Parental and perinatal factors affecting childhood anthropometry of very-low-birth-weight premature infants: a population-based survey.

BACKGROUND: The perinatal-neonatal course of very-low-birth-weight (VLBW) infants might affect their childhood growth. We evaluated the effect of parental anthropometry and perinatal and neonatal morbidity of VLBW neonates on their childhood growth. METHODS: We obtained parental anthropometry, height and weight at age 6-10.5 years of 334 children born as VLBW infants. Parental, perinatal and neonatal data of these children were tested for association with childhood anthropometry. RESULTS: (1) Maternal and paternal weight standard deviation score (SDS) and discharge weight (DW) SDS were associated with childhood weight SDS (R(2)= 0.111, p < 0.00001); (2) Maternal and paternal height SDS, corrected gestational age (GA) at discharge, maternal assisted reproduction and SGA status were associated with childhood height SDS (R(2)= 0.208, p < 0.00001); (3) paternal weight SDS, DW SDS and surfactant therapy were associated with childhood body mass index (BMI) SDS (R(2)= 0.096, p < 0.00001). 31.1% of VLBW infants had DW SDS < -1.88, and are to be considered small for gestational age ('SGA'). One quarter of these infants did not catch up by age 6-10.5 years. CONCLUSION: Childhood anthropometry of VLBW infants depends on parental anthropometry, postnatal respiratory morbidity and growth parameters at birth and at discharge. Almost one-third of VLBW premature infants had growth restriction at discharge from neonatal intensive care unit (NICU), a quarter of whom did not catch up by age 6-10.5 years.

Early-onset group B Streptococcus sepsis in high risk neonates born after prolonged rupture of membranes.

BACKGROUND: According to the U.S. Centers for Disease Control guidelines, prolonged rupture of membranes mandates intrapartum antimicrobial prophylaxis for group B Streptococcus whenever maternal GBS status is unknown. OBJECTIVES: To evaluate the local incidence, early detection and outcome of early-onset GBS sepsis in neonates born at 35-42 weeks gestation after PROM to women with unknown GBS status who were not given intrapartum antimicrobial prophylaxis. METHODS: During a 1 year period we studied all neonates born beyond 35 weeks gestation with maternal PROM > or =18 hours, unknown maternal GBS status and without prior administration of IAP. Complete blood count, C-reactive protein, blood culture and polymerase chain reaction amplification of bacterial 16S rRNA gene were performed in blood samples collected immediately after birth. Unfavorable outcome was defined by one or more of the following: GBS bacteremia, clinical signs of sepsis, or positive PCR. RESULTS: Of the 3616 liveborns 212 (5.9%) met the inclusion criteria. Only 12 (5.7%) of these neonates presented signs suggestive of sepsis. PCR was negative in all cases. Fifty-eight neonates (27.4%) had CRP > 1.0 mg/dl and/or complete blood count abnormalities, but these were not significantly associated with unfavorable outcome. Early-onset GBS sepsis occurred in one neonate in this high risk group (1/212 = 0.47%, 95% CI 0.012-2.6). CONCLUSIONS: In this single-institution study, the incidence of early-onset GBS sepsis in neonates born after PROM of 18 hours, unknown maternal GBS status and no intrapartum antimicrobial prophylaxis was 0.47%.

[Identical, for better and for worse].

We report on identical premature twins (monochorionic diamniotic). As fetuses, they both demonstrated sonographic and MRI evidence of cerebral bilateral ventriculomegaly. Neonatal brain US showed bilateral ventriculomegaly, similar in both twins. During follow-up, these physical and imaging similarities persisted. To the best of our knowledge, this is the first report on similar bilateral ventriculomegaly in Identical Twins (IT). A genetic origin of this finding in our IT is suggested. Should more cases of ventriculomegaly be reported in the future in several sets of IT, cerebral ventriculomegaly can then be added to the list of similar CNS features observed in identical twins.

Parturition itself is the basis for fetal adrenal involution.

