup of newborns weighing less than 1500 g, Glasgow neonates had significantly lower birth weight, gestational age, platelet count, and sodium level when compared to Pomeranian newborns, while the latter had significantly lower 1 minute Apgar score, pH and base excess (BE) values. Glasgow clinical NEC stage was significantly more severe (IIB-IIIB) when compared to Pomeranian neonates. A higher proportion of full-term neonates in the present study--31.2%--was diagnosed with NEC than in the literature. Hyponatremia with severe acidosis and low platelet count (especially below 100 x 10(9)/L) may constitute an easily available laboratory finding serving as an indicator for surgical intervention in NEC. Statistical analysis revealed that the selection of treatment was influenced in the Glasgow group by birth weight and in the Pomeranian group by the clinical stage of NEC. Overall mortality was 32.8% in the whole group of 125 neonates, 34.4% in the Glasgow and 31.2% in the Pomeranian group. However, Glasgow neonates had significantly lower birth weight and gestational age and were more severely ill. The mortality in the subgroup of Scottish neonates with primary peritoneal drainage was 55.5%, the majority presenting with significantly lower birth weight and stage IIIB of necrotising enterocolitis. In conservatively treated neonates, mortality was 13% in the whole group, 9% in the Glasgow group and 15% in the Pomeranian group. Overall mortality in neonates treated surgically was 46.6%. In the Glasgow group it was 23% without and 42% with primary peritoneal drainage, respectively. Surgical mortality in the Pomeranian group was 42%. Overall mortality was 5.6% in full-term newborns, 3.2% in the Glasgow group and 7.8% in the Pomeranian group. Primary peritoneal drainage is a valuable, mildly invasive method of initial, and in some cases final, treatment in severely ill NEC babies, especially with low birth weight. This method was not used in the Pomeranian group.

Anastomosis, Surgical↗

[C-reactive protein concentrations during initial (empiric) treatment of neonatal sepsis].

INTRODUCTION: Neonatal septicaemia is characterized by high mortality so that intravenous antibiotics must be administered on clinical suspicion. Initial antibiotic therapy, before the results of microbiological evaluation, is based on empirical data in regard to sensitivity of prevalent bacterial strains. In the past years, aetiological causes of neonatal sepsis have been changed with an increased bacterial resistance to the usual combination of initial antibiotics. AIM: We compared changes of serum C-reactive protein (CRP) concentrations in neonates with proven neonatal sepsis in response to initial antibiotic therapy (inappropriate or appropriate). Our hypothesis was that changes of CRP levels during the first 48 hours of treatment and before microbiologic results could be useful in evaluation of effectiveness of empiric antibiotics. METHODS: Our prospective study included all neonates with suspected sepsis referred to our Intensive Care Unit from January 1992 to December 1996. Neonates received ampicillin and gentamycin/or amikacin (during the first week of life), while infants older than 7 days of life were given combination of cloxacillin and aminoglycozides. In patients with late neonatal sepsis who also had meninigitis, cloxacillin was substituted with ampicillin. Microbiological identification was performed with routine bacteriological methods. Susceptibility of isolated bacterial strains to antibiotics was performed by Kirby-Bauer disc-diffusion method. Serum concentration of CRP was measured by immunoturbidimetry (Turbox CRP, Orion Diagnostica) and CRP concentration higher than 20 mg/l was regarded as elevated. Blood sampling for CRP measurements were taken before the treatment (CRP0), and during the first (CRP1) and second (CRP2) day of empiric therapy. The interval between sampling was from 12 to 24 hours. RESULTS: A total of 1520 neonates were evaluated during this study period and 47 patients fulfilled criteria for final analysis. In 14 of 47 patients initial antibiotic treatment was inappropriate. The most frequent resistant strains was KI. pneumoniae (6) followed with St. aureus (4), E. coli (2) and Pseudomonas (2). During initial evaluation six patients had concomitant meningitis while two had concomitant septic arthritis and two necrotizing enterocolitis, respectively. Seven (50%) of 14 patients with non-adequate initial treatment died. In 33 cases of adequately treated septicaemia the course was uncomplicated and no lethal outcome was observed. In the first group of 14 patients who received inappropriate treatment serum CRP concentations (mg/L; mean and +/- SD) were: CRP0 = 107.5 +/- 65.6; CRP1 = 155.3 +/- 75.7; CRP2 = 209.1 +/- 67.0, while in 33 repeated samples of the 33 patients in the second group who received adequate treatment the following results were recorded: CRP0 = 124.0 +/- 78.1; CRP1 = 133.8 +/- 63.5; CRP2 = 94.6 +/- 46.4. Increase in serum CRP concentration in the first group during the first 48 hours of initial non-adequate therapy was significantly higher (p = 0.015, two way ANOVA) than in the second group with appropriate treatment. During the first 24 hours of treatment increase in serum concentration of CRP was registered in 12 (85.7%) of 14 measurements in patients with non-adequate therapy and in 19 (56.7%) of 33 measurements in patients with adequate therapy. In the first group during the second day of treatment, in 11 (78.6%) of 14 cases an increase in serum CRP concentration was recorded while in 3 (14.3%) cases CRP concentration decreased. In 31 (91.2%) of 34 measurements in patients with adequate treatment CRP concentration decreased during the second day of treatment and in only 3 (8.8%) cases CRP concentration increased. With an increase in serum concentration of CRP more than 10 mg/L in the second day of antibiotic treatment, probability of non-adequate antibiotic therapy (positive predictive value) was estimated to be 77.0%. Any recorded decrease of serum CRP concentration may confirm appropriate choice of antibiotics during the second day of treatment with probability of 93.3% (negative predictive value). DISCUSSION: Measurement of serum CRP concentration is useful for diagnosis of severe neonatal sepsis. In our study all isolated bacterial strains were comparable in their ability to activate systemic inflammatory response and CRP production. It is known that serial CRP measurements during neonatal sepsis are useful in making decision to cease antibiotic treatment. The highest serum CRP concentrations were detected during the first day of illness but, in some cases even with appropriate treatment, CRP peak levels due to sustained pro-inflammatory action of interleukin-6 production could be detected even 24 hours after treatment was started. Our study showed that in patients with non-adequate initial antibiotic therapy of neonatal sepsis serum CRP concentrations increase further during the second day of treatment. By contrast, the use of appropriate antibiotic therapy in the same time period followed the significant decrease of serum CRP levels in our patients. Therefore, increase of CRP level during initial treatment, especially during the second day of treatment of neonatal sepsis should be taken as indication for replacement of initial antibiotics, even before sensitivity of microbiological causes to given antibiotics is known.

