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PubMed2001

Onset of jaundice in glucose-6-phosphate dehydrogenase-deficient neonates.

OBJECTIVE: We asked whether neonatal jaundice associated with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency commences either in utero or in the immediate postnatal period and whether this perinatal bilirubinemia is the precursor of the subsequent neonatal jaundice and hyperbilirubinemia. METHODS: Mandatory serum total bilirubin (STB) determinations were performed within 3 hours of birth, to reflect the in utero state (first STB), and on the third day of life (second STB), with additional determinations as clinically necessary, on healthy, term male neonates at high risk for G-6-PD deficiency. G-6-PD Mediterranean mutation was determined by molecular means. G-6-PD-deficient neonates were compared with control participants. The relationship of first STB values to second STB and subsequent hyperbilirubinemia (defined as STB >/=256 micromol/L [15.0 mg/dL]) was determined. RESULTS: Both first and second STB values were significantly higher in the G-6-PD-deficient neonates (n = 52) than in control participants (n = 166; 50 +/- 12 micromol/L vs 44 +/- 10 micromol/L [2.9 +/- 0.7 mg/dL vs 2.6 +/- 0.6 mg/dL] and 174 +/- 52 micromol/L vs 152 +/- 52 micromol/L [10.2 +/- 3.1 mg/dL vs 8.9 +/- 3.0 mg/dL] for the first and second STB values, respectively). The rate of rise between these 2 points was greater in the G-6-PD-deficient neonates (2.6 +/- 0.9 micromol/L/h vs 2.2 +/- 0.9 micromol/L/h [0.15 +/- 0.05 mg/dL/h vs 0.13 +/- 0.05 mg/dL/h). Sixteen (30.8%) of the G-6-PD-deficient neonates developed hyperbilirubinemia compared with 10 (6%) of control participants (relative risk: 5.11; 95% confidence interval: 2.47-10.56). In both G-6-PD-deficient and normal populations, first STB values correlated significantly with both second STB values and with those who subsequently developed hyperbilirubinemia. Significantly more G-6-PD-deficient neonates with a first STB value greater than or equal to the mean developed hyperbilirubinemia compared with those with first STB less than the mean: 13 of 28 neonates versus 3 of 24 (relative risk: 3.7; 95% confidence interval: 1.20-11.51). This difference did not reach statistical significance in the control group. CONCLUSIONS: Higher first STB values, an increased risk of hyperbilirubinemia in G-6-PD-deficient neonates with first STB value greater than or equal to the mean, and significant correlation between first STB values and second STB values and hyperbilirubinemia suggest that jaundice in G-6-PD-deficient neonates commences in the immediate perinatal period, most likely in utero.

Bilirubin↗
PubMed2003

Extrauterine growth restriction remains a serious problem in prematurely born neonates.

BACKGROUND: Poor growth is a common problem in premature neonates and may be associated with neurodevelopmental delay. OBJECTIVE: To evaluate the incidence of extrauterine growth restriction (growth values < or =10th percentile of intrauterine growth expectation based on estimated postmenstrual age in premature (23-34 weeks' estimated gestational age) neonates at the time they are discharged from the hospital. DESIGN/METHODS: Using a database formed from a computer-assisted tool that generates clinical progress notes and discharge summaries on neonatal intensive care unit admissions, we reviewed data on neonates discharged from 124 neonatal intensive care units between January 1, 1997, and December 31, 2000. We evaluated neonates who were born between 23 and 34 weeks' estimated gestational age without congenital anomalies and who were cared for at and discharged from the same hospital. For each patient, we compared the discharge growth values to the expected values based on our intrauterine growth data and postmenstrual age on the day of discharge. We defined extrauterine growth restriction as having a measured growth value (weight, length or head circumference) that was < or =10th percentile of the predicted value. In each specific birth weight and estimated gestational age group, we counted the number of neonates < or =10th percentile for each growth parameter and calculated the percentage of patients who had values < or =10th percentile at discharge. Using logistic regression, we evaluated the factors associated with extrauterine growth restriction for weight, length, and head circumference. RESULTS: Our sample included 24 371 premature neonates. Data on discharge weight, length, and head circumference was available on 23 970, 17 203, and 20 885 neonates, respectively. The incidence of extrauterine growth restriction was common (28%, 34%, and 16% for weight, length, and head circumference, respectively). For each growth parameter, the incidence of extrauterine growth restriction increased with decreasing estimated gestational age and birth weight. Factors independently associated with extrauterine growth restriction were male gender, need for assisted ventilation on day 1 of life, a history of necrotizing enterocolitis, need for respiratory support at 28 days of age, and exposure to steroids during the hospital course. CONCLUSIONS: Extrauterine growth restriction remains a serious problem in premature neonates especially for neonates who are small, immature, and critically ill.

