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PubMed2001

Neonatal seizures and neonatal epileptic syndromes.

The neonatal period is defined as the first 28 days of life of a term infant; for premature infants the limit of this period is 44 completed weeks of the infant's conceptional age (CA)-defined as the chronological age plus gestational age (GA) at birth. The clinical and electroencephalographic (EEG) manifestations of seizures during this period are determined primarily by the development features of the immature brain at the time of seizure onset, but are also related to the type and diversity of etiologies and risk-factors for seizures neonates may face early in life. Neonatal seizures may be strikingly different from the clinical and electrical seizures of older children and adults. In addition, findings from basic science investigations suggest that immature animals are more likely to experience seizures in response to injury than more mature animals, although the developing brain is less susceptible to seizure-induced injury.

Brain↗

PubMed2004

Stratum corneum acidification in neonatal skin: secretory phospholipase A2 and the sodium/hydrogen antiporter-1 acidify neonatal rat stratum corneum.

At birth, human stratum corneum (SC) displays a near-neutral surface pH, which declines over several days to weeks to months to an acidic pH, comparable to that of adults. Recent studies suggest that an acidic pH is required for normal permeability barrier homeostasis and SC integrity/cohesion. We assessed here the basis for postnatal acidification in the neonatal rat, where SC pH, as measured with a flat surface electrode, declines progressively from near-neutral levels (pH 6.63) on postnatal days 0 to 1 to adult levels (pH 5.9) or even below over the subsequent 7 to 8 d. The postnatal decline in SC pH was paralleled by a progressive activation of a pH-dependent hydrolytic enzyme, beta-glucocerebrosidase. Because SC acidification could not be linked to commonly implicated exogenous factors, such as bacterial colonization, or the deposition of sebaceous gland products. We next assessed whether changes in one or more of three endogenous mechanisms demonstrate postnatal activity changes that contribute to the progressive development of an acidic SC pH. Although the histidine-to-urocanic acid pathway has been implicated in acidification of the adult SC, surface pH is completely normal in histidase-deficient (his/his, Peruvian) mice, ruling out a requirement for this mechanism. In contrast, when sodium/hydrogen antiporter-1 (NHE1), which predominantly acidifies membrane domains at the stratum granulosum-SC interface, is inhibited, postnatal acidification of the SC is partially blocked. Likewise, SC secretory phospholipase A2 (sPLA2) activity, measured with a fluorometric assay, is low at birth, but increases progressively (by 66%) over the first 5 d after birth, and inhibition of sPLA2 between days 0 to 1 and days 5 to 6 delays postnatal SC acidification. Together, these results describe a neonatal model, in which the development of an acidic surface pH can be ascribed, in part, to progressive SC acidification by two endogenous mechanisms, namely, sPLA2 and NHE1, which are known to be important for acidification of adult rodent SC. Conversely, the impaired acidification of neonatal SC, which has important functional and clinical consequences, can be explained by the relatively low activities of one or both of these mechanisms at birth.

Acids↗

PubMed1988

Neonatal depression and birth asphyxia in the low birthweight neonate.

In 392 low birthweight neonates, acidosis as evident from umbilical artery pH 7.1 or less was strongly associated with Apgar score 6 or lower at 1 minute. However, most cases that were depressed (Apgar score 6 or lower at 1 minute) were not acidotic. Neonatal depression was most strongly and directly correlated with gestational age. Neonatal depression and birth asphyxia are distinct entities.

Acidosis↗

PubMed1992

Intravenous immune globulin for the prevention of nosocomial infection in low-birth-weight neonates. The Multicenter Group for the Study of Immune Globulin in Neonates.

BACKGROUND: Nosocomial infection is a major risk for premature infants with very low birth weights. One reason for their susceptibility to infection may be antibody deficiency, since there is little transfer of maternal IgG to the fetus before 32 weeks' gestation. METHODS: We conducted a multicenter, double-blind study of neonates weighing 500 to 1750 g at birth. A total of 588 neonates were randomly assigned, with stratification for birth weight, to receive periodic intravenous infusions of either immune globulin (500 mg per kilogram of body weight per day) or a placebo. Mortality, morbidity, and nosocomial infection during the next 56 days were assessed. RESULTS: The infusions were well tolerated; mild, reversible adverse reactions occurred in five infants in each group. There was a significant reduction in the risk of a first nosocomial infection in the recipients of immune globulin as compared with the placebo recipients (relative risk, 0.7; 95 percent confidence interval, 0.5 to 0.9). About 85 percent of the nosocomial infections were bacterial; the majority of these were caused by coagulase-negative staphylococci or Staphylococcus aureus. The neonates who received immune globulin had fewer mean days of hospitalization than the controls (62 vs. 68, P = 0.15); among the infants with infections, the difference in the mean length of the hospital stay was even greater (80 days vs. 101 days, P = 0.02). CONCLUSIONS: For premature infants weighing between 500 and 1750 g at birth, treatment with intravenous infusions of immune globulin is safe and reduces the risk of nosocomial infection.

