Prolonged early antibiotic use and bronchopulmonary dysplasia in very low birth weight infants.

OBJECTIVE: The objective of the article is to determine if > 48 hours of antibiotic treatment during the 1st week of life is associated with subsequent isolation of bacteria from the endotracheal tube (ETT), and an increased risk of bronchopulmonary dysplasia (BPD). STUDY DESIGN: Retrospective cohort study of very low birth weight infants. Routine weekly surveillance ETT cultures were obtained to monitor bacterial colonization in all intubated infants. Risk factors for BPD were assessed using unadjusted and multivariable analyses. RESULTS: In the study sample (n = 906), infants with BPD (n = 182) were more likely to have received > 48 hours antibiotic treatment (31 vs. 14%, p < 0.01) and have a resistant gram-negative bacilli in ETT (7 vs. 2%, p = 0.0001) compared with infants without BPD. Treatment with > 48 hours of antibiotics remained associated with BPD (adjusted odds ratio, 2.2; 95% confidence interval, 1.4-3.5) after controlling for confounding variables. CONCLUSIONS: Antibiotic duration > 48 hours in the 1st week of life was associated with subsequent BPD and the presence of resistant bacteria in routine ETT cultures.

Knowledge of preconception health care among primary care physicians in Delaware.

Pregnancy outcomes including premature birth are influenced by multiple factors including preconception health. This study was designed to assess the knowledge of various aspects of preconception health care in clinical practice in the state of Delaware. After assuring content validity, a questionnaire was provided to primary care physicians in Delaware. A total of 94 Delaware clinicians completed the survey and 96 percent indicated they should provide preconception counseling. Physicians frequently discussed some aspects of preconception care including diabetes and weight management, while other topics including reproductive life plans, vaccinations, and HIV screening were less frequently discussed. Preconception health care has been recommended by the Centers for Disease Control and Prevention to improve the health of women of childbearing age. Our data indicate a need to increase education and programs regarding preconception health to Delaware primary care physicians.

Adjustment of high flow nasal cannula rates using real-time work of breathing indices in premature infants with respiratory insufficiency.

OBJECTIVE: To assess the feasibility of real-time monitoring of work of breathing (WOB) indices and the impact of adjusting HFNC flow on breathing synchrony and oxygen stability in premature infants. STUDY DESIGN: A prospective, observational study of infants stable on HFNC. The flow adjusted per predetermined algorithm. Respiratory inductive plethysmography (RIP) noninvasively measured WOB. A high-resolution pulse oximeter collected oxygen saturation and heart rate data. Summary statistics and mixed linear models were used. RESULTS: Baseline data for 32 infants, final analysis of 21 infants. Eighty-one percent with abnormal WOB. Sixty-two percent demonstrated 20% improvement in WOB. For infants with gestational age <28 weeks, an incremental increase in HFNC flow rate decreased WOB (p < 0.001) and improved oxygen saturation and stability (p < 0.01). CONCLUSIONS: Premature infants do not receive optimal support on HFNC. The use of a real-time feedback system to adjust HFNC is feasible and improves WOB, oxygen saturation, and oxygen stability. This technology may improve the utility of HFNC in premature infants.

Forgotten parent: NICU paternal emotional response.

PURPOSE: To evaluate and compare the presence of perceived paternal stress and depressive symptomatology in fathers of preterm infants over time. SUBJECTS: Fathers of NICU infants born before 30 weeks of gestation. DESIGN: Prospective convenience sample. METHODS: Consenting fathers were given 2 self-report questionnaires: Center for Epidemiologic Studies-Depression Scale (CES-D) and Parent Stressor Scale: Infant Hospitalization (PSS:IH) on 7th (time 1), 21st (time 2), and 35th (time 3) days of life. Objective measurement of illness severity was quantified by Score for Neonatal Acute Physiology. Statistical methods included generalized linear estimating equation and mixed linear modeling. MAIN OUTCOME MEASURES: Stress and depressive symptomatology in fathers of preterm infants. RESULTS: Stress scores (PSS:IH) were unchanged over time (P = .62) indicating that fathers (n = 35) remain significantly stressed. Individual subcomponents of stress (parent role alteration, infant appearance/behavior, NICU sights/sounds) also remained constant over the study period (P = .05 for each). Stress scores over time were not modified by demographic characteristics (marriage, education, insurance). Mean depressive symptomatology scores (CES-D) decreased over time (P = .04). The percentage of fathers with elevated CES-D scores (>16) decreased from a baseline 60% but did not diminish between times 2 (39%) and 3 (36%). Parent Stressor Scale: Infant Hospitalization stress scores were correlated with CES-D depressive symptomatology scores (P < .01). Socioeconomic factors influenced initial CES-D scores, but only marriage ameliorated subsequent changes in measurements. Objective measurement of infant illness (Score for Neonatal Acute Physiology) did not influence paternal CES-D or PSS:IH scores. CONCLUSION: Fathers of premature infants in a medical NICU demonstrated elevated levels of stress that persisted across time for all domains of measured stress. Paternal self-reported stress and depressive symptomatology was independent of infant illness. One third of fathers had persistently elevated CES-D scores. If these findings are representative of general NICU population, then the emotional needs of our fathers are not being fully addressed.

