Imad R. Makhoul

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.

Hemivertebra: Prenatal Diagnosis, Incidence and Characteristics

Objective: Hemivertebra is a rare congenital spinal anomaly where only one side of the vertebral body develops, resulting in deformation of the spine, such as scoliosis, lordosis, or kyphosis. We aimed to determine the incidence and clinical characteristics of hemivertebra. Patients and Methods: We present three fetuses with a prenatal ultrasonographic diagnosis of hemivertebra at 15–22 weeks’ gestation, and we determine the incidence and clinical characteristics of hemivertebra among 78,500 live-born infants at a tertiary medical center in Israel. Results: There were 26 cases of hemivertebra (0.33/1,000 live-born infants): male/female ratio 1/1, Jewish/Arab ratio 10/16, and ratio of single/multiple type of hemivertebrae 17/9. Twenty-three out of 26 infants (88.5%) with hemivertebra had additional congenital anomalies (cranial, cardiac, renal, intestinal, and skeletal). Conclusions: Hemivertebra is not an infrequent finding in fetuses and live-born infants. Comprehensive ultrasonographic screening of the fetus allows early prenatal diagnosis of hemivertebra, and provides parents with helpful information for their decision regarding the fate of pregnancy.

Iatrogenesis in Neonatal Intensive Care Units: Observational and Interventional, Prospective, Multicenter Study

OBJECTIVES. The goals were to determine the incidence of iatrogenic events in NICUs and to determine whether awareness of iatrogenic events could influence their occurrence. METHODS. We performed a prospective, observational, interventional, multicenter study including all consecutive infants hospitalized in 4 NICUs. In the first 3 months (observation period), the medical teams were unaware of the study; in the next 3 months (intervention period), they were made aware of daily ongoing monitoring of iatrogenic events by a designated “Iatrogenesis Advocate.” RESULTS. The numbers of infants admitted to the NICUs were comparable during the observation and intervention periods (328 and 369 infants, respectively). There was no difference between the 2 periods with respect to the number of infants of <1500 g, hospitalization days, or mean daily occupancy of the NICUs. Although the prevalence rates of iatrogenic events were comparable in the observation and intervention periods (18.0 and 18.2 infants with iatrogenic events per 100 hospitalized infants, respectively), the incidence rate decreased significantly during the intervention period (3.2 and 2.4 iatrogenic events per 100 hospitalization days of new admissions, respectively). Of all iatrogenic events, 7.9% were classified as life-threatening and 45.1% as harmful. There was no death related to an iatrogenic event. Eighty-three percent of iatrogenic events were considered preventable, of which 26.9% resulted from medical errors in ordering or delivery of medical care. Only 1.6% of all iatrogenic events were intercepted before reaching the infants, and only 47.0% of iatrogenic events were corrected. For younger and smaller infants, the rate of iatrogenic events was higher (57% at gestational ages of 24 to 27 weeks, compared with 3% at term) and the iatrogenic events were more severe and harmful. Increased length of stay was associated independently with more iatrogenic events. CONCLUSIONS. Neonatal medical teams and parents should be aware of the burden of iatrogenesis, which occurs at a significant rate.

Neonatal lenticulostriate vasculopathy: further characterisation.

Background: Lenticulostriate vasculopathy (LSV) is sometimes detected on routine brain ultrasonography in neonates, and is often associated with various perinatal and neonatal abnormalities. However, most reports on LSV are retrospective with no controls. Objectives: To compare the perinatal and neonatal clinical characteristics of neonates with LSV with matched controls and to summarise all published reports of LSV. Design: A prospective study that summarises the clinical, laboratory, and neurosonographic data of neonates with LSV. Methods: Of 1184 neonates admitted to the neonatal intensive care unit (NICU) during a three year period, 857 had a routine head ultrasound examination. Twenty one had LSV, and were compared with 42 matched controls with regard to gestational, perinatal, neonatal, laboratory, and neurosonographic characteristics. Results: LSV was detected in 21 of the 857 (2.45%) neonates. It was bilateral in 10 of the 21 cases and located in the thalamus (n = 14) and basal ganglia (n = 7). Infants with LSV were not significantly different from matched controls in most tested variables. However, compared with the control group, the LSV group included significantly more multiple births and more disturbances in amniotic fluid volume, but less meconial amniotic fluid. In addition, the patients with LSV required fewer blood transfusions and less phototherapy. Conclusions: Except for more multiple births, neonates with LSV did not display more adverse findings than their matched controls.

Insulin in human milk: postpartum changes and effect of gestational age

Objective: To determine if human milk insulin (HMI) concentrations are affected by gestational age and postnatal age. Design and setting: An observational study carried out in a level III neonatal intensive care unit. Insulin concentrations were determined in human milk of 90 parturient mothers who delivered between 30 and 41 weeks gestation. Samples were collected on days 3 and 10 after delivery. Results: HMI concentrations for mothers of preterm infants were not significantly different from those of full term infants, on either day 3 or 10 post partum. When results for all 90 mothers were pooled, regardless of gestational age, HMI concentration fell significantly from day 3 to day 10 (50.1 (34.6) v 41.1 (28.5) μU/ml; p = 0.01; mean (SD)). However, this decrease was only significant for mothers delivering at term (37–41 weeks). Conclusions: HMI concentrations were not influenced by gestational age at delivery. They decreased post partum, mainly in mothers of term infants. The postnatal changes in HMI concentrations and the effects of oral insulin on the immature intestinal mucosa warrant further investigation.

