Related Articles

OBJECTIVE

Individuals with Down syndrome (DS) are at increased risk of several morbidities with lifelong health consequences. Little is known about mortality or morbidity risks in early infancy among very-low-birth-weight (VLBW) infants with DS. Our objective was to compare survival and neonatal morbidities between VLBW infants with DS and VLBW infants with other non-DS chromosomal anomalies, other non-chromosomal birth defects, and VLBW infants without major birth defects.

METHODS

Data were collected prospectively for infants weighing 401-1500 grams born and/or cared for at one of the study centers participating in the NICHD Neonatal Research Network from 1994 through 2008. Risk of death and morbidities including patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), late onset sepsis (LOS), retinopathy of prematurity (ROP), and bronchopulmonary dysplasia (BPD), were compared between VLBW infants with DS and infants in the other groups.

RESULTS

Infants with DS were at increased risk of death (adjusted relative risk [RR] 2.47, 95% confidence interval [CI] 2.00-3.07), PDA, NEC, LOS, and BPD relative to infants with no birth defects. Decreased risk of death (RR 0.40, 95% CI 0.31-0.52) and increased risks of NEC and LOS were observed when comparing infants with DS to infants with other non-DS chromosomal anomalies. Relative to infants with non-chromosomal birth defects, infants with DS were at increased risk of PDA and NEC.

CONCLUSION

The increased risk of morbidities among VLBW infants with DS provides useful information for counseling parents and for caretakers in anticipating the need for enhanced surveillance for prevention of these morbidities.

Background

Approximately 826,000 children, mostly young infants, die annually from invasive pneumococcal disease. A 6-10-14-week schedule of pneumococcal conjugate vaccine (PCV) is efficacious but neonatal PCV may provide earlier protection and better coverage. We conducted an open randomized controlled trial in Papua New Guinea to compare safety, immunogenicity and priming for memory of 7-valent PCV (PCV7) given in a 0-1-2-month (neonatal) schedule with that of the routine 1-2-3-month (infant) schedule.

Methods

We randomized 318 infants at birth to receive PCV7 in the neonatal or infant schedule or no PCV7. All infants received 23-valent pneumococcal polysaccharide vaccine (PPV) at age 9 months. Serotype-specific serum IgG for PCV7 (VT) serotypes and non-VT serotypes 2, 5 and 7F were measured at birth and 2, 3, 4, 9, 10 and 18 months of age. Primary outcomes were geometric mean concentrations (GMCs) and proportions with concentration ≥0.35 µg/ml of VT serotype-specific pneumococcal IgG at age 2 months and one month post-PPV.

Results

We enrolled 101, 105 and 106 infants, respectively, into neonatal, infant and control groups. Despite high background levels of maternally derived antibody, both PCV7 groups had higher GMCs than controls at age 2 months for serotypes 4 (p<0.001) and 9V (p<0.05) and at age 3 months for all VTs except 6B. GMCs for serotypes 4, 9V, 18C and 19F were significantly higher (p<0.001) at age 2 months in the neonatal (one month post-dose2 PCV7) than in the infant group (one month post-dose1 PCV7). PPV induced significantly higher VT antibody responses in PCV7-primed than unprimed infants, with neonatal and infant groups equivalent. High VT and non-VT antibody concentrations generally persisted to age 18 months.

Conclusions

PCV7 is well-tolerated and immunogenic in PNG neonates and young infants and induces immunologic memory to PPV booster at age 9 months with antibody levels maintained to age 18 months.

Trial Registration

ClinicalTrials.gov NCT00219401NCT00219401

Background

Influenza vaccine immunogenicity in premature infants is incompletely characterized.

Objective

To assess the immunogenicity of trivalent, inactivated influenza vaccine (TIV) in extremely low-birth-weight (ELBW, ≤1000 grams birth weight), premature (<30 weeks gestation) infants. We hypothesized that geometric mean titers (GMT) of influenza antibody would be lower in premature than in full-term (≥37 week) infants.

Design/Methods

In this prospective, multicenter study, former premature and full-term infants ages, 6–17 months, received 2 doses of TIV during the 2006–7 or 2007–8 influenza seasons. Sera were drawn before dose 1 and 4–6 weeks after dose 2. Antibody was measured by hemagglutination inhibition.