State infant mortality: an ecologic study to determine modifiable risks and adjusted infant mortality rates.

OBJECTIVE: To determine factors contributing to state infant mortality rates (IMR) and develop an adjusted IMR in the United States for 2001 and 2002. DESIGN/METHODS: Ecologic study of factors contributing to state IMR. State IMR for 2001 and 2002 were obtained from the United States linked death and birth certificate data from the National Center for Health Statistics. Factors investigated using multivariable linear regression included state racial demographics, ethnicity, state population, median income, education, teen birth rate, proportion of obesity, smoking during pregnancy, diabetes, hypertension, cesarean delivery, prenatal care, health insurance, self-report of mental illness, and number of in-vitro fertilization procedures. Final risk adjusted IMR's were standardized and states were compared with the United States adjusted rates. RESULTS: Models for IMR in individual states in 2001 (r2 = 0.66, P < 0.01) and 2002 (r2 = 0.81, P < 0.01) were tested. African-American race, teen birth rate, and smoking during pregnancy remained independently associated with state infant mortality rates for 2001 and 2002. Ninety five percent confidence intervals (CI) were calculated around the regression lines to model the expected IMR. After adjustment, some states maintained a consistent IMR; for instance, Vermont and New Hampshire remained low, while Delaware and Louisiana remained high. However, other states such as Mississippi, which have traditionally high infant mortality rates, remained within the expected 95% CI for IMR after adjustment indicating confounding affected the initial unadjusted rates. CONCLUSIONS: Non-modifiable demographic variables, including the percentage of non-Hispanic African-American and Hispanic populations of the state are major factors contributing to individual variation in state IMR. Race and ethnicity may confound or modify the IMR in states that shifted inside or outside the 95% CI following adjustment. Other factors including smoking during pregnancy and teen birth rate, which are potentially modifiable, significantly contributed to differences in state IMR. State risk adjusted IMR indicate that other factors impact infant mortality after adjustment by race/ethnicity and other risk factors.

Increased preeclampsia in mothers delivering very low-birth-weight infants between 1994 and 2006.

We sought to determine if there has been any change in the proportion of mothers with preeclampsia in a sample of very low-birth-weight (VLBW) infants over time. We performed a retrospective cohort study. Study sample included infants with birth weights 1500 g or less cared for from July 1994 to July 2006 ( n = 2045) from a single level 3 neonatal intensive care unit in Delaware. The main outcome examined was the occurrence of maternal preeclampsia over the study time. The proportion of mothers with preeclampsia delivering VLBW infants increased over time. After controlling for potential confounding variables, the odds of maternal preeclampsia were increased (1.3, 95% confidence interval 1.2 to 1.5) in infants born between 2003 and 2006 compared with those born between 1994 and 1997. In our population of VLBW infants, the proportion of mothers with the diagnosis of preeclampsia increased over time. From our investigation, we cannot determine if the increase in the proportion of mothers with preeclampsia is related to a true increase in the disease, changes in diagnostic surveillance, or other factors.

Assessment of neonatal ventilation during high-frequency oscillatory ventilation.

