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PubMed2002

Respiratory distress in neonates with special reference to pneumonia.

OBJECTIVE: (i) To find causes of respiratory distress in neonates brought to a referral neonatal unit with symptoms suggestive of respiratory disorder; (ii) to evaluate clinical signs for diagnosis of neonatal pneumonia; (iii) To determine bacterial etiology of neonatal pneumonia; and (iv) To determine indicators of fatality in neonatal pneumonia. DESIGN: Prospective descriptive. SETTING: Referral neonatal unit of a teaching hospital. SUBJECTS: 150 neonates admitted with respiratory symptoms consecutively. METHODS: All neonates presenting with respiratory symptoms were included in the study. The diagnosis of the cause of respiratory distress was based on guidelines recommended by the National Neonatology Forum. Clinical features, FiO2 requirement, sepsis screen, X-ray chest, blood culture and antibiotic sensitivity, arterial blood gases and other relevant investigations were documented in a structured proforma. The neonates were regularly followed up for outcome. Multivariate unweighted logistic regression was done to find out the indicators of fatality in neonatal pneumonia for those variables which were significantly associated with outcome on univariate analysis. RESULTS: Pneumonia was found to be the most common cause (68.6%) of respiratory distress in neonates. Other conditions included hydline membrane disease (HMD), transient tachypneia of new born (TTNB), birth asphyxia with hypoxic ischemic encephalopathy (HIE) and meconium aspiration syndrome (MAS). Clinical signs and symptoms were non specific and did not differentiate between pneumonia and other causes of respiratory distress. Respiratory rate was less than 60 per minute in 11.6% neonates with pneumonia. The most common organism responsible for neonatal pneumonia was Klebsiella pneumoniae. Chest X-ray was clear in 15% of neonates with pneumonia. On univariate analysis weight < 2000 g, gestation age < 34 weeks, age at presentation < 72 hours, lethargy, absent neonatal reflexes, shock, positive C-reactive protein, positive ventilatory support, blood culture positivity, Silverman Score >3, FiO2 >40%, pH < 7.2, alveolar arterial gradient (AaDO2) > 250 mmHg and arterial alveolar tension ratio (a/A) of < 0.25 were significantly associated with mortality in neonates with pneumonia. However, on multivariate analysis, only AaDO2 of > 250 mmHg was found to be independent predictor of fatality in neonatal pneumonia. CONCLUSION: Pneumonia was the most common cause of respiratory distress in neonates. Clinical features and X-ray chest missed the diagnosis of pneumonia in 15 cases and had to be corroborated with sepsis screen and blood culture. AaDO2 > 250 mmHg was an independent predictor of fatality in neonatal pneumonia

Analysis of Variance↗
PubMed2000

Surveillance protocol for the detection of intracranial abnormalities in premature neonates.

OBJECTIVE: To determine the optimal timing of cranial ultrasound scans (USs) for identifying preterm neonates weighing less than 1500 g at birth who develop intracranial complications of prematurity. DESIGN/SETTING: Observational study at an urban county hospital. METHODS: Serial USs from neonates with less than 1500-g birth weight (BW) admitted to the neonatal intensive care unit between January 1995 and December 1996 were reviewed by a pediatric neuroradiologist in a blinded random manner. RESULTS: Two hundred forty-eight neonates (78%) underwent at least 3 USs, 32 (10%) had 2 USs and 37 (12%) only 1 US. The initial US was normal in 156 neonates (49%) and abnormal in 161 (57%). The principal abnormalities included intraventricular hemorrhage (IVH) (n = 74), periventricular echogenicity (PVE) (n = 68), ventriculomegaly (n = 7), and solitary cysts (n = 9). Severe IVH (n = 17) occurred in 13 (11.4%) of 114 neonates at less than 1000-g BW and 4 (5%) of 79 neonates of BW 1000 to 1250 g. In 11 cases (65%), the severe IVH was clinically unsuspected. For neonates weighing less than 1000 g, IVH was diagnosed by days 3 to 5 in 10 (77%) of 13, by days 10 to 14 in 11 (84%) of 13, and by day 28 in all neonates; for neonates 1001 to 1250 g, IVH was diagnosed in 1 (24%) of 4 by days 3 to 5, 2 (50%) of 4 by days 10 to 14, and 3 (75%) of 4 by day 28. One infant's condition was diagnosed on routine US before discharge from the hospital. Cystic periventricular leukomalacia (PVL) was noted in 9 neonates; in 4 of the 9 cases, increased PVE was present on the initial US and cyst formation was obvious by the second US. For 4 neonates (3 with BW <1000 g), all routine USs were negative and cystic PVL was noted on the predischarge US in these cases. Nonobstructive ventriculomegaly in the absence of IVH or cystic PVL was observed in 14 neonates. In 6, it was noted on the initial screening US; in 4 of the cases, it evolved after the third screening US. Two hundred fifty-six neonates had a US before discharge from the hospital; 181 (72%) were normal and 75 (28%) abnormal. Nine significant lesions were identified by the US before discharge from the hospital (ie, severe IVH [n = 1], cystic PVL [n = 4], and ventriculomegaly [n = 4]). CONCLUSIONS: The following screening protocol is recommended: (1) Neonates of less than 1000-g BW: initial US on days 3 to 5 (should identify at least 75% of cases of IVH and some PVE abnormalities); second US on days 10 to 14 (should detect at least 84% of IVH and identify early hydrocephalus and early cyst formation); third scan on day 28 (should detect all cases of IVH, as well as assess PVE and ventricular size); and final scan before discharge from the hospital (should detect approximately 20% of significant late-onset lesions). (2) Neonates of 1000- to 1250-g BW: initial US at days 3 to 5 (should detect at least 40% of significant abnormalities); a second scan at day 28 (should detect at least 70% of significant abnormalities); and a predischarge scan (should detect all late-onset significant lesions). (3) Neonates of 1251- to 1500-g BW: an initial scan at days 3 to 5; and a second scan before discharge from the hospital if the clinical course is complicated. Arch Pediatr Adolesc Med. 2000;154:822-826

Age Factors↗
PubMed1996

In vitro evaluation of neonatal human immunity against the pig.