Apgar Score↗
PubMed1997

Neonatal screening for inborn errors of metabolism: cost, yield and outcome.

OBJECTIVES. To systematically review the literature on inborn errors of metabolism, neonatal screening technology and screening programmes in order to analyse the costs and benefits of introducing screening based on tandem mass-spectrometry (tandem MS) for a wide range of disorders of amino acid and organic acid metabolism in the UK. To evaluate screening for cystic fibrosis, Duchenne muscular dystrophy and other disorders which are tested on an individual basis. HOW THE RESEARCH WAS CONDUCTED. Systematic searches were carried out of the literature on inborn errors of metabolism, neonatal screening programmes, tandem MS-based neonatal screening technology, economic evaluations of neonatal screening programmes and psychological aspects of neonatal screening. Background material on the biology of inherited metabolic disease, the basic philosophy, and the history and current status of the UK screening programme was also collected. Relevant papers in the grey literature and recent publications were identified by hand-searching. Each paper was graded. For each disease an aggregate grade for the state of knowledge in six key areas was awarded. Additional data were prospectively collected on activity and costs in UK neonatal screening laboratories, and expert clinical opinion on current treatment modalities and outcomes. These data were used to construct a decision-analysis model of neonatal screening technologies, comparing tandem MS with the existing phenylketonuria screening methods. This model determined the cost per additional case identified and, for each disease, the additional treatment costs per case, and the cost per life-year saved. All costs and benefits were discounted at 6% per annum. One-way sensitivity analysis was performed showing the effect of varying the discount rate, the incidence rate of each disorder, the number of neonates screened and the cost of tandem MS, on the cost per life-year gained. RESEARCH FINDINGS. The UK screening programmes for phenylketonuria and congenital hypothyroidism have largely achieved the expected objectives and are cost-effective. Current concerns are the difficulty of maintaining adequate coverage, perceived organisational weaknesses, and a lack of overview. For many of the organic acid disorders it was necessary to rely on data obtained from clinically-diagnosed cases. Many of these diseases can be treated very effectively and a sensitive screening test was available for most of the diseases. Except for cystic fibrosis, there have been no randomised controlled trials of the overall effectiveness of neonatal screening. Despite the anxiety generated by the screening process, there is strong parental support for screening. The effects of diagnosis through screening on subsequent reproductive behaviour is less clear. Conflicts exist between current concepts and the traditional principles of screening. The availability of effective treatment is not an absolute prerequisite: early diagnosis is of value to the family concerned and, to the extent that is leads to increased use of prenatal diagnosis, may help to reduce the overall burden of disease. Neonatal screening is also of value in diseases which present early but with non-specific symptoms. Indeed, almost all of the diseases considered could merit neonatal screening. The majority of economic evaluations failed to incorporate the health benefits from screening, and therefore failed to address the value of the information which the screening programmes provided to parents. The marginal cost of changing from present technology to tandem MS would be approximately 0.60 pounds per baby at a workload of 100,000 samples a year, and 0.87 pounds at 50,000 samples per year. The ability to screen for a wider range of diseases would lead to the identification of some 20 additional cases per 100,000 infants screened, giving a laboratory cost per additional diagnosis of 3000 pounds at an annual workload of 100,000 babies per year.(ABSTRACT TRUNCATED)

Cost-Benefit Analysis↗
PubMed2003

Kangaroo care is effective in diminishing pain response in preterm neonates.

OBJECTIVE: To test the efficacy of maternal skin-to-skin contact, or kangaroo care (KC), on diminishing the pain response of preterm neonates to heel lancing. DESIGN: A crossover design was used, in which the neonates served as their own controls. Subjects Preterm neonates (n = 74), between 32 and 36 weeks' postmenstrual age and within 10 days of birth, who were breathing without assistance and who were not receiving sedatives or analgesics in 3 level II to III neonatal intensive care units in Canada. INTERVENTIONS: In the experimental condition, the neonate was held in KC for 30 minutes before the heel-lancing procedure and remained in KC for the duration of the procedure. In the control condition, the neonate was in the prone position in the isolette. The ordering of conditions was random. MAIN OUTCOME MEASURES: The primary outcome was the Premature Infant Pain Profile, which is composed of 3 facial actions, maximum heart rate, and minimum oxygen saturation changes from baseline in 30-second blocks. Videotapes, taken with the camera positioned on the neonate's face so that an observer could not tell whether the neonate was being held or was in the isolette, were coded by research assistants who were naïve to the purpose of the study. Heart rate and oxygen levels were continuously monitored into a computer for later analysis. A repeated-measures analysis of covariance was used, with order of condition and site as factors and severity of illness as a covariate. RESULTS: Premature Infant Pain Profile scores across the first 90 seconds from the heel-lancing procedure were significantly (.002<P<.04) lower by 2 points in the KC condition. CONCLUSIONS: For preterm neonates who are 32 weeks' postmenstrual age or older, KC seems to effectively decrease pain from heel lancing. Further study is needed to determine if younger neonates or those requiring assistance in breathing, or older infants or toddlers, would benefit from KC, or if it would remain effective over several procedures. Given its effectiveness, and that parents of neonates in critical care units want to participate more in comforting their children, KC is a potentially beneficial strategy for promoting family health.

