Physical growth and cognitive abilities in concordant versus discordant birth weight twins at three years old.

BACKGROUND: Discordant birth weight twins have been shown to have high rates of adverse perinatal outcomes, but little is known about their growth and development. AIM: To determine whether smaller and larger birth weight premature twins in concordant and discordant birth weight groups differ on measures of physical growth and intelligence at 3 years. STUDY DESIGN: Prospective cohort study. Eight-four children, 52 concordant and 32 discordant birth weight twin pairs, were measured for height, weight, and head circumference and on intelligence at 3 years. Perinatal and demographic variables, including birth weight, head circumference, small for gestational age, zygosity, in vitro fertilization, gender and social class were recorded. RESULTS: Smaller and larger birth weight twins did not differ significantly from each other on any growth parameters in either concordant or discordant birth weight groups at 3 years of age. Smaller birth weight twins in the discordant birth weight group performed significantly less well on Verbal, Performance, and Full Scale IQ scores (Verbal IQ for smaller twins was 8.6 points lower, p<0.005; Performance IQ, 11.9 points lower, p<0.03; Full Scale IQ, 12.4 points lower, p<0.004), but there were no significant intra-twin differences between larger and smaller birth weight concordant twins. CONCLUSIONS: Smaller discordant birth weight twins performed significantly less well on intelligence, although they did not differ significantly from their larger twins on growth parameters at 3 years old. We conclude that smaller discordant birth weight twins had less optimal intra-uterine environments than their larger birth weight twin, which affected both their birth weights and brain development.

Amplitude-integrated electroencephalography in the NICU: frequent artifacts in premature infants may limit its utility as a monitoring device.

BACKGROUND: Amplitude-integrated electroencephalography has become an important tool for assessing cortical status noninvasively. Newer units have the additional feature of visualizing the raw electroencephalogram, which has resulted in the identification of frequent artifacts. OBJECTIVE: To highlight the problem of artifacts and to introduce caution when using the amplitude-integrated electroencephalography technique to assess cortical function in the premature population. METHODS: Ten premature infants were evaluated. Compressed amplitude-integrated electroencephalography recordings were made by using a pair of standard electroencephalogram electrodes attached to the scalp frontotemporal areas. Impedance was maintained at <10 kOmega. Continuous amplitude-integrated electroencephalography recordings were performed for at least 60 minutes on several occasions in the first month. Artifacts were identified as follows: large amplitude difference between the wave peaks and troughs, a jagged appearance to wave peaks and troughs, and large deflections of the overall tracing in either a positive or negative direction from baseline. RESULTS: Forty-eight amplitude-integrated electroencephalography recordings were reviewed. Of 1683 total segments analyzed, 529 (31.4%) were categorized as normal brain waves, 1013 (60.2%) as artifacts, and 142 (8.4%) as indeterminate. Generally, when the amplitude-integrated electroencephalography tracing is of modest amplitude, normal brain waves predominated, whereas with upward spikes in amplitude the accompanying raw electroencephalogram was classified as artifact. CONCLUSIONS: Artifacts contribute substantially to the amplitude-integrated electroencephalography tracing, rendering it problematic as an assessment tool in premature infants. Artifacts may be influenced by muscle activity, electrode positioning, and application techniques. Caution is recommended when using amplitude-integrated electroencephalography as an assessment tool in this population.

Corrected end-tidal carbon monoxide closely correlates with the corrected reticulocyte count in coombs' test-positive term neonates.

OBJECTIVE: To evaluate clinical usefulness of corrected end-tidal carbon monoxide (ETCOc) measurements in healthy, term, Coombs' test-positive neonates and correlate it to the corrected reticulocyte count (RC). METHODS: ETCOc and RC were determined (at 36 +/- 12 hours of age) in 50 Coombs' test-positive neonates and compared with the ETCOc values of 50 Coombs' test-negative neonates. RESULTS: Fifty percent of Coombs' test-positive infants had RCs <5% (within a normal range for a healthy newborn) and ETCOc = 1.8 +/- 0.34 parts per million (ppm) and likely did not exhibit hemolysis. Among infants with elevated RCs, 72% had RCs between 5% and 8% and ETCOc = 2.77 +/- 0.68 ppm, and 28% had RCs >8% and ETCOc = 4.52 +/- 0.83 ppm. There was an almost linear correlation (r = 0.86) between the RC and the ETCOc among Coombs' test-positive infants. The 50 Coombs' test-negative infants had ETCOc = 1.6 +/- 0.45 ppm. Serial ETCOc measurements were performed in 14 Coombs' test-positive infants: in all but 1 infant ETCOc values declined over time. CONCLUSIONS: There is a good correlation between ETCOc and RC in Coombs' test-positive infants. ETCOc >2.5 ppm predicts a significant elevation of RC in 90% of Coombs' test-positive infants.

New methods advance treatment for respiratory distress syndrome.