The critical shortage of organ donors has greatly limited the number of clinical allotransplantations. This is particularly true for neonatal patients, for whom xenotransplantation could provide an alternative therapeutic option to allotransplantation. The role of neonatal infant immunity in xenotransplantation is not, however, clearly understood. We examined both the proliferative responses of human neonatal lymphocytes to pig aortic endothelial cells and serum levels of neonatal natural antipig xenoantibody. Neonatal human lymphocytes and serum were isolated from umbilical cord blood. Adult human lymphocytes and serum were used as controls. A one-way xenogeneic mixed lymphocyte-endothelial cell reaction was performed, and lymphocyte proliferation was measured by tritiated thymidine uptake. Neonatal human lymphocytes recognized and proliferated in response to pig aortic endothelial cells (mean 63,926 +/- 26,054 counts per minute). The level of xenogeneic mixed lymphocyte-endothelial cell reaction of neonatal lymphocytes was significantly lower (p < 0.004) than that of adult human lymphocytes (mean 122,444 +/- 33,132 counts per minute). An enzyme-linked immunosorbent assay was performed to determine the binding of natural immunoglobulin M and G antibodies to pig endothelial cells. Whole-cell enzyme-linked immunosorbent assay demonstrated neonatal human serum to contain very low binding levels of natural antipig immunoglobulin M xenoantibody compared with adult serum. Like adult serum, neonatal human serum contained natural antipig immunoglobulin G xenoantibody. Neonatal serum was not cytotoxic to pig endothelial cells, suggesting that immunoglobulin G was not the predominant xenoreactive antibody. To assess whether neonatal pig endothelial cells also expressed xenoantigens, adult and neonatal cultured pig endothelial cells were examined by enzyme-linked immunosorbent assay with adult human serum. Adult human natural immunoglobulin M xenoantibody recognized not only adult pig endothelial cell xenoantigens but also neonatal pig endothelial cell xenoantigens. The binding levels of adult natural antipig immunoglobulin M xenoantibodies to adult and neonatal pig endothelial cells were similar, suggesting that neonatal pig aortic endothelial cells express xenoantigens. The findings of low binding levels of cytotoxic antipig immunoglobulin M xenoantibody and low levels of lymphocyte xenoreactivity to pig endothelial cells in human neonates suggests that pig organs may eventually be a suitable source of xenografts for human neonates.

Adult↗
PubMed2002

Interleukin-11 levels in healthy and thrombocytopenic neonates.

Thrombocytopenia is common in sick neonates, and affected neonates have adverse outcomes compared with those without thrombocytopenia. As impaired platelet production underlies many neonatal thrombocytopenias, affected neonates are potential candidates for hemopoietic growth factor therapy. Although recombinant human (rh) thrombopoietin remains under therapeutic development, rhIL-11, which stimulates megakaryocytopoiesis and increases platelet counts after chemotherapy, is already licensed for clinical use. However, nothing is known about IL-11 in neonates. We therefore measured plasma IL-11 by ELISA in healthy term neonates, stable preterm neonates with or without thrombocytopenia, and preterm neonates with sepsis or necrotizing enterocolitis (NEC) with or without thrombocytopenia. At birth IL-11 was undetectable (<10 pg/mL) in healthy term neonates (n = 20) and 27 of 31 (87%) stable preterm neonates. Three stable preterm neonates with detectable IL-11 (mean+/-SD, 11.3 +/- 0.4 pg/mL; median, 11.6 pg/mL) suffered chorioamnionitis, the remaining neonate (IL-11, 14 pg/mL) being one of nine with early onset thrombocytopenia (present by <72 h of age). IL-11 was also measured in 58 preterm neonates with suspected sepsis or NEC. In 25 of 58, sepsis or NEC was unconfirmed and IL-11 was undetectable. By contrast, 14 of 33 with proven sepsis or NEC had elevated IL-11 (median, 14.9 pg/mL; range, 11.2-92.2 pg/mL). Of these 33 neonates, 19 developed thrombocytopenia: nine of 19 (47%) had detectable IL-11 and 10 of 19 (53%) did not (p > 0.05). Although its role in platelet production in neonates remains unclear, these data suggest that IL-11 is involved in the endogenous cytokine response to sepsis or NEC in preterm neonates. Further studies of IL-11 in neonates are warranted to assess its role both in platelet production and in mediation of the endogenous inflammatory response.

Enterocolitis, Necrotizing↗
PubMed2006

Twenty-four-hour esophageal impedance-pH monitoring in healthy preterm neonates: rate and characteristics of acid, weakly acidic, and weakly alkaline gastroesophageal reflux.

