Assessment of preterm infants' readiness to commence breastfeeding

Preterm infants commence breastfeeding when health-care professionals deem them to be ready. However, the optimal timing for commencement of breastfeeding is unclear. Currently, there is little guidance for neonatal care providers to decide when to initiate breastfeeding among preterm infants. A mixed-methods study was conducted to develop and test the Preterm Sucking Readiness (PTSR) scale in four phases. The first phase involved a chart audit to explore the use of age as a criterion by investigating when preterm infants meet feeding milestones as well as other factors that may affect an infant’s readiness to engage in nutritive sucking behaviour. The second phase utilised focus groups to explore and define how neonatal care providers decide when to commence breastfeeding. To gain consensus on the criteria mentioned by the focus groups, a Delphi survey was conducted in phase 3, involving neonatal providers across Australia and New Zealand. Phase 4 of the study involved an observational study that was used to test the six-item PTSR. The age at which specific feeding milestones were reached was consistent with what has been previously described in the literature. The chart audit showed that the time taken to the first feeding attempt in the preterm infant population was affected by gestational age at birth, birth weight, and specific interventions. Staff also considered age along with other criteria when deciding when to initiate feeding. Consensus on nine criteria for inclusion into the six-item PTSR was achieved using the Delphi technique. Three items of PTSR showed significant differences between the preterm and fullterm infant groups. Only two items, feeding-readiness behaviour and low pulse oximetry during handling, explained the variance in breastfeeding behaviour. The inter-rater variability ranged between moderate and very good for the PTSR items. The results of this study indicate the importance of assessing behavioural cues as an indication of breastfeeding readiness in the preterm infant population, once an infant is deemed physiologically stable. Age continues to be a factor in some clinicians' decisions to commence breastfeeding. However, age alone cannot be used to decide if an infant is ready to engage in breastfeeding. Further research is needed to confirm these findings.

Lung recruitment and endotracheal suction in ventilated preterm infants measured with electrical impedance tomography

Aims Although suctioning is a standard airway maintenance procedure, there are significant associated risks, such as loss of lung volume due to high negative suction pressures. This study aims to assess the extent and duration of change in end-expiratory level (EEL) resulting from endotracheal tube (ETT) suction and to examine the relationship between EEL and regional lung ventilation in ventilated preterm infants with respiratory distress syndrome. Methods A prospective observational clinical study of the effect of ETT suction on 20 non-muscle-relaxed preterm infants with respiratory distress syndrome (RDS) on conventional mechanical ventilation was conducted in a neonatal intensive care unit. Ventilation distribution was measured with regional impedance amplitudes and EEL using electrical impedance tomography. Results ETT suction resulted in a significant increase in EEL post-suction (P < 0.01). Regionally, anterior EEL decreased and posterior EEL increased post-suction, suggesting heterogeneity. Tidal volume was significantly lower in volume-guarantee ventilation compared with pressure-controlled ventilation (P = 0.04). Conclusions ETT suction in non-muscle-relaxed and ventilated preterm infants with RDS results in significant lung volume increase that is maintained for at least 90 min. Regional differences in distribution of ventilation with ETT suction suggest that the behaviour of the lung is heterogeneous in nature.

Growth patterns in preterm infants born appropriate for gestational age

Aim: This study aimed to document the growth patterns of a contemporary cohort of preterm infants born appropriate for gestational age (AGA). It was hypothesised that preterm AGA (PT-AGA) infants would display poorer growth than full-term AGA (FT-AGA) infants. Methods: Sixty-four PT-AGA infants and 64 FT-AGA infants were assessed at 0, 4, 8 and 12 months of corrected age (CA). Measurements of weight and length were recorded at each of the specified ages. Centers for Disease Control and Prevention growth data were used to calculate Z-scores for weight and length based on CA. Results: The mean length and weight Z-scores of PT-AGA infants were found to be significantly less than those of FT-AGA infants at term, 4, 8 and 12 months of CA (P < 0.001). The mean weight Z-score of PT-AGA infants was found to be less than their mean length Z-score at each time point, though the differences were not significant. Conclusions: The results of this study suggest that PT-AGA infants are likely to display poorer growth than FT-AGA infants until at least 1 year of CA. Long-term growth monitoring in this population is recommended. © 2008 The Authors.

