Hypertriglyceridemia in extremely low birth weight infants receiving lipid emulsions.

OBJECTIVE: To determine the prevalence of high TG levels in extremely low birth weight (ELBW) infants and what the risk factors are for high TG levels. STUDY DESIGN: We performed a prospective observational study of triglyceride concentrations in extremely low birth weight infants receiving lipid infusions. Lipid infusions were begun at 0.5 grams/kg/day at age one day and the dose advanced by 0.5 grams/kg/day. Triglyceride concentrations were drawn when the dose reached 1 and 2 grams/kg/day. We compared infants with normal triglyceride levels (≤200 mg/dl) with those with elevated triglyceride levels (>200 mg/dl) with univariate and multivariate analysis. RESULTS: There were 75 infants included in the analysis. Twenty (26.7% , 95% CI = 16.6-36.7%) had triglyceride levels >200 mg/dl. On multiple logistic regression analysis, lower birth weight was associated with the risk of an elevated triglyceride level. Triglyceride levels >200 mg/dl did not predict future mortality or morbidity. CONCLUSION: Elevated TG levels occur commonly in ELBW infants and are associated with a lower birth weight.

Resuscitation of infants born at 22 weeks gestation: a 20-year retrospective.

OBJECTIVE: To compare the characteristics of infants born at 22 weeks gestational age (GA) who were resuscitated at birth with those of infants who were not resuscitated. STUDY DESIGN: We reviewed records of all the infants with a GA of 22 0/7 through 22 6/7 weeks who were born alive at William Beaumont Hospital from 1990 through 2009. Deliveries were attended by a neonatologist if they were in the hospital at the time of delivery or requested by the obstetrician and otherwise were attended by a pediatric resident or neonatal nurse practitioner. RESULT: There were 85 infants born alive at 22 weeks GA during the study period. Thirty-six were intubated in the delivery room and defined as having been resuscitated. Two of them survived. On multivariate analysis, a higher birth weight (odds ratio 2.39 per 100 g increase, 95% confidence interval 1.21 to 4.73) and the presence of a neonatologist at delivery (odds ratio 6.72, 95% confidence interval 1.72 to 26.2) were each associated with an increased likelihood of resuscitation. CONCLUSION: Infants born at 22 weeks GA were more likely to be resuscitated if they were larger or if the delivery was attended by a neonatologist. We encourage neonatal groups to follow the recommendations of the American Academy of Pediatrics Committee on the Fetus and Newborn regarding initiation of resuscitation in these infants: inform parents that a good outcome is very unlikely and respect the parents' choice of whether resuscitation should be initiated.

Comparison of cardiac Z-score with cardiac asymmetry for prenatal screening of congenital heart disease.

OBJECTIVE: To determine the best screening tests for discriminating early indicators of cardiac hypoplasia in congenital heart disease (CHD) from normal variations in fetal cardiac growth. METHODS: We retrospectively examined fetal echocardiograms from 90 infants with confirmed CHD: Group 1 (n = 35) with right-sided obstructive lesions and Group 2 (n = 55) with left-sided obstructive lesions. Our control group comprised 2735 normal fetuses, from which we determined fetal cardiac Z-scores of right ventricle (RV), left ventricle (LV), aorta (Ao) and pulmonary artery (PA) diameters and ratios of right to left ventricle (RV:LV) and pulmonary artery to aorta (PA:Ao) size. We compared our control group to Groups 1 and 2 using ANOVA and area under receiver-operating characteristics curve (AUC) analysis. RESULTS: For Group 1, RV:LV ratio, RV-Z-score and PA:Ao ratio were the best screening tests, with highest AUCs (0.879, 0.868 and 0.832, respectively). For Group 2, the Ao-Z-score, PA:Ao and RV:LV ratios were the best screening tests, with AUCs of 0.770, 0.723 and 0.716, respectively. CONCLUSION: None of the screening tests was found to be a perfect early discriminator for the cardiac lesions tested. Although ratios of PA:Ao and RV:LV are useful, they should be combined with fetal cardiac Z-scores to maximize screening sensitivity.