OBJECTIVE: To determine alterations in high-frequency oscillatory ventilation (HFOV) performance during clinical ventilator management. DESIGN: Clinical investigation. SETTING: Two level III intensive care nurseries in Wilmington, Delaware, and Philadelphia, Pennsylvania. PATIENTS: Thirty infants 1.49 +/- 1.01 kg with respiratory distress receiving HFOV. INTERVENTIONS: Due to the demonstrated benchtop load sensitivity of the HFOV (SensorMedics 3100), we hypothesized that measured tidal volume (Vt/kg) and high-frequency minute ventilation (HFMV) would vary inversely with respiratory rate adjustments and that ventilator performance will be affected with endotracheal tube (ETT) suctioning. Both Vt/kg and HFMV were recorded using a novel hot-wire anemometry technique at the time of ETT suctioning or changes in ventilator settings. MEASUREMENTS AND MAIN RESULTS: During HFOV it was found that Vt/kg = 2.52 +/- 0.68 mL/kg and HFMV = 69 +/- 45 ([mL/kg]2 x Hz); effective ventilation was observed in the range of HFMV = 29-113 ([mL/kg]2 x Hz). HFMV decreased with an increase in breathing frequency. Although there was a significant increase in the mean Vt/kg after suctioning events, there was no difference in Vt/kg or HFMV after disconnection of the ETT alone. There were significant alterations in HFOV performance as a result of clinical adjustments in respiratory rate and suctioning. In addition, we found that measured Vt during clinically effective HFOV is at least equivalent to expected deadspace. CONCLUSIONS: Measurement of tidal volume and HFMV may be clinically important in optimizing HFOV performance both during ETT suctioning and adjustments to breathing frequency.

Tidal volume monitoring during emergency neonatal transport.

OBJECTIVE: The study aim was to identify the frequency with which tidal volumes were achieved in a target range in infants requiring positive pressure ventilation on emergency transport. STUDY DESIGN: We performed a prospective observational study of infants requiring continued positive pressure ventilation during emergency transport after resuscitation and stabilization. Blindly recorded data were analyzed for percentage of breaths that were below range, in range, and above desired range of 4-6 mL/kg. RESULT: Fourteen patients were monitored during transport from the delivery room to the neonatal intensive care unit, and 15 patients were monitored during inter-facility transport. During delivery room transport, 21 and 7% of patients were in target range greater than 50 and 90% of the time, respectively. During inter-hospital transport, 60 and 7% of patients were in target range greater than 50 and 90% of the time, respectively. CONCLUSION: Clinical assessment of appropriate ventilation is difficult and often inaccurate during emergency neonatal transport. Improved monitoring of respiratory function to guide clinical status during transport is necessary. More investigation and implementation are urgently needed.

Increasing illness severity in very low birth weight infants over a 9-year period.

BACKGROUND: Recent reports have documented a leveling-off of survival rates in preterm infants through the 1990's. The objective of this study was to determine temporal changes in illness severity in very low birth weight (VLBW) infants in relationship to the outcomes of death and/or severe IVH. METHODS: Cohort study of 1414 VLBW infants cared for in a single level III neonatal intensive care unit in Delaware from 1993-2002. Infants were divided into consecutive 3-year cohorts. Illness severity was measured by two objective methods: the Score for Neonatal Acute Physiology (SNAP), based on data from the 1st day of life, and total thyroxine (T4), measured on the 5th day of life. Death before hospital discharge and severe intraventricular hemorrhage (IVH) were investigated in the study sample in relation to illness severity. The fetal death rate was also investigated. Statistical analyses included both univariate and multivariate analysis. RESULTS: Illness severity, as measured by SNAP and T4, increased steadily over the 9-year study period with an associated increase in severe IVH and the combined outcome of death and/or severe IVH. During the final 3 years of the study, the observed increase in illness severity accounted for 86% (95% CI 57-116%) of the variability in the increase in death and/or severe IVH. The fetal death rate dropped from 7.8/1000 (1993-1996) to 5.3/1000 (1999-2002, p = .01) over the course of the study. CONCLUSION: These data demonstrate a progressive increase in illness in VLBW infants over time, associated with an increase in death and/or severe IVH. We speculate that the observed decrease in fetal death, and the increase in neonatal illness, mortality and/or severe IVH over time represent a shift of severely compromised patients that now survive the fetal time period and are presented for care in the neonatal unit.

Effect of inhaled corticosteroids on markers of pulmonary inflammation and lung maturation in preterm infants with evolving chronic lung disease.

BACKGROUND: Chronic lung disease (CLD) is one of the most severely disabling conditions of extremely low-birth-weight infants. Systemic corticosteroids are effective but cause many adverse effects. Targeted therapy with inhaled corticosteroids may be an effective and less toxic alternative. STUDY OBJECTIVE: To evaluate the additive effect of inhaled corticosteroids on markers of lung inflammation in infants receiving a 7-day course of systemic steroids. METHODS: Preterm neonates weighing 1 kg or less and aged 12 to 28 days who were prescribed a 7-day course of systemic corticosteroids for evolving CLD were studied prospectively and randomized to receive either a tapering 4-week course of beclomethasone metered-dose inhaler (MDI) (n = 5) or placebo MDI (n = 6). Primary outcome variables were the levels of pro- and anti-inflammatory cytokines, IL-8, TNF-alpha, IL-1alpha, and sIL-2R. RESULTS: This study was terminated early following literature reports of the adverse neurodevelopmental effects of dexamethasone. Measurements of respiratory and serum IL-8, IL-1alpha and TNF-alpha were similar between the study group taking inhaled and systemic corticosteroids and the study group taking systemic steroids alone. No differences were found between the two groups in relation to dynamic compliance or resistance. CONCLUSIONS: The addition of inhaled corticosteroids to a 7-day systemic course of corticosteroids did not alter cytokine response or improve pulmonary function.