CONTEXT: Newborn infants show a postnatal decline in androgen levels as the fetal adrenal glands involute. HYPOTHESIS: Placental factors up-regulate dehydroepiandrosterone sulfate (DHEA-S) generation. Hence, regardless of age, parturition will result in fetal adrenal involution and decline in DHEA-S levels. SUBJECTS AND METHODS: Premature neonates (n = 30) with gestational age 26-35 wk were studied. Adrenal volume by ultrasonography and serum DHEA-S, cortisol, and androstendione levels were followed weekly between d 1 and 28 of life. RESULTS: Serum DHEA-S was high on d 1 of life, declining rapidly regardless of gestational age during the first week of life (P < 0.001), and serum androstenedione and cortisol levels followed a similar pattern. Androstenedione levels showed a rise as of d 21 of life in boys but not in girls. The adrenals decreased in ultrasonographic volume from d 1 to 14 of life (P < 0.001), regardless of gestational age. CONCLUSIONS: Involution of the adrenal is faster than previously reported and, regardless of gestational age, occurs within the first week of life in terms of hormone secretion and within 2 wk in adrenal size. Involution involves a decline in DHEA-S but also in androstenedione and cortisol secretion, with a change in enzymatic activity. Males and females differ in their androstenedione levels and enzymatic activity. Parturition itself is the basis for fetal adrenal involution, supporting a key role for placental factors in maintaining the fetal adrenal and generating adrenal androgens.

Infected subgaleal hematoma in a neonate.

Subgaleal hematoma (SGH) is an infrequent finding in neonates, occurring mostly after vacuum extraction deliveries. SGH can cause anemia, hypovolemic shock, and death. To date, only one case of neonatal infected SGH has previously been reported. We describe a term neonate with severe polymicrobial infection complicating SGH, including anaerobic bacteria, and with unique imaging features.

Approach to term neonates born after maternal intrapartum fever and unknown maternal group B Streptococcus status: value of serum C-reactive protein and 16S rRNA gene PCR amplification.

Thirty-six term neonates born after maternal intrapartum fever, with premature rupture of membranes <18 hours and unknown maternal group B Streptococcus status had blood samples for complete blood count, C-reactive protein, culture, and 16S rRNA gene polymerase chain reaction amplification. Only 2 neonates were symptomatic and none had leukopenia, C-reactive protein >1.0 mg/dL, bacteremia, or positive polymerase chain reaction.

Candidal versus bacterial late-onset sepsis in very low birthweight infants in Israel: a national survey.

Candidal infections are one of the common causes of late-onset sepsis (LOS) among very low birthweight (VLBW) infants, and are associated with substantial morbidity and mortality. The aim of this study was to evaluate the perinatal and neonatal risk factors for fungal LOS compared with bacterial LOS in VLBW infants. This was a population-based observational study of VLBW infants in 28 neonatal intensive care units across Israel, with information on 11,830 infants born between 1995 and 2002 from the Israeli National VLBW infant database. The study population comprised 3054 infants with one or more episodes of LOS. Univariate analysis and logistic regression models were used to compare perinatal and neonatal risk factors between infants with fungal sepsis only (N=179) and those with bacterial sepsis only (N=2630). The mean birthweight and gestational age of infants with candidal LOS were significantly lower (940 g; 27.1 weeks) than those in the bacterial LOS group (1027 g; 28.3 weeks) (P<0.001). Logistic regression analysis showed that candidal sepsis, in contrast to bacterial sepsis, was independently associated with decreasing gestational age and bronchopulmonary dysplasia (BPD). In addition, BPD only [odds ratio (OR) 1.84; 95% confidence intervals (CI) 1.03-3.23] and BPD with postnatal steroid therapy (OR 2.66; 95% CI 1.59-4.46) were independently associated with an increased risk for candidal sepsis.

[Predictors and empiric anti-microbial therapy of late-onset sepsis in the neonatal intensive care unit].

BACKGROUND: Whenever suspicion of late-onset sepsis (LOS) is raised, sepsis workup is performed and empiric anti-microbial therapy (AMT) is initiated. However, the prescribed AMT may often be inappropriate for the eradication of the causative pathogen. STUDY AIM: To evaluate the clinical, interventional and laboratory predictors of LOS, and to evaluate the appropriateness of empiric AMT in late-onset neonatal sepsis. PATIENTS AND METHODS: The medical records of all neonates admitted to a tertiary NICU during a 1-year period were retrospectively reviewed. Out of 352 infants admitted, 84 neonates developed 96 suspected septic events beyond 3 days of age and comprised the study population. LOS was defined as clinical signs of sepsis accompanied with positive blood and/or urine and/or CSF cultures obtained at the onset of the septic event. For each infant, we collected demographic and perinatal characteristics, neonatal diagnoses and interventions, clinical signs and laboratory abnormalities at onset of sepsis, the AMT instituted, and microbiological data. RESULTS: Of the 96 events of suspected LOS, 26 (27.0%) positive blood cultures, w ith coagulase-negative St aphylococcus (CoNS), Klebsiella and Candida accounting for 22/ 26 (84.7%) of these events. In four out of 75 events (5.3%), urine culture was positive. Logistic regression multivariate analysis showed that birth weight (OR=0.9, 95% CI: 0.82-0.99; p=0.031), apnea/bradycardia (OR=3.16, 95% CI: 1.08-9.25; p=0.036), and platelet count < 100,000/mm3 (OR=7.04, 95% CI: 1.21-40.9; p=0.03) were significantly associated with LOS. Out of 29 proven septic events, 14 (48.3%) had received AMT within 3 days prior to onset of LOS. In 26/29 (89.7%) of proven septic events, empirical AMT was started after sepsis work-up, mostly vancomycin 18/29 (62.0%), imipenem 14/29 (48.3%), and amphotericin B 9/29 (31.0%). Out of the 26 proven septic events treated with empiric AMT, the causative pathogen was sensitive to the prescribed AMT in 24 (92.3%) of the cases. CONCLUSIONS: Significant predictors of LOS include lower birth weight, apnea/bradycardia and thrombocytopenia. Empirical AMT was initiated in 90% of proven septic events and was appropriate in 92.3% of these cases. When confronted with suspected LOS in the NICU setting, empiric coverage of CoNS, Klebsiella and fungi should be considered, based on the infant's condition and on local microbiological data.