Anti-Bacterial Agents↗

[Associations of genetic polymorphisms in the EPHX1 gene and the GSTT1 gene with low birth weight in neonates].

OBJECTIVE: To investigate whether genetic polymorphisms in the microsomal epoxide hydrolase gene (EPHX1) and the glutathione S-transferase theta1 gene (GSTT1) are associated with low birth weight in neonates. METHODS: Using standard questionnaires, 246 singleton live born mother-neonates pairs (73 cases were mother-low birth weight neonate pairs and 173 controls were mother-non low birth weight neonate pairs) were investigated by the trained field workers with case-control study at the hospital in Anqing, Anhui Province, China between 1998 and 1999. A total of 246 neonates were genotyped for genetic polymorphisms in the EPHX1 gene and the GSTT1 gene by a polymerase chain reaction-restriction fragment length polymorphism assay. Multiple linear regression models were used to estimate the association of the genetic polymorphisms in the EPHX1 gene and the GSTT1 gene with neonatal low birth weight, adjusting for maternal age, education, parity, neonatal sex and gestational age. RESULTS: EPHX1 His139His homozygote was not associated with low birth weight among neonates, compared with EPHX1 His139Arg heterozygote/Arg139Arg homozygote before and after adjustment confounders. GSTT1 absent genotype group also was not associated with low birth weight among neonates, compared with GSTT1 present genotype group before and after adjustment confounders. When both EPHX1 139 polymorphism and GSTT1 polymorphism were considered, a significant reduction in birth weight was found among neonates with EPHX1 His139His homozygote and GSTT1 absent genotype (OR=3.46, P=0.035). CONCLUSION: The combination between genetic polymorphisms in the EPHX1 gene and the GSTT1 gene in neonates is significantly associated with neonatal low birth weight.

Birth Weight↗

The safety and efficacy of oral dextrose for relieving pain following venepuncture in neonates.

The objective of this study was to assess the efficacy and safety of oral 30% dextrose during venepuncture in neonates. Neonates admitted in the Special Care Nursery for jaundice from September 200 to January 2001 were recruited for this double-blind randomised controlled trial. The intervention consisted of administration of either 2 ml of oral 30% dextrose or 2 ml of sterile water 2 minutes before venepuncture. The primary outcome measure was the cumulative Neonatal Infant Pain Scale (NIPS) score at 3 minutes after venepuncture and the duration of cry assessed from a videotaped recording. Twenty-six neonates received 30% dextrose and 26 neonates received sterile water. The cumulative NIPS score at 3 minutes (median, IQR) after venepuncture for neonates given 30% dextrose (13, 6.8-21) was significantly (p = 0.03) lower than that for neonates given sterile water (21, 13.8-21). The duration of cry in neonates given 30% dextrose (median 45 sec IQR 1.5-180.8 sec) was significantly (p = 0.03) shorter than that in neonates given sterile water (median 191 sec IQR 52.3-250 sec). No neonates developed diarrhoea, fever or rash during the 24 hour observation period. Both the intra-rater (ICC 0.993 95% CI 0.988-0.996) and inter rater (ICC 0.988 95% CI 0.980-0.993) agreement on the 3-minute NIPS score were good. In conclusion oral 30% dextrose given 2 minutes before venepuncture was effective in reducing neonatal pain following venepuncture. It is a simple, safe and fast acting analgesic and should be considered for minor invasive procedure in term neonates.