Blood Specimen Collection↗
PubMed2003

Granulocyte transfusions for neonates with confirmed or suspected sepsis and neutropaenia.

BACKGROUND: Neonatal sepsis causes significant neonatal mortality and morbidity. Neonates, especially preterm infants, have an immaturity of granulopoeisis and have a limited capacity for progenitor cell proliferation. This results in the frequent occurrence of neutropaenia in septic neonates. Neutropaenic septic neonates have a higher mortality than neonates who are septic but not neutropaenic. Transfusion of granulocytes to septic neutropaenic neonates, therefore, may help reduce mortality and morbidity. OBJECTIVES: The primary objective of this review was to determine the efficacy and safety of granulocyte preparations (granulocyte and buffy coat transfusions) as adjuncts to antibiotics for the treatment of confirmed or suspected sepsis in neonates with neutropaenia in reducing all-cause mortality during hospital stay and adverse neurological outcome at a year of age or later. Secondary objectives were to determine the effects of granulocyte transfusions on length of hospital stay in survivors to discharge, adverse effects (fluid overload, transmission of blood borne infections, pulmonary complications and sensitisation to donor leukocyte antigens) and immunologic outcomes at a year of age or later. SEARCH STRATEGY: Searches for eligible trials were made in September 2002 of the following electronic databases: The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2002), MEDLINE, EMBASE, CINAHL. The proceedings of the Pediatric Academic Societies, which were published in the journal, Pediatric Research, were searched from 1987 onwards. The Cambridge Database of Scientific Abstracts (1982 onwards) and Dissertation Abstracts on disc (1960 onwards) were also searched. Communications with prominent authors in the field and additional searches in the reference lists of identified trials were performed SELECTION CRITERIA: Randomised and quasi-randomised studies were included, if the participants were neonates with suspected or confirmed sepsis and neutropaenia who received granulocyte preparations (granulocyte concentrates prepared by leukophoresis or buffy coat transfusions prepared by simple centrifugation of blood) at any dose or duration compared with placebo or no granulocyte transfusion, each as adjuncts to antibiotics or compared to other adjuncts to antibiotics to treat sepsis (e.g. intravenous immunoglobulin). Studies were included if any of the following outcomes were reported: all-cause mortality during hospital stay, neurological outcome at one year of age or later, length of hospital stay in survivors at discharge, adverse effects or immunological outcome at one year or later DATA COLLECTION AND ANALYSIS: Trials identified by the search strategy were assessed for eligibility for inclusion in the review. Full text versions of the eligible trials were obtained. Data of interest were extracted on paper forms. Relative risk (RR) and risk difference (RD) with 95% confidence intervals using the fixed effects model were reported for dichotomous outcomes. Pre-specified subgroup analyses were done and reported. MAIN RESULTS: Four eligible studies were identified. A total of 44 infants with sepsis and neutropaenia on antibiotics were randomised in three trials to granulocyte transfusions OR placebo/no transfusion. In another trial, 35 infants with sepsis and neutropaenia on antibiotics were randomised to granulocyte transfusion or intravenous immunoglobulin. When granulocyte transfusions were compared with placebo or no transfusion, there was no significant difference in all-cause mortality [typical RR 0.89 (95% CI 0.43, 1.86), typical RD -0.05 (95% CI -0.31, 0.21)]. There was no statistical heterogeneity in the results of the included trials. When granulocyte transfusions were compared with intravenous immunoglobulin, there was a reduction in all-cause mortality of borderline statistical significance [RR 0.06 (95% CI 0.00, 1.04), RD -0.34(95% CI -0.60, -0.09), NNT 2.9 (95% CI 1.7, 11.1)]. Pulmonary complication, seen in four infants (4%), was the only adverse effect reported. This adverse effect was noticed in the two trials which used buffy coat transfusions. None of the trials reported on neurological outcome at one year of age or later, length of hospital stay in survivors to discharge or immunological outcome at one year of age or later. REVIEWER'S CONCLUSIONS: Currently, there is inconclusive evidence from RCTs to support or refute the routine use of granulocyte transfusions in neonates with sepsis and neutropaenia to reduce mortality and morbidity. Researchers can be encouraged to conduct adequately powered multicentre trials of granulocyte transfusions to clarify their role in neonates with sepsis and neutropaenia. Other adjuncts to antibiotics aimed at improving host defence mechanisms such as colony stimulating factors, IVIG and pentoxifylline should also be tested in RCTs.