Pathogen-specific early mortality in very low birth weight infants with late-onset sepsis: a national survey.

BACKGROUND: Late-onset sepsis (LOS) is an important cause of mortality among very low birth weight (VLBW) infants, and deaths occurring within 3 days after the onset of sepsis can probably be ascribed to sepsis. We examined the association of sepsis due to specific pathogens with the risk for early mortality after the onset of LOS, adjusted for perinatal and neonatal risk factors. METHODS: From 1995 through 2001, information about 10,215 infants was gathered and deposited in the Israel National VLBW Infant Database. The study population was composed of 2644 infants, of which each had >or=1 events of LOS (totalling 3462 events). Logistic regression models were used to calculate the crude and adjusted risk for early mortality. RESULTS: Early mortality was associated with 179 LOS events (5.2% of 3,462); the range of pathogens associated with these events included coagulase-negative staphylococci (CoNS), which were the cause of 1.8% of LOS events associated with early mortality, and Pseudomonas species, which were the cause of 22.6% of such events. Early mortality after LOS, adjusted for neonatal risk factors, was significantly associated with sepsis due to certain pathogens: Pseudomonas species (odds ratio [OR], 12.3); Klebsiella species (OR, 6.3); Serratia species (OR, 6.2); Escherichia species (OR, 4.3); Enterobacter species (OR, 4.1); and Candida species (OR, 3.2), compared with sepsis due to CoNS . In addition, lower gestational age, lower chronological age, small size for gestational age, and grade 3-4 intraventricular hemorrhage, each had an independent association with early mortality. CONCLUSIONS: Klebsiella sepsis and Pseudomonas sepsis were associated with a 6.3-fold and 12.3-fold increased risk of early mortality, respectively, and accounted for 41.9% of all early deaths associated with LOS. Considering the aggressive nature of sepsis caused by these pathogens, empiric antibiotic therapy active against these organisms is worth consideration for VLBW infants with presumed LOS.

Frequency of change of ventilator circuit in premature infants: Impact on ventilator-associated pneumonia.

OBJECTIVE: Ventilator-associated pneumonia (VAP) is associated with substantial mortality. The frequency of changing the ventilator circuit (VC) might influence the occurrence rate of VAP. In premature infants receiving ventilatory support, the question regarding the frequency of changing VC is as yet unsettled. DESIGN: A prospective, randomized, and controlled trial in 60 premature neonates receiving ventilatory support. INTERVENTIONS: We investigated the impact of two VC change regimens on VAP in premature infants, either every 24 hrs or every 72 hrs. In each patient, the humidifier, inspiratory tube, and expiratory tube were changed and cultured at the assigned intervals along with cultures of tracheal aspirates. Blood cultures were obtained whenever there was clinical evidence of pneumonia or sepsis. MEASUREMENTS AND MAIN RESULTS: The two study groups did not differ significantly in gestational age, birth weight, gender, duration of mechanical ventilatory support, surfactant therapy, duration of hospitalization, mortality rate, rate of bloodstream infection, or rate of colonization of tracheal aspirate, humidifier, and expiratory tube by microbes. The inspiratory tube was significantly less colonized in the 72-hr group as compared to the 24-hr group (p <.05). The rate of VAP per 1000 ventilator days was not higher in the 72-hr group, compared with the 24-hr group (23.3 vs. 37.7; not significant). Switching from a 24-hr to a 72-hr change policy would save our neonatal intensive care unit a yearly sum of $14,000 (US). CONCLUSIONS: Extending the VC-change interval in premature infants from 24 hrs to 72 hrs is safe and cost-effective.