Results

Over two years, 41 premature and 42 full-term infants were enrolled; 36 and 33 of these infants, respectively, had post-vaccination titers available. Premature infants weighed less (mean 1.3 – 1.8 kg difference) at the time of immunization than full-term infants. Pre-vaccination titers did not differ between groups. Premature infants had higher post-vaccination antibody GMT than full-term infants to H1 (2006–7, 1:513 v. 1:91, P=0.03; 2007–8, 1:363 v. 1:189, P=0.02) and B/Victoria (2006–7, 1:51 v. 1:10, P=0.02). More premature than full-term infants had antibody titers ≥ 1:32 to B/Victoria (85% v. 60%, p=0.04) in 2007–8. Two (5%) premature and 8 (19%) full-term infants had adverse events, primarily fever, within 72 hours after vaccination. No child had medically-diagnosed influenza.

Conclusions

Former premature infants had antibody responses to two TIV doses greater than or equal to those of full-term children. Two TIV doses are immunogenic and well tolerated in ELBW, premature infants 6–17 months old.

Immunization of Kenyan newborns with 7-valent pneumococcal conjugate vaccine is safe and immunogenic. Compared with the Expanded Programme on Immunization schedule beginning at 6 weeks, it stimulates similar antibody concentrations at 18 weeks and induces equal responses to a 9-month booster dose.

Background. In developing countries, newborn immunization with pneumococcal conjugate vaccines (PCVs) could protect young infants who are at high risk of invasive pneumococcal disease (IPD) but might lead to immune tolerance.

Methods. In a randomized trial, young infants received 7-valent PCV at 6, 10, and 14 weeks (Expanded Programme on Immunization [EPI] group) or 0, 10, and 14 weeks (newborn group). Safety was monitored actively at 2–7 days and then passively. Serum samples obtained at birth and 6, 10, 14, 18, 36, and 37 weeks were assayed by enzyme-linked immunosorbent assay for anticapsular immunoglobulin G concentration and avidity. Infants were boosted with either 7-valent PCV or one-fifth dose of pneumococcal polysaccharide vaccine at 36 weeks. Nasopharyngeal swab samples were obtained at 18 and 36 weeks.

Results. Three-hundred neonates and young infants were enrolled. Newborn vaccination was well tolerated. Adverse events occurred equally in each group; none was related to immunization. One infant, immunized at birth, died of unrelated neonatal sepsis. At 18 weeks, protective concentrations (≥0.35 μg/mL) were achieved against each serotype by ≥87% of infants with no significant differences between groups. Geometric mean concentrations were higher in the EPI group for serotypes 4, 9V, 18C, and 19F at 18 weeks and for serotype 4 at 36 weeks. Avidity was greater in the newborn group for serotypes 4, 6B, and 19F at 18 weeks and for serotype 19F at 36 weeks. Booster responses and vaccine-type/nonvaccine-type carriage prevalence did not differ between groups.

Conclusions. PCV was safe, immunogenic, and primed for memory when given at birth. There was no evidence of immune tolerance. Vaccination beginning at birth offers an alternative to control IPD in vulnerable young infants.

In very low birth weight (VLBW) infants, acute renal impairment (ARI) is common but there is no consensus about criteria for its diagnosis. Neutrophil gelatinase-associated lipocalin (NGAL) is an early and sensitive indicator of renal impairment in experimental animals, children, and adults. Urinary NGAL (UNGAL) is detectable in VLBW infants; however, there is no reference range in this population. The objective of this study is to define the reference range for UNGAL in VLBW infants with no risk factors for ARI. UNGAL concentration was determined in urine samples collected from day of life (DOL) 4 through DOL 30 in 50 newborns with uncomplicated clinical courses, selected from a total of 145 prospectively enrolled appropriate for gestational age (AGA) inborn VLBW premature infants. The birth weight and gestational age ranges were 790–1490 grams and 26–33 weeks, respectively. The median, 95th and 99th percentiles, and range of pooled UNGAL values were 5 ng/ml, 50 ng/ml, 120ng/ml, and 2–150 ng/ml, respectively. Greater variability and higher quantile levels of UNGAL were observed in females vs. males. In conclusion, a reference range for UNGAL in VLBW infants, similar to that in children and adults, has been established.

