Respiratory sinus arrhythmia during feeding: a measure of vagal regulation of metabolism, ingestion, and digestion in preterm infants.

Respiratory sinus arrhythmia (RSA), a non-invasive indicator of vagal regulation of the heart, and heart period (HP) were monitored before, during, and after oral or gastric-tube bolus feedings in 32 preterm infants. Group 1 infants (n=15) were < or =30 weeks gestational age (GA) at birth (mean 28.3 weeks) and group 2 infants (n=17) were > or =31 weeks GA at birth (mean=33.2 weeks). Mean postmenstrual ages at the time of study were 33.5 +/- 2.3 (SD) weeks in group 1 and 33.9 +/- 1.6 (SD) weeks in group 2. RSA and HP decreased in both groups during feeding. However, postfeeding RSA and HP increased toward prefeed levels only for group 2 infants. In addition, RSA and HP changes during feeding were correlated only for group 2 infants. The results suggest that the preterm infant may experience a maturational lag in vagal function and in the influence of vagal activity on metabolic mechanisms (i.e. heart rate) related to ingestive needs. This maturational lag may contribute to continued feeding difficulties and may be a measurable marker of subtle neurodevelopmental problems.

Hepatitis B vaccination of premature infants: a reassessment of current recommendations for delayed immunization.

OBJECTIVE: Current American Academy of Pediatrics and United States Public Health Service Immunization Practices Advisory Committee recommendations for hepatitis B immunization in premature infants weighing <2 kg at birth born to hepatitis B surface antigen (HBSAg)-negative mothers are to delay the initiation of vaccination until such infants reach 2 kg or until 2 months of age. This proposal to delay vaccination at birth in these low-risk infants was based on limited studies not conducted in the United States. We sought to reassess current recommendations to delay administration of hepatitis B vaccine in low-risk premature infants by determining the immunogenicity of early hepatitis B vaccination in a US population and identifying variables associated with poor immunogenicity. METHODS: A total of 148 infants <37 weeks' gestation born to mothers negative for HBSAg were recruited at birth and stratified to three birth weight groups: <1000 g, 1000 to 1500 g, and >1500 g. Recombinant hepatitis B vaccine was administered within the first week of life, at 1 to 2 months of age, and at 6 to 7 months of age. Serum obtained at birth and after the second and third doses of vaccine was tested for antibody to HBSAg. Variables associated with poor response were sought prospectively by collecting demographic and clinical data. RESULTS: A total of 118 subjects (83%) completed the study. Postsecond dose sera were available for 117 infants and postthird dose sera were available for 112 infants. The seroprotection rate (attaining >/=10 mIU/mL HBS antibody) after two doses was low (25%) regardless of birth weight; infants weighing <1000 g at birth had the poorest response (11%). The seroprotection response rate after three doses of vaccine increased with birth weight; infants weighing 1500 g at birth (group 3; 84% response rate). The seroprotection response rate of group 3 infants after three doses of vaccine, although low, could not be differentiated from the response rates reported for full-term infants using 95% confidence intervals. Of all infants who did not achieve protective levels of antibody after three doses of vaccine, 96% (26/27) weighed <1700 g at birth. The geometric mean HBS antibody levels in responders were 88 and 386 mIU/mL after two and three doses, respectively. Of 36 children with a birth weight >1500 g, 33 (91%) achieved levels of HBS antibody >100 mIU/mL after three doses of vaccine, compared with 25/35 (71%) of infants with birth weight <1500 g. Using logistic regression analysis, nonresponders were more likely than were responders to have been treated with steroids (26% vs 9%) and to have had a low birth weight (1037 g vs 1455 g). In addition, the seroresponse rate of black infants was more likely than that of white infants to be associated with poor weight gain (falling off 2 percentile ranks in weight) in the first 6 months of life: 22% of black and 60% of white children who failed to gain weight adequately responded to vaccination, compared with 92% of black and 70% of white children who were growing adequately. Of interest, the only infant with a birth weight of >1700 g who did not make protective levels of specific antibody after three doses of vaccine was 2300 g at birth, but had inadequate weight gain in the first 6 months of life. CONCLUSIONS: This study supports current recommendations of the American Academy of Pediatrics and the Centers for Disease Control and Prevention for delaying the initiation of hepatitis B immunization beyond the first week of life for premature infants at low risk for hepatitis B infection, particularly in newborns weighing <1700 g at birth. In addition, we have identified variables other than birth weight that were associated with an inadequate immune response to early hepatitis B vaccination in premature infants, such as poor weight gain in the first 6 months of life

Regulation of surfactant protein D in human fetal lung.