Pneumothorax and nasal continuous positive airway pressure ventilation in premature neonates: a note of caution.

The nasal continuous positive airway pressure (NCPAP) ElectroMedical Equipment (EME) system has recently gained wide use in premature infants. However, occasional impingement of the expiratory tubing exit by mattress, coverings, or walls of infant warmers is of concern because of risk for obstruction and pneumothorax. The purpose of this study was to verify whether the use of NCPAP, namely Aladdin-1 (EME, Brighton, England), increases the risk for pneumothorax. The study included premature infants with respiratory distress who necessitated one or more of the following modes: oxygen via head box, NCPAP, synchronized intermittent mandatory ventilation (SIMV), or high frequency oscillatory ventilation (HFOV). For every patient, we recorded the modes of respiratory support, duration of use, and the occurrence of pneumothorax during every mode (number of pneumothorax cases/100 days of support). Among 163 sick premature neonates, pneumothorax developed in 0.17, 1.77, 0.3, and 6 cases per 100 days of oxygen via head box, NCPAP, SIMV, and HFOV, respectively. Pneumothorax developed more often during NCPAP than with SIMV. Pneumothorax in premature infants might be increased with the use of the newly developed NCPAP system. In these circumstances, possible accidental obstruction of the exit of its expiratory tubing could be contributory to this complication.

Neonatal course and outcome of twins from reduced multifetal pregnancy versus non-reduced twins.

BACKGROUND: Multifetal pregnancy reduction has been implemented for improving the outcome of multifetal pregnancies. Recent studies reported no difference in pregnancy outcome between reduced twins and non-reduced twins, but the neonatal course and subsequent outcome in reduced twin pregnancies were not well documented. OBJECTIVE: To compare the neonatal course and outcome, as well as the gestational and labor characteristics in twins from reduced multifetal pregnancies and in non-reduced twins. METHODS: This is a retrospective case-control study of the neonatal course of twins from reduced multifetal pregnancies. We found 64 mothers with multifetal pregnancy reduction who delivered twins during 1989-1997; 64 gestational age-matched non-reduced twin pregnancies served as controls. The following neonatal variables were examined: major malformations; small birth weight for gestational age; and neonatal morbidities including respiratory distress syndrome, apnea, pneumothorax, bronchopulmonary dysplasia, hyperbilirubinemia, sepsis, necrotizing enterocolitis, retinopathy of prematurity, seizures, intraventricular hemorrhage, periventricular leukomalacia, ventriculomegaly, and hydrocephalus. In addition, we evaluated several neonatal interventions (surfactant replacement, mechanical ventilation, phototherapy, total parenteral nutrition), and some laboratory abnormalities (thrombocytopenia, leukopenia, anemia, and hypoglycemia), duration of hospitalization, and neonatal mortality. RESULTS: Gestational and labor variables were not significantly different between multifetal pregnancies reduced to twins and non-reduced twin pregnancies. The neonatal morbidity and mortality were not significantly different between twin neonates from multifetal pregnancy reduction and non-reduced control twins. CONCLUSIONS: Multifetal pregnancy reduction to twins appears to bear no adverse effect on the intrauterine course of the remaining fetuses or their neonatal course and outcome when born after 28 weeks of gestation.

Factors influencing oral colonization in premature infants.

BACKGROUND: Factors influencing the oral flora of premature infants have not been adequately investigated. OBJECTIVE: To investigate the effects of gestational age and of anti-bacterial therapy on the oral flora of premature infants. METHODS: Oral cultures were obtained at age 1 day and age 10 days from 65 premature infants, divided into three groups: a) 24 neonates of 30-34 weeks gestation who did not receive ABT, b) 23 neonates of 30-34 weeks gestation who received ABT, and c) 18 neonates < 30 weeks gestation who received ABT. RESULTS: Oral bacterial colonization increased from day 1 to day 10 of life. In 24-34 week neonates, gestational age did not affect early bacteremia or oral colonization at birth. Neither gestational age nor ABT affected late bacteremia or oral colonization at day 10. In 30-34 week neonates with ABT, the oral flora consisted mainly of non-Escherichia coli gram-negative bacteria, whereas those who did not receive ABT grew mainly alpha-hemolytic streptococci, Klebsiella pneumoniae and E. coli. In neonates < 30 weeks who received ABT the oral flora were mainly coagulase-negative staphylococci. Oral colonization with anaerobes was zero and colonization with fungi was minimal. CONCLUSIONS: Acquisition of oral bacteria rose from day 1 to day 10 of life, regardless of gestational life or ABT. On day 10 of life, the spectrum of oral bacterial flora changed following ABT and consisted mainly of coagulase-negative Staphylococcus and non-E. coli gram-negative bacteria. Oral colonization showed few fungi but no anaerobes. These microbiologic observations merit attention when empirical anti-microbial therapy is considered in premature infants suspected of having late-onset sepsis.