In the Finnish Otitis Media Vaccine Trial, the now-licensed pneumococcal conjugate vaccine containing polysaccharides conjugated to protein CRM197 (PncCRM) and the experimental pneumococcal polysaccharide-meningococcal outer membrane protein complex conjugate vaccine (PncOMPC), showed similar efficacy profiles against acute otitis media despite different antibody concentrations in sera. We now report the opsonophagocytic activities (OPA) in these sera. OPA, antibody concentration, and avidity for serotypes 6B, 19F, and 23F were determined in sera of infants who received either pneumococcal conjugate (PCV) or control vaccine at 2, 4, and 6 months of age and either the homologous or pneumococcal polysaccharide vaccine at 12 months of age. OPA varied by vaccine and serotype. The majority of PCV recipients had positive OPA after the fourth dose, while OPA was undetectable in the control group. Coinciding with the efficacy data, the concentration of antibodies required for 50% killing was low for 6B and high for 19F for both PCVs. Contradictory to the efficacy data, PncOMPC induced lower functional capacity to 23F than PncCRM. OPA correlated with antibody concentration, while avidity and functional capacity of antibodies showed no correlation. The OPA data provide valuable additional information for serotype-specific differences in protection and when evaluating serotype-specific immunogenicity and should thus be considered when defining serological correlates of protection.

Background

Very low birth weight (VLBW) infants (< 1,500 g) with bronchopulmonary dysplasia (BPD) develop lung damage caused by mechanical ventilation and maturational arrest. We compared functional lung development after discharge from hospital between VLBW infants with and without BPD.

Methods

Comprehensive lung function assessment was performed at about 50, 70, and 100 weeks of postmenstrual age in 55 sedated VLBW infants (29 with former BPD [O2 supplementation was given at 36 weeks of gestational age] and 26 VLBW infants without BPD [controls]). Mean gestational age (26 vs. 29 weeks), birth weight (815 g vs. 1,125 g), and the proportion of infants requiring mechanical ventilation for ≥7 d (55% vs. 8%), differed significantly between BPD infants and controls.

Results

Both body weight and length, determined over time, were persistently lower in former BPD infants compared to controls, but no significant between-group differences were noted in respiratory rate, respiratory or airway resistance, functional residual capacity as determined by body plethysmography (FRCpleth), maximal expiratory flow at the FRC (V'max FRC), or blood gas (pO2, pCO2) levels. Tidal volume, minute ventilation, respiratory compliance, and FRC determined by SF6 multiple breath washout (representing the lung volume in actual communication with the airways) were significantly lower in former BPD infants compared to controls. However, these differences became non-significant after normalization to body weight.

Conclusions

Although somatic growth and the development of some lung functional parameters lag in former BPD infants, the lung function of such infants appears to develop in line with that of non-BPD infants when a body weight correction is applied. Longitudinal lung function testing of preterm infants after discharge from hospital may help to identify former BPD infants at risk of incomplete recovery of respiratory function; such infants are at risk of later respiratory problems.

The licensure of new pneumococcal conjugate vaccines (PCVs) relies on immunogenicity data. When defining correlates of protection, vaccine efficacy data must be included. In the FinOM Vaccine Efficacy Trial, the PncOMPC vaccine showed an efficacy profile similar to that of the licensed PncCRM vaccine despite different antibody responses after primary and booster vaccinations. We determined antibody kinetics and avidities in a subgroup of infants participating in the FinOM trial. A total of 166 infants in three vaccine groups were immunized at 2, 4, 6, and 12 months of age with 7-valent PCV, PncCRM or PncOMPC, or hepatitis B vaccine. Concentrations of serum immunoglobulin G (IgG) against pneumococcal capsular polysaccharides were determined at 2, 4, 6, 7, 12, 13, and 24 months of age, and the avidity index (AI) to serotypes 6B, 19F, and 23F were determined at 7, 12, 13, and 24 months of age by enzyme immunoassay. Both PCVs were highly immunogenic, but they demonstrated different kinetics of antibody response; the concentration of IgG against serotypes 6B, 19F, and 23F declined faster after the third and fourth doses of vaccine in the PncCRM group than in the PncOMPC group. For both PCVs, the mean AI of anti-6B and -23F, but not of anti-19F, increased during the follow-up, which is in line with serotype-specific protection in the FinOM trial. Our data suggest that the kinetics and avidities of antibodies should be considered, in addition to antibody responses, when defining correlates of protection.

