Association of septic shock caused by early-onset group B streptococcal sepsis and periventricular leukomalacia in the preterm infant.

Early-onset group B streptococcal sepsis frequently produces shock in preterm infants, a condition also felt to be contributory to the development of periventricular leukomalacia. During a 2-year study period, 628 preterm infants who were admitted to the neonatal intensive care unit underwent serial sonographic brain scanning; periventricular leukomalacia was diagnosed in eight infants (1.2%). The four infants (100%) who survived group B streptococcal sepsis with septic shock developed periventricular leukomalacia, whereas none of the four survivors (0%) of septic shock caused by other organisms and three of 27 survivors (11%) of shock not caused by infection developed periventricular leukomalacia. Because of the frequency of this lesion, it is suggested that all preterm survivors of group B streptococcal sepsis with septic shock should have serial sonography screening for detection of periventricular leukomalacia. Early detection will not assure cure but may facilitate prognostication, follow-up, and earlier institution of rehabilitative therapy to produce a better outcome.

Adult respiratory distress syndrome in full-term newborns.

Since 1984, 11 newborns with severe respiratory distress have been treated whose clinical characteristics appear distinctive. Characteristics of these neonates were as follows: (1) they were full term by obstetric and neonatal criteria, (2) they had diffuse bilateral alveolar opacification on chest radiographs during the acute illness, (3) each had an acute perinatal triggering insult, (4) the neonates required continuous positive pressure ventilation for at least 48 hours with FiO2 greater than 0.50 for at least 12 hours, (5) they needed positive end-expiratory pressure of 6 cm of H2O or greater within three days of the triggering event, (6) there were no other known causes of these clinical conditions. Ten (91%) neonates had evidence of other organ dysfunction in addition to the lungs. Trials of hyperventilation in nine and tolazoline in five failed to improve oxygenation. Ten infants who underwent trials of increased positive end-expiratory pressure greater than or equal to 6 cm of H2O without other concurrent changes in ventilator settings responded with prompt increases in PaO2 (median increase 84 mm Hg, range 22 to 196 mm Hg). All 11 babies survived but required prolonged mechanical ventilation and supplemental oxygen. We suggest that adult respiratory distress syndrome can and does occur in newborns. A trial of positive end-expiratory pressure greater than or equal to 6 cm of H2O should be considered in full-term infants with severe respiratory distress in whom other causes can be excluded.

Mucocutaneous and invasive candidiasis among very low birth weight (less than 1,500 grams) infants in intensive care nurseries: a prospective study.

To determine whether mucocutaneous candidiasis presages the development of invasive candidiasis and to assess factors influencing the development of mucocutaneous candidiasis and invasive candidiasis among infants requiring neonatal intensive care, all infants admitted to our neonatal intensive care unit during a 47-month period were prospectively examined twice weekly for mucocutaneous candidiasis. Because 16 of 18 (89%) infants in whom invasive candidiasis (defined by positive cultures of blood, CSF, deep tissue or greater than or equal to 2 supra-pubic urine aspirates) developed had birth weights less than 1,500 g, further analysis was focused toward the very low birth weight group. Of 358 very low birth weight infants hospitalized for less than three days and serially studied until discharge from the neonatal intensive care unit, mucocutaneous candidiasis developed in 28 (7.8%), invasive candidiasis developed in 16 (4.5%), and in 323 there was no evidence of mucocutaneous candidiasis or invasive candidiasis. Although many risk factors were shown by univariate analysis to be significantly more common among those with invasive candidiasis and mucocutaneous candidiasis, adjustment for the covariant effects of duration of hospitalization and gestational age revealed that only prolonged duration of antibiotic therapy and duration of endotracheal intubation were significantly associated with invasive candidiasis. Invasive candidiasis developed later in nine of 28 (32%) infants with mucocutaneous candidiasis despite nystatin therapy of mucocutaneous candidiasis in all nine (median duration of therapy before invasive candidiasis, nine days). Very low birth weight infants in whom mucocutaneous candidiasis develops are at significantly greater risk of invasive candidiasis developing later than those in whom mucocutaneous candidiasis did not develop (9/28 v 7/330, P less than .001).