Decreased incidence of pneumothorax in VLBW infants after increased monitoring of tidal volumes.

BACKGROUND AND OBJECTIVE: Pneumothorax is common in very low birth weight (VLBW) infants. In our NICU, we noted an above average incidence of pneumothorax compared with similar NICUs based on Vermont Oxford Network benchmarking. The quality improvement project was designed to decrease the incidence of pneumothorax in VLBW infants in a tertiary care NICU. METHODS: The project was divided into 2 periods. During period 1, all VLBW infants were followed for 6 months for the presence of pneumothorax. A multidisciplinary team met regularly to review cases of pneumothorax and identify potential causes. High tidal volumes (VT) (>6 mL/kg) were noted around the time of occurrence of pneumothorax. Guidelines were developed for improved monitoring and rapid feedback of VT and peak inspiratory pressure between nursing staff and clinicians. During period 2, these guidelines were implemented and VLBW infants were again followed for 6 months. The incidence of pneumothorax was tracked. Run charts were used to monitor changes. RESULTS: The incidence of pneumothorax in VLBW infants decreased from 10.4% to 2.6% after the intervention (P = .04). By using process control, a reduction in pneumothorax was achieved in period 2. CONCLUSIONS: Increased vigilance and real-time monitoring of VT and peak inspiratory pressure decreased the incidence of pneumothorax in our population of VLBW infants. These interventions can be considered in other NICUs with an above-average risk adjusted incidence of pneumothorax in VLBW infants. Our data illustrate the benefits of comparative benchmarking and organized quality improvement in advancing patient care outcomes.

Increased odds of necrotizing enterocolitis after transfusion of red blood cells in premature infants.

OBJECTIVES: To determine if infants with very low birth weight who receive packed red blood cell (PRBC) transfusions have increased odds of developing necrotizing enterocolitis (NEC), to determine the rate of NEC after PRBC transfusion, and to characterize the blood transfused preceding the onset of NEC. STUDY DESIGN: A retrospective cohort design was used. The study population included infants with a birth weight of <1500 g who were from a single center. NEC after transfusion was defined as NEC that occurred in the 48 hours after initiation of PRBC transfusion. Statistical analysis included unadjusted and multivariable analyses. RESULTS: The study sample included 2311 infants. A total of 122 infants (5.3%) developed NEC, and 33 (27%) of 122 NEC cases occurred after transfusion. NEC occurred after 33 (0.5%) of 6484 [corrected] transfusions. Infants who received a transfusion had increased adjusted odds (odds ratio: 2.3 [95% confidence interval: 1.2-4.2]) of developing NEC compared with infants who did not receive a transfusion. PRBCs transfused before NEC were predominantly (83%) from male donors and were a median of 5 days old. CONCLUSIONS: In our study sample, PRBC transfusion was associated with increased odds of NEC. The rate of NEC after transfusion was 1.4%. From our data we could not determine if PRBC transfusions were part of the causal pathway for NEC or were indicative of other factors that may be causal for NEC.

Attitudes toward pay-for-performance initiatives among primary care osteopathic physicians in small group practices.

CONTEXT: Pay-for-performance (P4P) programs reward physicians who meet-and electronically document-specific healthcare standards during patient encounters, incentivizing certain aspects of medical care. Although such documentation can be time consuming and technology intensive, noncompliance can result in decreased physician reimbursement. OBJECTIVE: To assess the attitudes of primary care osteopathic physicians toward P4P initiatives. METHODS: In 2006, a 20-item questionnaire was mailed to 1000 osteopathic physicians randomly pulled from the American Osteopathic Association database for this cross-sectional, survey-based study. Distinctions were not made between physician practice type or group size when the mailing list was compiled. RESULTS: Two hundred thirty responses were received for a response rate of 23%. Of these respondents, 123 physicians (54%) were in primary care practices comprising fewer than five physicians. Of these practitioners, 94% felt unprepared for P4P initiatives, 81% did not have the resources for appropriate technological investments, and 75% required additional P4P education and training to respond to P4P initiatives. In addition, the 28% of respondents who used electronic medical records were almost five times more likely (odds ratio, 4.80; 95% confidence interval, 1.91-12.06) to report that they could meet P4P reporting requirements. The majority of survey respondents were skeptical that P4P would appropriately capture the quality of their work and did not believe that health outcomes should influence their reimbursement. CONCLUSIONS: Although the current study's sample size may limit generalizability, small group primary care osteopathic physicians will need assistance-both technological and educational-to meet P4P measures.