OBJECTIVE: Gastroesophageal reflux is a physiologic process and is considered pathologic (gastroesophageal reflux disease) when it causes symptoms or results in complications. It is common in preterm infants and occurs in healthy neonates. Twenty-four-hour pH monitoring commonly is used in children for diagnosis of gastroesophageal reflux disease, and abnormal reflux is considered with detection of increased esophageal acid exposure. However, in neonates, relatively few gastroesophageal reflux episodes cause esophageal acidification to pH < 4. Premature infants receive frequent feeds, which can induce a weaker acid secretory response than that observed in older infants and adults. As a consequence, gastric pH may be > 4 for prolonged periods, and reflux of gastric contents might be less acidic or even alkaline. Esophageal impedance monitoring can detect weakly acidic and even alkaline gastroesophageal reflux. The role of weakly acidic reflux in the pathophysiology of gastroesophageal reflux disease in preterm infants is not clear. To date, studies that have used impedance-pH in neonates assessed the association between nonacid reflux and cardiorespiratory symptoms, but no impedance data from healthy preterm neonates have been available to determine whether those symptomatic neonates had an increased number of weakly acidic reflux episodes or increased reactivity to a physiologic number of reflux events. Our aim with this study was to provide impedance-pH values for acid, weakly acidic, and weakly alkaline reflux from healthy preterm neonates. METHODS: Esophageal impedance was recorded for 24 hours in 21 asymptomatic preterm neonates by replacing the conventional feeding tube with a specially designed feeding tube that included 9 impedance electrodes (8 French). All neonates were asymptomatic, with spontaneous breathing. Reflux monitoring was performed after comprehensive explanation and on receipt of written parental consent. Esophageal and gastric pH were monitored using a separate parallel pediatric catheter (6 French). According to the corresponding pH change, impedance-detected reflux was classified as acid, weakly acidic, and weakly alkaline. For each infant, the total number of reflux events, the acid exposure and bolus exposure times at 2 cm above the respiratory inversion point, and average proximal extent of reflux were calculated. RESULTS: Twenty-six preterm neonates were recruited into this study. A preliminary analysis was performed, and tracings were classified according to their quality and the presence of technical artifacts (spontaneous pH and impedance drifts, esophageal probe migration, and dysfunction of 1 or more impedance channels). Five studies were excluded because of 1 or more technical artifacts; a total of 21 neonates represent the final cohort included. At birth, the infants had a median postmenstrual age of 32 weeks, and the measurements were performed at a median age of 12 days. The total recording time was 23.7 +/- 2 hours. Gastric pH was higher than 4 during 69.3 +/- 20.4% of the recording time. The median number of reflux events in 24 hours was 71, 25.4% (range: 0%-53.1%) of which were acid, 72.9% (range: 45.3%-98.0%) were weakly acidic, and 0% (range: 0%-8.1%) were weakly alkaline. Compared with fasting periods, feeding periods tended to be associated with a higher number of total reflux events per hour. The acidity of reflux, however, was significantly different: during fasting, the number of acid reflux episodes per hour was higher, whereas during feeding, the number of weakly acidic reflux episodes was increased. Most reflux events were only liquid, whereas gas was present either mixed with liquid or pure only in 7.7% of all reflux episodes detected. The proximal esophageal segments were reached in 90% of reflux episodes. Reflux-related acid exposure (pH drops associated with impedance-detected reflux) was 1.66% (range: 0%-6.43%), whereas total acid exposure (associated and not associated with reflux detected by impedance) was 5.59% (range: 0.04%-20.69%). There was no relationship between the number or acidity of reflux events and anthropometric parameters such as weight and gestational age. CONCLUSIONS: We present the first study using 24-hour impedance-pH recordings in asymptomatic premature neonates. Previous studies that used pH-metry suggested that neonatal cardiorespiratory symptoms could be related to acid gastroesophageal reflux. However, pH-metry could not detect accurately weakly acidic or nonacid reflux. Our healthy premature neonates had approximately 70 reflux events in 24 hours, 25% of which were acid, 73% were weakly acidic, and 2% were weakly alkaline. The number of reflux events per hour (2-3 per hour) was slightly lower than that described in premature neonates with cardiorespiratory events (4 per hour). We confirmed that weakly acidic reflux is more prevalent than acid reflux, particularly so during the feeding periods. In contrast, similar to healthy adults, weakly alkaline reflux was very rare. We confirmed findings from previous studies in which most reflux events were pure liquid during both fasting and during postprandial periods and gas reflux was very rare. As in neonates with cardiorespiratory symptoms, the majority of reflux events in asymptomatic preterms reached the proximal esophagus or pharynx, and there were no differences between acid and weakly acidic reflux. The lack of differences between asymptomatic and diseased infants contravenes the hypothesis for macro- or microaspiration but does not exclude hypersensitivity to reflux as a cause for respiratory symptoms. The acid exposure that was related to reflux events and detected by impedance was significantly lower than the total acid exposure during 24 hours. Increased acid exposure could be attributable to pH-only reflux events or, less frequently, to slow drifts of pH from baselines at approximately 5 to values < 4. These changes were not accompanied by a typical impedance pattern of reflux but by slow drifts in impedance in 1 or 2 channels. Our findings confirm the need for the use of impedance together with pH-metry for diagnosis of all gastroesophageal reflux events. The relationship between gastroesophageal reflux and cardiorespiratory events in neonates and older infants has been studied extensively. The current evidence for such a relationship is controversial. This study provides values of impedance-pH monitoring for acid, weakly acidic, and weakly alkaline reflux from healthy preterm neonates that can be used for comparison when evaluating gastroesophageal reflux in preterm infants with a cardiorespiratory disease.

Buffers↗
PubMed2004

Requirements of NK cells and proinflammatory cytokines in T cell-dependent neonatal autoimmune ovarian disease triggered by immune complex.