Granulocytes↗
PubMed2006

Breastfeeding or breast milk for procedural pain in neonates.

BACKGROUND: Physiological changes brought about by pain may contribute to the development of morbidity in neonates. Clinical studies have shown reduction in the changes in physiological parameters and pain score measurements following pre-emptive analgesic administration in situations where the neonate is experiencing pain or stress. Nonpharmacological measures (such as holding, swaddling, breastfeeding) and pharmacological measures (such as acetaminophen, sucrose and opioids) have been used for this purpose. OBJECTIVES: The primary objective of this review was to evaluate the effectiveness of breastfeeding or supplemental breast milk in reducing procedural pain in neonates. The secondary objective was to conduct subgroup analyses based on the type of control intervention, type of painful procedure, gestational age and the amount of supplemental breast milk given. SEARCH STRATEGY: A literature search was performed using MEDLINE (1966 - Feb 2006), EMBASE (1980 - Feb 2006), CINAHL (1982 - Feb 2006), Cochrane Central Register of Controlled Trials (Issue 4, 2005 of Cochrane Library), abstracts from the annual meetings of the Society for Pediatric Research (1994 - 2006) and major pediatric pain conference proceedings. No language restrictions were applied. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials of breastfeeding or supplemental breast milk versus no treatment/other measures in neonates were eligible for inclusion in this review. The study must have reported on either physiologic markers of pain or validated pain scores. DATA COLLECTION AND ANALYSIS: The methodological quality of the trials was assessed using the information provided in the studies and by personal communication with the authors. Data on relevant outcomes were extracted and the effect size was estimated and reported as relative risk (RR), risk difference (RD) and weighted mean difference (MD) as appropriate. MAIN RESULTS: Eleven eligible studies were identified. Marked heterogeneity in terms of control intervention and pain assessment measures were noted among the studies. Neonates in the breastfeeding group had statistically significantly less increase in the heart rate, reduced proportion of crying time and reduced duration of crying compared to swaddled group or pacifier group. Neonates in the breastfeeding group had a significant reduction in duration of crying compared to fasting (no intervention) group, but there was no significant difference when compared to glucose group. Premature Infant Pain Profile scores were significantly different between the breastfeeding group when compared to placebo group and the group positioned in mother's arms. However, these scores were not statistically significantly different in the breastfeeding group when compared to the no treatment group and the glucose group. Douleur Aigue Nouveau-ne scores were significantly different in the breastfeeding group when compared to the placebo group and the group positioned in mother's arms, but not when compared to the glucose group. Neonates in the supplemental breast milk group had significantly less increase in the heart rate and Neonatal Facial Coding Score compared to the placebo group. The differences in the duration of crying time and oxygen saturation change between supplemental breast milk group and the placebo group were not statistically significant. Neonates in the supplemental breast milk group had significantly higher increase in the heart rate changes and duration of crying time compared to glucose/sucrose group. No study was identified that has evaluated safety/effectiveness of repeated administration of breastfeeding or supplemental breast milk for pain relief. AUTHORS' CONCLUSIONS: If available, breastfeeding or breast milk should be used to alleviate procedural pain in neonates undergoing a single painful procedure compared to placebo, positioning or no intervention. Administration of glucose/sucrose had similar effectiveness as breastfeeding for reducing pain. The effectiveness of breast milk for repeated painful procedures is not established and further research is needed. These studies should include various control interventions including glucose/ sucrose and should target preterm neonates.

Breast Feeding↗
PubMed1993

Abnormalities of the neonatal ear: otoscopic observations, histologic observations, and a model for contamination of the middle ear by cellular contents of amniotic fluid.

It is unknown whether childhood ear disease could be present long before symptoms provoke an initial otoscopic examination. A newborn middle ear might or might not start in a pristine, privileged state. The clinician evaluating later infant and childhood ear disease is often unaware of the status of a patient's ear from the neonatal period, the earliest time at which the tympanic membrane can be evaluated. Adding to the physician's handicap, normative otoscopic and histologic data on the neonatal ear are incomplete. In order to test the hypothesis that disease in the neonatal middle ear may be more common than is generally appreciated, the population of critically ill neonates was selected for study since this group can provide both clinical as well as histologic data. This manuscript is divided into three parts. Clinically, otoscopic observations were analyzed on infants in an intensive care unit. Histologically, neonatal temporal bones were studied for normal anatomy and pathology of the middle ear and antrum. Experimentally, an animal study was performed to evaluate the potential effect of amniotic fluid cellular contents aspirated into the middle ear. I. Clinical Otoscopic Observations. Daily otoscopic examination was conducted on 44 neonates in an intensive care unit. Specific parameters of the otoscopic examination were evaluated to compare with the normal, translucent tympanic membrane of the older child. The otoscopic appearance was found to be abnormal in 97.7% of neonatal ears. Of the otoscopic parameters evaluated, right ears averaged 2.6 abnormalities and left ears averaged 2.5 otoscopic abnormalities. The otoscopic appearance of the neonate in the neonatal intensive care unit is nearly universally abnormal. II. Temporal Bone Histologic Observations. One hundred eleven temporal bones from 56 neonates were collected for histologic study by light microscopy. Mesenchyme filling more than 60% of the middle ear space was found in 13 bones. Amniotic fluid cellular content was detected in 90 bones. Purulent otitis media was detected in 24 bones. Varying amounts of blood were found in the middle ear space of 34 bones. Only 7 of the bones had no significant middle ear abnormality. It is concluded that in the critically ill neonate, the middle ear and antrum usually contain cellular or fluid material, often in significant volume, that would not be considered normal in the older patient. III. An Animal Model Simulating Contamination of the Middle Ear by Cellular Contents of Amniotic Fluid.(ABSTRACT TRUNCATED AT 400 WORDS)