Invasive neonatal candidiasis: comparison of albicans and parapsilosis infection.

Severe infections caused by non-albicans Candida species are being increasingly reported among infants in neonatal intensive care units. To assess relative severity, mortality rates for C. albicans (CA) and C. parapsilosis (CP) infections in one neonatal intensive care unit from 1980 to 1990 were compared. Invasive candidiasis was defined as Candida recovery from a normally sterile body fluid or site with clinical signs of infection. Invasive candidiasis was diagnosed and systemic antifungal therapy initiated in 45 infants, 29 with CA and 16 with CP. No differences were found between CA and CP for birth weight, gestational age, age or weight at onset, presence of necrotizing enterocolitis, gastrointestinal or genitourinary anomalies, death (all causes), prior incidence or duration of antibiotics, parenteral nutrition, steroids or endotracheal intubation. Candida infection as the cause of death was more frequent with CA than CP (7 of 29 vs. 0 of 16; P = 0.034). Infants with CA were more likely to have antecedent thrush (P = 0.007) and perineal Candida dermatitis (P less than 0.02); those with CP were more likely to have vascular catheters at the time of positive culture (P less than 0.02). Though both pathogens occur in similar neonatal intensive care unit infants and can cause severe disease, CA appears more likely to result in death than CP.

Persistently positive cultures and outcome in invasive neonatal candidiasis.

BACKGROUND: A persistently positive culture >24 h after starting antibiotic therapy has been correlated with adverse outcome in several invasive bacterial infections, but few reports address persistent positivity and outcome in infections caused by fungi and other pathogens that replicate more slowly and therefore may succumb less quickly to therapy. METHODS: To assess whether positive culture >24 h after achieving target doses (amphotericin > or =0.5 mg/kg/day or fluconazole > or =6 mg/kg/day) of systemic antifungal therapy predicts focal infectious complication(s) or death from infection, we compared neonatal intensive care unit infants who had persistent (P+) or nonpersistent (P-) positive cultures with invasive candidiasis (clinical signs of infection and recovery of Candida from a normally sterile site) at this center from January 1, 1981, through June 30, 1999. Infants who died < or = 24 h after attaining target dosing, recovered without therapy, had a focal infectious complication already present at the time target dosing was achieved or were diagnosed with invasive candidiasis only postmortem were excluded. RESULTS: We identified 58 P+ (29, 12 and 7 had positive cultures for >7, >14 and > or =21 days, respectively) and 38 P- infants. No differences were found between P+ and P- for birth weight; gestational age; gender; onset age; central vascular catheters; necrotizing enterocolitis, surgery or bacterial sepsis; or duration of parenteral nutrition, antibiotics, tracheal intubation or postnatal steroids. P+ were more likely to have blood or cerebrospinal fluid involvement (68 vs. 45%, P = 0.03). Distribution of Candida species was similar (albicans in 53 vs. 63% for P+ vs. P-). P+ were significantly more likely to develop later "fungus ball" uropathy (16 of 56 vs. 2 of 32, P = 0.01), to develop renal infiltration (11 of 56 vs. 1 of 32, P = 0.03) and to die from invasive candidiasis (11 of 58 vs. 0 of 38, P = 0.003) than P-. P+ were also more likely to develop endocarditis, abscess, ventriculitis and invasive dermatitis, although P > 0.05. Focal complication increased as duration of P+ increased (48, 55, 67 and 71% at >1, >7, >14 and > or =21 days, P = 0.06). When comparing only those with positive blood and/or cerebrospinal fluid culture, similar patterns were observed, although only death and focal complication or death from invasive candidiasis attained significance. CONCLUSIONS: These observations suggest that in neonatal invasive candidiasis: (1) cultures usually remain positive >24 h after attaining target antifungal doses; (2) aggressive imaging for focal complications may be reserved for infants with persistently positive cultures after several days of antifungal therapy at target doses or have signs strongly suggestive of focal complication; (3) focal complications and/or death from candidiasis increase with persistence; (4) focal complications increase with duration of persistence; (5) serial culture of infected site(s) helps predict outcome and the need for aggressive surveillance and intervention for focal complications.

Genotypic analysis of a cluster of systemic Candida albicans infections in a neonatal intensive care unit.