Cross Infection↗

PubMed2003

Neonatal lupus: review of proposed pathogenesis and clinical data from the US-based Research Registry for Neonatal Lupus.

Congenital heart block (CHB), a life-threatening manifestation of neonatal lupus, offers aunique opportunity to study the effect or arm of immunity and define the pathogenicity of an autoantibody in mediating tissue injury. This review focuses on our recent in vitro model which supports a cascade from antibody insult to unchecked fibrosis. In brief, it is proposed that the fetal cardiac myocyte undergoes apoptosis which facilitates transfer of intracellular Ro and La antigens to the surface where they are bound by circulating maternal autoantibodies (anti-SSA/Ro-SSB/La antibodies). Scavenging macrophages phagocytose these inadvertently "opsonized" cardiocytes, leading to the secretion of pro-inflammatory and pro-fibrotic cytokines, the latter of which transdifferentiate fibroblasts into myofibroblasts and thereby promote scarring. Immunohistologic study of a heart from a neonate dying of CHB supports this model in that macrophages and myofibroblasts were demonstrated. To facilitate both basic and clinical research, a Research Registry for Neonatal Lupus was established in 1994 by the U.S. National Institute of Arthritis, Musculoskeletal and Skin Diseases. Maternal and fetal outcomes are addressed as well as recurrence rates. Laboratory evaluation and management decisions during pregnancy are provided.

Animals↗

PubMed2000

Metabolic activation capacity of neonatal mice in relation to the neonatal mouse tumorigenicity bioassay.

The neonatal mouse tumorigenicity bioassay is a well-developed animal model that has recently been recommended as an alternative tumorigenicity bioassay by the International Conference on Harmonization (ICH) for Technical Requirements for the Registration of Pharmaceuticals for Human Use. There are sufficient data to conclude that this animal model is highly sensitive to genotoxic chemical carcinogens that exert their tumorigenicity through mechanisms involving the formation of covalently bound exogenous DNA adducts that lead to mutation. On the other hand, it is not sensitive to chemical carcinogens that exert tumorigenicity through a secondary mechanism. The metabolizing enzymes present in the neonatal mouse, particularly the cytochromes P450, are critical factors in determining the tumorigenic potency of a chemical tested in this bioassay. However, compared to the metabolizing enzymes of the adult mouse and rat, the study of the metabolizing enzymes in neonatal mouse tissues has been relatively limited.

Animals↗

PubMed1981

Critical care problems in neonates. Colloid osmotic pressure in healthy and sick neonates.

Clinical usefulness of colloid osmotic pressure (COP) measurements in adults has been well established. However, data in healthy and sick neonates are sparse. The present study established the COP changes in healthy term and preterm infants and in critically ill neonates. COP in healthy term (16.9 +/- 1.9 mm Hg) and preterm (15.4 +/- 1.3) infants was significantly lower than adults (21.6 +/- 3.6). Even in sick neonates, COP correlated with gestational age (n = 78, r = 0.63, p less than 0.001 , birth weight (r = 0.58, p less than 0.001) and total protein (n = 71, r = 0.58, p less than 0.001). Critically ill preterm infants with hyaline membrane disease had the lowest COP (11.5 +/- 1.2). Administration of 10% albumin failed to increase the COP significantly. In critically ill preterm infants who survived, the COP increased during the first postnatal week, whereas in nonsurvivors COP decreased significantly to less than 10 mm Hg.

Blood Proteins↗

PubMed1994

Prevalence of Helicobacter pylori in neonates and young infants undergoing ERCP for diagnosis of neonatal cholestasis.

This study was carried out to determine the prevalence of Helicobacter pylori infection in 20 neonates and young infants from lower socioeconomic background undergoing endoscopic retrograde cholangiopancreatography (ERCP) examination for diagnosis of neonatal cholestasis. One young asymptomatic infant (5%) who was breast-feeding with complementary formula had H. pylori infection. Endoscopy showed a normal appearing mucosa and histology demonstrated mild superficial acute gastritis. A follow-up gastroscopy performed 14 months after the initial study showed normal histology without evidence of H. pylori, suggesting that the infection was transient. Nineteen (95%) of the 20 mothers had H. pylori infection, including the mother with the infant positive for H. pylori. All mothers had gastritis on biopsy specimens. Despite the high prevalence of H. pylori in the mothers, infection in neonates and young infants was uncommon.