Administration, Oral↗

[Apoptosis in neonatal rat lung exposed to hyperoxia].

OBJECTIVE: Exposure to high concentrations of oxygen in the neonatal period may impair lung growth and is a major contributing factor to the development of bronchopulmonary dysplasia (BPD). Cell death from hyperoxic injury may occur through either an apoptotic or nonapoptotic pathway. The aim of the present study was to investigate the effect of hyperoxia on caspase-3 and p53 gene expression and apoptosis in the lungs of neonatal rats, so as to determine the type of cell death that occurs in the lungs of neonatal rats exposed to hyperoxia. METHODS: Hyperoxic lung injury model was established by exposing to 95% O(2) in the neonatal period of Spraque-Dawley rats. The levels of caspase-3 mRNA and p53 mRNA expression in the lungs of neonatal rats exposed to 95% hyperoxia or room air were detected by RT-PCR. To quantify PCR products, PCR products were electrophoretically separated with 1.5% agarose gels. The optical density (A) values of the DNA bands were quantified by complete gel documentation and analysis system. The A ratios of p53/beta-actin denoted the relative content of p53 mRNA, results were showed as mean +/- standard deviation. The specific positive or negative bands of caspase-3 in electrophoresis gels were counted, Fisher's exact test of propabilities was used to determined statistically significant differences between two groups. We determined the extent of apoptosis taking place in the lungs of neonatal rats exposed to 95% hyperoxia using terminal deoxyribonucleotide transferase-mediated deoxyuridine triphosphate-fluorescence nick-end labeling (TUNEL) in 7-d-old neonatal lung. Under light microscope, five areas of lung parenchyma were systematically and randomly photographed from each animal and positive cells among 500 lung cells were calculated. Results were showed as mean +/- standard deviation. RESULTS: We found increased levels of p53 messenger RNA, a gene associated with apoptosis, in the lungs of neonatal rat born and raised in 95% hyperoxia. Moderate increase in the level of p53 mRNA was found in the hyperoxic-treated group at 24 h (q = 3.2305, P > 0.05). Significant increase in the level of p53 mRNA was found in the hyperoxic-treated group at 48 h (q = 7.2941, P < 0.01). The levels of p53 mRNA expression in neonatal rat lungs exposed to 95% O(2) for 72 h or 96 h returned to normal level. The levels of caspase-3 mRNA expression were very low or absent in the hyperoxic-treated groups at 12 h, 24 h, 48 h, 72 h and 96 h or in the air-breathing groups at 12 h, 24 h, 48 h, 72 h and 96 h. An increase in the number of cells undergoing apoptosis was found in the hyperoxic-treated group at 7 d (F = 56.5010, P < 0.001) which was significantly greater than the number of apoptotic cells found in the lungs of rats of the same age exposed to room air. CONCLUSION: Our results suggested that 95% hyperoxia could temporarily up-regulate the gene expression of p53, which induced the transcription of p21(WAF/CIP1) mRNA. Furthermore, p21(WAF/CIP1) could lead to cell cycle arrest and inhibit proliferation of lung cells. Meanwhile, p53 could also promote apoptosis of lung cells. Therefore, exposure to high concentrations of oxygen in the neonatal period may impair lung growth and is a major contributing factor to the development of bronchopulmonary dysplasia (BPD), and hyperoxia may affect the future lung growth and lead to barrier of lung development. The treatments of anti-apoptosis and promoting alveoli growth hold a promising perspective in hyperoxic lung injury. The level and ratio of caspase-3 gene expression were very low or absent in the lungs of neonatal rats exposed to 95% O(2) or room air. We speculated that caspase-3 gene expression was not essential in the hyperoxia induced lung cell apoptosis in neonatal rats.

Animals↗

Subaponeurotic haemorrhage in Malaysian neonates.