Background

Medical and public health importance of pneumococcal infections justifies the implementation of measures capable of reducing their incidence and severity, and explains why the recently marketed heptavalent pneumococcal conjugate vaccine (PCV-7) has been widely studied by pediatricians. This study was designed to evaluate the impact of PCV-7 administered at 3, 5 and 11 months of age on respiratory tract infections in very young children.

Methods

A total of 1,571 healthy infants (910 males) aged 75–105 days (median 82 days) were enrolled in this prospective cohort trial to receive a hexavalent vaccine (DTaP/IPV/HBV/Hib) and PCV-7 (n = 819) or the hexavalent vaccine alone (n = 752) at 3, 5 and 11 months of age. Morbidity was recorded for the 24 months following the second dose by monthly telephone interviews conducted by investigators blinded to the study treatment assignment using standardised questionnaires. During these interviews, the caregivers and the children's pediatricians were questioned about illnesses and the use of antibiotics since the previous telephone call. All of the data were analysed using SAS Windows v.12.

Results

Among the 1,555 subjects (98.9%) who completed the study, analysis of the data by the periods of follow-up demonstrated that radiologically confirmed community-acquired pneumonia (CAP) was significantly less frequent in the PCV-7 group during the follow-up as a whole and during the last period of follow-up. Moreover, there were statistically significant between-group differences in the incidence of acute otitis media (AOM) in each half-year period of follow-up except the first, with significantly lower number of episodes in children receiving PCV-7 than in controls. Furthermore, the antibiotic prescription data showed that the probability of receiving an antibiotic course was significantly lower in the PCV-7 group than in the control group.

Conclusion

Our findings show the effectiveness of the simplified PCV-7 schedule (three doses administered at 3, 5 and 11–12 months of age) in the prevention of CAP and AOM, diseases in which Streptococcus pneumoniae plays a major etiological role. A further benefit is that the use of PCV-7 reduces the number of antibiotic prescriptions. All of these advantages may also be important from an economic point of view.

AIMS—To investigate the effects of small for gestational age (SGA) in very low birthweight (VLBW) infants on growth and development until the fifth year of life.
METHODS—VLBW (< 1500 g) infants, selected from a prospective study, were classified as SGA (n = 115) on the basis of birth weight below the 10th percentile for gestational age and were compared with two groups of appropriate for gestational age (AGA) infants matched according to birth weight (AGA-BW; n = 115) or gestation at birth (AGA-GA; n = 115). Prenatal, perinatal, and postnatal risk factors were recorded, and duration and intensity of treatment were computed from daily assessments. Body weight, length, and head circumference were measured at birth, five and 20 months (corrected for prematurity), and at 56 months. General development was assessed at five and 20 months with the Griffiths scale of babies abilities, and cognitive development at 56 months with the Columbia mental maturity scales, a vocabulary (AWST) and language comprehension test (LSVTA).
RESULTS—Significant group differences were found in complications (pregnancy, birth, and neonatal), parity, and multiple birth rate. The AGA-GA group showed most satisfactory growth up to 56 months, with both the AGA-BW and SGA groups lagging behind. The AGA-GA group also scored significantly more highly on all developmental and cognitive tests than the other groups. Developmental test results were similar for the SGA and AGA-BW groups at five and 20 months, but AGA-BW infants (lowest gestation) had lower scores on performance intelligence quotient and language comprehension at 56 months than the SGA group. When prenatal and neonatal complications, parity, and multiple birth were accounted for, group differences in growth remained, but differences in cognitive outcome disappeared after five months.
CONCLUSIONS—Being underweight and with a short gestation (SGA and VLBW) leads to poor weight gain and head growth in infancy but does not result in poorer growth than in infants of the same birth weight but shorter gestation (AGA-BW) in the long term. SGA is related to early developmental delay and later language problems; however, neonatal complications may have a larger detrimental effect on long term cognitive development of VLBW infants than whether they are born SGA or AGA.



Background

Gambian infants frequently acquire Streptococcus pneumoniae soon after birth. We investigated the indirect effect of 7-valent pneumococcal conjugate vaccine (PCV-7) on pneumococcal acquisition in newborn Gambian babies.