Placental infection with Ureaplasma species is associated with histologic chorioamnionitis and adverse outcomes in moderately preterm and late-preterm infants

Objective The human Ureaplasma species are the microbes most frequently isolated from placentae of women who deliver preterm. The role of Ureaplasma species has been investigated in pregnancies at <32 weeks of gestation, but currently no studies have determined the prevalence of ureaplasmas in moderately preterm and late-preterm (hereafter, “moderate/late preterm”) infants, the largest cohort of preterm infants. Methods Women delivering moderate/late preterm infants (n = 477) and their infants/placentae (n = 535) were recruited, and swab specimens of chorioamnion tissue, chorioamnion tissue specimens, and cord blood specimens were obtained at delivery. Swab and tissue specimens were cultured and analyzed by 16S ribosomal RNA polymerase chain reaction (PCR) for the presence of microorganisms, while cord blood specimens were analyzed for the presence of cytokines, chemokines, and growth factors. Results We detected microorganisms in 10.6% of 535 placentae (443 were delivered late preterm and 92 were delivered at term). Significantly, Ureaplasma species were the most prevalent microorganisms, and their presence alone was associated with histologically confirmed chorioamnionitis in moderate/late preterm and term placentae (P < .001). The presence of ureaplasmas in the chorioamnion was also associated with elevated levels of granulocyte colony-stimulating factor (P = .02). Conclusions These findings have important implications for infection and adverse pregnancy outcomes throughout gestation and should be of major consideration for obstetricians and neonatologists.

Systemic Inflammation in Preterm Infants

Even though mortality among preterm infants has decreased, their risk for chronic complications such as bronchopulmonary dysplasia (BPD) and neurological disability remains significant. One common risk factor for these is exposure to inflammation. The fetus may be exposed prenatally during maternal chorioamnionitis. Pre-eclampsia is also associated with low-grade maternal inflammation. Postnatally, local and systemic inflammation is present during respiratory distress syndrome (RDS). Furthermore, septic infections in the preterm infant are an important source of inflammatory stimuli and can lead to death in only a few hours. The diagnosis of septic infection is difficult, since reliable diagnostic markers are unavailable. This thesis evaluates peri- and postnatal systemic inflammation in preterm infants in septic infections, in RDS treated with mechanical ventilation and surfactant treatment, and in preterm infants prenatally exposed to chorioamnionitis and pre-eclampsia. Surface expressions of the activation markers CD11b, CD54, and CD62L, determined by flow cytometry on circulating phagocytes and T lymphocytes, serve as indicators of systemic inflammation. The main findings: I) In preterm infants with developing late-onset sepsis and fulminant necrotizing enterocolitis, a significant increase in CD11b expression on circulating phagocytes is already present on the day of onset of clinical symptoms. II) In preterm infants with RDS, circulating phagocytes become activated within hours after start of mechanical ventilation. In preterm infants treated for RDS with nasal continuous positive airway pressure, no such activation occurs. III) In preterm infants, RDS is associated during the first days of life with fewer circulating helper and cytotoxic T lymphocytes, of which the greater proportions are activated. Even greater proportions of circulating T cells are activated in infants subsequently developing BPD. IV) In preterm infants born after maternal pre-eclampsia, RDS-associated phagocyte CD11b up-regulation is greater than in preterm infants not exposed to pre-eclampsia during the first week of life. These findings suggest that I) an increase in CD11b expression on circulating phagocytes can identify preterm infants with late-onset sepsis as early as at sampling for blood culture and may thus aid in the diagnosis. II) In preterm infants with RDS, initiation of mechanical ventilation, but not the use of nasal continuous positive airway pressure, promotes a systemic inflammatory reaction; exogenous surfactant does not seem to promote inflammation. III) In addition to activation of circulating cells of the innate immunity in preterm infants with RDS, the circulating cells of the adaptive immunity are activated. The activation of adaptive immunity may link acute inflammation and development of chronic inflammation-associated problems such as BPD. IV) Maternal pre-eclampsia may prime neonatal immunity to react more strongly to postnatal stimuli. In conclusion, the preterm infant is exposed to numerous potentially injurious events such as intrauterine inflammation, respiratory distress syndrome (RDS), and systemic infections, all evoking systemic inflammation. Due to ongoing development of the lung and the brain, this may, in addition to acute injury, lead to aberrant lung and brain development and to clinical syndromes of BPD and neurologic sequelae.

Long-Term Burden and Respiratory Effects of Respiratory Syncytial Virus Hospitalization in Preterm Infants — The SPRING Study

The health status of premature infants born 32(1)-35(0) weeks' gestational age (wGA) hospitalized for RSV infection in the first year of life (cases; n = 125) was compared to that of premature infants not hospitalized for RSV (controls; n = 362) through 6 years. The primary endpoints were the percentage of children with wheezing between 2-6 years and lung function at 6 years of age. Secondary endpoints included quality of life, healthcare resource use, and allergic sensitization. A significantly higher proportion of cases than controls experienced recurrent wheezing through 6 years of age (46.7% vs. 27.4%; p = 0.001). The vast majority of lung function tests appeared normal at 6 years of age in both cohorts. In children with pulmonary function in the lower limit of normality (FEV1 Z-score [-2; -1]), wheezing was increased, particularly for cases vs. controls (72.7% vs. 18.9%, p = 0.002). Multivariate analysis revealed the most important factor for wheezing was RSV hospitalization. Quality of life on the respiratory subscale of the TAPQOL was significantly lower (p = 0.001) and healthcare resource utilization was significantly higher (p<0.001) in cases than controls. This study confirms RSV disease is associated with wheezing in 32-35 wGA infants through 6 years of age.