In a 30-month prospective study, between January 1987 and June 1989, 101 of 64,424 Malaysian neonates (1.6 per 1000 livebirths) born in the Maternity Hospital, Kuala Lumpur were found to have subaponeurotic haemorrhage shortly after delivery. The incidence was highest in neonates weighting 4000 gm or more. There was no significant difference in incidence of this condition in neonates of different ethnic origins. Hypoprothrombinemia was present in only 5/101 (5.0%) of the affected neonates. Sixty seven (66.3%) of the neonates with subaponeurotic haemorrhage had history of trial of vacuum extraction. The incidence of subaponeurotic haemorrhage was significantly higher in neonates delivered by vacuum extraction than by other modes of delivery in this hospital (41.4 per 1000 livebirths in neonates delivered by vacuum extraction versus 1.0 per 1000 livebirths in neonates delivered by other modes). Those neonates who developed subaponeurotic haemorrhage without trial of vacuum extraction had a history of either prolonged labour or difficult delivery. Thirty-three (32.7%) of the neonates with subaponeurotic haemorrhage developed anaemia which required blood transfusion and 3/33 (9.1%) were in shock. Fifty seven (56.4%) of the neonates with subaponeurotic haemorrhage developed hyperbilirubinemia due to the haemorrhage. Four (7.0%) of them had severe unconjugated hyperbilirubinemia which required exchange transfusion. The results of this study suggest that subaponeurotic haemorrhage in Malaysian neonates was commonly associated with vacuum extraction and was not a benign condition.

Extraction, Obstetrical↗

Deficient total cell content of CR3 (CD11b) in neonatal neutrophils.

Neonatal neutrophils (PMN) show a well-documented defect in chemotaxis that is associated with several abnormalities of PMN structure and function, including deficient surface expression of CR3 (CD11b), a critical adhesion molecule, on chemoattractant-activated PMN. After activation of PMN with additional stimuli including calcium ionophores, we also found deficient surface CR3 (but normal CR1) expression on neonatal PMN suggesting that abnormal signaling mechanisms are not likely to explain the deficient CR3 expression on activated neonatal PMN. Therefore, we hypothesized that deficient surface expression of CR3 on stimulated neonatal neutrophils is caused by a deficiency in total cell content of CR3. We tested this hypothesis using three different methods to compare the total quantity of CR3 in neonatal versus adult PMN. Western blotting of serial twofold dilutions of PMN lysates from five adult and neonatal pairs, using a monoclonal antibody (MoAb) against CR3 (21PM19C), consistently showed diminished CR3 content in neonatal PMN. A sandwich enzyme-linked immunosorbent assay, in which the CR3 heterodimers in PMN lysates were captured by MoAb to the beta-chain, CD18 (R15.7), then detected with a biotinylated MoAb to the alpha-chain, CD11b (anti-Mac-1), showed that neonatal PMN lysates contain about 66% of adult PMN levels of CR3 (P < 0.03; n = 6). PMN fixed with paraformaldehyde and permeabilized with saponin were studied by immunofluorescence flow cytometry to determine total (surface plus intracellular) CR3 content using phycoerythrin-conjugated MoAb to CR3 (anti-Leu15). Mean total cell CR3 content (in relative fluorescence units) was 58 +/- 14 for adult PMN and 27 +/- 6 for neonatal PMN (n = 5; P = 0.013). In each method, total cell content of CR1 was equivalent for neonatal versus adult PMN. We conclude that neonatal PMN are markedly deficient in total cell CR3 content compared with adult PMN. This result provides a primary explanation for deficient CR3 surface expression on activated neonatal PMN that, in turn, may be important in the chemotactic defect of these cells.

Adult↗

Prenatal marijuana exposure and neonatal outcomes in Jamaica: an ethnographic study.

OBJECTIVE: To identify neurobehavioral effects of prenatal marijuana exposure on neonates in rural Jamaica. DESIGN: Ethnographic field studies and standardized neuro-behavior assessments during the neonatal period. SETTING: Rural Jamaica in heavy-marijuana-using population. PARTICIPANTS: Twenty-four Jamaican neonates exposed to marijuana prenatally and 20 nonexposed neonates. MEASUREMENTS AND MAIN RESULTS: Exposed and nonexposed neonates were compared at 3 days and 1 month old, using the Brazelton Neonatal Assessment Scale, including supplementary items to capture possible subtle effects. There were no significant differences between exposed and nonexposed neonates on day 3. At 1 month, the exposed neonates showed better physiological stability and required less examiner facilitation to reach organized states. The neonates of heavy-marijuana-using mothers had better scores on autonomic stability, quality of alertness, irritability, and self-regulation and were judged to be more rewarding for caregivers. CONCLUSIONS: The absence of any differences between the exposed on nonexposed groups in the early neonatal period suggest that the better scores of exposed neonates at 1 month are traceable to the cultural positioning and social and economic characteristics of mothers using marijuana that select for the use of marijuana but also promote neonatal development.

Adolescent↗

Neonatal renal artery blood flow velocities using color Doppler ultrasonography.