Predictive factors affecting survival in stage II colorectal cancer: is lymph node harvesting relevant?

PURPOSE: Lymph node status is important in colorectal cancer. Multiple studies indicate a relationship between the number of nodes harvested and survival. This is important in patients with stage II disease where the role of adjuvant therapy is unclear. This study sought to analyze the impact of lymph node harvest on survival in patients with stage II colorectal cancer. METHODS: The data of our hospital's colorectal tumor registry from 1997 to 2008 was reviewed. The records of 3534 patients of all stages were analyzed; of these patients, 913 patients with stage II colorectal cancer underwent curative resection. A univariate analysis estimated 5-year survival by Kaplan-Meier analysis based on various lymph node groupings. Patients were further analyzed with respect to sex, age, tumor grade, and tumor location. Multivariate linear regression analysis by the Cox proportional hazards model was performed using these variables to analyze survival relative to lymph node harvesting. RESULTS: Of 913 stage II patients, the mean age was 71 years and 48% were male. Univariate analysis of the number of lymph nodes harvested found that ≥24 nodes removed was a significant and independent factor for improved survival in stage II (P = .009) and ≥36 nodes in stage III cancers (P = .008). Cox proportional hazards ratios found male sex (P < .03) and poorly differentiated tumors (P < .015) to be negative independent risk factors for survival. Tumor location in the sigmoid was associated with improved survival (P < .02). CONCLUSION: Patients with stage II disease had an improved survival when ≥24 lymph nodes were harvested, and patients with stage III disease had improved survival with up to a 36 node harvest. Male sex and poorly differentiated tumors had a worse prognosis, and tumors located in the sigmoid were associated with improved survival in stage II cancers. An increased lymph node harvest is recommended to improve survival in these stages.

Fetal echocardiography: z-score reference ranges for a large patient population.

OBJECTIVES: The main goal was to develop new z-score reference ranges for common fetal echocardiographic measurements from a large referral population. METHODS: A retrospective cross-sectional study of 2735 fetuses was performed for standard biometry (biparietal diameter (BPD) and femoral diaphysis length (FDL)) and an assessment of menstrual age (MA). Standardized fetal echocardiographic measurements included aortic valve annulus and pulmonary valve annulus diameters at end-systole, right and left ventricular diameters at end-diastole, and cardiac circumference from a four-chamber view of the heart during end-diastole. Normal z-score ranges were developed for these echocardiographic measurements using MA, BPD and FDL as independent variables. This was accomplished by using first standard regression analysis and then weighted regression of absolute residual values for each parameter in order to adjust for inconstant variance. RESULTS: A simple, linear regression model was the best description of the data in each case and correlations between fetal cardiac measurements and the independent variables were excellent. There was significant heteroscedasticity of standard deviation with increasing gestational age, which also could be modeled with simple linear regression. After this adjustment, the residuals conformed to a normal distribution, validating the calculation and interpretation of z-scores. CONCLUSION: Development of reliable z-scores is possible for common fetal echocardiographic parameters by applying statistical methods that are based on a large sample size and weighted regression of absolute residuals in order to minimize the effect of heteroscedasticity. These normative ranges should be especially useful for the detection and monitoring of suspected fetal cardiac size and growth abnormalities.

Cyclical infection prevalence in small groups.

To investigate variability of endemic infection prevalence within groups, we contrasted three SIS models. A deterministic compartmental (DC) model was used to estimate means without stochastic variation; a stochastic compartmental (SC) model calculated variation around an equilibrium prevalence. An agent-based model (ABM) enabled serial observations of individuals. Under scenarios in which most infection arose from within the group and if the group was small, then Fast Fourier Transform analysis of the ABM showed significant low frequency oscillations of infection prevalence. This suggests that estimation of endemic prevalence among small groups should include some serial measurements to detect oscillatory behavior.

Maximizing statistical power in group-randomized vaccine trials.