Methods

Twenty-one villages were randomised to receive PCV-7 to all subjects (11 vaccinated villages) or to infants aged 2–30 months (10 control villages). Other control villagers received Meningococcal C conjugate vaccine. From 328 babies born during the trial, nasopharyngeal swabs were collected after birth, then weekly until 8 weeks of age when they received their first dose of PCV-7. Pneumococcal carriage and acquisition rates were compared between the study arms and with a baseline study.

Results

57.4% of 2245 swabs were positive for S. pneumoniae. Overall carriage was similar in both arms. In vaccinated villages fewer infants carried pneumococci of vaccine serotypes (VT) (16.9% [31/184] vs. 37.5% [54/144], p<0.001) and more carried pneumococci of non-vaccine serotypes (NVT) (80.9% [149/184] vs. 75.7% [109/144], p = 0.246). Infants from vaccinated villages had a significantly lower acquisition rate of VT (HR 0.39 [0.26–0.58], p<0.001) and increased acquisition of NVT (HR 1.16 [0.87–1.56], p = 0.312). VT carriage (51.6% vs. 37.5%, p = 031 in control and 46.1% vs. 16.8%, p<0.001 in vaccinated villages) and acquisition rates (HR 0.68 [0.50–0.92], p = 0.013 in control villages and HR 0.31 [0.19–0.50], p<.001 in vaccinated villages) were significantly lower in both study arms than in the baseline study. NVT carriage (63.2% vs. 75.7%, p = 0.037 in control and 67.2% vs. 75.3%, p = 0.005 in vaccinated villages) and acquisition rates (HR 1.48 [1.06–2.06], p = 0.022) and (HR 1.52 [1.11–2.10], p = 0.010 respectively) were significantly higher.

Conclusion

PCV-7 significantly reduced carriage of VT pneumococci in unvaccinated infants. This indirect effect likely originated from both the child and adult vaccinated populations. Increased carriage of NVT pneumococci needs ongoing monitoring.

Trial Registration

ISRCTN Register 51695599

Aims: To determine if very low birth weight (VLBW; birth weight <1500 g) is associated with reduced lung function and respiratory health in adolescence and, if it is, whether this impairment is associated with prematurity or intrauterine growth restriction.

Methods: A geographically defined cohort of 128 VLBW infants and an age, sex, and school matched comparison group born in 1980/81 were studied. The cohort and comparison group were assessed at 15 years of age. The birth weight ratio of the index cases (observed birth weight/expected birth weight for the gestation) was determined to assess the degree of growth restriction. Respiratory support received during the neonatal period was obtained from hospital records. Smoking habits and respiratory morbidity were obtained through questionnaires. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and forced expiratory flow when 25–75% of FVC is expired (FEF25–75%) were measured using a portable spirometer. The values are expressed as percentage predicted for height, age, and gender using standard reference values. Adjustments were made for smoking habits of mother and children.

Results: The differences in means between index and comparison groups for FEF25–75% (-12.42%; p < 0.001) and FEV1/FVC (-3.53%; p < 0.001) ratio were statistically significant. The differences in FVC and FEV1 were not significant. No correlation was found between the birth weight ratio and lung function among the index cohort. Chronic cough, wheezing, and asthma were more common among the index cohort than in the comparison group. Within the index group, there was no difference in lung function between those who received and those who did not receive respiratory support.

Conclusion: Adolescents who were VLBW compared with matched controls showed medium and small airways obstruction. This was associated with prematurity rather than intrauterine growth restriction or having received respiratory support during the neonatal period. The index VLBW cohort compared with their controls were also more prone to chronic cough, wheezing, and asthma.

The measurement of serotype-specific anti-capsular polysaccharide antibodies remains the mainstay of pneumococcal (Pn) vaccine evaluation. New methods that allow the simultaneous measurement of antibodies to several antigens in small volumes of serum, and that agree well with existing techniques, are urgently required to support the increasing number of concomitant vaccines delivered in the infant immunization schedules and the use of extended-valency Pn vaccines. We therefore compared a relatively new multiplexed platform for measuring anti-Pn antibodies with the existing WHO consensus enzyme-linked immunosorbent assay (ELISA). A panel of 50 pediatric samples (34 collected after receipt of a heptavalent pneumococcal conjugate vaccine [PCV7] and 16 without PCV7) was analyzed across two different laboratories using a new multiplex electrochemiluminescence (ECL)-based detection assay developed for the quantitation of IgG serotype-specific antipneumococcal antibodies, and the results were compared to those obtained using the WHO consensus ELISA. For the seven serotypes measured, there was good agreement between the techniques and laboratories. The most notable difference was found between the ECL assay and the ELISA: concentrations tended to be higher in the ECL assay. For serotypes 6B, 9V, 18C, and 23F, the average increases in concentration ranged from 48 to 102%. However, the agreement rates on the proportions of samples with concentrations surrounding 0.35 μg/ml were >82% for all serotypes tested. Agreement between the two laboratories running the ECL assay was generally good: agreement on proportions of samples with concentrations surrounding 0.35 μg/ml was in excess of 92%, and agreement on average antibody concentrations was within 31%. We conclude that the Meso Scale Discovery (MSD) platform provides a promising new technique for the simultaneous measurement of antipneumococcal antibodies.