Amniotic Fluid↗
PubMed1978

The pharmacokinetics and metabolism of the anilide local anaesthetics in neonates. I. Lignocaine.

The pharmacokinetics and metabolism of lignocaine in premature neonates was studied after subcutaneous administration. The collection of serial urine together with a limited number of blood samples from neonates enabled simultaneous computer fitting of data to a pharmacokinetic model. The disposition kinetics of lignocaine in four neonates were compared with similar data reported for adults. Neonates had prolonged t1/2 (neonate mean: 3.16 h; adult mean: 1.80 h), and an increased total volume of distribution (neonate mean: 2.75 l/kg; adult mean: 1.11 l/kg) compared with adults. Total plasma clearance (Cltp) normalised on body weight showed no significant difference between neonates (mean: 0.610 l/h/kg) and adults (mean: 0.550 l/h/kg). The urinary excretion of lignocaine and several of its metabolites was studied in 8 neonates and 11 adults. Neonates were shown to excrete much more unchanged lignocaine (mean: 19.67%) compared with adults (mean: 4.27%) and the proportion of the dose excreted as 4-hydroxyxylidine is considerably reduced in neonates (neonate mean: 8.89%; adult mean: 63.78%). The use of the two pharmacokinetic parameters, t1/2 and Cltp, as indices of drug elimination ability are discussed.

Adult↗
PubMedDate not supplied

Zinc and copper in preterm neonates: relationship with breast milk.

The study was conducted to assess copper and zinc levels in neonate's serum, mother's serum, neonate's hair and urine and to ascertain association between them. It is of concern whether zinc and copper deficiency is present at birth and maternal blood and breast milk zinc and copper levels have any effect on this. The study sample included 155 neonates with gestational age 26-41 wks and birth weight 0.550-3.800 kg. Mother's serum, breast milk, neonate's serum, hair, urine samples were analysed for zinc and copper by atomic absorption spectrophotometry. Gestational age was estimated either singly or by combination of date of last normal menses, fetal ultrasonography, and postnatal measures of physical and neurological development by clinical examination and weight by Secca electronic balance. The neonates were classified into term and preterm, small (SGA) and appropriate for gestational age (AGA). Neonates over 37 wks and 2.5 kg served as controls. To assess the dependency, relationship and effectiveness of quantitative predictive variables on the predictions of values, multiple regression analysis was used. Neonates between 26-30 wks gestational age and < 2.5 kg birth weight had significantly low serum zinc and copper. Breast milk zinc was low in mothers delivering preterm and < 2.5 kg neonates. Urinary copper and zinc levels were high in preterm appropriate for gestational age (Pre AGA) than term neonates. Multiple regression analysis revealed that neonate's serum Cu, serum Zn, hair Cu, hair Zn, urine Cu and urine Zn had contribution variability of 49.8%, 51.8%, 49.2%, 16.6%, 52.2% and 68.9%, respectively. The effect of mother's serum, breast milk, and neonate's serum copper and zinc collectively was significant for serum copper (F = 29.59) and hair zinc (F = 32.03). Preterm and low birth weight infants during subsequent growth and development should be supplemented with zinc and copper when on breast feeding.

Copper↗
PubMed1998

Changes in urinary 6beta-hydroxycortisol/cortisol ratio after birth in human neonates.

