Diuretics for very low birth weight infants in the first 28 days: a survey of the U.S. neonatologists.

OBJECTIVE: The objective of this study was to describe factors influencing diuretic use by neonatologists caring for very low birth weight neonates. STUDY DESIGN: We surveyed 400 U.S. neonatologists. Respondents made therapeutic decisions in clinical scenarios involving very low birth weight infants at 7, 14 and 28 days of age. RESULT: Response rate was 39%. Diuretic therapy was chosen in 31% of scenario decisions, with pro re nata dosing selected early and regular dosing more common at later ages. Diuretic use was strongly associated with method of respiratory support, and was chosen less often by those also choosing fluid restriction and those concerned about patent ductus arteriosus risk. After adjusting for these factors, excessive weight gain, expected improvement in work of breathing and expected decrease in ventilator days were also associated with diuretic use. CONCLUSION: The extent of and expectations for diuretic therapy by neonatologists caring for very low birth weight neonates may exceed evidence for efficacy.

Unilateral diaphragmatic palsy in association with a subclavian vein thrombus in a very-low- birth-weight infant.

Phrenic nerve paralysis due to iatrogenic injury is not uncommon in neonates. We report an unusual case of acquired unilateral paralysis of the diaphragm in a very-low-birth-weight infant, associated with a thrombus secondary to percutaneous subclavian vein catheterization. Conservative management resulted in complete resolution of the paralyzed diaphragm.

Lactobacillus acidophilus sepsis in a neonate.

Lactobacillus species are non-spore-forming, anaerobic, gram-positive rods that cause disease in immunocompromised adults. Few cases have been described in children. We present the case of a 2-month-old infant who apparently developed Lactobacillus acidophilus sepsis from an infected central venous catheter. Physicians should be aware that although Lactobacillus species rarely cause disease in children, they should be considered a possible pathogen when isolated from the blood of a newborn infant.

Allergic gastroenteropathy in preterm infants.

OBJECTIVES: To determine the clinical presentation, histopathologic features, and outcome of biopsy-proven allergic gastroenteropathy (AGE) in preterm infants. We hypothesized that AGE is a more frequent cause of gastrointestinal disease in this population than previously suspected. STUDY DESIGN: The retrospective portion of the study, from 1992 to 1997, included preterm infants <37 weeks' gestation who underwent biopsy because of suspected AGE. The prospective portion, from January to December 1998, included 20 infants undergoing endoscopy and biopsy because of suspected AGE. RESULTS: Twenty-five infants (12 retrospective/13 prospective) with mean gestational age of 29 weeks at birth and mean postnatal age at diagnosis of 78 days were diagnosed with AGE. Three clinical patterns of presentation were noted: group 1, gastroesophageal reflux disease (n = 5); group 2, non-specific feeding intolerance (n = 8); and group 3, lower gastrointestinal bleeding (n = 12). Ten patients had negative biopsy findings (3 retrospective/7 prospective) and had clinical features indistinguishable from those of groups 1 and 2. Patients in group 3 were most likely to have positive biopsy findings (12 of 12). Fifteen patients responded to a casein hydrolysate formula, and 10 patients required an amino acid-based formula. Patients with AGE who had eosinophilic infiltration and villous atrophy took longer to recover than those with eosinophilic infiltration alone (P <.03). Subsequently, most have tolerated formula challenges and are currently tolerating cow's milk. CONCLUSIONS: AGE may be an under-recognized cause of gastrointestinal symptoms in preterm infants. Confirmation with endoscopy and biopsy can be done safely and provides the basis for appropriate dietary management.

Placental blood sampling: an aid to the diagnosis of neonatal sepsis.

