Prediction of hyperglycemia in preterm newborn infants

Many conditions are associated with hyperglycemia in preterm neonates because they are very susceptible to changes in carbohydrate homeostasis. The purpose of this study was to evaluate the occurrence of hyperglycemia in preterm infants undergoing glucose infusion during the first week of life, and to enumerate the main variables predictive of hyperglycemia. This prospective study (during 1994) included 40 preterm neonates (gestational age <37 weeks); 511 determinations of glycemic status were made in these infants (average 12.8/infant), classified by gestational age, birth weight, glucose infusion rate and clinical status at the time of determination (based on clinical and laboratory parameters). The clinical status was classified as stable or unstable, as an indication of the stability or instability of the mechanisms governing glucose homeostasis at the time of determination of blood glucose; 59 episodes of hyperglycemia (11.5%) were identified. A case-control study was used (case = hyperglycemia; control = normoglycemia) to derive a model for predicting glycemia. The risk factors considered were gestational age (<=31 vs. >31 weeks), birth weight (<=1500 vs. >1500 g), glucose infusion rate (<=6 vs. >6 mg/kg/min) and clinical status (stable vs. unstable). Multivariate analysis by logistic regression gave the following mathematical model for predicting the probability of hyperglycemia: 1/exp{-3.1437 + 0.5819(GA) + 0.9234(GIR) + 1.0978(Clinical status)} The main predictive variables in our study, in increasing order of importance, were gestational age, glucose infusion rate and, the clinical status (stable or unstable) of the preterm newborn infant. The probability of hyperglycemia ranged from 4.1% to 36.9%.

Urinary tract infection in full-term newborn infants: value of urine culture by bag specimen collection

OBJETIVE: to evaluate the efficacy of urine culture by bag specimen for the detection of neonatal urinary tract infection in full-term newborn infants. Retrospective study (1997) including full-term newborn infants having a positive urine culture (>100,000 CFU/ml) by bag specimen collection. The urinary tract infection diagnosis was confirmed by positive urine culture (suprapubic bladder aspiration method). The select cases were divided into three groups, according to newborn infant age at the bag specimen collection: GI (< 48 h, n = 17), GII (48 h to 7 d, n = 35) and GIII (> 7 d, n = 9). Sixty one full-term newborn infants were studied (5.1 % of total infants). The diagnosis was confirmed on 19/61 (31.1 %) of full-term infants born alive. Distribution among the groups was: GI = 2/17 (11.8 %), GII = 10//35 (28.6 %), and GIII = 7/9 (77.7 %). The most relevant clinical symptoms were: fever (GI - 100 %, GII - 91.4 %) and weight loss (GI - 35.3 %, GII - 45.7 %). Urine culture results for specimens collected by suprapubic aspiration were: E. coli GI (100 %), GII (40 %) and GIII (28.6 %), E. faecalis GI (30%), Staphylococcus coagulase-negative GII (20 %) and GIII (42.8 %), and Staphylococcus aureus GII (10 %). Correlation between positive urine culture collection (bag specimen method) and urinary tract infection diagnosis, using relative risk analysis, produced the following results: GI=0.30 (CI95% 0.08-1.15), GII=0.51 (CI 95% 0.25-1.06) and GIII=3.31 (CI95% 1.8-6.06) The most frequent urinary tract infection clinical signs in the first week were fever and weight loss, while non-specific symptomatology occurred later. E. coli was most frequent infectious agent, although from the 7th day of life, staphylococcus was noted. The urine culture (bag specimen method) was effective in detecting urinary tract infection only after the 7th day of life.

Relationship between plasma creatinine concentration and glomerular filtration in preterm newborn infants