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%.

PCR-Based Diagnosis of Neonatal Staphylococcal Bacteremias

ABSTRACT 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.

Congenital Hypothyroidism and Nonimmune Hydrops Fetalis: Associated?

Hydrops fetalis (HF) consists of an abnormal accumulation of fluid in two or more fetal compartments, including ascites, pleural effusion, pericardial effusion, and skin edema. Almost all observed cases of HF are of the nonimmune type, the causes of which remain undetermined in 15% of patients. We report a newborn infant with nonimmune hydrops fetalis (NIHF) and congenital hypothyroidism. The infants mother was healthy and there were no malformations of the placenta or umbilical cord. The infant did not show any structural abnormalities of his central nervous, cardiovascular, gastrointestinal, or urinary tract systems, and there was no evidence of anemia, infectious disease, or inborn error of metabolism. An immune-based process was unlikely, because the blood group of the mother and infant was A-positive and results of an indirect Coombs test in the mother and a direct Coombs test in the infant were negative. The patients condition gradually improved with mechanical ventilation, repeated thoracocentesis, and total parenteral nutrition. By day 5 of age the skin edema, pericardial effusion, and ascites disappeared, but accumulation of significant amounts of chylous pleural fluid persisted. Because of lethargy, FT4 and thyroid-stimulating hormone levels were obtained and showed hypothyroidism. Thyroid hormone supplementation was then started, and within 4 days the infant became more vigorous and was weaned from mechanical ventilation. After 7 days, the chylothorax resolved completely as the serum thyroxine level normalized. No reaccumulation of pleural effusion was noticed. The infant started to gain weight and was discharged from the hospital at 35 days of age. A possible pathophysiologic association between congenital hypothyroidism and NIHF is discussed. NIHF may be caused by lymphatic congestion attributable to an impairment of lymphatic flow and a delayed return of lymph to the vascular compartment. There could be a possibility that because of thyroid hormone deficiency in this patient, there was reduced adrenergic stimulation of the lymphatic system. This could result in a sluggish flow of the lymph with engorgement of the lymphatic system, leakage of lymph into the pleura and the interstitial spaces, and the production of chylothorax with NIHF. Animal studies demonstrate a direct relationship between lymph flow rate or lung liquid clearance and adrenergic receptor activity in the lymphatic system. These observations support our hypothesis that deficient adrenergic activity in congenital hypothyroidism might lead to chylothorax with NIHF in the fetus. We speculate that thyroid hormone may play a role in the regulation of adrenergic receptors in the lymphatic system and lungs, thus modulating both the lymphatic flow rate and lung liquid clearance, and facilitating the resolution of chylothorax. Examination of thyroid functions should be included in the investigation of fetuses and neonates with NIHF of an obscure origin.

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.

Intratracheal pulmonary ventilation versus conventional mechanical ventilation in a rabbit model of surfactant deficiency.

ABSTRACT: Intratracheal pulmonary ventilation (ITPV) enhances the clearance of CO2 from dead space and lungs by a bias flow of gas administered in the distal trachea. ITPV flow is continuously administered through a separate catheter placed within an endotracheal tube (ETT). After exiting from catheters tip in the distal trachea, the flow of gas is redirected outward away from the lungs. We hypothesized that, compared with conventional mechanical ventilation (CMV), ITPV may increase minute CO2 clearance (Vco2), reduce the partial pressure of CO2 dioxide in arterial gas (Paco2), and reduce distal tracheal peak inspiratory pressure (dPIP). We induced surfactant deficiency in 15 adult rabbits by lung lavage with 10 mL/kg normal saline. Animals were ventilated through a double-lumen 4.0 ETT, inserted through a tracheotomy incision. dPIP, distal positive end expiratory pressure, and distal mean airway pressure were monitored, and the mean exhaled CO2 concentration was measured. For ventilator rates (respiratory rate) of 30, 45, and 70 breaths/min, the study included two phases: phase I compared CO2 clearance and Paco2 between ITPV and CMV using similar ventilatory pressures; phase II evaluated the effectiveness of ITPV in reducing dPIP and tidal volume (Vt), compared with CMV, while maintaining eucapnea. When comparing ITPV and CMV, the following results (mean ± SD) were achieved at respiratory rate of 30, 45, and 70 breaths/min, respectively. Phase I ITPV resulted in mean percent reduction of Paco2 by 31.4 ± 10%, 37.1 ± 9.7% and 38.3 ± 9%; mean percent increase in Vco2 by 61.3 ± 29%, 56 ± 23%, and 98 ± 40%, compared with CMV. Phase II ITPV resulted in mean percent reduction of dPIP by 35.5 ± 14%, 38 ± 10.8%, and 37.2 ± 13.7%, and mean percent reduction in Vt by 34.7 ± 12.9%, 36.4 ± 15%, and 52.7 ± 10.7%, compared with CMV. The changes in Paco2, Vco2 (phase I), and dPIP and Vt (phase II) were all significantly more than 25% (p < 0.05). Oxygenation and pH were not significantly different between ITPV and CMV. We conclude that, in a surfactant deficiency rabbit model, ITPV is an efficient mode of assisted ventilation that increases CO2 clearance and reduces ventilator pressures required for adequate ventilation. We speculate that ITPV can minimize lung barotrauma associated with mechanical ventilation.