A model of neonatal autoimmune disease has been described recently in which an epitope-specific autoantibody to murine zona pellucida 3 induces severe ovarian disease in neonatal, but not adult, mice (neonatal AOD). The autoantibody forms immune complex with endogenous ovarian zona pellucida 3, and a pathogenic CD4(+) T cell response is triggered. The basis for the predominant neonatal susceptibility has not been clarified. In this study innate immunity, including neonatal NK cells, in neonatal AOD was investigated. Neonatal spleen contained readily detectable NK1.1(+)TCRVbeta(-), but not NK1.1(+)TCRVbeta(+), cells. Ab depletion of NK1.1(+)TCRVbeta(-) cells inhibited neonatal AOD development. Moreover, in adoptive transfer of neonatal AOD, recipient disease was ameliorated when either donor or recipient NK cells were depleted. Thus, NK cells operate in both induction and effector phases of the disease. IFN-gamma was produced by neonatal NK cells in vivo, and it may be important in neonatal AOD. Indeed, ovaries with neonatal AOD expressed high levels of IFN-gamma and TNF-alpha which correlated with disease severity, and the disease was inhibited by IFN-gamma or TNF-alpha Ab. Importantly, disease was enhanced by recombinant IFN-gamma, and treatment of T cell donors with IFN-gamma Ab also significantly reduced adoptive transfer of neonatal AOD. Finally, neonatal AOD was ameliorated in mice deficient in FcgammaRIII and was enhanced in FcgammaRIIB-deficient mice. We conclude that neonatal NK cells promote pathogenic T cell response at multiple stages during neonatal autoimmune disease pathogenesis. Also operative in neonatal AOD are other mediators of the innate system, including proinflammatory cytokines and FcgammaRIII signaling.

Animals↗
PubMed2006

Acute renal failure in neonatal sepsis.

OBJECTIVE: To evaluate the occurrence of acute renal failure (ARF) and the factors associated with it in cases of neonatal sepsis. METHODS: The case control study was conducted in the referral neonatal intensive care unit of a tertiary teaching hospital. 200 out born neonates with sepsis admitted to the nursery from January to July 2003 were evaluated for presence of ARF (cases) or not (controls). Sepsis was diagnosed on the basis of either a positive sepsis screen (immature: total (I:T) neutrophil ratio > 0.2, micro-ESR > age in days + 2 mm or> 15 mm, CRP> 6 mg/dl, TLC< 5000 cells/mm3; 2 or more positive) or a positive blood culture in symptomatic neonates. ARF was defined as blood urea nitrogen (BUN)> 20mg/dl on two separate occasions at least 24 hours apart. Oliguria was defined as urine output < 1 ml/Kg/hr. RESULTS: 52 out of 200 (26%) neonates with sepsis had ARF; only 15% of ARF was oliguric. The mean gestation of neonates with ARF was similar to those without ARF (36.1+/-4.1 wks vs. 36.6+/-3.5 wk; p = 0.41). A significantly higher number of babies with ARF weighed less than 2500 gm as compared to those without ARF (86.5% vs 67.6%; p = 0.008). The association of meningitis, disseminated intravascular coagulation (DIC) and shock was also significantly higher in neonates with ARF (46.8% vs 26.2%, p = 0.01; 65.4% vs 20.3%, p < 0.001; 71.2% vs 27.0%, p < 0.001 respectively). Mortality in neonates who developed ARF was significantly higher (70.2% vs 25%, p < 0.001). Factors including gestational age, weight, onset of sepsis, culture positivity, associated meningitis, asphyxia, shock, prior administration of nephrotoxic drugs were subjected to univariate analysis for prediction of fatality in neonates with sepsis and ARF; only shock was found to be a significant predictor of fatality (p< 0.001). ARF had recovered in 22 out of 49 neonates in whom data was available; three patients had left against medical advice. The mean duration of recovery in these 22 neonates was 5.5 days (range 1-14 days). Presence of co-existing morbidities (perinatal asphyxia/congestive heart failure (CHF)/ necrotising enterocolitis (NEC)) or nephrotoxic drugs did not alter the frequency of recovery of ARF in septic neonates (45.5% vs 44.4%,p = 0.944; 41% vs 52%, p = 0.308 respectively). CONCLUSION: Renal failure occurred in 26% neonates with sepsis. Although ARF in neonates has been reported to be predominantly oliguric, it was observed that ARF secondary to neonatal sepsis was predominantly non oliguric. Low birth weight was an important risk factor for the development of ARF. The mortality being three times higher in neonates with ARF demands a greater awareness of this entity among practitioners and better management of this condition.

Acute Kidney Injury↗
PubMed1997

Iatrogenic vascular lesions in extremely low birth weight and low birth weight neonates.

PURPOSE: Aggressive treatment has improved the long-term outcome of extremely low birth weight (ELBW) and low birth weight (LBW) neonates, but it has also increased the risk of iatrogenic lesions. The aim of this paper is to evaluate the incidence of vascular injuries observed in the neonatal intensive care unit of our hospital. METHODS: From 1987 to 1994, 2898 neonates were admitted to the neonatal intensive care unit; 335 of them were either LBW or ELBW (11.5%). A review of the charts of these neonates disclosed nine neonates (four male, five female) with vascular lesions (2.6%); the mean gestational age of these patients was 28.7 weeks (range, 24 to 33 weeks), the mean weight at birth was 880 g (range, 590 to 1450 g), and the mean weight at diagnosis was 1825 g (range, 1230 to 2700 g). In the same period, 10 neonates with vascular injuries were reported in the 2563 neonates who weighed more than 1500 g (0.3%). The injuries observed in LBW and ELBW group were arteriovenous fistulas (two bilateral) at the femoral level (six neonates), carotid lesion (one neonate), and limb ischemia (two neonates). Injury was associated with venipuncture in seven neonates, and with umbilical catheter in one; the case of carotid lesion was related to surgical error. No general symptoms were observed. RESULTS: The carotid lesion and five arteriovenous fistulas were repaired by microsurgical techniques; one case of limb ischemia was resolved with thrombolytic drugs, whereas an amputation at the knee level was required in the other after 10 days of medical treatment. One neonate with an arteriovenous fistula was just observed according to the parents' wishes. At clinical and echo-color Doppler follow-up, seven of nine neonates had normal vascular function without sequelae. CONCLUSIONS: In our experience, LBW and ELBW neonates are at greater risk than older neonates of the development of iatrogenic vascular lesions. We advocate aggressive microsurgery, medical treatment, or both to obtain good results and prevent late sequelae.