BACKGROUND

Gram-negative bacilli (GNB) cause as many as 20% of episodes of late-onset sepsis among very low birth weight (VLBW, birth weight < or =1500 g) infants in the neonatal intensive care unit. As the gastrointestinal (GI) tract can serve as a reservoir for GNB, we hypothesized that VLBW infants with prior GI tract colonization with gentamicin-susceptible GNB who developed bloodstream infections (BSI) would do so with gentamicin-susceptible GNB.

METHODS

A prospective cohort study of VLBW infants was performed in 2 level III neonatal intensive care units from September 2004 to October 2007. GI tract surveillance cultures were obtained weekly. Risk factors for GNB BSI and for GI tract colonization with GNB were assessed.

RESULTS

Fifty-one (7.3%) of 698 subjects experienced 59 GNB BSIs of which 34 occurred by 6 weeks of life and 625 (90%) of 698 subjects were colonized with GNB. Overall, 25% of BSI and 16% of GI tract isolates were nonsusceptible to gentamicin and colonization with the same species and same gentamicin susceptibility profile preceded 98% of GNB BSIs. Vaginal delivery, birth weight < or =750 g, GI tract pathology, increased use of central venous catheters, use of vancomycin, mechanical ventilation, and H2 blockers/proton pump inhibitors were associated with GNB BSI. Vaginal delivery, birth weight >1000 g, and treatment with carbapenem agents were associated with GNB colonization.

CONCLUSIONS

These data support the use of empiric gentamicin to treat late-onset sepsis in infants colonized with gentamicin-susceptible GNB. Targeted GI tract surveillance cultures of infants with specific risk factors during weeks 2 to 6 of life could be used to guide empiric therapy for late-onset sepsis.

Summary

Daycare attendance and very low birth weight (VLBW, ≤1500 grams) are associated with respiratory morbidity during childhood. The objective of this study was to evaluate whether daycare attendance is associated with even higher risk for respiratory problems among VLBW children. We hypothesized that VLBW children attending daycare, in a private home or daycare center, are at higher risk for respiratory problems than VLBW children not attending daycare. We also investigated whether the effect of daycare is independent or synergistic with respiratory risk resulting from being VLBW, as indicated by having bronchopulmonary dysplasia (BPD) as a neonate. We conducted a prospective study of VLBW children followed from birth to age 2–3 (N=715). Logistic regression was used to evaluate the relationship between daycare attendance and respiratory problems, adjusting for known neonatal risk factors for poor respiratory outcomes. Attending daycare in either a private home or in a daycare center was significantly associated with higher risk of lower respiratory infections than never attending. Attending a daycare center was also associated with higher risk for wheezy chest, cough without a cold, and respiratory medication use. While having BPD was associated with increased risk for respiratory problems, daycare attendance and BPD were not found to be synergistic risk factors for respiratory problems among VLBW children, but acted independently to increase risk. This implies that the increase in risk for respiratory problems associated with daycare attendance maybe similar among VLBW children and those of normal birth weight.