Fluid management and dosage regimens of drugs in preterm infants should be based on the glomerular filtration rate. The current methods to determine glomerular flitration rate are invasive, time-consuming, and expensive. In contrast, creatinine clearance can be easy obtained and quickly determined. The purpose of this study was to compare plasma creatinine on the third and seventh day of life in preterm newborn infants, to evaluate the influence of maternal creatinine, and to demonstrate creatinine clearance can be used as a reliable indicator of glomerular filtration rate. We developed a prospective study (1994) including 40 preterm newborns (gestational age < 37 weeks), average = 34 weeks; birth weight (average) = 1840 g, in the first week of life. Inclusion criteria consisted of: absence of renal and urinary tract anomalies; O2 saturation 3 92%; adequate urine output (>1ml/kg/hr); normal blood pressure; absence of infections and no sympathomimetic amines in use. A blood sample was collected to determine plasma creatinine (enzymatic method) on the third and seventh day of life and creatinine clearance (CrCl) was obtained using the following equation: , k = 0.33 in preterm infant All plasma creatinine determinations showed normal values [third day: 0.78 mg/dl ± 0.24 (mean ± SD)and seventh day: 0.67 mg/dl ± 0.31 - (p>0.05)]. Also all creatinine clearance at third and seventh day of life were normal [third day: 19.5 ml/min ± 5.2 (mean ± SD) and seventh day: 23.8 ml/min ± 7.3 - (p>0,05)]. All preterm infants developed adequate renal function for their respective gestational age. In summary, our results indicate that, for clinical practice, the creatinine clearance, using newborn length, can be used to estimate glomerular filtration rate in preterm newborn infants.

Urinary tract infection in full-term newborn infants: risk factor analysis

OBJECTIVE: To analyze the correlation of risk factors to the occurrence of urinary tract infection in full-term newborn infants. PATIENTS AND METHODS: Retrospective study (1997) including full-term infants having a positive urine culture by bag specimen. Urine collection was based on: fever, weight loss > 10% of birth weight, nonspecific symptoms (feeding intolerance, failure to thrive, hypoactivity, debilitate suction, irritability), or renal and urinary tract malformations. In these cases, another urine culture by suprapubic bladder aspiration was collected to confirm the diagnosis. To compare and validate the risk factors in each group, the selected cases were divided into two groups: Group I - positive urine culture by bag specimen collection and negative urine culture by suprapubic aspiration, and Group II - positive urine culture by bag specimen collection and positive urine culture by suprapubic aspiration . RESULTS: Sixty one infants were studied, Group I, n = 42 (68.9%) and Group II, n = 19 (31.1%). The selected risk factors (associated infectious diseases, use of broad-spectrum antibiotics, renal and urinary tract malformations, mechanical ventilation, parenteral nutrition and intravascular catheter) were more frequent in Group II (p<0.05). Through relative risk analysis, risk factors were, in decreasing importance: parenteral nutrition, intravascular catheter, associated infectious diseases, use of broad-spectrum antibiotics, mechanical ventilation, and renal and urinary tract malformations. CONCLUSION: The results showed that parenteral nutrition, intravascular catheter, and associated infectious diseases contributed to increase the frequency of neonatal urinary tract infection, and in the presence of more than one risk factor, the occurrence of urinary tract infection rose up to 11 times.

Monitoring the treatment of sepsis with vancomycin in term newborn infants

A prospective study was conducted to determine if standardized vancomycin doses could produce adequate serum concentrations in 25 term newborn infants with sepsis. Purpose: The therapeutic response of neonatal sepsis by Staphylococcus sp. treated with vancomycin was evaluated through serum concentrations of vancomycin, serum bactericidal titers (SBT), and minimum inhibitory concentration (MIC). METHOD: Vancomycin serum concentrations were determined by the fluorescence polarization immunoassay technique , SBT by the macro-broth dilution method, and MIC by diffusion test in agar . RESULTS: Thirteen newborn infants (59.1%) had adequate peak vancomycin serum concentrations (20--40 mg/mL) and one had peak concentration with potential ototoxicity risk (>40 µg/mL). Only 48% had adequate trough concentrations (5--10 mg/mL), and seven (28%) had a potential nephrotoxicity risk (>10 µg/mL). There was no significant agreement regarding normality for peak and trough vancomycin method (McNemar test : p = 0.7905). Peak serum vancomycin concentrations were compared with the clinical evaluation (good or bad clinical evolution) of the infants, with no significant difference found (U=51.5; p=0.1947). There was also no significant difference between the patients' trough concentrations and good or bad clinical evolution (U = 77.0; p=0.1710). All Staphylococcus isolates were sensitive to vancomycin according to the MIC. Half of the patients with adequate trough SBT (1/8), also had adequate trough vancomycin concentrations and satisfactory clinical evolution. CONCLUSIONS: Recommended vancomycin schedules for term newborn infants with neonatal sepsis should be based on the weight and postconceptual age only to start antimicrobial therapy. There is no ideal pattern of vancomycin dosing; vancomycin dosages must be individualized. SBT interpretation should be made in conjunction with the patient's clinical presentation and vancomycin serum concentrations. Those laboratory and clinical data favor elucidation of the probable cause of patient's bad evolution, which would facilitate drug adjustment and reduce the risk of toxicity or failing to achieve therapeutic doses.