Surfactant protein D (SP-D) is a collagenous glycoprotein, produced by lung type II cells, that has structural and functional similarities with SP-A. In this study we postulated that SP-D and SP-A gene expression are regulated in a similar fashion to provide a coordinated local immune defense response to pulmonary infection. We determined content of SP-D protein and mRNA in second-trimester fetal lung and in postnatal tissue by protein blotting and hybridization analyses. Low levels of SP-D mRNA and protein were detected at 16 wk gestation, before appearance of SP-A, and levels increased during gestation. The content of SP-D did not change during 5 days of explant culture, whereas SP-A increased manyfold. Dexamethasone treatment during culture increased SP-D mRNA and protein about 2-fold with maximal response after 1 to 3 days' exposure to 100 nM steroid; under the same conditions SP-A mRNA content is inhibited. There was no significant change in SP-D mRNA after treatment of explants with adenosine 3',5'-monophosphate (cAMP) analog or interferon-gamma, agents which increase SP-A gene expression, nor after exposure to phorbol ester, tumor necrosis factor-alpha, or lipopolysaccharide at concentrations that reduced levels of SP-A mRNA by approximately 50%. We conclude that SP-D in the human lung is under developmental and glucocorticoid regulation occurring at a pretranslational level. SP-D is not influenced by inflammatory mediators that regulate SP-A, suggesting that these two proteins are not coordinately regulated in response to lung infection.

Cytokine elevations in infants with bacterial and aseptic meningitis.

We sought to determine whether the detection of cytokines, produced during the inflammatory response, would aid in the diagnosis of meningitis in young infants. We measured cerebrospinal fluid (CSF) and plasma levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF) in 62 infants less than 6 months of age whose condition was evaluated for meningitis. Twenty infants had culture-proved meningitis, 22 had aseptic meningitis, and 20 control infants had no evidence of meningitis. The CSF IL-6 levels were elevated in all 20 infants with bacterial meningitis and in 9 of 22 infants with aseptic meningitis but were undetectable in all control subjects. Furthermore, CSF IL-6 levels were 10 times greater in infants with bacterial versus aseptic meningitis (p < 0.001). Levels of TNF in CSF were detected in 12 of 20 infants with bacterial meningitis and were undetectable in infants with aseptic meningitis and in control infants (p < 0.02). Plasma IL-6 and TNF levels were unreliable for the detection of meningitis in this patient population. We conclude that the presence of IL-6 in the CSF reliably identifies infants with meningitis and that the presence of CSF TNF is a highly specific indicator of bacterial meningeal inflammation.

Cytokine elevations in critically ill infants with sepsis and necrotizing enterocolitis.

We hypothesized that plasma levels of cytokines such as interleukin-6 and tumor necrosis factor (TNF) are elevated in critically ill infants with sepsis and necrotizing enterocolitis (NEC) and that the magnitude of their elevation is correlated with mortality rate. We measured plasma levels of interleukin-6 and TNF in 62 newborn infants with suspected sepsis or NEC. Eighteen infants had bacterial sepsis, 9 had bacterial sepsis plus NEC, and 15 had NEC but negative culture results. Twenty comparably ill infants with negative results on culture of systemic specimens served as study control subjects. Interleukin-6 levels were five- to tenfold higher in infants with bacterial sepsis plus NEC at the onset of disease than in infants with bacterial sepsis alone, in infants with NEC but negative culture results, and in control infants (p < 0.01). These differences persisted throughout the 48-hour study period. Interleukin-6 levels were also significantly higher in nonsurvivors than in survivors (p < 0.001). In contrast, plasma TNF values were not consistently increased in any of the groups. We conclude that plasma interleukin-6 is a more reliable indicator of bacterial sepsis and NEC than plasma TNF and may identify infants who might benefit from immunotherapeutic strategies.