AIM—To determine the visual outcome at 7-8 years in very low birth weight (VLBW: birth weight <1500 g) infants screened for retinopathy of prematurity (ROP).
METHODS—In 1986 all 413 VLBW infants admitted to neonatal units in New Zealand were enrolled in a prospective study of acute ROP. Surviving infants were traced and assessed at a home visit. Visual assessment comprised examination for abnormal and range of eye movements, visual fields, distance and near visual acuity, stereopsis, and photorefraction.
RESULTS—Of 338 infants surviving to discharge, 313 (93%) had been examined for acute ROP. ROP was present in 66 (21%: ROP+), absent in 247 (ROP−), with 25 not examined (NA). 298 children (96% survivors resident in New Zealand: 91% all survivors) were assessed. Any visual problem occurred in 79% ROP+ and 60% ROP−/NA (p<0.01). Distance visual acuity less than 4/10 in the worse eye occurred in 29% ROP+ and 15% ROP−/NA (p<0.05); and in the better eye in 19% ROP+ and 5% ROP−/NA (p<0.001). Any myopia in the worse eye occurred in 36% ROP+ and 18% ROP−/NA (p<0.01); and in the better eye in 25% ROP+ and 11% ROP−/NA (p<0.01). Strabismus, including treated, occurred in 33% ROP+ and 19% ROP−/NA (p<0.05). Overall, 11% had astigmatism and 18% hypermetropia with no difference between the groups.
CONCLUSION—In a population based study it was confirmed that VLBW is associated with an increased risk of visual problems at school age. A history of ROP is associated with an additional risk of poor outcome, including a near doubling of poor distance acuity, myopia, and strabismus.



Objectives

Human milk (HM) feeding is associated with lower incidence and severity of costly prematurity-specific morbidities compared to formula feeding in very low birth weight (VLBW; <1,500 g) infants. However, the costs of providing HM are not routinely reimbursed by payers and can be a significant barrier for mothers. This study determined the initial maternal cost of providing 100 mL of HM for VLBW infants during the early neonatal intensive care unit (NICU) stay.

Methods

This secondary analysis examined data from 111 mothers who provided HM for their VLBW infants during the early NICU stay. These data were collected during a multisite, randomized clinical trial where milk output and time spent pumping were recorded for every pumping session (n = 13,273). The cost analysis examined the cost of the breast pump rental, pump kit, and maternal opportunity cost (an estimate of the cost of maternal time).

Results

Mean daily milk output and time spent pumping were 558.2 mL (SD = 320.7; range = 0–2,024) and 98.7 minutes (SD = 38.6; range = 0–295), respectively. The mean cost of providing 100 mL of HM varied from $2.60 to $6.18 when maternal opportunity cost was included and from $0.95 to $1.55 when it was excluded. The cost per 100 mL of HM declined with every additional day of pumping and was most sensitive to the costs of the breast pump rental and pump kit.

Conclusions

These findings indicate that HM is reasonably inexpensive to provide and that the maternal cost of providing milk is mitigated by increasing milk output over the early NICU stay.

Abstract

Objectives

Human milk (HM) feeding is associated with lower incidence and severity of costly prematurity-specific morbidities compared to formula feeding in very low birth weight (VLBW; <1,500 g) infants. However, the costs of providing HM are not routinely reimbursed by payers and can be a significant barrier for mothers. This study determined the initial maternal cost of providing 100 mL of HM for VLBW infants during the early neonatal intensive care unit (NICU) stay.

Methods

This secondary analysis examined data from 111 mothers who provided HM for their VLBW infants during the early NICU stay. These data were collected during a multisite, randomized clinical trial where milk output and time spent pumping were recorded for every pumping session (n = 13,273). The cost analysis examined the cost of the breast pump rental, pump kit, and maternal opportunity cost (an estimate of the cost of maternal time).

Results

Mean daily milk output and time spent pumping were 558.2 mL (SD = 320.7; range = 0–2,024) and 98.7 minutes (SD = 38.6; range = 0–295), respectively. The mean cost of providing 100 mL of HM varied from $2.60 to $6.18 when maternal opportunity cost was included and from $0.95 to $1.55 when it was excluded. The cost per 100 mL of HM declined with every additional day of pumping and was most sensitive to the costs of the breast pump rental and pump kit.

Conclusions

These findings indicate that HM is reasonably inexpensive to provide and that the maternal cost of providing milk is mitigated by increasing milk output over the early NICU stay.

Background

Heightened immunogenicity, measured one month after the primary series of pneumococcal conjugate vaccine (PCV), in African children was previously hypothesized to be due to increased rates of nasopharyngeal pneumococcal colonization during early infancy.

Methods

We analyzed the effect of selected vaccine-serotype (6B, 19F and 23F) nasopharyngeal colonization prior to the first PCV dose or when colonized for the first time prior to the second or third (2nd/3rd) PCV dose on serotype quantitative and qualitative antibody responses.