Five very low birth weight infants developed systemic Candida albicans infection during a 6-week period in an urban neonatal intensive care unit. In an effort to assess whether a common source outbreak was present, the genomic DNA of the clinical isolates was compared by EcoRI and XbaI restriction fragment analysis and Southern blot hybridization with 27A, a species-specific, transposon-like probe. Although the restriction fragment analysis suggested strong similarities among the isolates, the hybridization patterns demonstrated that all strains were genotypically distinct. The parallel use of at least two restriction enzymes was important for differentiating the isolates. Rapid genotypic analysis of clinical isolates from a cluster of C. albicans infections permits determination of whether a common source is probable, facilitates epidemiologic decisions and may reduce infection control measures and attendant costs.

Ureaplasma urealyticum and chronic lung disease in very low birth weight infants during the exogenous surfactant era.

BACKGROUND: An association between recovery of Ureaplasma urealyticum from the respiratory tract of very low birth weight (VLBW) infants (< or =1500 g) and later chronic lung disease (CLD) was reported by several authors before the routine use of exogenous surfactant (SURF). We sought to assess whether this relation persists in the era of routine SURF. METHODS: We prospectively studied a cohort of 105 VLBW infants who required mechanical ventilation at < 12 h of age. Tracheal aspirates for U. urealyticum culture were obtained before administration of SURF or antibiotics. Clinicians were unaware of U. urealyticum status. Chest radiographs at 28 days were reviewed by a single pediatric radiologist, blinded to U. urealyticum status. Sample size was predetermined to detect a 30% increase in CLD among those with U. urealyticum recovery from tracheal culture (U. urealyticum-positive) with alpha <0.05 and beta <0.20. RESULTS: Of the study infants 22 were U. urealyticum-positive and 83 were U. urealyticum-negative. No differences were found between the groups for birth weight, gestational age, gender, inborn, antenatal or postnatal steroid use, SURF therapy, non-U. urealyticum infection, necrotizing enterocolitis, patent ductus arteriosus, intraventricular hemorrhage or cystic periventricular leukomalacia. At 28 days U. urealyticum-positive patients were significantly more likely to have CLD than U. urealyticum-negative [15 of 22 (68%) vs. 30 of 83 (36%); P < 0.02]. The U. urealyticum-positive patients also required significantly longer courses of supplemental oxygen and mechanical ventilation. No significant differences were found for CLD at 36 weeks postconception or duration of hospitalization, although type II error could not be excluded for these secondary endpoints. CONCLUSIONS: Respiratory U. urealyticum at or shortly after birth remains associated with CLD at 28 days despite routine use of SURF. Controlled trials of anti-Ureaplasma therapy in U. urealyticum-positive VLBWs as soon after birth as possible may determine whether CLD, duration of respiratory support and attendant costs can be decreased.

Frequent resistance of clinical group B streptococci isolates to clindamycin and erythromycin.

OBJECTIVE: To determine both the frequency of reported penicillin allergy in parturients and the frequency of resistance in vitro of clinical isolates of group B streptococci to clindamycin and erythromycin. METHODS: One hundred clinical isolates of group B streptococci were tested to determine the frequency of resistance to clindamycin, erythromycin, penicillin G, vancomycin, and cefazolin. The frequency of beta-lactam allergy and reported allergic reaction also were recorded for all consecutive laboring women during the 4-month study. RESULTS: The frequency of group B streptococcal resistance to clindamycin was 15% and to erythromycin was 16%. No isolates were resistant to penicillin G, vancomycin, or cefazolin. Twelve percent of the 963 women who delivered during the study reported a penicillin allergy, but only 30% of those could describe their allergic reaction. CONCLUSION: In vitro resistance of group B streptococci to clindamycin and erythromycin occurred frequently in this population. Whereas the importance of this finding in vivo is uncertain, it raises concern about the possibility of inadequate prophylaxis using currently recommended alternatives in penicillin-allergic patients. Artful questioning of women reporting penicillin allergy may lessen the likelihood of using these less desirable agents in the setting of intrapartum antimicrobial prophylaxis.

Spontaneous resolution of nonimmune hydrops fetalis secondary to human parvovirus B19 infection.