Early diagnosis of congenital toxoplasmosis in newborn infants using IgG subclasses against two Toxoplasma gondii recombinant proteins

The aim of this work was to evaluate the utility of ELISA-based testing of total IgG (IgGt) antibodies and its subclasses (IgG1, IgG2, IgG3 and IgG4) against soluble (STAg) and recombinant (rSAG1 and rMIC3) antigens of Toxoplasma gondii for diagnosing congenital toxoplasmosis. Sera from 217 newborns initially testing positive for specific IgM in filter paper dried blood spots were tested for specific IgM and IgG by ELFA-VIDAS®. Congenital toxoplasmosis was confirmed in 175 and ruled out in 42 infants. The validity of the ELISA tests was determined using the persistence of IgG antibodies (ELFA-VIDAS® kit) at the end of 12 months, which is considered the reference test for the diagnosis of congenital toxoplasmosis. The frequency of positivity with IgGt against STAg, rSAG1 and rMIC3 was found in 97.2%, 96.3% and 80.2%, respectively, of the newborns with confirmed congenital toxoplasmosis. IgG1 reacted with all three antigens, while IgG3 and IgG4 reacted preferentially with rMIC3. Higher mean values of reactivity (sample optical density/cut-off) were found for all subclasses when using rMIC3. All of the antigens showed high sensitivity and low specificity in detecting anti-T. gondii IgGt and IgG1 and low sensitivity and high specificity in detecting IgG3 and IgG4. In conclusion, the combined detection of IgG antibody subclasses against recombinant toxoplasmic antigens may be useful for the early diagnosis of congenital toxoplasmosis.

Amino acid composition of parturient plasma, the intervillous space of the placenta and the umbilical vein of term newborn infants

The objective of the present study was to determine the levels of amino acids in maternal plasma, placental intervillous space and fetal umbilical vein in order to identify the similarities and differences in amino acid levels in these compartments of 15 term newborns from normal pregnancies and deliveries. All amino acids, except tryptophan, were present in at least 186% higher concentrations in the intervillous space than in maternal venous blood, with the difference being statistically significant. This result contradicted the initial hypothesis of the study that the plasma amino acid levels in the placental intervillous space should be similar to those of maternal plasma. When the maternal venous compartment was compared with the umbilical vein, we observed values 103% higher on the fetal side which is compatible with currently accepted mechanisms of active amino acid transport. Amino acid levels of the placental intervillous space were similar to the values of the umbilical vein except for proline, glycine and aspartic acid, whose levels were significantly higher than fetal umbilical vein levels (average 107% higher). The elevated levels of the intervillous space are compatible with syncytiotrophoblast activity, which maintain high concentrations of free amino acids inside syncytiotrophoblast cells, permitting asymmetric efflux or active transport from the trophoblast cells to the blood in the intervillous space. The plasma amino acid levels in the umbilical vein of term newborns probably may be used as a standard of local normality for clinical studies of amino acid profiles.

Plasma amino acids in pregnancy, placental intervillous space and preterm newborn infants

Plasma amino acid levels have never been studied in the placental intervillous space of preterm gestations. Our objective was to determine the possible relationship between plasma amino acids of maternal venous blood (M), of the placental intervillous space (PIVS) and of the umbilical vein (UV) of preterm newborn infants. Plasma amino acid levels were analyzed by ion-exchange chromatography in M from 14 parturients and in the PIVS and UV of their preterm newborn infants. Mean gestational age was 34 ± 2 weeks, weight = 1827 ± 510 g, and all newborns were considered adequate for gestational age. The mean Apgar score was 8 and 9 at the first and fifth minutes. Plasma amino acid values were significantly lower in M than in PIVS (166%), except for aminobutyric acid. On average, plasma amino acid levels were significantly higher in UV than in M (107%) and were closer to PIVS than to M values, except for cystine and aminobutyric acid (P < 0.05). Comparison of the mean plasma amino acid concentrations in the UV of preterm to those of term newborn infants previously studied by our group showed no significant difference, except for proline (P < 0.05), preterm > term. These data suggest that the mechanisms of active amino acid transport are centralized in the syncytiotrophoblast, with their passage to the fetus being an active bidirectional process with asymmetric efflux. PIVS could be a reserve amino acid space for the protection of the fetal compartment from inadequate maternal amino acid variations.