The past 20 years of hard labor in neonatal respiratory distress have resulted in several important advances arising from our understanding of lung chemistry and physiology. Our knowledge of surfactant chemistry has enabled us to identify infants at high risk for developing neonatal distress due to surfactant deficiency, reducing this risk with antenatal corticosteroid treatment, and improving the neonatal outcome by means of administration of effective surfactant replacement. Recognition of the roles of oxygen toxicity and barotrauma in promoting lung injury has premitted the development of more effective means of assisted ventilation less likely to injure the lungs of severely ill infants with pulmonary failure. Nitric oxide has proven to be an effective pulmonary vasodilator and permits the successful treatment of patients with pulmonary hypertension who might previously have required an invasive surgical treatment to achieve a desirable clinical outcome.

Soluble E-selectin, soluble L-selectin and soluble ICAM-1 in bronchopulmonary dysplasia, and changes with dexamethasone.

OBJECTIVE: To evaluate longitudinal change in arterial blood plasma levels of soluble adhesion molecules in infants of <30 weeks' gestation with respiratory distress syndrome (RDS) and to look for differences in these levels in neonates who subsequently developed bronchopulmonary dysplasia (BPD) compared with those neonates who did not, and also to investigate the effect of dexamethasone treatment on levels of soluble adhesion molecules in plasma. METHODS: We measured plasma concentrations of soluble L-selectin (sL-selectin), soluble E-selectin (sE-selectin), and soluble intercellular adhesion molecule-1 on days 1, 3, 7, 14, 21, and 28 of life and before and 2 to 3 days after initiating a 6-day course of dexamethasone treatment. Infants with RDS were followed until discharge and were classified as non-BPD and either 1) BPD day 28 reflecting oxygen requirement on day 28 but not at 36 corrected weeks or 2) BPD 36 weeks reflecting oxygen requirement at 36 (corrected) weeks' gestation. The classification of presence or absence of BPD by oxygen requirement was supported by and was consistent with radiologic findings of BPD for all infants. The difference between BPD day 28 and BPD 36 weeks was supported by more extensive radiologic effects in the latter. RESULTS: The arterial plasma level of sL-selectin in infants who had RDS and did not develop BPD was significantly decreased compared with term healthy infants, as was the level of sE-selectin. Compared with infants who had RDS and did not develop BPD, sL-selectin levels were even further decreased in infants who had RDS and did develop BPD both at birth and throughout the first 4 weeks of life (day 1 through day 28). Infants with BPD also showed increasing levels of sE-selectin during this period of time, whereas infants without BPD did not. Levels of soluble intercellular adhesion molecule-1 in infants without BPD were not different from infants with BPD initially but increased in infants with BPD compared with infants without BPD, significant on day 28 in both groups. Dexamethasone treatment increased concentration of sL-selectin and decreased concentration of sE-selectin. CONCLUSIONS: Low sL-selectin may be an early indicator of enhanced risk for BPD. Low levels of sL-selectin and increasing levels of sE-selectin may be risk factors for BPD. The effects of dexamethasone treatment include significant modulation of adhesion molecules.

Neonatal outcome of triplet versus twin and singleton pregnancies: a matched case control study.

OBJECTIVE: To determine the neonatal outcome of triplet gestations versus that of singletons and twins matched for gestational age. STUDY DESIGN: All live born triplet gestations delivered between 1 April 1993 and 31 March 2000 were compared to an age matched control group consisting of live born twins and singletons. The neonatal outcome of 116 sets of triplets was compared to that of 116 sets of twins and 116 singletons. RESULTS: During a 7-year period 116 sets of triplet pregnancies were reviewed. Of 116 sets of live born triplets (348 newborns), 70.67% triplets were born between 33- and 36-week gestation, 28.44% between 28 and 32 weeks and 0.86% less than 28 weeks. Triplets were smaller in weight than singletons but not twins. Apgar score, use of prenatal steroid and sex ratio were similar in the three groups. Incidence of respiratory distress syndrome (RDS), use of surfactant, infants requiring intubation, pneumothorax, patent ductus arteriosus, sepsis, intraventricular hemorrhage, periventricular leucomalacia, retinopathy of prematurity, necrotizing enterocolitis, gastroesophageal reflux and jaundice requiring phototherapy were not statistically different among the three groups. Incidence of major and minor congenital anomalies, percent neonatal intensive care unit (NICU) admissions, and mean duration of NICU stay were also similar. There was no influence of birth order on neonatal outcome of triplet pregnancy and outcome did not significantly change over 7 years of the study period. CONCLUSIONS: Triplets have a similar outcome to twins and singletons when matched for gestational age. Since outcome is dependent on gestational age, the closer the gestational age is to term the better is the outcome.

End-tidal CO2 as a function of tidal volume in mechanically ventilated infants.

OBJECTIVE: To test the hypothesis that end-tidal CO(2) (PETCO(2)) varies with tidal volume (Vt) in preterm infants. DESIGN: Intervention study, nonrandomized trial. SETTING: Neonatal ICU, regional referral center. SUBJECTS: 29 preterm infants 790 to 2135 g in weight requiring mechanical ventilation studied on 73 occasions. INTERVENTION: Measurement of PETCO(2) during variations of Vt. MEASUREMENT: Statistical correlation of PETCO(2) to Vt. RESULT: PETCO(2) is minimal when Vt is either too low or too high. CONCLUSION: Vt, through its effect on dead space/Vt (Vd/Vt) ratios and arterial-alveolar CO(2) differences, has a significant effect on PETCO(2). Observation of PETCO(2) across a range of Vt can be used to select an appropriate Vt for preterm infants requiring mechanical ventilation.