Biopsy↗

PubMed1999

Intrapartum antibiotics and early onset neonatal sepsis caused by group B Streptococcus and by other organisms in Australia. Australasian Study Group for Neonatal Infections.

OBJECTIVE: Early onset group B streptococcal (EOGBS) infection, the major neonatal infection in industrialized countries, can be prevented by intrapartum antibiotics, but population studies are lacking. This study aimed to determine the incidence of early onset infections caused by group B Streptococcus (GBS) and other organisms in Australia and to assess intrapartum antibiotic use. DESIGN: Longitudinal, prospective surveillance of neonatal infections in Australian neonatal units from 1991 to 1997. Early onset infection defined as clinical sepsis in first 48 h after birth, with positive cultures of blood or cerebrospinal fluid or positive urine GBS antigen detection. RESULTS: The incidence of EOGBS sepsis fell from 2.0 per 1000 live births (95% confidence interval, 1.4, 2.5) in 1991 to 1993, to 1.3 (1.2, 1.4) in 1993 to 1995, to 0.5 (0.4, 0.7) in 1995 to 1997 (P < 0.0001). The incidence in Aboriginal babies was 5.2 (1.8, 8.6) in 1991 to 1993, 5.1 (3.0, 7.2) in 1993 to 1995 and 1.8 (1.1, 2.5) in 1995 to 1997 (P < 0.05). The incidence of early onset infections caused by organisms other than GBS also fell, from 1.2 per 1000 live births (0.8, 1.7) in 1991 to 1993, to 0.8 (0.7, 0.9) in 1993 to 1995 and 0.5 (0.3, 0.7) in 1995 to 1997 (P < 0.0001). In 1991, 3 of 9 study hospitals had a formal policy on intrapartum antibiotic use, whereas in 1997 all 11 hospitals had a formal policy (P=0.002). CONCLUSIONS: A steady fall in EOGBS infections in Australia from 1991 to 1997 has been associated with increasing use of intrapartum antibiotics. Increased antibiotic use is probably causal in the fall in GBS, because the incidence of early onset infections caused by other organisms has also fallen.

Anti-Bacterial Agents↗

PubMed2005

Very low birth weight preterm infants with early onset neonatal sepsis: the predominance of gram-negative infections continues in the National Institute of Child Health and Human Development Neonatal Research Network, 2002-2003.

BACKGROUND: Early onset neonatal sepsis (EOS, occurring in the first 72 hours of life) remains an important cause of illness and death among very low birth weight (VLBW) preterm infants. We previously reported a change in the distribution of pathogens associated with EOS from predominantly gram-positive to primarily gram-negative organisms. OBJECTIVE: To compare rates of EOS and pathogens associated with infection among VLBW infants born at centers of the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network during 3 time periods: 1991-1993; 1998-2000; and 2002-2003. STUDY DESIGN: Prospectively collected data from the NICHD Neonatal Research Network VLBW registry were retrospectively reviewed. Rates of blood culture confirmed EOS, selected maternal and infant variables and pathogens associated with infection were compared between 2002-2003 and 2 previously published cohorts. RESULTS: During the past 13 years, overall rates of EOS have remained stable (15-19 per 1000 live births of infants 401-1500 g). More than one-half of early infections in the 2002-2003 cohort were caused by gram-negative organisms (53%), with Escherichia coli the most common organism (41%). Rates of group B streptococcal infections remain low (1.8 per 1000 live births). Between 1991-1993 and 1998-2000, there was a significant increase in rates of E. coli infections; but in 2002-2003, there was no significant change (7.0 per 1000 live births). Infants with EOS continue to be at significantly increased risk for death compared with uninfected infants. CONCLUSION: EOS remains an uncommon but important cause of morbidity and mortality among VLBW infants. Gram-negative organisms continue to be the predominant pathogens associated with EOS.

Age of Onset↗

PubMedDate not supplied

Normal values of neonatal lower limbs: an evaluation of 1,000 neonates.