Nutrition, growth and body composition in preterm infants

The goal of neonatal nutrition in the preterm infant is to achieve postnatal growth and body composition approximating that of a normal fetus of the same postmenstrual age and to obtain a functional outcome comparable to infants born at term. However, in clinical practice such a pattern is seldom achieved, with growth failure and altered body composition being extensively reported. The BabyGrow preterm nutrition study was a longitudinal, prospective, observational study designed to investigate nutrition and growth in 59 preterm infants following the implementation of evidence-based nutrition guidelines in the neonatal unit at Cork University Maternity Hospital. Nutrient delivery was precisely measured during the entire hospital stay and intakes were compared with current international recommendations. Barriers to nutrient delivery were identified across the phases of nutritional support i.e. exclusive parenteral nutrition and transition (establishment of enteral feeds) phases of nutrition and nutritional strategies to optimise nutrient delivery were proposed according to these phases. Growth was measured from birth up to 2 months corrected age and body composition was assessed in terms of fat mass and lean body mass by air displacement plethysmography (PEA POD) at 34 weeks gestation, term corrected age and 2 months corrected age. Anthropometric and body composition data in the preterm cohort were compared with a term reference group from the Cork BASELINE Birth Cohort Study (n=1070) at similar time intervals. The clinical and nutritional determinants of growth and body composition during the neonatal period were reported for the first time. These data have international relevance, informing authoritative agencies developing evidence-based practice guidelines for neonatal nutritional support. In the future, the nutritional management of preterm infants may need to be individualised to consider gestational age, birth weight as well as preterm morbidity.

Cellular immune responses of preterm infants after vaccination with whole-cell or acellular pertussis vaccines.

Based on studies reporting specific antibody titers, it is recommended to vaccinate preterm infants against Bordetella pertussis according to their chronological age. However, as specific T-cell responses also are involved in the protection against B. pertussis, we have determined whether highly preterm infants (<31 weeks) are able to mount these immune responses during vaccination. Forty-eight premature infants were vaccinated at 2, 3, and 4 months of their chronological age with an acellular (Pa; n = 24) or a whole-cell (Pw; n = 24) tetravalent diphtheria-tetanus-pertussis-polio vaccine, and blood samples were collected at 2, 3, and 6 months of age. Most of the Pa- and Pw-vaccinated infants developed at 3 or 6 months of age a gamma interferon (IFN-gamma) response to the B. pertussis antigens, accompanied by an interleukin-5 (IL-5) and IL-13 secretion for the Pa-vaccinated infants. No association was found between a very low infant birth weight, the occurrence of severe infections, and corticosteroid treatment or the administration of gammaglobulins with a low level of antigen-induced IFN-gamma secretion. We conclude that like full-term infants, most preterm infants are able to mount a specific cellular immune response to the administration of the first doses of an acellular or a whole-cell pertussis vaccine.

Persistence at one year of age of antigen-induced cellular immune responses in preterm infants vaccinated against whooping cough: comparison of three different vaccines and effect of a booster dose.

Due to their high risk of developing severe Bordetella pertussis (Bp) infections, it is recommended to immunize preterm infants at their chronological age. However, little is known about the persistence of their specific immune responses, especially of the cellular responses recognized to play a role in protection. We compared here the cellular immune responses to two major antigens of Bp between three groups of one year-old children born prematurely, who received for their primary vaccination respectively the whole cell vaccine Tetracoq(®) (TC), the acellular vaccine Tetravac(®) (TV), or the acellular vaccine Infanrix-hexa(®) (IR). Whereas most children had still detectable IFN-γ responses at one year of age, they were lower in the IR-vaccinated children compared to the two other groups. In contrast, both the TV- and the IR-vaccinated children displayed higher Th2-type immune responses, resulting in higher antigen-specific IFN-γ/IL-5 ratios in TC- than in TV- or IR-vaccinated children. The IFN-γ/IL-5 ratio of mitogen-induced cytokines was also lower in IR- compared to TC- or TV-vaccinated children. No major differences in the immune responses were noted after the booster compared to the pre-booster responses for each vaccine. The IR-vaccinated children had a persistently low specific Th1-type immune response associated with high specific Th2-type immune responses, resulting in lower antigen-specific IFN-γ/IL-5 ratios compared to the two other groups. We conclude that antigen-specific cellular immune responses persisted in one year-old children born prematurely and vaccinated during infancy at their chronological age, that a booster dose did not significantly boost the cellular immune responses, and that the Th1/Th2 balance of the immune responses is modulated by the different vaccines.