OBJECTIVE: Urinary 6beta-hydroxycortisol/cortisol (6beta-OHF/C) ratio was measured in human neonates to assess the CYP3A enzyme activity. METHODS: Urinary 6beta-OHF/C ratio was determined on the day of birth in 94 neonates including those born prematurely. In addition, changes in the ratios after birth were also determined in 81 neonates. RESULTS: On the day of birth, a significant positive correlation was found between urinary 6beta-OHF/C ratios and gestational age (r = 0.476) and birth weight (r = 0.283). There was no gender difference in the urinary 6beta-OHF/C ratios in human neonates. Furthermore, delivery modes such as cesarean section and vaginal delivery did not appear to affect the urinary 6beta-OHF/C ratio. The mean ratio of urinary 6beta-OHF/C observed in 39 mature neonates (more than 37 weeks of gestational age) was higher than that observed in adults (16.5 vs 9.9). Within 5 days after birth, the ratio rapidly decreased to less than that in adults. In contrast, the mean ratio of urinary 6beta-OHF/C observed in 42 premature neonates (under 37 weeks of gestational age) was significantly lower than that observed in mature neonates (5.3 vs 16.5) and was virtually unchanged during the 14-days after birth. Therefore, no significant difference was observed in the mean ratio of urinary 6beta-OHF/C between mature and premature neonates at 5 days after birth. CONCLUSION: From these results, it was concluded that on the day of birth, mature neonates might possess a higher activity of CYP3A enzyme compared with premature neonates, and that the CYP3A enzyme activity in mature neonates might be promptly changed at an early stage after birth.

Aryl Hydrocarbon Hydroxylases↗
PubMed2006

Risk factors for early neonatal sepsis.

OBJECTIVE: The aim of this study was to identify maternal risk factors for early neonatal sepsis and perinatal outcome in a population of very low birth-weight newborns. STUDY DESIGN: During January 1995 to December 2000, 786 live preterm neonates were born in our institute with birth-weight < or =1,500 g. A cross-sectional study was designed and two groups were identified: 50 neonates who developed early neonatal sepsis and 736 neonates without early sepsis. RESULTS: The prevalence of early sepsis among the neonates was 6.3% (50/786). The following maternal risk factors were significantly associated with early neonatal sepsis: advanced maternal age, high gravidity, the administration of multiple courses of prenatal steroids and tocolytic agents, (i.e., magnesium and indomethacin) and chorioamionitis with premature rupture of membranes. Using a multivariate analysis, the use of tocolytic drugs was found as an independent risk factor for early neonatal sepsis (OR=4.8; 95% CI 1.1-1.6; P=0.019) and so was low gestational age (OR 0.98; 95% CI 0.007-0.017; P=0.017). The following variables of the neonate were significantly associated with early neonatal sepsis: low birth-weight, umbilical blood pH of less than 7.2 and the use of oxygen. CONCLUSIONS: The use of tocolytic drugs and low gestational age are independent risk factors for early neonatal sepsis.

Cross-Sectional Studies↗
PubMed1997

Hyporeactivity of neonatal platelets is not caused by preactivation during birth.

UNLABELLED: Little information exists concerning platelet function in neonates due to the small blood volume. Most studies using conventional aggregation methods have shown a diminished response to various agonists. This is in contrast to the lack of a bleeding tendency and to a short bleeding time in healthy neonates. In previous work we have shown that in healthy term neonates even after an uncomplicated delivery signs of thrombin generation can be demonstrated. This activation of the clotting system may also lead to platelet activation in the neonate. We investigated by means of flow cytometry the expression of activation markers GMP 140 and GP 53 on the surface of neonatal platelets and GP 53 intracellularly by means of a newly developed assay. The expression of GMP 140 and of GP 53 after thrombin stimulation was significantly higher on adult rather than neonatal platelets, while there was no difference between neonatal and adult platelets using GP 53 as intracellular marker. In none of the healthy term neonates after an uncomplicated delivery were activated platelets demonstrated. CONCLUSION: Our data show that the decreased reactivity of neonatal platelets is not caused by preactivation during birth but rather represents a developmental phenomenon. Possibly the observed hyporeactivity of neonatal platelets to thrombin helps to prevent harmful effects of birth stress on the clotting system of neonates.

Antigens, CD↗
PubMed1984

Abnormal bile acid pool and composition in neonates of spontaneously diabetic Wistar BB rats and its change during development.

Streptozotocin-induced diabetes during pregnancy in rats causes a decrease in primary bile acid pool in neonates. To rule out direct drug effect on the fetus as the basis for this change, studies of bile acid pool and composition at birth and during subsequent development was carried out in neonates of spontaneously diabetic Wistar BB rats and compared to control neonates. The cholic acid pool in neonates of diabetic rats was lower when compared to control neonates at birth. The pool of secondary bile acids was markedly increased in neonates of diabetic rats, with increases in lithocholic and 3 beta,12 alpha-dihydroxycholanoic acid. With age, the cholic acid pool of neonates from diabetic rats was increased and at 3 months of age it was actually higher than in control neonates. The pool of chenodeoxycholic at diabetes onset age was lower in neonates of diabetic rats. HDL-cholesterol was lower in neonates of diabetic rats at 1 week, but this reversed at 3 months of age. These studies firmly establish that neonates of diabetic rats have abnormal bile acid pool and composition at birth which changes to adult diabetic pattern with age.