The purpose of this study was to establish normal values for neonatal hip range of motion, knee range of motion, tibial torsion, and foot alignment. Normal values for examination of the lower extremity in the neonate are not well-documented in the orthopaedic literature. One-thousand healthy neonates were examined by the orthopaedic residency under the supervision of an attending doctor. A total of 527 girls (53%) and 473 boys (47%) were examined. Results were compared and analyzed for mean, range, and standard deviations. There was a wide normal range for each category measured. For all categories, boys and girls had essentially the same values. There were no differences between right and left values. Normal values for these measurements have not previously been reported from such a large series.

Female↗

PubMed1983

Causes of neonatal deaths in a pediatric hospital neonatal unit. An autopsy study of a ten-year period.

A study is presented of 1020 consecutive autopsies on newborn infants who died during the first 28 days of life at the Children's Hospital, University of Helsinki, during 1969-1978. The infants were grouped into four categories according to their weight at birth and into early (0-7 days) and late (8-28 days) neonatal groups according to their age at death. 77.5% of the cases fell into the early neonatal group. The most common causes of death were hyaline membrane disease (HMD) and cerebral haemorrhage (CH), which together accounted for 41.9% of all the deaths. Congenital anomaly was the second most common group of causes, comprising 35.3% of the cases. A gradual fall in the total number of deaths was conspicuous during the ten-year period. There was a statistically significant decrease in the number of deaths from HMD and CH in the weight categories 1001-1500 g and 1501-2500 g. The fall is considered to reflect improvement in both obstetrics and neonatal medicine.

Autopsy↗

PubMed2003

Neonatal transfers by advanced neonatal nurse practitioners and paediatric registrars.

OBJECTIVE: To evaluate the safety and practicality of using advanced neonatal nurse practitioners (ANNPs) to lead acute neonatal transfers. DESIGN: Comparison of transport times, transport interventions, and physiological variables, covering the first four complete years of operating a transport service that uses ANNPs and specialist paediatric registrars (SpRs) interchangeably. SETTING: Tertiary neonatal transport service. PATIENTS: The first 51 transfers of sick infants under 28 days of age by an ANNP led transport team into Nottingham compared with the next consecutive SpR led transfer after each ANNP led one. MAIN OUTCOME MEASURES: Transport times; interventions and support given during stabilisation for transfer and during transfer; condition on completion of transfer, assessed from blood glucose, systolic blood pressure, pH, oxygenation, and temperature. RESULTS: The ANNP led team responded more rapidly to requests for transfer and took longer to stabilise babies. The groups undertook similar numbers of procedures during stabilisation, and there were no differences in the ventilatory and other support that infants needed in transit. The infants transferred by the doctor led group had worse values for pH (doctor led, 7.31 (6.50-7.46); ANNP led, 7.35 (7.04-7.50), p = 0.02) and PaO(2) (doctor led, 6.7 (2.4-13.1); ANNP led, 8.7 (3.5-17.0); p = 0.008) before transfer (all values median (range)). Comparisons of the infant's condition before and after transfer showed a significant improvement in temperature for the infants transferred by ANNP led teams (36.8 degrees C (34.0-37.8) v 37.0 degrees C (34.6-38.0), p = 0.001) and in oxygen saturation (96% (88-100) v 98% (92-100), p = 0.01). There were no differences between the ANNP and doctor led groups in the values obtained for any variable after transfer. CONCLUSIONS: Clinical condition on completion of transport is similar for babies transferred by ANNP and doctor led teams. ANNP led transport appears to be practical and safe.

England↗

PubMed1987

Proposed guidelines for screening of metabolic and endocrine diseases of dependent neonates of the U.S. Armed Forces. Derived from a survey of state guidelines for neonatal screening of metabolic diseases.

State regulations for neonatal screening for metabolic diseases do not optimally serve the needs of the dependents of the U.S. Armed Forces. Guidelines are therefore proposed for the neonatal screening for metabolic disease based both on responses received across the United States and on the unique needs of the U.S. Armed Forces. The guidelines agree with the policies outlined by various national medical and scientific organizations. It is suggested that neonates be screened for phenylketonuria (PKU), hypothyroidism, galactosemia, and maple syrup urine disease (MSUD). The screening program is cost-effective and feasible. Prior to implementing the program throughout the U.S. military, a pilot program based at the Armed Forces Institute of Pathology should be started.

Costs and Cost Analysis↗

PubMed1998

Testing neonate-infant membrane oxygenators with the University of Texas neonatal pulsatile cardiopulmonary bypass system in vitro.