Statistical power in group-randomized vaccine trials is complex: group randomization may increase power by capturing more transmission effects but may decrease power as more individuals are affected by a common source of variance. The former effect dominates when most infections arise from within the group and the latter when most arise outside. This process is complicated further when individuals possess partial natural immunity. Vaccine trials typically compare infection frequency (as measured by agent or antibody detection) in vaccinated vs. unvaccinated groups. To assess the relative contributions to statistical power by direct agent detection vs. serological detection of recent infection, we constructed stochastic compartmental models using differential equations describing all possible discrete states of the group. We contrasted models where natural immunity was absent, altered only the susceptible state, or altered both the susceptible and infected states. We observed the effects of endemic infection levels, the fraction of infection arising from outside the group, infectiousness vs. susceptibility vaccine effects and waning rates. There was significant enhancement of statistical power when serological testing separated infected and susceptible classes into subsets by natural immunity status.

A stochastic model of vaccine trials for endemic infections using group randomization.

To clarify the determinants of vaccine trial power for non-typable Haemophilus influenzae, we constructed stochastic SIS models of infection transmission in small units (e.g. day-care centres) to calculate the equilibrium distribution of the number infected. We investigated how unit size, contact rate (modelled as a function of the unit size), external force of infection and infection duration affected the statistical power for detection of vaccine effects on susceptibility or infectiousness. Given a frequency-dependent contact rate, the prevalence, proportion of infections generated internally and the power to detect vaccine effects each increased slightly with unit size. Under a density-dependent model, unit size had much stronger effects. To maximize information allowing inference from vaccine trials, contact functions should be empirically evaluated by studying units of differing size and molecular methods should be used to help distinguish internal vs. external transmission.

Cost of diarrhea-associated hospitalizations and outpatient visits in an insured population of young children in the United States.

OBJECTIVE: To assess the financial and clinical burden of diarrhea- and rotavirus-associated disease among a population of privately insured US children. METHODS: For the period 1993 through 1996, we analyzed medical claims data from a large, administrative database containing information on approximately 300,000 children <5 years of age to examine trends in, and costs associated, with hospitalizations and outpatient visits for diarrhea. RESULTS: An annual average of 1,186 diarrhea-associated hospitalizations (35 per 10,000 children <5 years) and 33 386 outpatient visits (943 per 10,000 children <5 years) were reported, accounting for 4% of all hospitalizations and 2% of all outpatient visits among children <5 years of age. Diarrhea-associated hospitalizations and outpatient visits showed a distinct winter-spring peak consistent with that of rotavirus infection. The excess of diarrhea-associated events occurring during the winter-spring peak accounted for an average of 50% of all diarrhea-associated hospitalizations and 18% of all diarrhea-associated outpatient visits. The median cost (in 1998 constant dollars) of a diarrhea-associated hospitalization was $2,307, and that for a rotavirus-associated hospitalization was $2,303. Median costs of diarrhea- and rotavirus-associated outpatient visits were $47 and $57, respectively. CONCLUSIONS: Diarrhea is an important cause of morbidity in this insured population of young children. The epidemiologic features of diarrhea-associated events suggest that rotavirus is an important contributor to the overall morbidity from diarrhea. These disease burden and cost estimates should provide useful information with which to assess the costs and benefits of future interventions for rotavirus-associated illness.

An outbreak of Campylobacter jejuni infections associated with food handler contamination: the use of pulsed-field gel electrophoresis.

In 1998, an outbreak of Campylobacter jejuni infections occurred in Kansas among persons attending a school luncheon; community cases were also reported. In a cohort study of luncheon attendees, 27 (17%) of 161 persons reported illness. Consuming gravy (relative risk [RR], 4.2; 95% confidence interval [CI], 1.5-11.7) or pineapple (RR, 2.4; 95% CI, 1.0-5.7) was associated with illness. Both foods were prepared in a kitchen that served 6 other schools where no illness was reported. A cafeteria worker at the luncheon had a diarrheal illness and was the likely source of the outbreak. The pulsed-field gel electrophoresis (PFGE) patterns of the isolates from the food handler and those of 8 lunch attendees were indistinguishable. Isolates from 4 community patients differed. This was the first use of PFGE in a Campylobacter outbreak in the United States; its use was critical in determining that community cases were not linked.