Many instances of nonimmune hydrops fetalis ascribed to human parvovirus B19 have been reported. The leading proposed pathophysiologic mechanism of hydrops in affected fetuses is viral invasion of red blood cell progenitors, causing a profound reticulocytopenic fetal anemia. Although the natural history of fetal parvovirus infection remains to be elucidated fully, there have been recent reports of funipuncuture and intrauterine blood transfusions to diagnose and manage this problem. We report two pregnancies in which parvovirus-related hydrops fetalis was observed to resolve without intervention, followed by uncomplicated vaginal deliveries of healthy infants. These observations emphasize the need for further investigation before recommending routine fetal blood transfusion in affected cases.

Maternal and transplacental pharmacokinetics of cefazolin.

OBJECTIVE: To evaluate the intrapartum pharmacokinetics of cefazolin, including delivery to amniotic fluid (AF) and fetal compartments, and to ascertain that adequate cefazolin concentrations are attained to exceed the mean concentration inhibiting 90% (MIC(90)) of group B streptococcus strains. METHODS: Cefazolin (1 g) was administered intravenously at five separate time intervals (0.5, 1, 2, 4, and 6 hours) before elective cesarean at term to 26 women with intact membranes and with no significant infections or cardiovascular, liver, or renal disease. Samples of maternal blood, cord blood, and AF were obtained at the time of delivery. Exact collection times relative to cefazolin infusion were noted. Amniotic fluid contaminated with blood or meconium was excluded. Cefazolin concentration was measured by high-pressure liquid chromatography. RESULTS: All maternal and cord plasma cefazolin levels, except one, were above the MIC(90) for Streptococcus agalactiae (group B streptococcus). For AF, all cefazolin levels, except two, were above the MIC(90). CONCLUSIONS: Cefazolin concentrations greater than or equal to the MIC(90) for group B streptococcus were attained in nearly all maternal, fetal, and AF samples. This information, together with the knowledge that there is rare resistance of group B streptococcus to cefazolin, supports the use of cefazolin as a better alternative than clindamycin or erythromycin for group B streptococcus prophylaxis in patients with a nonanaphylactic penicillin allergy.

Ultrasound attenuation coefficient in the fetal liver as a function of gestational age.

An apparent increase in the ultrasound attenuation coefficient per unit frequency, alpha f, of fetal liver as a function of gestational age has been observed. Measurements were made in utero with a 25 megasample/sec RF digitizer and a real time ultrasound system with a 5 MHz scan head. A precise measurement of alpha f was employed in which the intercept was tied to 0 at a frequency of 0. In 178 examinations of normal pregnancies, the linear regression of the alpha f increased 26% between 26 and 40 weeks gestation. This statistically significant increase (p less than 0.0001) is consistent with several observations, those of Parker et al. of increased attenuation in liver when glycogen is added, the increasing glycogen storage in the liver before birth, and our own pre- and postnatal measurements reported elsewhere. A noninvasive assay for glycogen content would have important applications in medicine and biomedical science. However, an increase in measurement accuracy and precise correlation with glycogen content will be required to make meaningful predictions in individual cases, as opposed to the present statistical trends.

Polymicrobial sepsis among intensive care nursery infants.

To determine the incidence, characteristics, and course of polymicrobial sepsis among infants in intensive care nurseries, we reviewed all such episodes in our neonatal unit from September 1971 through June 1986. We identified 15 episodes (3.9% of all cases of culture-proven sepsis during the survey period) in which blood or cerebrospinal fluid (CSF) culture yielded multiple organisms felt to represent true pathogens. Mortality associated with late-onset polymicrobial sepsis (7 of 10; 70%) was significantly higher (P less than .001) than in late-onset monomicrobial sepsis (86 of 370; 23%). Six patients were 37 weeks' gestation or greater at birth, and five were younger than 4 days of age when the polymicrobial culture was obtained. Group D streptococci were recovered in eight cases (53%). Gastrointestinal foci appeared to be common among infants with late-onset polymicrobial infection (5 of 10), while prolonged rupture of membranes was frequently associated with early-onset infection (4 of 5). Though recovery of multiple organisms from blood or CSF may not always be significant, one should not immediately assume contamination. A report of more than one organism growing from a normally sterile body fluid in an intensive care nursery infant should be considered significant, and therapy should be adjusted to provide appropriate antimicrobial agents for all reported organisms if the infant has not substantially improved in the interval since the culture was actually obtained.