Neurologic complications are already well documented after cardiopulmonary bypass (CPB) procedures in neonates and infants. Physiologic pulsatile flow CPB systems may be the alternative to the currently used steady-flow CPB circuits. In addition to the pulsatile pump, a membrane oxygenator should be chosen carefully, because only a few membrane oxygenators are suitable for physiologic pulsatile flow. We have tested four different types of neonate-infant membrane oxygenators for physiologic pulsatility with The University of Texas neonate-infant pulsatile CPB system in vitro. Evaluation criteria were based on mean ejection time, extracorporeal circuit (ECC) pressure, and upstroke of dp/dt. The results suggested that the Capiox 308 hollow-fibre membrane oxygenator produced the best physiologic pulsatile waveform according to the ejection time, ECC pressure, and the upstroke of dp/dt. The Minimax Plus and Masterflo Infant hollow-fibre membrane oxygenators also produced adequate pulsatile flow. Only the Variable Prime Cobe Membrane Lung (VPCML) Plus flat-sheet membrane oxygenator failed to reach the criteria for physiologic pulsatility. Depending on the oxygenator used, the lowest priming volume of the infant CPB circuit was 415 ml and the highest 520 ml.

Brain Diseases↗

PubMed2003

Fetal and neonatal neurologic case histories: assessment of brain disorders in the context of fetal-maternal-placental disease. Part 2: Neonatal neurologic consultations in the context of adverse antepartum and intrapartum events.

The more conventional role of the pediatric neurologist involves the evaluation of the child after birth. Although the pediatric neurologist rarely attends the delivery of the neonate, consultation by the neurologist should begin immediately following stabilization by the neonatal resuscitation team. Four interrelated aspects of the neurologist's clinical assessment will be discussed in the context of reaching a consultative opinion, which must incorporate knowledge of chronologic events before as well as during labor and delivery. This evaluation encompasses an assessment of levels of arousal, increased or decreased muscle tone, presence of seizures, and effects of systemic diseases on the central nervous system, which are the essential elements of a complete neurologic examination. Documentation of the neonate's neurologic condition, together with knowledge of maternal, fetal, and placental diseases, will help anticipate neuroresuscitative decisions, as well as subsequent neurologic deficits.

Arousal↗

PubMed1978

Abnormal colonization of neonates in an intensive care unit: means of identifying neonates at risk of infection.

The current investigation was designed to select infants in the neonatal intensive care unit (ICU) at highest risk of infection. The data, derived from a prospective study of 223 neonates, indicate that neonates in an ICU develop their initial aerobic pharyngeal flora according to one of the three patterns shown in Table 1, one of which (low titer or no growth) is dependent on antibiotic therapy. Of particular importance is the finding that infants with normal flora (alpha-streptococci predominating) or cultures showing low titers (less than 10(4) colony-forming units (cfu)/ml) or no growth did not become infected. All infections occurred in the group of infants with abnormal pharyngeal colonization (18 infections in 115 abnormally colonized infants): with a single exception the infecting organism showed the cultural characteristics of the colonizing organism. Consequently one can pinpoint the relatively small number of infants at particular risk of infection and predict what the infecting organism will be if infection occurs.

Anti-Bacterial Agents↗

PubMed1979

Neonatal mononuclear cell metabolism: further evidence for diminished monocyte function in the neonate.

The metabolic capacity of neonatal monocytes was compared to the metabolic capacity of adult monocytes by two entirely different methods: the selective diminution of monocyte contamination of whole mononuclear cells and the isolation of relatively purified populations of monocytes. Monocyte removal from whole mononuclear cells produced a diminution in the pyruvate kinase (PK) activity (from 28.6 +/- 1.1 to 15.6 +/- 1.2 nmoles/min/10(7) cells) and an increase in adenosine triphosphate (ATP) content (from 7.9 +/- 1.0 to 9.5 +/- 0.8 nmoles/10(7) cells) in adult cells. No change in PK activity (from 13.5 +/- 1.3 to 14.0 +/- 1.3) was observed in cord cells, but the ATP content of cord cells was higher after monocytes depletion (from 4.7 +/- 0.5 to 6.2 +- 0.7). The suggestion of metabolic vulnerability was confirmed by metabolic analysis of isolated adult and cord monocytes. The PK activity of adult monocytes was greater than that of cord monocytes (57 +/- 9 and 25 +/- 0.3, respectively) and the ATP content of adult monocytes (5.7 +/- 0.2) was greater than that of cord monocytes (2.3 +/- 0.1). The data confirm prior observations of diminished energy metabolism in neonatal mononucler cells and suggest that the metabolic perturbations may, in part, correlate with functional immaturity of the neonatal monocyte.

Adenosine Triphosphate↗