Lymphocyte subpopulations in bronchopulmonary dysplasia.

A key role for inflammation in the etiology of bronchopulmonary dysplasia (BPD) has been proposed. In the present study we have evaluated lymphocyte subpopulations in 39 premature infants with respiratory distress syndrome (RDS) who did or did not develop BPD. The absolute number of lymphocytes was lower among infants with RDS who developed BPD compared with those who did not over the first two weeks of life ( p < 0.020) as were percentage and absolute number of CD4(+) T cells. By contrast, the proportions of CD3(+)CD8(+) lymphocyte cells were not statistically different between non-BPD and BPD infants. B cell percentage was significantly decreased in BPD infants only on day 7. NK "bright" cells (CD56(+)) were highly enriched in all RDS groups. Interestingly, the percentage of CD4(+) T cells expressing CD62L was selectively reduced in BPD infants. As a whole these data suggest that reduction of CD4(+) T cells and especially those important in tissue migration and immune surveillance may be a factor in the pathogenesis of BPD.

Diagnostic value of cytokines and C-reactive protein in the first 24 hours of neonatal sepsis.

The first objective of this article was to determine the diagnostic accuracy of tumor necrosis factor-alpha, interleukin-6 (IL-6), and interleukin-8 (IL-8) in differentiating infected from noninfected neonates during the first 24 hours of suspected sepsis and to compare them to the currently used laboratory parameters: C-reactive protein (CRP), immature-to-total neutrophil ratio, and leukocyte and platelet count. The secondary objective was to compare the cytokine levels in subpopulations of neonates. Seventy-five premature and 30 term infants were enrolled. Blood samples for the "currently used laboratory tests" and the cytokine levels were obtained at the first suspicion of sepsis ("0-hour") and 18 to 30 hours later ("24-hours"). Patients were classified as septic (48) or nonseptic (57). Thirty-two septic patients had positive blood cultures and 16 showed clinical signs of sepsis. Twenty septic patients had early-onset and 28 had late-onset sepsis. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were calculated for each test. Receiver-operating characteristic curves were analyzed to determine the optimal thresholds. A combination of CRP > 10 pg/mL plus IL-6 > 18 pg/mL (sensitivity = 89%, specificity = 73%, PPV = 70%, NPV = 90%) was the best "0-hour" test, and CRP (sensitivity = 78%, specificity = 94%) was the best "24-hours" test. Lower IL-6 at 0-hour (p = 0.018) and IL-8 at 24 hours (p = 0.023) were detected among the patients infected with coagulase-negative staphylococci then with other bacteria. In conclusion, a combination of CRP + IL-6 provided additional diagnostic accuracy for differentiation between septic and nonseptic patients during the first 24 hours of suspected sepsis.

Functional residual capacity (FRC) does not predict response to surfactant in preterm infants.

We tested the hypothesis that the initial functional residual capacity (FRC) of preterm infants with hyaline membrane disease (HMD) could predict the response to surfactant replacement (Survanta, 4 mL/kg/dose), with a better initial FRC being correlated with a greater improvement in PaO2, a/A PO2 ratio, and FRC. Thirty-four preterm infants were studied on 41 occasions. FRC and arterial blood gases were measured immediately prior to treatment. FRC was measured by the helium dilution method. Arterial blood gases were measured again after 30, 60, and 120 minutes. FRC was measured after 120 minutes. Twenty-seven treatments resulted in an increase in PaO2 >10 mmHg (responders); 14 did not (nonresponders). There was no correlation between initial FRC, change in FRC, and change in PaO2 (r2 = 0.07). These results suggest that there is no relationship between initial FRC and response to surfactant treatment.

Basement membrane biomarkers in very low birth weight premature infants. Association with length of NICU stay and bronchopulmonary dysplasia.

Basement membranes, critical for vital organs like the lungs, consist of two interwoven homopolymers, one assembled by type IV collagens and one by laminins. We hypothesized their serum antigens C-IV and P1, respectively, to be global measures for the maturity of these organs. In 39 very low birth weight premature neonates (means: gestational age, 25.8 weeks; birth weight, 779 g) requiring intensive care, we analyzed these biomarkers during the first two months post partum. Median C-IV and P1 exceeded adult levels by one order of magnitude. The individuals with the lowest first week C-IV values (mean: 667 ng/ml) required significantly longer neonatal intensive care unit stays than those with the highest values (mean: 2,467 ng/ml), on average 109 vs. 80 days (p = 0.008) irrespective of gestational age. Patients diagnosed with bronchopulmonary dysplasia (BPD) at 36 weeks postconceptional age, already in their first week of life displayed C-IV levels lower than in controls, suggesting a defect in pulmonary basement membrane remodeling. This is the first identification by a matrix biomarker of a BPD-antecedent state.