OBJECTIVE: To determine the usefulness of placental blood cultures in establishment of the diagnosis of early onset sepsis. STUDY DESIGN: Babies born to mothers with suspected intraamniotic fluid infection had blood cultures obtained from a branch of the umbilical vein on the fetal surface of the placenta immediately after delivery. The babies at highest risk (n = 35) had subsequent neonatal blood cultured from a peripheral vein (group 1), whereas 26 newborns at a lower risk did not (group 2). A group of 20 term babies born after uncomplicated labor and vaginal delivery or by elective cesarean delivery served as control subjects. RESULTS: Placental blood cultures were more often positive for pathogens in group 1 (7 of 35; 20%; 0.09 to 0.36) than in group 2 (0 of 26; 0 to 0.11) or control subjects (0 of 20; 0 to 0.14; p < 0.02). Within group 1, placental blood cultures were more often positive (7 of 35; 20%; 0.09 to 0.36) than subsequent neonatal blood cultures (1 of 35; 3%; 0 to 0.15; p < 0.05). Contaminants were cultured in 3 of 81 (4%; 01 to 0.11) placental samples (all from group 1) compared with 1 of 35 (3%; 0 to 0.11) neonatal samples (difference not significant). CONCLUSIONS: A carefully obtained culture of placental blood may be a useful addition or substitute for neonatal blood culturing in newborns at risk for early-onset sepsis by virtue of maternal risk factors.

Pre-discharge outcomes of 22-27 weeks gestational age infants born at tertiary care centers in Connecticut implications for perinatal management.

There is a lack of regional data on survival and morbidity of extremely premature infants born and resuscitated at tertiary care centers. This study analyzes such data from three tertiary care perinatal centers in Connecticut and provides a paradigm for its use in developing guidelines for evidence-based ethical considerations in infants at the threshold of viability. Outcomes of inborn infants 22 to 27 weeks gestation (based on obstetric estimates) who were actively resuscitated at three regional perinatal tertiary-care centers (representing 80% of such infants from Connecticut) were studied retrospectively. Survival and cumulative major morbidities at discharge, stratified by gestational age, were analyzed. Of the 405 infants studied, 278 (69%) survived to discharge. There were no survivors beyond three days at 22 weeks gestational age. Unfavorable outcome defined as death or major morbidity (> or = grade 2 intraventricular hemorrhage, periventricular leukomalacia, > or = Stage 3 retinopathy of prematurity, necrotizing enterocolitis > or = Stage 2, and severe bronchopulmonary dysplasia at 36 weeks postmenstrual age.) was seen in > 85% of 23 and 24 weeks gestation infants. At 25 weeks approximately equal to 30% of infants were discharged without an unfavorable outcome. At 26 and 27 weeks gestation 43% and 61% respectively escaped unfavorable outcomes with > 85% rates of survival. Current regional data such as these would help in developing guidelines for the perinatal management of premature infants at the threshold of viability.

Effects of dexamethasone on blood pressure in premature infants with bronchopulmonary dysplasia.

OBJECTIVE: To determine the incidence and time course of blood pressure elevation in dexamethasone-treated premature infants with bronchopulmonary dysplasia. METHODS: In a prospective, self-controlled, consecutive case study, 16 ventilator-dependent very low birth weight neonates treated with dexamethasone were studied. Systolic, diastolic, and mean arterial pressure and heart rate were recorded at three specific times daily. Data were recorded from day 1 of dexamethasone treatment through the duration of therapy and up to 2 weeks after its completion. Retrospective daily data were collected for up to 14 days before therapy. RESULTS: The 788 daily observations (a systolic and diastolic average of the three blood pressure recordings per day) were recorded for 16 infants, a mean of 49 +/- 11 daily observations each (range, 24 to 67). Systolic and diastolic blood pressures before dexamethasone therapy were correlated to corrected gestational age. At initiation of dexamethasone, blood pressures increased significantly from days 1 to 2. For all observations, mean systolic pressure was 51 +/- 9.5 mm Hg before dexamethasone therapy, compared with 64 +/- 10.2 mm Hg during therapy (p < 0.01); diastolic pressure was 29 +/- 6.7 mm Hg before therapy compared with 41 +/- 8.2 mm Hg during therapy (p < 0.01). After completion of dexamethasone therapy, pressures continued to increase: systolic, 67 +/- 8.8 mm Hg (p < 0.01); diastolic, 42 +/- 6.2 mm Hg (not significant). Both systolic and diastolic pressures increased as a function of weight and age; when we controlled for these covariates, an independent effect of dexamethasone itself on the group was shown. Of the 2182 individual systolic pressure readings, 9.4% were considered in the hypertensive range. The six infants treated with hydralazine had higher mean systolic pressures before dexamethasone therapy than did infants without hydralazine (56 +/- 9.4 mm Hg vs 46 +/- 6.4 mm Hg; p < 0.001) and were 2 weeks older at initiation of therapy. CONCLUSIONS: Blood pressure significantly increases during dexamethasone therapy, particularly within the first 48 hours, and does not return to baseline levels after therapy. Those infants most likely to be labeled hypertensive tend to be older at initiation of therapy but do not appear to have any other significant risk factors.