Late postnatal systemic steroids predispose to retinopathy of prematurity in very-low-birth-weight infants: a comparative study.

BACKGROUND AND OBJECTIVE: Retinopathy of prematurity (ROP) develops mostly in very-low-birth-weight (VLBW) premature infants. Besides prematurity and hyperoxia, other variables have been brought up as risk factors for ROP. We aimed to search risk factors for ROP by comparing two groups of preemies, one with and the other without ROP. PATIENTS AND METHODS: During 2004-2006, 27 VLBW premature infants developed ROP (ROP group). For each neonate in the ROP group, we chose a neonate born at similar gestational age (GA) (+/-1 week) but without ROP (control group). For each neonate of both groups, we recorded demographic, maternal, gestational, intrapartum, neonatal, interventional, growth and ophthalmologic data from patients' medical records. RESULTS: Eleven of the tested variables were significantly different between the ROP and control groups in univariate analysis. However, only seven of these variables remained significantly different between groups when controlling each variable for GA: bronchopulmonary dysplasia (BPD, p=0.04), duration of hospitalization (p=0.017), high-frequency oscillatory ventilation (HFOV, p=0.033), duration of oxygen therapy (p=0.023), surfactant therapy (p=0.045), inhaled steroids (p=0.015) and systemic steroids for BPD (p=0.007). These seven significant variables were related to respiratory morbidity and interventions. Multiple stepwise logistic regression including all significant variables in the univariate analysis showed that only systemic steroids remained significantly different between groups (p=0.007, OR 5.42, 95% CI 1.60-18.34). CONCLUSION: Significantly more neonates in the ROP group received late postnatal systemic steroids as compared to controls. We speculate that steroids, by altering insulin growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) expression, might contribute to the pathogenesis of ROP.

Values of C-reactive protein, procalcitonin, and Staphylococcus-specific PCR in neonatal late-onset sepsis.

AIM: To evaluate the predictive value of relevant clinical and laboratory parameters (complete blood count (CBC), C-reactive protein (CRP), procalcitonin (PCT) and Staphylococcus-specific polymerase chain reaction (PCR)) in neonates with suspected late-onset sepsis (LOS). METHODS: NICU neonates were prospectively followed for septic events. One hundred and eleven neonates developed 148 suspected septic events beyond 3 d of age. We recorded the clinical signs and laboratory abnormalities at onset of sepsis, serum CRP and PCT, Staphylococcus-specific PCR, microbiological data, and empiric antimicrobial therapy. RESULTS: Variables significantly associated with subsequently confirmed LOS included hypotension (relative risk (RR) = 5.6, 95% CI 3.29-9.53), mechanical ventilation (RR = 2.46, 95% CI 1.24-4.86), immature/total neutrophil ratio (I/T) > 0.2 (RR = 5.13, 95% CI 2.54-10.31), CRP > 1.0 mg/dl (RR = 2.85, 95% CI 1.32-6.15), and small-for-gestational-age (SGA) status (RR = 2.13, 95% CI 1.03-4.38). PCT was not significantly associated with LOS. For detection of staphylococcal bacteremia, Staphylococcus-specific PCR showed: sensitivity 57.1%, specificity 94.7%, positive predictive value 53.3%, and negative predictive value 95.4%. CONCLUSION: Hypotension, mechanical ventilation, I/T > 0.2, CRP > 1.0 mg/dl, and SGA status at onset of sepsis are significant predictors of proven neonatal LOS. Staphylococcus-specific PCR might be of value in ruling out staphylococcal sepsis.

PCR-based diagnosis of neonatal staphylococcal bacteremias.

We compared PCR with blood cultures in the diagnosis of neonatal staphylococcal sepsis. Significant association was observed between PCR-based and culture-based diagnosis of staphylococcal bacteremia. Positive and negative predictive values for PCR were 100% and 98%, respectively. These data indicate that PCR may serve as a useful adjunct for the rapid diagnosis of staphylococcal sepsis.