Arteriovenous Fistula↗
PubMed2003

US birth weight/gestational age-specific neonatal mortality: 1995-1997 rates for whites, hispanics, and blacks.

OBJECTIVE: In recent years, gains in neonatal survival have been most evident among very low birth weight, preterm, and low birth weight (LBW) infants. Most of the improvement in neonatal survival since the early 1980s seems to be the consequence of decreasing birth weight-specific mortality rates, which occurred during a period of increasing preterm and LBW rates. Although the decline in neonatal mortality has been widely publicized in the United States, research suggests that clinicians may still underestimate the chances of survival of an infant who is born too early or too small and may overestimate the eventuality of serious disability. So that clinicians may have current and needed ethnic- and race-specific estimates of the "chances" of early survival for newborn infants, we examined birth weight/gestational age-specific neonatal mortality rates for the 3 largest ethnic/racial groups in the United States: non-Hispanic whites, Hispanics, and non-Hispanic blacks. Marked racial variation in birth weight and gestational age-specific mortality has long been recognized, and growing concerns have been raised about ongoing and increasing racial disparities in pregnancy outcomes. Our purpose for this investigation was to provide an up-to-date national reference for birth weight/gestational age-specific neonatal mortality rates for use by clinicians in care decision making and discussions with parents. METHODS: The National Center for Health Statistics linked live birth-infant death cohort files for 1995-1997 were used for this study. Singleton live births to US resident mothers with a reported maternal ethnicity/race of non-Hispanic white, non-Hispanic black, or Hispanic (n = 10 610 715) were selected for analysis. Birth weight/gestational age-specific neonatal mortality rates were calculated using 250 g/2-week intervals for each ethnic/racial group. RESULTS: The overall neonatal mortality rates for whites, Hispanics, and blacks were 3.24, 3.45, and 8.16 neonatal deaths per 1000 live births, and the proportion of births <28 weeks was 0.35%, 0.45%, and 1.39%, respectively. Newborns who weighed <1500 g comprised <2.5% of all births in each racial/ethnic group but accounted for >50% of neonatal deaths. For whites, Hispanics, and blacks, >50% of newborns 24 to 25 weeks of gestational age survived. For most combinations of birth weights <3500 g and gestational ages of <37 weeks, the neonatal mortality rate was lowest among blacks, compared with whites or Hispanics. At these same gestational age/birth weight combinations, Hispanics have slightly lower mortality rates than whites. For combinations of birth weights >3500 g and gestational ages of 37 to 41 weeks, Hispanics had the lowest neonatal mortality rate. In these birth weight/gestational age combinations, where approximately two thirds of births occur, blacks had the highest neonatal mortality rate. CONCLUSIONS: Compared with earlier reports, these data suggest that a substantial improvement in birth weight/gestational age-specific neonatal mortality has occurred in the United States. Regardless of ethnicity/race, the risk of a neonatal death does not exceed 50% (the suggested definition for the limit of viability), except for birth weights below 500 g and gestational ages <24 weeks. Notwithstanding, ethnic/racial variations in neonatal mortality rates continue to persist, both in overall rates and within birth weight/gestational age categories. Blacks continue to have higher proportions for preterm and LBW births, compared with either whites or Hispanics. At the same time, blacks experience lower risks of neonatal mortality for preterm and LBW infants, while having higher risks of mortality among term, postterm, normal birth weight, and macrosomic births.

Black or African American↗
PubMed1990

Clinical pharmacokinetics of antibacterial drugs in neonates.

Neonatal patients are surviving longer due to the rapid advances in medical knowledge and technology. Our understanding of the developmental physiology of both preterm and full term neonates has also increased. It is now apparent that differences in body composition and organ function significantly affect the pharmacokinetics of antibacterial drugs in neonates, and dosage modifications are required to optimise antimicrobial therapy. The penicillins and cephalosporins are frequently used in neonates. Although ampicillin has replaced benzylpenicillin (penicillin G) for empirical treatment of neonatal sepsis, many of the other penicillins may be used in neonates for the management of various infections. Increased volume of distribution (Vd) and decreased total body clearance (CL) affect the disposition of penicillins and cephalosporins. Decreased renal clearance (CLR) due to decreased glomerular filtration and tubular secretion is responsible for the decreased CL for most of the beta-lactams. Aminoglycoside Vd is affected by the increased total body water content and extracellular fluid volume of neonates. The increased Vd, in part, accounts for the extended elimination half-life (t1/2) observed in neonates. Aminoglycoside CL is dependent on renal glomerular filtration which is markedly decreased in neonates, especially those preterm. These drugs appear to be less nephrotoxic and ototoxic in neonates than in older patients, and the role of serum concentration monitoring should be limited to specific neonatal patients. Other antibiotics such as vancomycin, teicoplanin, chloramphenicol, rifampicin, erythromycin, clindamycin, metronidazole and cotrimoxazole (trimethoprim plus sulfamethoxazole) may be used in certain clinical situations. The emergence of staphylococcal resistance to penicillins has increased the need for vancomycin. With the exceptions of vancomycin and chloramphenicol, the efficacy and safety of these other agents in neonates have not been established. The need for serum vancomycin concentration monitoring may be limited, as with aminoglycosides, while safety concerns warrant the routine monitoring of serum chloramphenicol concentrations in neonates. Dosing guidelines are provided, based on the pharmacokinetics of the drugs and previously published recommendations. These dosing guidelines are intended for initial therapy, and close therapeutic monitoring is recommended for maintenance dose requirements to optimise patient outcome. There has been an enormous increase in our knowledge of neonatal physiology and drug disposition. Fortunately, many of the antibacterial drugs used in neonates (e.g. penicillins and cephalosporins) are relatively safe. It will be important to evaluate all newly developed antibiotics in neonates to assure their maximum efficacy and safety.