Intrapartum chemoprophylaxis for group B streptococcus infection to prevent neonatal disease: who should be treated?

The purpose of this study was to examine the maternal risk factors associated with early onset Group B streptococcus (GBS) sepsis and determine the potential impact of intrapartum chemoprophylaxis using these risk factors. Using a computerized perinatal database, 26,525 deliveries over a five-year period (1989 to 1994) were identified. Neonates with GBS-positive cultures were identified and the neonatal and maternal chart of each case was reviewed. Twenty-six neonates (1 of 1000) had GBS sepsis documented by blood or cerebrospinal fluid culture. Maternal risk factor(s) were identified in 13 (50%) cases: preterm labor (5), preterm premature rupture of the membranes (5), prolonged rupture of membranes (6), sibling affected by symptomatic GBS infection (2), or maternal fever during labor (5). There were four mothers whose neonates had GBS sepsis in spite of intrapartum antibiotics. Intrapartum chemoprophylaxis for GBS based on risk factors alone will identify only half of the neonates who develop disease. Extension of intrapartum chemoprophylaxis to patients with risk factors appears to be necessary to prevent early onset disease in the other half. Since 85.7% of our total obstetrical population has no risk factors, this policy would require treating 1749 women to prevent one case of GBS sepsis. Chemoprophylaxis could be more appropriately targeted if mothers colonized with GBS could be identified in early labor.

Necrotizing enterocolitis: laboratory indicators of surgical disease.

The timely distinction between infants with necrotizing enterocolitis (NEC) who need surgery and those who are likely to recover with medical management is important, but it may be difficult clinically. Because pneumoperitoneum is not always present, additional markers of bowel gangrene are needed. Among 73 babies managed for NEC over the study period, 49 (67%) met the study criteria of Bell's stage > 1, and their records were reviewed to determine the usefulness of common laboratory tests in predicting outcome. The patients were divided into three groups based on management. Group 1 (7 patients) required surgery at the time of initial presentation because of pneumoperitoneum. The remaining 42 patients were initially managed medically, 19 of whom (group 2) recovered successfully; the other 23 (group 3) required surgery. The combination of certain laboratory tests, ie, white blood cell count (WBC), immature:total neutrophil ratio (I:T), platelet count (PLT), and base excess (BE), was of significance in distinguishing between infants who would need surgery and those who would recover with medical therapy (group 3 v group 2) 4 to 12 hours or 12 to 24 hours after the diagnosis of NEC was established. A scoring scale was developed, with a point for each of the following: WBC < 9,000/mm3, I:T > .5, PLT < 200,000/mm3, and BE < or = -2. A score of > or = 3 during 4 to 12 hours after diagnosis of NEC strongly predicted the presence of surgical disease (positive predictive value, 100%; negative predictive value, 76%; specificity, 100%; sensitivity, 64%).(ABSTRACT TRUNCATED AT 250 WORDS)

Fetal myocardial calcification associated with maternal cocaine use.