Streptococcus mitis infection in newborns.

Although neonatal infections caused by Streptococcus viridans have been suggested to be less severe than those caused by classic neonatal pathogens, little is known about neonatal infections caused by specific species within this group of bacteria. We report six infants who had S. mitis isolated from blood culture. All were infected at < or = 3 days of age; five of the mothers had perinatal risk factors for neonatal sepsis. Five infants were preterm and three had birth weights < or = 2500 gm. Hematologic abnormalities were common. Two died as a result of the infection. Antibiotic susceptibility testing of four isolates revealed resistance to penicillin and ampicillin in three and resistance to gentamicin in two. In vivo resistance was not observed. S. mitis is not part of normal skin flora, should not be assumed to be a contaminant, and can cause severe neonatal disease. If S. mitis or S. viridans are recovered from a normally sterile body site and the patient fails to improve with penicillin therapy, it seems prudent to switch to vancomycin until susceptibility results are available.

Group C streptococcal infection in a term newborn infant.

Group C streptococci were recovered from the cerebrospinal fluid of a term infant with symptoms whose mother had received intrapartum antibiotic therapy for chorioamnionitis. This case highlights that beta-hemolytic streptococci of Lancefield groups other than A or B can be isolated from a normally sterile site and should be considered as pathogens. It also underscores the potential importance of sampling cerebrospinal fluid in an infant with symptomatic suspected sepsis, especially in the setting of exposure to maternal antimicrobial agents.

Medico-legal consultation: an expanded role of the tertiary neonatologist.

Between January 1982 and December 1984, the neonatologists at the University of Michigan Medical Center were asked to render 115 consultations regarding potential medical litigation. Requests for consultation were made by attorneys representing plaintiffs in 36 per cent of cases and defendants in 64 per cent (hospitals, 32 per cent, physicians, 30 per cent, private industry, 2 per cent). A review of these cases indicates frequently recurring themes, especially fetal distress, postdate pregnancies, and birth trauma among obstetrical cases, and neurologic injury, birth asphyxia, meconium aspiration, and hypoglycemia among neonatal cases. In many instances, incomplete documentation in the medical record and poor physician-patient communications were the issues leading to litigation. In 49 per cent of plaintiff cases reviewed, outcomes were felt not be related to the medical care rendered. Sixty-one per cent of defendant cases were felt to be strongly defensible; in 30 per cent of cases significant doubt as to defensibility existed. The physician practicing perinatal or neonatal medicine must be aware of the areas of vulnerability to malpractice litigation and the need for adequate documentation and patient communication. The daily activities of the tertiary neonatologist support his credentials as an expert medical witness in his specialty.

Improving the timing of antibiotic administration to high-risk newborns.

OBJECTIVES: To describe the timing of initiation of administration of parenteral antibiotics to infants with suspected sepsis at birth, identify barriers to prompt administration, and assess the effectiveness of subsequent interventions designed to minimize these barriers. The goals were to administer antibiotics within 1 hour of the physician order and within 2 hours of birth with more than 80% compliance for both goals. STUDY DESIGN: Retrospective chart review and prospective interventions involved 488 infants born at the University of Michigan Medical Center with indications for antibiotic therapy at birth. After an initial audit of the charts of 56 infants and the identification of poor compliance with the goals, unit policies and educational programs were developed to facilitate timely antibiotic administration. After a second audit demonstrated improvement but failure to attain the target compliance rates, review of individual cases with the responsible physician and nurse was initiated. Time intervals between birth, writing the order for antibiotics, noting the order by the nurse, and administration of antibiotics were tracked for an additional 20 months after these interventions. RESULTS: Before the interventions, antibiotics were administered to 28% of infants within 1 hour of the physician order (mean +/- SEM 1.58 +/- 0.11 hours) and to 19% within 2 hours of birth (3.12 +/- 0.16 hr). By the conclusion of the study, antibiotics were administered to 87% (p < 0.0001) of infants within 1 hour of the physician order (0.79 +/- 0.04 hour; p < 0.001) and to 92% (p < 0.0001) within 2 hours of birth (1.26 +/- 0.06 hours; p < 0.001). CONCLUSIONS: Administration of the first dose of parenteral antibiotics to newborns with suspected sepsis at birth frequently takes more than 1 hour after the order is written and more than 2 hours after birth. Efforts to identify and minimize common barriers significantly improved the timing of antibiotic administration. Additional improvement was attained by means of continued surveillance and individual feedback to caregivers of infants when timing objectives were not fulfilled.