A quadricuspid pulmonic valve diagnosed in a live newborn by two-dimensional echocardiography.

Quadricuspid pulmonic valve is a rare congenital anomaly which appears to occur in the absence of other cardiac or systemic anomalies. It predominates in males and tends to be clinically quiescent. The first case of quadricuspid pulmonic valve in a live newborn infant diagnosed by two-dimensional echocardiography is presented here with a review of the literature.

Spontaneous closure of atrial septal defects in premature vs. full-term neonates.

Our hypotheses were that the following factors influenced closure of atrial septal defects (ASDs) detected in neonates: estimated gestational age (EGA), the presence of a persistent ductus arteriosus (PDA), severity of pulmonary disease, gender, and the initial size of the ASD. Our population consisted of 82 newborns (38 premature and 44 term) who were found before the age of 1 month to have an ASD. Closure of ASDs was analyzed using both Kaplan-Meier survival analysis and the Cox proportional hazards model, each with the five covariates. The hazard ratio (or ratio of instantaneous closure rates) of term vs preterm infants was 3.60 (95% CI = 1.80-7.20), whereas the hazard ratio for infants with a PDA (compared to infants with no PDA) was 2.41 (95% CI = 1.28-4.54). Multivariate analysis showed that each of these terms (PDA and EGA) were independent predictors of ASD closure. The hazard ratio of ASD closure for each of four levels of pulmonary disease was 0.632 [95% CI = 0.453-0.881]. We conclude that the majority of neonatal ASDs will close, with EGA and PDA acting as important influences on closure.

Doppler velocity and flow through the aortic isthmus in normal term neonates.

Our hypothesis was that the relationship between the internal aortic diameter and the Doppler flow velocity across the aortic isthmus could be modeled by applying the principle of conservation of mass flow. The aortic diameter decreased at the isthmus by a mean of 18% (t = 11.02, p < 0.0001), while the flow velocity increased by a mean of 44% (t = 10.09, p < 0.0001). The mean peak mass flow rate was 34. 5 ml/s preisthmus and 32.9 ml/s at the isthmus with excellent correlation (r = 0.830). We conclude that the increase in Doppler velocity observed in the descending aorta can be explained by the normal narrowing observed at the aortic isthmus and application of the continuity equation for conservation of mass flow.

Recurrence risk of supraventricular tachycardia in pediatric patients.

We analyzed risk of recurrence of supraventricular tachycardia (SVT) in 70 pediatric patients using both Kaplan-Meier survival analysis and logistic regression of likelihood of recurrence, each with covariates: (1) age at onset of SVT; (2) presence of Wolff-Parkinson-White syndrome (WPW), and (3) gender. Among 38 patients who had onset of SVT <1 year, only 11 had a recurrence, while among 32 older patients, 30 had a recurrence of SVT (p < 0.00001, Fisher's exact test). The survival analyses, stratified by age at onset <1 versus >1 year, were significantly different (p < 0.0001) as was stratification by presence of WPW (p < 0.01). Logistic regression analysis showed that the only significant predictor of recurrence was age at onset; the additional information provided by presence of WPW and gender did not significantly add to the prediction of recurrence. The odds ratio of recurrence for age at onset >1 versus <1 year was 34.6, with a 95% confidence interval of 6.98-172.

Fetal cardiac asymmetry: a marker for congenital heart disease.