Aminoglycosides↗
PubMed2001

Burden of morbidities and the unmet need for health care in rural neonates--a prospective observational study in Gadchiroli, India.

BACKGROUND: Majority of the neonates in developing countries are born and cared for in rural homes but the available information is mostly hospital based. OBJECTIVES: To estimate: (i) the incidence of various neonatal morbidities and associated case fatality in home-cared rural neonates, (ii) proportion of neonates with indications for health care, and (iii) the proportion who actually receive it. DESIGN: Prospective observational study. SETTING: Rural homes. METHODS: Neonates in 39 study villages in the Gadchiroli district (Maharashtra, India) were observed during one year (1995-96) by 39 trained female village health workers at birth and during neonatal period (0-28 days) by making eight home visits. A physician checked the data and the morbidities were diagnosed by a computer program. Vital statistics in these villages was independently collected. RESULTS: Out of 1016 live births, 95% occurred at home and 763 (75&%) neonates were observed. The agreement between observations by health workers and physician was 92%. Total 48.2& neonates suffered high risk morbidities (associated case fatality >10%), 72.2% suffered low risk morbidities, and 17.9% gained inadequate weight (less than 300 g). Seventeen percent neonates developed clinical picture suggestive of sepsis. Though 54.4% neonates had indications for health care and 38 out of total 40 neonatal deaths occurred in these, only 2.6% received medical attention. The neonatal mortality rate was 52.4/1000 live births. CONCLUSION: Nearly half of the neonates in rural homes developed high risk morbidities ten times the neonatal morbidity rate and needed health care but practically none received it. The magnitude of care gap suggests an urgent need for developing home-based neonatal care to reduce neonatal morbidities and mortality

Cause of Death↗
PubMed1998

P-Selectin support of neonatal neutrophil adherence under flow: contribution of L-selectin, LFA-1, and ligand(s) for P-selectin.

To further define the neonatal neutrophil's ability to localize to inflamed tissue compared with adult cells, we examined the neonatal neutrophil interactions with P-selectin monolayers under two conditions: (1) attachment under constant shear stress and flow and (2) detachment where cells were allowed to attach in the absence of shear stress and then shear stress is introduced and increased in step-wise increments. Cord blood and adult neutrophils had minimal interactions with unstimulated human umbilical vein endothelial cells (HUVECs) at a constant shear stress of 2 dynes/cm2. There was a marked increase in the number of both neonatal and adult cells interacting (interacting cells = rolling + arresting) with HUVECs after histamine stimulation, although the neonatal value was only 40% of adult (P < .05). Neonatal neutrophils also had significantly decreased interaction with monolayers of Chinese hamster ovary (CHO) cells transfected with human P-selectin (CHO-P-selectin; 60% of adult values, P < .003). Of the interacting cells, there was a lower fraction of neonatal cells that rolled compared with adult cells on both stimulated HUVECs and CHO-P-selectin. That neonatal neutrophil L-selectin contributes to the diminished attachment to P-selectin is supported by the following: (1) Neonatal neutrophils had significantly diminished expression of L-selectin. (2) Anti-L-selectin monoclonal antibody reduced the number of interacting adult neutrophils to the level seen with untreated neonatal neutrophils, but had no effect on neonatal neutrophils. In contrast, L-selectin appeared to play no role in maintaining the interaction of either neonatal or adult neutrophils in the detachment assay. Once attachment occurred, the neonatal neutrophil's interaction with the P-selectin monolayer was dependent on LFA-1 and to other ligands to a lesser degree based on the following: (1) Control neonatal neutrophils had decreased rolling fraction compared with adult neutrophils, although the total number of interacting neutrophils was equal between groups. (2) Anti-LFA-1 treatment resulted in an increase in the rolling fraction of both neonatal and adult neutrophils. However, whereas the number of interacting adult neutrophils remained unchanged, the number of neonatal neutrophils decreased with increased shear stress. We speculate that this increased detachment of neonatal cells is due to differences in neutrophil ligand(s) for P-selectin.

Adult↗
PubMed2000

Identification of neonatal hearing impairment: evaluation of transient evoked otoacoustic emission, distortion product otoacoustic emission, and auditory brain stem response test performance.