BACKGROUND: It is essential to evaluate the renal function for the management of high risk neonates. Color Doppler ultrasound technique can provide a useful information to evaluate the neonatal renal artery blood flow velocities. This study was performed to obtain the normative data of renal blood flow velocities in preterm and fullterm neonates and to compare the renal blood flow velocities with the aortic blood flow velocities. The normal volumetric state of fluid balance and renal function are essential in the management of the sick neonates. METHODS: The renal peak systolic blood flow velocity (renal PSFV), the renal mean blood flow velocity (renal MFV), the renal end diastolic blood flow velocity (renal EDFV) and the renal resistance index (renal RI) and also the cardiac output, the aortic peak systolic blood flow velocity (aortic PSFV) and the aortic mean blood flow velocity (aortic MFV) were serially recorded from one to 7 days after birth in 16 preterm and one to 5 days in 23 normal fullterm neonates. RESULTS: The renal PSFV was significantly increased with the postnatal age, and the renal MFV was significantly increased between three and five days of age in the preterm neonates. In the fullterm neonates there was no significant change of the renal PSFV between one and five days of age, but the renal MFV was significantly increased between three and five days of age. There were no statistically significant differences of the renal PSFV, the renal MFV, the renal EDFV and the renal RI between the preterm and the fullterm neonates in the first five days after birth. The cardiac output in the preterm neonates was higher than that in the fullterm neonates: on day 3; 313 +/- 59 vs. 254 +/- 40 ml/kg/min. (p < 0.001) and on day 5; 357 +/- 95 vs. 280 +/- 35 ml/kg/min. (p < 0.01). The renal blood flow velocities were not significantly correlated with the aortic blood flow velocities in the normal fullterm neonates, whereas, in the preterm neonates the renal PSFV correlated with the cardiac output (r = 0.35, p < 0.01), the aortic PSFV (r = 0.45, p < 0.001) and the aortic MFV (r = 0.39, p < 0.01), and the renal MFV also correlated with the aortic PSFV (r = 0.30, p < 0.05) and the aortic MFV (r = 0.32, p < 0.05). CONCLUSIONS: The increased renal flow velocities with the postnatal age in the preterm infants might depend on the increased cardiac output.

Aorta↗

Neonatal abstinence syndrome after in utero exposure to selective serotonin reuptake inhibitors in term infants.

OBJECTIVE: To compare the prevalence and clinical characteristics of neonatal abstinence syndrome in neonates exposed and not exposed to selective serotonin reuptake inhibitors (SSRIs) in utero. DESIGN: Cohort study. SETTING: Tertiary care center. Patients One hundred twenty term infants, of whom 60 had prolonged in utero exposure to SSRIs, including paroxetine hydrochloride, fluoxetine, citalopram hydrobromide, sertraline hydrochloride, and venlafaxine hydrochloride. MAIN OUTCOME MEASURES: Neonatal abstinence syndrome was assessed with the Finnegan score as follows: score of 8 or above, severe; score of 4 to 7, mild; and score of 0 to 3, normal. All infants were followed up with a standardized protocol that included repeated Finnegan score assessments and cardiorespiratory monitoring until normalization of the Finnegan score. RESULTS: Of the 60 neonates exposed to SSRIs in utero, 8 showed severe and 10 showed mild symptoms of a neonatal abstinence syndrome. All nonexposed neonates had a normal Finnegan score. In neonates who developed severe symptoms, the maximum mean daily Finnegan scores were recorded within 2 days after birth, although maximum individual scores were recorded as long as 4 days after birth. CONCLUSIONS: Neonatal abstinence syndrome occurs in 30% of neonates exposed to SSRIs in utero. These neonates should be monitored for at least 48 hours after birth. The long-term effects of prolonged exposure to SSRIs, particularly in neonates who develop severe symptoms, have yet to be determined.

Adult↗

Postnatal management of fetal and neonatal alloimmune thrombocytopenia: the role of matched platelet transfusion and IVIG.

We evaluated the effects of platelet transfusions and intravenous immunoglobulin (IVIG) in neonates with fetal and neonatal alloimmune thrombocytopenia (FNAIT) with and without antenatal treatment with IVIG. Records of neonates with FNAIT admitted between January 2000 and November 2005 were reviewed. The patients were divided into group I, treated antenatally with IVIG for known FNAIT, and group II, postnatally diagnosed with FNAIT. The primary outcome was the time interval to reach a platelet level above 100 x 10(9)/L in relation to the type of treatment. Nineteen neonates with FNAIT were identified, 13 in group I and 6 in group II. In group I, four children were born with a platelet count above 100 x 10(9)/L and never needed treatment, and four received a single matched platelet transfusion at birth with a maintained response. Five neonates received IVIG and one matched transfusion, with all but one rapidly responding. In antenatally treated cases, postnatal IVIG had no apparent effect on the platelet count. In group II, two neonates died on day 1 with severe intracranial hemorrhage. Two of the four other patients responded to a number of unmatched platelet transfusions, with one neonate rapidly responding after one matched transfusion, while another needed nine matched transfusions before a persistent adequate platelet count was reached after 9 weeks. Postnatal IVIG had no apparent effect on the platelet count in any of our cases. In neonates with FNAIT treated antenatally with IVIG, neonatal management using a single matched platelet transfusion was adequate in all cases. In neonatally diagnosed cases not treated before birth, multiple matched platelet transfusions may be required. We found no evidence to support the use of IVIG in neonates with FNAIT.