Comparison of direct immunofluorescence, conventional cell culture and polymerase chain reaction techniques for detecting respiratory syncytial virus in nasopharyngeal aspirates from infants

A total of 316 samples of nasopharyngeal aspirate from infants up to two years of age with acute respiratory-tract illnesses were processed for detection of respiratory syncytial virus (RSV) using three different techniques: viral isolation, direct immunofluorescence, and PCR. Of the samples, 36 (11.4%) were positive for RSV, considering the three techniques. PCR was the most sensitive technique, providing positive findings in 35/316 (11.1%) of the samples, followed by direct immunofluorescence (25/316, 7.9%) and viral isolation (20/315, 6.3%) (p < 0.001). A sample was positive by immunofluorescence and negative by PCR, and 11 (31.4%) were positive only by RT-PCR. We conclude that RT-PCR is more sensitive than IF and viral isolation to detect RSV in nasopharyngeal aspirate specimens in newborn and infants.

Inhaled nitric oxide in the management of persistent pulmonary hypertension of the newborn: a meta-analysis

OBJECTIVES: To evaluate the use of inhaled nitric oxide (NO) in the management of persistent pulmonary hypertension of the newborn. METHODS: Computerized bibliographic search on MEDLINE, CURRENT CONTENTS and LILACS covering the period from January 1990 to March 1998; review of references of all papers found on the subject. Only randomized clinical trials evaluating nitric oxide and conventional treatment were included. OUTCOMES STUDIED: death, requirement for extracorporeal membrane oxygenation (ECMO), systemic oxygenation, complications at the central nervous system and development of chronic pulmonary disease. The methodologic quality of the studies was evaluated by a quality score system, on a scale of 13 points. RESULTS: For infants without congenital diaphragmatic hernia, inhaled NO did not change mortality (typical odds ratio: 1.04; 95% CI: 0.6 to 1.8); the need for ECMO was reduced (relative risk: 0.73; 95% CI: 0.60 to 0.90), and the oxygenation was improved (PaO2 by a mean of 53.3 mm Hg; 95% CI: 44.8 to 61.4; oxygenation index by a mean of -12.2; 95% CI: -14.1 to -9.9). For infants with congenital diaphragmatic hernia, mortality, requirement for ECMO, and oxygenation were not changed. For all infants, central nervous system complications and incidence of chronic pulmonary disease did not change. CONCLUSIONS: Inhaled NO improves oxygenation and reduces requirement for ECMO only in newborns with persistent pulmonary hypertension who do not have diaphragmatic hernia. The risk of complications of the central nervous system and chronic pulmonary disease were not affected by inhaled NO.

TNF-a and IL-10 levels in tracheobronchial lavage of ventilated preterm infants and subsequent lung function

The role of airway inflammation in ventilated preterm newborns and the risk factors associated with the development of chronic lung disease are not well understood. Our objective was to analyze the association of the airway inflammatory response in ventilated preterm infants by serial measurements of TNF-a and IL-10 in tracheobronchial lavage (TBL) with perinatal factors and lung function measured early in life. A series of TBL samples were collected from ventilated preterm infants (less than 32 weeks of gestational age) and concentrations of TNF-a and IL-10 were measured by ELISA. Pulmonary function tests were performed after discharge by the raised volume rapid compression technique. Twenty-five subjects were recruited and 70 TBL samples were obtained. There was a significant positive association between TNF-a and IL-10 levels and length of time between the rupture of the amniotic membranes and delivery (r = 0.65, P = 0.002, and r = 0.57, P < 0.001, respectively). Lung function was measured between 1 and 22 weeks of corrected age in 10 patients. Multivariable analysis with adjustment for differences in lung volume showed a significant negative association between TNF-a levels and forced expiratory flow (FEF50; r = -0.6; P = 0.04), FEF75 (r = -0.76; P = 0.02), FEF85 (r = -0.75; P = 0.03), FEF25-75 (-0.71; P = 0.02), and FEV0.5 (r = -0.39; P = 0.03). These data suggest that TNF-a levels in the airways during the first days of life were associated with subsequent lung function abnormalities measured weeks or months later.