OBJECTIVES: The purpose of this study was to compare the performance of transient evoked otoacoustic emissions (TEOAEs), distortion product otoacoustic emissions (DPOAEs), and auditory brain stem responses (ABRs) as tools for identification of neonatal hearing impairment. DESIGN: A total of 4911 infants including 4478 graduates of neonatal intensive care units, 353 well babies with one or more risk factors for hearing loss (Joint Committee on Infant Hearing, 1994) and 80 well babies without risk factor who did not pass one or more neonatal test were targeted as the potential subject pool on which test performance would be assessed. During the neonatal period, they were evaluated using TEOAEs in response to an 80 dB pSPL click, DPOAE responses to two stimulus conditions (L1 = L2 = 75 dB SPL and L1 = 65 dB SPL L2 = 50 dB SPL), and ABR elicited by a 30 dB nHL click. In an effort to describe test performance, these "at-risk" infants were asked to return for behavioral audiologic assessments, using visual reinforcement audiometry (VRA) at 8 to 12 mo corrected age, regardless of neonatal test results. Sixty-four percent of these subjects returned and reliable VRA data were obtained on 95.6% of these returnees. This approach is in contrast to previous studies in which, by necessity, efforts were made to follow only those infants who "failed" the neonatal screening tests. The accuracy of the neonatal measures in predicting hearing status at 8 to 12 mo corrected age was determined. Only those infants who provided reliable, monaural VRA test results were included in the analysis. Separate analyses were performed without regard to intercurrent events (i.e., events between the neonatal and VRA tests that could cause their results to disagree), and then after accounting for the possible influence of intercurrent events such as otitis media and late-onset or progressive hearing loss. RESULTS: Low refer rates were achieved for the stopping criteria used in the present study, especially when a protocol similar to the one recommended in the National Institutes of Health (1993) Consensus Conference Report was followed. These analyses, however, do not completely describe test performance because they did not compare neonatal screening test results with a gold standard test of hearing. Test performance, as measured by the area under a relative operating characteristic curve, were similar for all three neonatal tests when neonatal test results were compared with VRA data obtained at 8 to 12 mo corrected age. However, ABRs were more successful at determining auditory status at 1 kHz, compared with the otoacoustic emission (OAE) tests. Performance was more similar across all three tests when they were used to identify hearing loss at 2 and 4 kHz. No test performed perfectly. Using either the two- or three-frequency pure-tone average (PTA), with a fixed false alarm rate of 20%, hit rates for the neonatal tests, in general, exceeded 80% when hearing impairment was defined as behavioral thresholds > or =30 dB HL. All three tests performed similarly when a two-frequency (2 and 4 kHz) PTA was used as the gold standard; OAE test performance decreased when a three-frequency PTA (adding 1 kHz) was used as the gold standard definition. For both PTA and all three neonatal screening measures, however, hit rate increased as the magnitude of hearing loss increased. CONCLUSIONS: Singly, all three neonatal hearing screening tests resulted in low refer rates, especially if referrals for follow-up were made only for the cases in which stopping criteria were not met in both ears. Following a protocol similar to that recommended in the National Institutes of Health (1993) Consensus Conference report resulted in refer rates that were less than 4%. TEOAEs at 80 dB pSPL, DPOAE at L1 = 65, L2 = 50 dB SPL and ABR at 30 dB nHL measured during the neonatal period, and as implemented in the current study, performed similarly at predicting behavioral hearing status at 8 to 12

Acoustic Stimulation↗
PubMed2002

Clinical manifestations of rotavirus infection in the neonatal intensive care unit.

OBJECTIVES: This report describes clinical signs of rotavirus infection (RVI) among neonates admitted to a neonatal intensive care unit (NICU), compares these signs between term and preterm neonates and assesses the seasonal distribution of RVI in the NICU with that of the community. METHODS: After an initial prevalence study of 28 days, a prospective longitudinal study in the NICU was conducted. During the next 48 months from December 1, 1991 to November 30, 1995, term and preterm NICU patients were evaluated daily for pre-defined deviations in their baseline gastrointestinal status. Fecal specimens of neonates who fulfilled the entry criteria were tested for rotavirus by a monoclonal antibody-based enzyme immunoassay and by immunoelectron microscopy. Demographic and outcome data for these neonates were collected. In addition data assessing RVI in the community were collected during this period. RESULTS: The prevalence of RVI among NICU patients was 18.4%. Of 194 neonates included in the longitudinal study, 95 had RVI. Neonates with RVI differed from those without RVI with respect to frequent stooling (P = 0.0005), higher percentage of bloody mucoid stools (P = 0.003) and higher percentage of watery stools (P = 0.023). The odds of these three clinical outcomes were approximately 2.5 times higher in neonates with RVI than in neonates without RVI. Among neonates included in the study advanced necrotizing enterocolitis occurred at the same rate (15%) among those with and without RVI. Comparisons between term and preterm neonates with RVI showed that frequent stooling (P = 0.003) and watery stools (P = 0.0001) occurred more often among term neonates, whereas bloody mucoid stools (P = 0.001), abdominal distention (P = 0.03) and intestinal dilatation (P = 0.016) were more common in preterm neonates. The seasonal distribution of RVI in NICU paralleled its distribution in the community. CONCLUSION: RVI appears prevalent in the NICU setting. An absence of watery stools in a neonate should not preclude consideration of RVI when evaluating gastrointestinal signs among neonates. The clinical spectrum of RVI differs in term and preterm infants.

Analysis of Variance↗
PubMed2005

Early intervention care programme for parents of neonates.

Parents with neonates in the neonatal intensive care unit (NICU) experience different needs at different stages of their neonates' stay in the NICU. The needs of parents with neonates in NICU's play an important role in aspects such as the ability to cope with changing parental roles and emotions, the relationship between parent and infant and the managing of the parents' own needs. The aim of this study was to develop an intervention care programme for parents with neonates in the NICU. This intervention care programme will empower parents to manage their own needs and the needs of their neonates while the neonate is admitted to the NICU and after discharge from the NICU / hospital. Literature is available on care programmes for neonates, but not on programmes for the parents of neonates in NICU. The study was a multi-phased study, using qualitative methodologies to determine the needs of South African parents with neonates in level III NICU's. In phase I, the needs of parents with neonates in NICU were elicited qualitatively. The needs were identified from the data and the results led to the implementation of phase II. In phase II the question was adjusted and new data was collected. Phase III was implemented to validate the data derived from phases I and II. The data was categorised in different need categories and these categories were used to plan an intervention care programme for parents with neonates in NICU's. The programme provides information to address needs as identified by parents in the research study and as derived from the literature. Need categories identified from the study and literature were as follows: information, communication, emotional, learning, discharge and individual needs. This programme is available in electronic format to enable parents to obtain information according to their changing needs and to provide unlimited access to updated information. The "Early intervention care programme for parents of neonates" will empower parents to manage their own needs and the needs of their neonates while the neonate is admitted to the NICU and after discharge from the NICU / hospital.