Female↗

Timing of scheduled cesarean delivery in patients on a teaching versus private service: adherence to American College of Obstetricians and Gynecologists guidelines and neonatal outcomes.

OBJECTIVE: The purpose of this study was to compare adherence to American College of Obstetricians and Gynecologists guidelines for the timing of scheduled cesarean delivery in patients of a resident teaching service and patients of a private service to determine the neonatal intensive care unit admission rate and the most frequent admission diagnoses after scheduled cesarean delivery and to compare neonatal outcomes between the groups. STUDY DESIGN: A retrospective cohort was reviewed by medical record at a tertiary care center. The cases of 609 patients who were delivered by scheduled cesarean delivery were reviewed, and 296 patients were included. Data regarding demographics, dating, delivery, and outcome were collected and compared with the use of statistical software. RESULTS: Significant differences were noted between patients of a teaching service and patients of a private service, with respect to patient age (26.9 vs 30.7 years; P < .001), body mass index (33.7 vs 31.9 kg/m2; P = .030), race (40.4% white patients in resident teaching services vs 86.0% white patients in private services; P < .001), primary elective cesarean delivery (4 vs 23 deliveries; P = .013), and adherence to American College of Obstetricians and Gynecologists guidelines for the timing of elective delivery (96.3% vs 62%; P < .001), with no significant difference in number of neonatal intensive care unit admissions, severity of neonatal disease, or length of stay in the neonatal intensive care unit. The overall neonatal intensive care unit admission rate for all deliveries by scheduled cesarean delivery was 3.7%. The most frequent neonatal intensive care unit admission diagnoses were hypoglycemia and transient tachypnea of the newborn infant, with no severe sequelae of prematurity in either group. When controlled for fetal anomalies and infants who were born to pregestational diabetic mothers, no significant differences in number of admissions or outcomes were noted; however, 50% of the admissions to the neonatal intensive care units in both groups resulted from violations in American College of Obstetricians and Gynecologists criteria. CONCLUSION: The overall neonatal intensive care unit admission rate after scheduled cesarean delivery in this study is consistent with that reported in the neonatology literature. Patients of a teaching service were a demographically different group than those on the private service, were less likely to get an elective primary cesarean delivery, and were more likely to be delivered in adherence to American College of Obstetricians and Gynecologists guidelines, although this did not significantly affect the rates of admission to the neonatal intensive care unit or neonatal outcome.

Adolescent↗

The newborn drug development initiative workshop: Summary proceedings from the neurology group on neonatal seizures.

BACKGROUND: The neonatal period eclipses all other epochs of the human life span for the highest incidence of seizures. Neonatal seizures are most commonly incited by serious acute illnesses such as hypoxic-ischemic encephalopathy, birth trauma, or infection. OBJECTIVE: The goal of this article was to summarize some of the Neurology Group's discussion on neonatal seizures and their treatment with phenobarbital (PB). METHODS: Information for this article was gathered from a workshop held March 29 and 30, 2004, in Baltimore, Maryland, as part of the Newborn Drug Development Initiative. A group of national experts was invited to form the Neurology Group to review certain aspects of neonatal seizures. Literature reviews were conducted using MEDLINE searches for original research studies, commentaries, and review articles between 1980 and 2004 using the key words neonatal seizures, treatment, and phenobarbital. RESULTS: It has been empirically established that infants who experience seizures face substantially higher mortality and morbidity rates than those who do not. Basic research indicates that neonatal seizures themselves are not innocuous and actively contribute to adverse neurodevelopmental outcomes. Current worldwide clinical practice most often includes empiric treatment with PB for definite or suspected seizures in the newborn. Unfortunately, this common practice has never been proven by even a single, rigorous, randomized controlled trial. The Neurology Group identified the treatment of neonatal seizures with PB as an important topic in the practice of neonatal neurology for further investigation. Three possible frameworks for ethically acceptable, clinical treatment trials were explored. From these, a suitable scenario was selected-an electroencephalographer-blinded study of PB versus placebo in a homogeneous group of newborns who are at high risk of developing early subclinical electroencephalographic neonatal seizures (ENSs). Prospective video-electroencephalogram monitoring performed immediately after an insult (such as major cardiac surgery for a serious congenital heart defect) would establish the presence and number of subclinical ENSs. For a brief period of time, neonates with subclinical ENSs would be randomized to PB (dosed to match the PB-binding characteristics of the individual) or placebo. Clear criteria for escape from the study to active treatment are defined. CONCLUSION: The investigation proposed here could refute or confirm the contemporary practice of PB administration as the first-line treatment of neonatal seizures.