Maternal neurotic symptoms and infants' risk of developing persistent diarrhoea

A previously calculated predictive model for health risk selects infants who suffer 4-5 times more morbidity than their unselected peers. Preliminary results suggested that this risk is related to maternal neurotic symptomatology. To evaluate this hypothesis, 52 consecutive mothers whose infants had a positive predictive score (Group 1) and 52 in whom this was negative (Group 2) were evaluated by means of Goldberg's General Health Questionnaire (GHQ - 30). A total of 41.9% and 20.5% of the mothers in Groups 1 and 2, respectively, scored above 11 points in GHQ-30, established as the cut off point. It is concluded that among poor urban families in Santiago mothers of infants with high risk of persistent diarrhoea have increased frequency of detectable neurotic symptoms. New programs aimed at this type of infant should include psychological support for their mothers.

Lack of association between iron status at birth and growth of preterm infants

OBJECTIVE: To assess the association between iron status at birth and growth of preterm infants. METHODS: Ninety-five premature babies (26 to 36 weeks of gestational age) born from July 2000 to May 2001 in a public hospital in Rio de Janeiro, Southeastern Brazil, were followed up for six months, corrected by gestational age. Iron measurements at birth were available for 82 mothers and 78 children: hemoglobin, hematocrit, mean corpuscular volume and plasma iron. All children received free doses of iron supplement (2 mg/kg/day) during the follow-up period and up to two years of age. Multivariate linear regression analyses with repeated measurements were performed to assess factors associated to linear growth. RESULTS: Growth was more pronounced up to 40 weeks of gestational age, increasing about 1.0 cm/week and then slowing down to 0.75 cm/week. The multivariate analysis showed growth was positively associated with birth weight (0.4 cm/100 g; p<0.001) and negatively associated with gestational age at birth (-0.5 cm/week; p<0.001). There was no association between cord iron and mother iron measurements and growth (p>0.60 for all measures). Only two children had anemia at birth, whereas 43.9% of mothers were anemic (hemoglobin <11 g/dl). Also, there was no correlation between anemia indicators of mothers and children at birth (r<0.15; p>0.20). CONCLUSIONS: Maternal anemia was not associated with anemia in preterm infants and iron status of mothers and children at birth was not associated with short-term growth of preterm infants.

HIV rapid testing as a key strategy for prevention of mother-to-child transmission in Brazil

OBJECTIVE: To assess the feasibility of HIV rapid testing for pregnant women at maternity hospital admission and of subsequent interventions to reduce perinatal HIV transmission. METHODS: Study based on a convenience sample of women unaware of their HIV serostatus when they were admitted to delivery in public maternity hospitals in Rio de Janeiro and Porto Alegre, Brazil, between March 2000 and April 2002. Women were counseled and tested using the Determine HIV1/2 Rapid Test. HIV infection was confirmed using the Brazilian algorithm for HIV infection diagnosis. In utero transmission of HIV was determined using HIV-DNA-PCR. There were performed descriptive analyses of sociodemographic data, number of previous pregnancies and abortions, number of prenatal care visits, timing of HIV testing, HIV rapid test result, neonatal and mother-to-child transmission interventions, by city studied. RESULTS: HIV prevalence in women was 6.5% (N=1,439) in Porto Alegre and 1.3% (N=3.778) in Rio de Janeiro. In Porto Alegre most of women were tested during labor (88.7%), while in Rio de Janeiro most were tested in the postpartum (67.5%). One hundred and forty-four infants were born to 143 HIV-infected women. All newborns but one in each city received at least prophylaxis with oral zidovudine. It was possible to completely avoid newborn exposure to breast milk in 96.8% and 51.1% of the cases in Porto Alegre and Rio de Janeiro, respectively. Injectable intravenous zidovudine was administered during labor to 68.8% and 27.7% newborns in Porto Alegre and Rio de Janeiro, respectively. Among those from whom blood samples were collected within 48 hours of birth, in utero transmission of HIV was confirmed in 4 cases in Rio de Janeiro (4/47) and 6 cases in Porto Alegre (6/79). CONCLUSIONS: The strategy proved feasible in maternity hospitals in Rio de Janeiro and Porto Alegre. Efforts must be taken to maximize HIV testing during labor. There is a need of strong social support to provide this population access to health care services after hospital discharge.