Transillumination in neonatal diagnosis.

Transillumination is a safe, nonionizing, and noninvasive diagnostic technique that is particularly well-suited for use in the newborn. In addition, its portability, minimal expense, and facility make it a useful and necessary tool for the neonatal intensive care unit. This article reviews the principles of transillumination, describes equipment currently in use, and summarizes the clinical applications of transillumination.

Fetal skull fracture and brain injury after a maternal automobile accident. A case report.

A woman in labor and not wearing a seat belt sustained multiple fractures of the pelvis and femur while in an automobile accident. The fetus suffered fractures of the parietal and occipital bones. To minimize maternal pelvic and fetal injury, delivery by cesarean section was performed. The infant had generalized cerebral edema and intraventricular and subarachnoid hemorrhage, diagnosed shortly after birth. Motor abnormalities and residual injury to the periventricular white matter were evident at age 4 months. Use of seat belts may significantly diminish or prevent such injuries.

Evolving blood pressure dynamics for extremely preterm infants.

OBJECTIVE: To examine changes in arterial blood pressure (ABP) after birth in extremely preterm infants. STUDY DESIGN: Prospective observational study of infants 23(0/7) to 26(6/7) weeks gestational age (GA). Antihypotensive therapy use and ABP measurements were recorded for the first 24 h. RESULT: A cohort of 367 infants had 18 709 ABP measurements recorded. ABP decreased for the first 3 h, reached a nadir at 4 to 5 h and then increased at an average rate of 0.2 mm Hg h(-1). The rise in ABP from hour 4 to 24 was similar for untreated infants (n=164) and infants given any antihypotensive therapy (n=203), a fluid bolus (n=135) or dopamine (n=92). GA-specific trends were similar. ABP tended to be lower as GA decreased, but varied widely at each GA. CONCLUSION: ABP increased spontaneously over the first 24 postnatal hours for extremely preterm infants. The rate of rise in ABP did not change with antihypotensive therapy.

Evaluating retinopathy of prematurity screening guidelines for 24- to 27-week gestational age infants.

OBJECTIVE: To determine whether current retinopathy of prematurity (ROP) screening guidelines adequately identify treatable ROP in a contemporary cohort of extremely low gestation infants. STUDY DESIGN: Data from the Surfactant, Positive Pressure, and Pulse Oximetry Randomized Trial were used. Inborn infants of 24 (0)/7 to 27 (6)/7 weeks gestational age (GA) with consent before delivery were enrolled in 2005 to 2009. Severe ROP (type 1 ROP or treatment with laser, cryotherapy or bevacizumab) or death was the primary outcome for the randomized trial. Examinations followed the then current AAP (American Academy of Pediatrics) screening recommendations, beginning by 31 to 33 weeks postmenstrual age (PMA). RESULT: One thousand three hundred and sixteen infants were enrolled in the trial. Nine hundred and ninety-seven of the 1121 who survived to first eye exam had final ROP outcome determined. One hundred and thirty-seven (14% of 997) met criteria for severe ROP and 128 (93%) of those had sufficient data (without missing or delayed exams) to determine age of onset of severe ROP. PMA at onset was 32.1 to 53.1 weeks. In this referral center cohort, 1.4% (14/997) developed severe ROP after discharge. CONCLUSION: Our contemporary data support the 2013 AAP screening guidelines for ROP for infants of 24 (0)/7 to 27 (6)/7 weeks GA. Some infants do not meet treatment criteria until after discharge home. Post-discharge follow-up of infants who are still at risk for severe ROP is crucial for timely detection and treatment.