Two cases of fetal myocardial calcification confirmed postnatally are reported. In contrast to other reports, both infants survived with resolution of calcification by 6 and 12 months. Diagnostic investigations failed to confirm the presence of congenital infection. Both pregnancies were complicated by early cocaine use leading to the speculation that myocardial necrosis with subsequent calcification related to the toxic and/or vascular effects of cocaine was responsible. The finding of fetal myocardial calcification on prenatal ultrasound should prompt a search for causes, which may include cocaine exposure.

Effect of corticosteroids on the maturation of neutrophil motility in very low birthweight neonates.

Neutrophil (PMN) chemotaxis and chemokinesis were longitudinally studied in a group of 17 neonates with birthweights between 750 and 1250 g. Five of the 17 neonates were treated with prenatal betamethasone to attempt to prevent hyaline membrane disease, six received postnatal dexamethasone in an effort to reduce bronchopulmonary dysplasia, three received both, and three were not treated with corticosteroids. The group of 17 neonates were tested on four separate occasions: (1-2, 3-4, 7-8, and 10-14 postnatal days). PMN chemotaxis and chemokinesis were determined using a standard micropore filter assay. A group of 36 adults was used as additional controls. There were no significant differences noted in PMN chemotaxis or chemokinesis for the corticosteroid vs the noncorticosteroid-treated groups. In the total group of 17 neonates, there was depression in PMN chemotaxis compared with adult values, which lasted at least through postnatal day 8. By day 13 to 14, PMN chemotactic values were similar to those of adults. In contrast, chemokinesis, was depressed during the initial 14 days (except for the first 2 postnatal days). These data suggest that perinatal corticosteroid administration does not affect PMN motility in newborn infants.

Effect of labor and delivery on neonatal polymorphonuclear leukocyte number and function.

The ability of the neonate to mount an adequate polymorphonuclear leukocyte (PMN) response, either quantitatively or functionally, is impaired. To assess whether neonatal PMN number and function are altered by labor and delivery, three groups of infants were studied: cesarean section without labor (10), cesarean section after labor (10), and vaginal delivery (11). PMN counts were higher in the groups undergoing labor (p less than 0.01) compared with the cesarean section without labor group. Similarly, the labor groups had evidence of complement activation (increased C3a desarg) compared with the cesarean section without labor group. No differences were noted between the groups in measures of PMN motility (chemokinesis or chemotaxis) or PMN degranulation (plasma lysozyme), suggesting that normal labor and delivery does not contribute to the general PMN dysfunction of the neonate.

Prevention of transfusion-associated cytomegalovirus infection in neonatal patients by the removal of white cells from blood.

The usual methods employed to reduce the risk of transfusion-associated cytomegalovirus (TA CMV) disease have been to transfuse blood or cellular blood components that are CMV antibody-negative or to administer deglycerolized frozen red cells. To determine if the reduction of white cells (WBCs) in blood by filtration will also eliminate TA CMV disease in a high-risk population, 48 surviving very low birth weight (less than 1250 g) neonatal infants born to CMV-seronegative mothers at three participating institutions in the Hartford, Connecticut area and receiving at least one CMV-seropositive blood transfusion were studied. The incidence of TA CMV disease in 26 neonatal patients who received blood prepared by a modified spin-cool-filter technique and in 22 neonatal patients who received blood filtered through a WBC-reduction filter was compared with the incidence of transfusion-associated disease in similar populations reported in other studies. The CMV antibody prevalence of the blood donor population was found to be 37 percent. At the time of discharge of the individual neonatal infants in the population studied, and/or 2 to 6 months later, 47 of the 48 who had undergone transfusion had CMV antibody-negative serologic tests and/or urine culture. The other infant transiently seroconverted because of passive transfer of the antibody. None of the 48 neonatal infants had clinical evidence of CMV infection. This study indicates that WBC reduction of donor blood can reduce and perhaps prevent TA CMV disease in high-risk neonatal patients.

Cytomegalovirus antibody detection in blood donors and mothers of very low birth weight neonates by using three serologic methods.