Age Factors↗
PubMed2005

The neonate-6-hydroxydopamine-lesioned rat: a model for clinical neuroscience and neurobiological principles.

In 1973, a technique of administering 6-hydroxydopamine (2,4,5-trihydroxyphenylethylamine) intracisternally to neonate rats was introduced to selectively reduce brain dopamine (neonate-lesioned rat). This neonate treatment proved unique when compared to rats lesioned as adults with 6-hydroxydopamine--prompting the discovery of differing functional characteristics resulting from the age at which brain dopamine is reduced. A realization was that neonate-lesioned rats modeled the loss of central dopamine and the increased susceptibility for self-injury in Lesch-Nyhan disease, which allowed identification of drugs useful in treating self-injury in mentally retarded patients. The neonate-lesioned rat has also been proposed to model the hyperactivity observed in attention-deficit hyperactivity disorder. Because the neonate-lesioned rat exhibits enhanced sensitization to repeated NMDA receptor antagonist administration and has functional changes characteristic of schizophrenia, the neonate lesioning is believed to emulate the hypothesized NMDA hypofunction in this psychiatric disorder. Besides modeling features of neurological and psychiatric disorders, important neurobiological concepts emerged from pharmacological studies in the neonate-lesioned rats. One was the discovery of coupling of D1/D2-dopamine receptor function. Another was the progressive increase in responsiveness to repeated D1-dopamine agonist administration referred to as "priming" of D1-dopamine receptor function. Additionally, a unique profile of signaling protein expression related to neonate reduction of dopamine has been identified. Thus, from modeling characteristics of disease to defining adaptive mechanisms related to neonatal loss of dopamine, the neonate-lesioned rat has had a persisting influence on neuroscience. Despite an extraordinary legacy from studies of the neurobiology of this treatment, a host of unknowns remain that will inspire future investigations.

Age Factors↗
PubMed2003

Delivery modes and neonatal EEG: spatial pattern analysis.

BACKGROUND: Animal studies indicate that postnatal adaptation and development of neonates could be different due to the birth method and that these effects may last throughout adulthood. STUDY DESIGN: We applied a spatio-temporal analysis to EEG recordings of a group of neonates to investigate the influence of a cesarean section on maturation and extrauterine adaptation of the brain. EEG were recorded at 2 h and at 24 h after delivery. SUBJECTS: A spectral analysis technique, the so-called Karhunen-Loeve (KL) method, was applied to EEG of 10 neonates from vaginal delivery and 17 from C-section to obtain the spatio-temporal eigenpatterns. RESULTS: Spatio-temporal analysis showed noticeable pattern differences between the two groups. Compared to the C-section, the vaginal delivered neonate's EEG recordings showed a significant increase of amplitude at Fp1 in the pattern 24 h after the delivery, but not 2 h after delivery. Dynamics in this spectral analyses were not significantly different between both groups 2 h after delivery, but the regional differences increased during the next day between both groups. CONCLUSIONS: This could come from the early insufficient complexity in C-section neonates. Global EEG complexity in C-section neonates fell short of that of vaginal delivered neonates 2 h after delivery. Many aspects of pattern change in C-section neonates followed the nature of vaginal delivered neonates. These could be considered as parts of a retarded transition of C-section neonates in the early adaptation, but some of the differences in global EEG pattern could not be explained in this way. Pattern analysis suggests that the neuronal activities of the neonatal brain are changing regionally concurrent with bi-hemispheric global dynamics. Moreover, the delivery modes could have an influence on the early postneonatal adaptation of the physiological activity in brain.

Adult↗
PubMed2005

Pharmacokinetics of antivirals in neonate.

BACKGROUND: About 1000 neonates with HIV infection are born every day worldwide. The antiviral therapy for newborn infants is a real necessity. Pharmacokinetics is an important contribution to therapy and no review has been published on the pharmacokinetics of antivirals in neonates up to now. AIMS: This article provides a review on the pharmacokinetics of antivirals in the neonate. The pharmacokinetic parameters in the neonate are compared with those of the adult, and when possible, the pharmacokinetic parameters were compared in neonates of different ages. RESULTS: Zidovudine is the antiviral with the largest amount of information on its pharmacokinetics. The clearance (Cl; l/h/kg) of zidovudine is 0.15 (premature), 0.34 (1 day), 0.69 (7 days), 0.65 (< or =14 days), 1.14 (>14 days) and 1.56 (adult). t(1/2) (h) of zidovudine is 7.2 (premature), 4.2 (1 day), 4.0 (7 days), 3.1 (< or =14 days), 1.9 (>14 days) and 1.1 (adult). Zidovudine is mainly eliminated by conjugation with glucuronic acid and glucuronosyl transferase develops postnatally. Cl of lamivudine is 0.19 (1 day), 0.32 (7 days) and 0.30 (adult) and the Cl (l/h/m2) of didanosine is 65 (1 day) and 271 (7 days). A greater volume of distribution (Vd) has been observed in the neonate compared with the adult for nelfinavir, nevirapine and pleconaril. CONCLUSIONS: The pharmacokinetic parameters of antivirals differ in the neonate and in the adult. The Cl is reduced and t(1/2) is increased in the neonate compared with the adult for zidovudine, lamivudine and ganciclovir. t(max) is generally greater in the neonate than in the adult due to reduced absorption rate in the neonate. The Vd of nelfinavir, nevirapine and pleconaril is greater in the newborn than in the adult. The neonate is a developing organism and the pharmacokinetic parameters of antivirals vary during the first weeks of life.