Anticonvulsants↗

Effects of morphine analgesia in ventilated preterm neonates: primary outcomes from the NEOPAIN randomised trial.

BACKGROUND: Opioid analgesia is commonly used during neonatal intensive care. We undertook the Neurologic Outcomes and Pre-emptive Analgesia in Neonates (NEOPAIN) trial to investigate whether pre-emptive morphine analgesia decreases the rate of a composite primary outcome of neonatal death, severe intraventricular haemorrhage (IVH), and periventricular leucomalacia (PVL) in preterm neonates. METHODS: Ventilated preterm neonates (n=898) from 16 centres were randomly assigned masked placebo (n=449) or morphine (n=449) infusions. After a loading dose (100 microg/kg), morphine infusions (23-26 weeks of gestation 10 microg kg(-1) h(-1); 27-29 weeks 20 microg kg(-1) h(-1); 30-32 weeks 30 microg kg(-1) h(-1)) were continued as long as clinically justified (maximum 14 days). Open-label morphine could be given on clinical judgment (placebo group 242/443 [54.6%], morphine group 202/446 [45.3%]). Analyses were by intention to treat. FINDINGS: Baseline variables were similar in the randomised groups. The placebo and morphine groups had similar rates of the composite outcome (105/408 [26%] vs 115/419 [27%]), neonatal death (47/449 [11%] vs 58/449 [13%]), severe IVH (46/429 [11%] vs 55/411 [13%]), and PVL (34/367 [9%] vs 27/367 [7%]). For neonates who were not given open-label morphine, rates of the composite outcome (53/225 [24%] vs 27/179 [15%], p=0.0338) and severe IVH (19/219 [9%] vs 6/189 [3%], p=0.0209) were higher in the morphine group than the placebo group. Placebo-group neonates receiving open-label morphine had worse rates of the composite outcome than those not receiving open-label morphine (78/228 [34%] vs 27/179 [15%], p<0.0001). Morphine-group neonates receiving open-label morphine were more likely to develop severe IVH (36/190 [19%] vs 19/219 [9%], p=0.0024). INTERPRETATION: Pre-emptive morphine infusions did not reduce the frequency of severe IVH, PVL, or death in ventilated preterm neonates, but intermittent boluses of open-label morphine were associated with an increased rate of the composite outcome. The morphine doses used in this study decrease clinical signs of pain but can cause significant adverse effects in ventilated preterm neonates.

Analgesics, Opioid↗

Increased serum concentrations of soluble tumor necrosis factor receptors p55 and p75 in early onset neonatal sepsis.

Sepsis and pneumonia are major causes of morbidity and mortality in the neonatal period. The symptoms are variable and unspecific. So far, no reliable diagnostic test for neonatal infection has been found. In this study we measured serum levels of soluble tumor necrosis factor receptors (sTNFR) p55 and p75 in non-infected and infected neonates, and evaluated the diagnostic value of these mediators as tests for early detection of neonates with sepsis or pneumonia. Blood was collected on admission and after 3-4 days from 161 neonates consecutively admitted to the Neonatal Intensive Care Unit (NICU) during the first week of life. Twenty two neonates suffered from infection and 127 were classified as non-infected (controls). Samples were analyzed for p55 and p75, C-reactive protein (CRP) and white blood cell count with differential. Both preterm and term infected neonates had initially higher concentrations of p55 (both p <0.01) and p75 (p = 0.01 and p = 0.05, respectively) than controls. In non-infected neonates p55 levels decreased in the perinatal period, whereas p75 levels remained stable. Levels of both p55 and p75 decreased in neonates with infection during the perinatal period. CRP was a more specific parameter than p55 and p75 (CRP: 97%, p55: 65% and p75: 75%) whereas the sensitivity of all three parameters was at similar levels (CRP: 59%, p55: 70% and p75: 67%). We conclude that assessment of sTNFR may not improve accuracy in the diagnosis of early onset neonatal sepsis compared to the use of CRP.

Antigens, CD↗

Association between glucose-6-phosphate dehydrogenase deficiency and neonatal jaundice: interaction with multiple risk factors.

This nonconcurrent cohort study was carried out to evaluate the association of neonatal jaundice with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and its interactions with other risk factors. The G-6-PD enzyme activity of 12,379 neonates was screened by a semi-quantitative fluorometric assay and double-checked by a quantitative method to identify a G-6-PD deficient cohort of 333 neonates. Matched with these on birth date, sex and delivery hospital were a G-6-PD normal cohort of 653 neonates. Neonatal jaundice was defined by a peak serum bilirubin (PSB) level of > or = 15 mg/dl. A significant association between G-6-PD deficiency and neonatal jaundice was observed in male but not female neonates. There was an inverse dose-response relation between G-6-PD activity and neonatal jaundice among male neonates. Both hypoxia/asphyxia and maternal hepatitis B surface antigen (HBsAg) carrier status were associated with an increased risk of neonatal jaundice among G-6-PD deficient but not G-6-PD normal male neonates. Based on multiple regression analyses, an additively synergistic effect on PSB level and severe jaundice (PSB > or = 20 mg/dl) was observed for G-6-PD deficiency and maternal HBsAg carrier status.