We compared three serologic methods for cytomegalovirus (CMV) antibody detection and determined the CMV antibody seroprevalence of blood donors and mothers of very low birth weight (less than 1250 g) neonates in the Greater Hartford region. CMV serology was determined for 577 healthy blood donors as well as for 147 mothers of premature infants. Plasma from blood donors and sera from mothers were tested by either latex agglutination (LA) or by an immunofluorescent antibody assay (IFA), and results were compared with those from an enzyme-linked immunosorbent assay (ELISA). Sensitivity and specificity for LA to ELISA were significantly better than for IFA to ELISA [sensitivity 79/81 (97%) vs 171/202 (85%), and specificity 90/94 (96%) vs 257/347 (74%), p less than 0.01]. These differences remained whether plasma or sera were tested. Borderline values explained only two (33%) of six LA-ELISA as well as only 70 (58%) of 121 IFA-ELISA discordance. CMV seroprevalence rate for the donor blood population was 38%, and for the mothers was 53%. The LA assay is superior to the IFA assay for CMV screening of blood donors and maternal populations.

Enhancement of neonatal neutrophil motility (chemotaxis) with adult fresh frozen plasma.

We examined the effect of adult fresh frozen plasma (FFP) on neonatal neutrophil (PMN) motility (chemotaxis) using a micropore filter assay. Adult FFP was transfused into 13 neonates receiving FFP transfusion for suspected life-threatening sepsis. Blood was obtained from neonates before and after FFP transfusion for assessment of PMN chemotaxis. An increase in PMN chemotaxis was noted in 12 of the 13 neonates following FFP transfusion, with a mean percentage increase of 12 +/- 3% (p less than 0.01). PMN chemotaxis increased 13 +/- 2% (p less than 0.01) in four bacteremic infants and 11 +/- 5% (p = 0.06) in nine infants without bacteremia. Adult FFP transfusion may enhance impaired neonatal PMN motility and improve outcome from infection in newborn infants.

Modulation of neonatal neutrophil function by pentoxifylline.

Immunomodulating agents are being investigated for treatment of infection in newborn infants where morbidity and mortality remain high despite the continued development of new antibiotics. We studied the effect of the methylxanthine pentoxifylline on polymorphonuclear leukocyte (PMN) chemotaxis, F-actin content, and phagocytic activity as measured by nitroblue tetrazolium reduction and H2O2 production in neonates and adults to determine whether pentoxifylline might be useful in augmenting PMN function. The drug was found to have a dose-dependent effect on both neonatal and adult PMN function with enhancement at lower concentrations and suppression at higher concentrations. PMN chemotaxis increased 42% (p less than 0.01) in neonates and 16% (p less than 0.05) in adults at 100 micrograms/mL of pentoxifylline and it decreased 4 and 25%, respectively, at 4000 micrograms/mL. PMN nitroblue tetrazolium reduction increased by 34% in neonates and 23% (p less than 0.05) in adults at 100 micrograms/mL of pentoxifylline and decreased by 52 (p less than 0.01) and 74% (p less than 0.01), respectively, at 2000 micrograms/mL. Similar dose-dependent responses were noted with F-actin content and H2O2 production. These and other observations support the hypothesis that pentoxifylline has a broad range of effects on PMN but that a primary effect is alteration of PMN deformability. Pentoxifylline has potential clinical use as an immunomodulator in augmenting impaired PMN function in neonates and other immunocompromised hosts or in suppressing excessive PMN activity in certain disease processes.

Brief clinical report: a 46,XY phenotypic female with Smith-Lemli-Opitz syndrome.

A phenotypic female infant with Smith-Lemli-Opitz (SLO) syndrome was found to have a 46,XY karyotype. Autopsy showed normal tests for age and normal Wolffian duct structures. The serum testosterone level was unusually high, suggesting that the failure of virilization of the external genitalia in the child might be due to a defect in testosterone conversion to dihydrotestosterone or a lack of end-organ receptors for the same. An additional feature not previously described in association with SLO syndrome was present, which was clinical hypoglycemia with nesidioblastosis.