Antiviral Agents↗
PubMed1998

Rehospitalizations and outpatient contacts of mothers and neonates after hospital discharge after vaginal delivery.

OBJECTIVE: Our purpose was to determine whether length of hospital stay after vaginal delivery as determined by the discharging physician is associated with rehospitalizations or increased outpatient contacts by mothers and neonates and to assess the impact of home health care visits. STUDY DESIGN: An inception cohort study of all rehospitalizations and outpatient contacts of mothers and neonates after vaginal delivery at St. Joseph Hospital, Denver, Colorado, was done from January 1, 1994, to September 30, 1995. All Kaiser Permanente mother-neonate pairs in which the delivery was vaginal (excluding those with multiple gestations or birth weight < 2500 g) were included. Length of initial hospital stay was divided into three time periods: < or = 24 hours, 25 to 48 hours, and > 48 hours. The Colorado Kaiser Permanente Perinatal Database was used to identify perinatal and demographic factors that might have increased health care use. Additional information was sought in administrative databases, bill records, and inpatient charts. Mothers were followed up for 6 weeks and neonates for 28 days after delivery. Home care visits were provided to more than half the mothers and neonates by means of a standardized protocol. The main outcome measures were rehospitalizations and outpatient visits for mothers and neonate, controlling for home care visits. RESULTS: A total of 4323 mother-neonate pairs were identified. For the mothers, a longer initial hospital stay (> 48 hours) was significantly associated with both readmission (P < .01) and increased outpatient care use (P = .01) in the 6-week postpartum period. Thirty-five mothers (.81%) were rehospitalized by 6 weeks. Maternal factors associated with increased outpatient contacts were preeclampsia, preterm delivery, and instrument delivery. Sixty-seven neonates (1.55%) were readmitted to the hospital. Home care visits reduced the need for both readmissions and outpatient visits. CONCLUSIONS: For mothers in this cohort a longer initial hospital stay was significantly associated with hospital readmission and increased outpatient care in the postpartum period. Further analysis revealed that mothers with recognized potential and observed problems were rarely discharged in < or = 24 hours. We did not find statistically significant problems among neonates that were related to the length of their initial hospital stay. Those neonates receiving home care were less likely to require hospital readmission and less likely to seek outpatient care. It is unlikely that a single discharge policy will be appropriate for all mothers and neonates.

Adult↗
PubMed2003

Differences in transient outward current properties between neonatal and adult human atrial myocytes.

UNLABELLED: Knowledge of postnatal modulation of I(to) in human atrial myocytes is quite limited. The present study investigated the differences in I(to) properties between neonatal and adult human atrial myocytes. METHODS: Atrial myocytes were dissociated enzymatically from biopsies of human right atrial appendage. I(to) and action potentials were recorded by whole-cell patch-clamp technique. The expressed protein levels of Kv4.3 and KChIP2 in atrial tissue were detected by western blot technique. RESULTS: I(to) was present in all atrial cells (n = 37) from 10 neonatal patients (2.5-7 months). The mean value of I(to) density in neonatal atrial cells was significantly larger than in adult atrial cells. The time constants for I(to) current decay were significantly faster for neonatal cells, compared to adult cells. I(to) recovery from inactivation at holding potential of - 80 mV was significantly slower for neonatal atrial cells than for adult atrial cells. There was no difference in the voltage dependence of I(to) activation between neonatal and adult cells. The voltage-dependent inactivation slope factor was smaller for neonatal compared to adult atrial cells. A more significant frequency-dependent suppression of I(to) peak current and a more significant lengthening of APD(30) were observed in neonatal atrial cells compared to adult atrial cells. Western blots showed both Kv4.3 and KChIP2 are expressed in neonatal atria, but with significantly higher level of Kv4.3 and lower level of KChIP2 protein compared to adult. CONCLUSION: There are significant differences in the properties of I(to) between neonatal and adult human atrial cells, including a larger current density, faster inactivation and slower recovery from inactivation in the neonatal atrial cells. The physiological differences of I(to) are consistent with the different expression protein levels of Kv4.3 and KChIP2.

Action Potentials↗