Cohort Studies↗

Neonatal subglottic stenosis--incidence and trends.

OBJECTIVE/HYPOTHESIS: Neonatal subglottic stenosis is a known entity arising from endotracheal tube intubation. In the 1970s and 1980s, estimates of the incidence of subglottic stenosis were in the range of 0.9% to 8.3% of intubated neonates. Because of improved techniques of handling neonates who require ventilatory support, we thought the actual incidence of neonatal subglottic stenosis in the late 1990s was much lower. STUDY DESIGN: We retrospectively reviewed all neonatal intensive-care unit (NICU) admissions from 1997 at our institution, which serves as a level 3 NICU. We also performed a MEDLINE search of the reported incidence of neonatal subglottic stenosis between 1960 and 1999. METHODS: Analysis was performed to identify all children who developed subglottic stenosis at our institution. Data were also collected and analyzed with regard to average gestational age, average birth weight, average duration of intubation, and the number of children requiring tracheostomy. The reports identified in the literature were reviewed as to the incidence of subglottic stenosis. RESULTS: A total of 544 neonates were admitted to the unit. Of these, 281 were intubated for an average of 11 days. No patients developed subglottic stenosis. Three patients required tracheostomies for other reasons. All studies published after 1983 reported an incidence of neonatal subglottic stenosis as less than 4.0%, and all studies published after 1990 reported an incidence of neonatal subglottic stenosis as less than 0.63%. CONCLUSIONS: Although our report applies to only a single institution in a single year, after reviewing the literature we think a downward trend exists in the incidence of neonatal subglottic stenosis in the late 1990s. The current incidence of neonatal subglottic stenosis is likely between 0.0% and 2.0%.

Birth Weight↗

Gram-negative bacilli associated with catheter-associated and non-catheter-associated bloodstream infections and hand carriage by healthcare workers in neonatal intensive care units.

OBJECTIVE: Bloodstream infections caused by Gram-negative bacilli are a substantial cause of morbidity and mortality in infants in neonatal intensive care units. This study describes the species of Gram-negative bacilli causing bloodstream infections in two neonatal intensive care units, compares characteristics of catheter-related and non-catheter-related bloodstream infections, and compares species and antibiotic resistance patterns of these organisms with those isolated from the hands of nurses working in the same neonatal intensive care units. DESIGN: Interventional study. SETTING: Two high-risk neonatal intensive care units. PATIENTS: Neonates hospitalized for >or =24 hrs. INTERVENTIONS: Prospective surveillance for bloodstream infections was performed in two neonatal intensive care units from March 2001 to January 2003. Hand cultures were obtained quarterly from participating nurses immediately after they performed hand hygiene. MEASUREMENTS AND MAIN RESULTS: There were 298 episodes of bloodstream infections among 2,935 admissions (5.75 episodes per 1,000 patient-days); 77 of 298 (26%) episodes were caused by Gram-negative bacilli. Among these, 47 (61.0%) were catheter-related bloodstream infections (2.61 episodes per 1,000 catheter-days). Eleven and 24 Gram-negative bacilli species were isolated from neonates and nurses, respectively. The most common Gram-negative bacilli causing bloodstream infections were Klebsiella pneumoniae (38.7%), Escherichia coli (21.2%), Enterobacter cloacae (11.2%), and Serratia marcescens (11.2%). In contrast, Acinetobacter lwoffi (18.1%), K. pneumoniae (11.7%), E. cloacae (10.6%), K. oxytoca (10.6%), and Pseudomonas spp. (7.4%) were most commonly isolated from hands of nurses. E. coli, P. aeruginosa, E. cloacae, and E. aerogenes were significantly more likely to cause bloodstream infections than to be isolated from nurses' hands (all p < .001). Although 39% of bloodstream infections were non-catheter-related, there were no significant differences in types of organisms or antimicrobial resistance patterns between catheter-related bloodstream infections and non-catheter-related bloodstream infections (all p > or = .35). Resistance patterns were similar between Gram-negative bacilli isolates from neonates and nurses' hands except for a significantly higher proportion of resistance to cefotaxime and gentamicin among neonatal isolates of K. pneumoniae (p < .05). CONCLUSIONS: Gram-negative bacilli species isolated from neonatal bloodstream infections and nurses' hands varied significantly. Clean hands of providers are an unlikely source of endemic Gram-negative bacilli, suggesting that prevention strategies should focus more on control of endogenous neonatal flora or environmental sources.

Bacteremia↗