Oxidative stress in lavage fluid of preterm infants at risk of chronic lung disease

There is evidence that oxidative stress plays a role in the development of chronic lung disease (CLD), with immature lungs being particularly sensitive to the injurious effect of oxygen and mechanical ventilation. We analyzed total ascorbate, urate, and protein carbonyls in 102 bronchoalveolar lavage fluid samples from 38 babies (33 preterm, 24–36 wk gestation; 5 term, 37–39 wk gestation). Preterm babies had significantly decreasing concentrations of ascorbate, urate, and protein carbonyls during the first 9 days of life (days 1–3, 4–6, and 7–9, Kruskal-Wallis ANOVA: P 5 0.016, P , 0.0001, and P 5 0.010, respectively). Preterm babies had significantly higher protein carbonyl concentrations at days 1–3 and 4–6 (P 5 0.005 and P 5 0.044) compared with term babies. Very preterm babies (24–28 wk gestation) had increased concentrations of protein carbonyls at days 4–6 (P 5 0.056) and significantly decreased ascorbate concentrations at days 4–6 (P 5 0.004) compared with preterm babies (29–36 wk gestation). Urate concentrations were significantly elevated at days 1–3 (P 5 0.023) in preterm babies who subsequently developed CLD. This study has shown the presence of oxidative stress in the lungs of preterm babies during ventilation, especially in those who subsequently developed CLD.

A Multicenter, Randomised Open Study of Early Corticosteroid Treatment (OSECT) in Preterm Infants With Respiratory Illness: Comparison of Early and Late Treatment and of Dexamethasone and Inhaled Budesonide

AIM: To compare early (15 days) steroid therapy and dexamethasone with inhaled budesonide in very preterm infants at risk of developing chronic lung disease. METHODS: Five hundred seventy infants from 47 neonatal intensive care units were enrolled. Criteria for enrollment included gestational age 30%. Infants were randomly allocated to 1 of 4 treatment groups in a factorial design: early (15 days) dexamethasone, and delayed selective budesonide. Dexamethasone was given in a tapering course beginning with 0.50 mg/kg/day in 2 divided doses for 3 days reducing by half until 12 days of therapy had elapsed. Budesonide was administered by metered dose inhaler and a spacing chamber in a dose of 400 microg/kg twice daily for 12 days. Delayed selective treatment was started if infants needed mechanical ventilation and >30% oxygen for >15 days. The factorial design allowed 2 major comparisons: early versus late treatment and systemic dexamethasone versus inhaled budesonide. The primary outcome was death or oxygen dependency at 36 weeks and analysis was on an intention-to-treat basis. Secondary outcome measures included death or major cerebral abnormality, duration of oxygen treatment, and complications of prematurity. Adverse effects were also monitored daily. RESULTS: There were no significant differences among the groups for the primary outcome. Early steroid treatment was associated with a lower primary outcome rate (odds ratio [OR]: 0.85; 95% confidence interval [CI]: 0.61,1.18) but even after adjustment for confounding variables the difference remained nonsignificant. Dexamethasone-treated infants also had a lower primary outcome rate (OR: 0.86; 95% CI: 0.62,1.20) but again this difference remained not significant after adjustment. For death before discharge, dexamethasone and early treatment had worse outcomes than budesonide and delayed selective treatment (OR: 1.42; 95% CI: 0.93,2.16; OR: 1.51; 95% CI: 0.99,2.30 after adjustment, respectively) with the results not quite reaching significance. Duration of supplementary oxygen was shorter in the early dexamethasone group (median: 31 days vs 40-44 days). Early dexamethasone was also associated with increased weight loss during the first 12 days of treatment (52 g vs 3 g) compared with early budesonide, but over 30 days there was no difference. In the early dexamethasone group, there was a reduced incidence of persistent ductus arteriosus (34% vs 52%-59%) and an increased risk of hyperglycemia (55% vs 29%-34%) compared with the other 3 groups. Dexamethasone was associated with an increased risk of hypertension and gastrointestinal problems compared with budesonide but only the former attained significance. CONCLUSIONS: Infants given early treatment and dexamethasone therapy had improved survival without chronic lung disease at 36 weeks compared with those given delayed selective treatment and inhaled budesonide, respectively, but results for survival to discharge were in the opposite direction; however, none of these findings attained statistical significance. Early dexamethasone treatment reduced the risk of persistent ductus arteriosus. Inhaled budesonide may be safer than dexamethasone, but there is no clear evidence that it is more or less effective