Adaptation, Psychological↗
PubMed2005

Early intervention care programme for parents of neonates.

Parents with neonates in the neonatal intensive care unit (NICU) experience different needs at different stages of their neonates' stay in the NICU. The needs of parents with neonates in NICU's play an important role in aspects such as the ability to cope with changing parental roles and emotions, the relationship between parent and infant and the managing of the parents' own needs. The aim of this study was to develop an intervention care programme for parents with neonates in the NICU. This intervention care programme will empower parents to manage their own needs and the needs of their neonates while the neonate is admitted to the NICU and after discharge from the NICU/hospital. Literature is available on care programmes for neonates, but not on programmes for the parents of neonates in NICU. The study was a multi-phased study, using qualitative methodologies to determine the needs of South African parents with neonates in level III NICU's. In phase I, the needs of parents with neonates in NICU were elicited qualitatively. The needs were identified from the data and the results led to the implementation of phase II. In phase II the question was adjusted and new data was collected. Phase III was implemented to validate the data derived from phases I and II. The data was categorised in different need categories and these categories were used to plan an intervention care programme for parents with neonates in NICU's. The programme provides information to address needs as identified by parents in the research study and as derived from the literature. Need categories identified from the study and literature were as follows: information, communication, emotional, learning, discharge and individual needs. This programme is available in electronic format to enable parents to obtain information according to their changing needs and to provide unlimited access to updated information. The "Early intervention care programme for parents of neonates" will empower parents to manage their own needs and the needs of their neonates while the neonate is admitted to the NICU and after discharge from the NICU/hospital.

Adaptation, Psychological↗
PubMed2005

Low birth weight and preterm neonates: can they be managed at home by mother and a trained village health worker?

OBJECTIVE: Observations on a cohort of neonates in the preintervention year of the field trial of home-based neonatal care (HBNC) in rural Gadchiroli, India, showed that preterm birth and low birth weight (LBW), <2500 g, constituted the most important risk factors. Owing to a limited access to hospital care, most neonates were managed at home in the subsequent intervention years. The objective of this paper is to evaluate the feasibility and effectiveness of managing LBW and preterm neonates in home setting. DESIGN: We retrospectively analyzed data from the intervention arm (39 villages) in the HBNC trial. Feasibility was assessed by coverage and by quality (19 indicators) of care. Effectiveness was evaluated by change in case fatality (CF) and in the incidence of comorbidities in LBW or preterm neonates by comparing the preintervention year (1995 to 1996) with the intervention years (1996 to 2003). RESULTS: During 1996 to 2003, total 5919 live births occurred in the intervention villages, out of whom 5510 (93%) received HBNC. These included 2015 LBW neonates and 533 preterm neonates, out of whom 97% received only home-based care. The coverage and quality of interventions assessed on 19 indicators was 80.5%. The CF in LBW neonates declined by 58% (from 11.3 to 4.7%, p<0.001), and in preterm neonates, by 69.5% (from 33.3 to 10.2%, p<0.0001). Incidence of the major comorbidities, viz., sepsis, asphyxia, hypothermia and feeding problems, declined significantly. Preterm-LBW neonates without sepsis (270) received only supportive care -- CF in them decreased from 28.2 to 11.5% (p<0.01), and those with sepsis (53) received supportive care and antibiotics -- CF in them decreased from 61 to 13.2% (p<0.005). Supportive care contributed 75% and treatment with antibiotics 25% in the total averted deaths in preterm-LBW neonates. The intrauterine growth restriction (IUGR)-LBW neonates without sepsis (1409) received only supportive care -- the CF was unchanged, and 181 with sepsis received supportive care and antibiotics -- the CF decreased from 18.4 to 8.8% (p<0.05). Treatment with antibiotics explained entire reduction in mortality in IUGR neonates. In total, 55 deaths in LBW neonates were averted by supportive care and 35 by the treatment with antibiotics. CONCLUSIONS: Home-based management of LBW and the preterm neonates is feasible and effective. It remarkably improved survival by preventing comorbidities, by supportive care, and by treating infections.

Adult↗
PubMed1994

Increased granulocyte-colony stimulating factor (G-CSF) levels in neonates with perinatal complications.

We have investigated cord blood granulocyte-colony stimulating factor (G-CSF) levels in neonates with or without neonatal complications to examine some changes in the G-CSF levels in the neonatal period. The G-CSF levels were measured in 613 neonates by enzyme immunoassay. The results showed that G-CSF levels were distributed in a broad range from the level under the cutting point (31 pg/mL) to over the measurable range (2000 pg/mL). Normal neonates without perinatal complications were 322. In normal neonates, the G-CSF level correlated with the gestational age (r = 0.255, P < 0.01) and cord blood leukocyte count (r = 0.210, P < 0.01). The G-CSF values were under 100 pg/mL in 95% of normal neonates with a median of 35.0 pg/mL. We divided the neonates into two groups: a lower (< 100 pg/mL) and a higher (> or = 100 pg/mL), based on the G-CSF level. The percentage of neonates with higher G-CSF levels (> or = 100 pg/mL) was greater in neonates with perinatal complications than in normal neonates (< 100 pg/mL; P < 0.01). Compared with normal neonates, the percentages of the higher group were greater in neonates with infections (P < 0.01), fetal distress (P < 0.01), premature rupture of membranes (P < 0.05), neonatal asphyxia (P < 0.01) and meconium staining of amniotic fluid (P < 0.01). Neonates with higher G-CSF levels had larger numbers of peripheral leukocytes (P < 0.05) than did those with the lower G-CSF levels. Counts of leukocytes were parallel with those of neutrophils.(ABSTRACT TRUNCATED AT 250 WORDS)

Fetal Blood↗