Stress in fathers of surgical neonatal intensive care unit babies.

The purpose of this study was to identify and measure components of perceived stress in fathers of infants in a surgical neonatal intensive care unit (NICU). The Parent Stressor Scale: Infant Hospitalization (PSS:IH) was used to assess perceived stress in 22 fathers. Paternal stress was highest in the domains of "Parental Role Alteration" and "Infant Appearance and Behavior." "Sights and Sounds" did not appear to be associated with self-reported stress. This study demonstrates elevated levels of perceived stress among fathers of surgical NICU babies. Attention to fathers may be assisted by findings.

Ghrelin and cholecystokinin in term and preterm human breast milk.

AIM: To determine whether ghrelin and cholecystokinin (CCK) are present in significant quantities in term and preterm human breast milk, and to identify their source. METHODS: Samples were collected from 10 mothers who delivered term infants and 10 mothers who delivered preterm infants. Estimated fat content was measured. Ghrelin and CCK levels were measured in whole and skim breast milk samples using radioimmunoassays (RIA). Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed using RNA from human mammary epithelial cells (hMECs) and mammary gland with primers specific to ghrelin. RESULTS: The median ghrelin level in whole breast milk was 2125 pg/ml, which is significantly higher than normal plasma levels. There was a direct correlation between whole milk ghrelin levels and estimated milk fat content (r=0.84, p<0.001). Both the mammary gland and hMECs produced ghrelin. While CCK was detected in some samples, levels were insignificant. Infant gestational age, birthweight, maternal age, and maternal pre-pregnancy body mass index did not significantly affect the results. CONCLUSION: Ghrelin, but not CCK, is present in breast milk. Since the mammary gland produces ghrelin message, and ghrelin levels in breast milk are higher than those found in plasma, we conclude that ghrelin is produced and secreted by the breast.

Transfusion volume in infants with very low birth weight: a randomized trial of 10 versus 20 ml/kg.

BACKGROUND: Although preterm infants often require transfusions of red blood cells for anemia of prematurity, the optimal volume of blood to be transfused has not been established. OBSERVATIONS: Infants with birth weights between 500 and 1,500 g were randomly assigned to receive 10 or 20 mL/kg red blood cells. Infants with transfusions of 20 mL/kg had a greater hemoglobin (14.2 +/- 1.9 vs. 12.0 +/- 1.9 g/dL, P = 0. 003) and hematocrit (41.2 +/- 5.9 vs. 32.3 +/- 7.1%, P = 0.001) levels after transfusion compared with those who received transfusions of 10 mL/kg. There were no measured differences in pulmonary function in either group after transfusion. CONCLUSIONS: Transfusion with 20 mL/kg red blood cells produces a significantly greater increase in hemoglobin and hematocrit levels than does a transfusion with 10 mL/kg, without any detrimental effects on pulmonary function.

Are perinatal risk factors helpful in predicting and optimizing treatment strategies for transient hypothyroxinemia in very-low-birth-weight infants?

Transient hypothyroxinemia is common in premature infants and has been associated with intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), poor neurodevelopmental outcomes, and mortality. Recent trials have failed to show that supplemental thyroid hormone improves overall neurodevelopmental outcome. The objective of this article is too determine perinatal risk factors for transient hypothyroxinemia (TH). We studied a cohort of infants born between July 1993 and July 2000 who were less than 1500 g and who received a newborn screening for thyroid function ( n = 932). Total serum thyroxine (T(4)) was collected routinely on the fifth day of life. T (4) was correlated with gestational age (R = 0.59, p < 0.01). After controlling for potential confounding variables, gestational age, dopamine, and mechanical ventilation were found to be independently associated with low T (4) (overall model: r(2) = 0.41, p < 0.01). Number needed to treat (NNT) analysis showed treating all infants less than 27 weeks would lead to treating 6.3 infants for every one with a subsequent T(4) < 5 microg/dL. By combining gestational age and need for dopamine support, NNT = 2.4 for every one infant with subsequent T(4) < 5 microg/dL. Low gestational age, mechanical ventilation, and need for dopamine were associated with low T(4) levels and may be helpful in optimizing treatment strategies for TH.