OBJECTIVE: To determine the sensitivity of prenatally detected fetal cardiac asymmetry as a sonographic marker for congenital heart disease. METHODS: The normal ratios of pulmonary artery to aorta diameters and of right ventricle to left ventricle diameters were derived from normal fetuses scanned at 17 weeks or more in a 65-month period. Cross-sectional diameters of cardiac ventricles and great arteries were measured at the level of the valves at the time of the scan. Fetuses with confirmed cardiac anomalies detected prenatally during the study were examined to identify how many had cardiac asymmetry, determined by abnormal ratios. RESULTS: Linear regression analysis of the group of 881 normal fetuses showed the normal pulmonary artery to aorta diameter ratio remained constant throughout pregnancy and the normal right ventricle to left ventricle ratio increased slightly with progressing gestational age. The 90% confidence intervals were 0.79, 1.24 for the right ventricle to left ventricle ratio and 0.84, 1.41 for the pulmonary artery to aorta ratio. Of the 73 fetuses with abnormal hearts, 66% had either ventricular or great artery asymmetry (at least one of the two ratios was abnormal). However, if no asymmetry was present, the cardiac defect was more likely to be a minor one. CONCLUSION: Cardiac asymmetry was present in two-thirds of fetuses with cardiac anomalies diagnosed prenatally. If cardiac asymmetry is found, a more thorough examination of the fetal heart is indicated.

Double-outlet right ventricle: an antenatal diagnostic dilemma.

OBJECTIVE: The purpose of this study was to describe the antenatal ultrasonographic findings of fetuses with double-outlet right ventricle (DORV). DESIGN: The records were reviewed of all fetuses scanned in our ultrasound unit which were suspected of having DORV during a 6-year period ending in April 1996. A medical record search for all infants with a postnatal diagnosis of DORV was also undertaken to identify cases that were not detected antenatally. Records were examined to determine the accuracy of antenatal diagnosis and the reasons for diagnostic errors. Fetuses without follow-up were excluded. RESULTS: There were 20 fetuses with antenatally detected conotruncal defects that had DORV included in the differential diagnosis. Three fetuses were excluded, seven did not have DORV and ten were confirmed postnatally as having DORV. Two additional infants were found to have DORV from the medical record search, producing a total of 12 cases. Antenatal sonographic cardiac findings included malpositioned (overriding or transposed) great arteries (n = 11), ventricular septal defect (n = 11) and small pulmonary artery suggesting stenosis (n = 4). Confirmed postnatal cardiac findings that were missed antenatally included aortic coarctation (n = 2), right-sided aortic arch (n = 2) and pulmonary stenosis (n = 1). Seven of the 12 fetuses had extracardiac findings. Nine of the 12 fetuses tested had a normal karyotype. Eleven of the 12 infants were liveborn. Nine of these 11 survived the neonatal period and underwent surgical repair within the first year of life; two subsequently died. In total, seven fetuses survived and five did not. CONCLUSIONS: Most fetuses with DORV can be identified antenatally as having an abnormal heart. However, it is very difficult to distinguish this particular defect from other conotruncal abnormalities.

Sonographic screening to detect fetal cardiac anomalies: a 5-year experience with 111 abnormal cases.

OBJECTIVE: To determine whether there is a difference between the types of cardiac lesions detected as abnormal prenatally and those that are not detected. METHODS: Consecutive fetuses at 14 weeks' gestation or more were scanned in our unit from February 1990 through July 1995 and later were delivered at our hospital. Outcome information was obtained from neonatal echocardiograms and autopsies. Our results were compared to sensitivities for individual cardiac lesions based on pooled data from studies published previously. RESULTS: There were 111 fetuses with cardiac anomalies, of which 73 (66%) were identified correctly as abnormal prenatally. Sensitivities for the most common cardiac lesions were as follows: 87% atrioventricular septal (endocardial cushion) defects, 65% tetralogy of Fallot, 63% transposition of the great arteries, 50% aortic coarctation, and 44% isolated ventricular septal defects. The lesions that went undetected most frequently were isolated septal defects (n = 17); most of these were ventricular and small or moderate in size. Based on our sensitivities and those calculated from previous studies, the fetal cardiac lesions with the highest detection rates involve hypoplastic ventricles and atrioventricular septal defects, followed by lesions of the great arteries and finally by isolated septal defects. CONCLUSIONS: The sensitivity of sonographic screening to defect fetal cardiac anomalies varies with the type of lesion. Isolated septal defects are the most difficult lesions to detect.