Results

Colonization prior to receiving the first PCV was associated with lower geometric mean antibody concentrations (GMCs) one month after the third dose of PCV and six months later to the colonizing-serotype. Colonized infants also had lower geometric mean titers (GMTs) on opsonophagocytosis activity assay (OPA) and a lower proportion had titers ≥8 against the colonizing serotypes (19F and 23F) post vaccination. Colonization occurring only prior to the 2nd/3rd PCV dose was also associated with lower GMCs and OPA GMTs to the colonizing-serotype. The effect of colonization with serotypes 19F and 23F prior to PCV vaccination had a greater effect on a lower proportion of colonized infants having OPA titers ≥8 than the effect of colonization on the lower proportion with antibody ≥0.35 μg/ml.

Conclusion

Infant nasopharyngeal colonization at any stage before completing the primary series of PCV vaccination was associated with inferior quantitative and qualitative antibody responses to the colonizing-serotype.

Streptococcus pneumoniae is the leading bacterial opportunistic infection in HIV-infected individuals. Anti-retroviral treatment (ART) of HIV-infected individuals reduces their risk of invasive pneumococcal disease (IPD), however, it remains 20- to 40-fold greater compared with age-matched general population. This review summarizes the available published data on the immunogenicity, safety and efficacy of pneumococcal polysaccharide-protein conjugate vaccines (PCV) in HIV-infected children and adults.

 

Several studies have demonstrated that PCV are safe in the HIV-infected persons. Although PCV are immunogenic in HIV-infected infants, the antibodies produced are functionally impaired, there is possibly a lack or loss of anamnestic responses and immunity declines in later life However, quantitative and qualitative antibody responses to PCV in HIV-infected infants are enhanced when vaccination occurs whilst on ART, as well as if vaccination occurs when the CD4+ cell percentage is ≥ 25% and if the nadir CD4+ is >15%. Although the efficacy of PCV was lower, the vaccine preventable burden of hospitalization for IPD and clinical pneumonia were 18-fold and 9-fold greater, respectively, in HIV-infected children compared with –uninfected children.

In HIV-infected adults, PCV vaccination induces more durable and functional antibody responses in individuals on ART at the time of vaccination than in ART-naive adults, independently of baseline CD4+ cell count, although there does not appear to be much benefit from a second-dose of PCV. PCV has also been shown to reduce the risk of recurrent IPD by 74% in HIV-infected adults not on ART, albeit, also with subsequent decline in immunity and protection.

OBJECTIVES—To compare outcomes of care in selected neonatal intensive care units (NICUs) for very low birthweight (VLBW) or preterm infants in Scotland and Australia (study 1) and perinatal care for all VLBW infants in both countries (study 2).
DESIGN—Study 1: risk adjusted cohort study; study 2: population based cohort study.
SUBJECTS—Study 1: all 2621 infants of < 1500 g birth weight or < 31 weeks' gestation admitted to a volunteer sample of hospitals comprising eight of all 17 Scottish NICUs and six of all 12 tertiary NICUs in New South Wales and Queensland in 1993-1994; study 2: all 5986infants of 500-1499 g birth weight registered as live born in Scotland and Australia in 1993-1994.
MAIN OUTCOMES—Study 1: (a) hospital death; (b) death or cerebral damage, each adjusted for gestation and CRIB (clinical risk index for babies); study 2: neonatal (28 day) mortality.
RESULTS—Study 1. Data were obtained for 1628 admissions in six Australian NICUs, 775 in five Scottish tertiary NICUs, and 148 in three Scottish non-tertiary NICUs. Crude hospital death rates were 13%, 22%, and 22% respectively. Risk adjusted hospital mortality was about 50% higher in Scottish than in Australian NICUs (adjusted mortality ratio 1.46, 95% confidence interval (CI) 1.29 to 1.63,p < 0.001). There was no difference in risk adjusted outcomes between Scottish tertiary and non-tertiary NICUs. After risk adjustment, death or cerebral damage was more common in Scottish than Australian NICUs (odds ratio 1.9, 95% CI 1.5 to 2.5). Both these risk adjusted adverse outcomes remained more common in Scottish than Australian NICUs after excluding all infants < 28 weeks' gestation from the comparison. Study 2. Population based neonatal mortality in infants of 500-1499 g was higher in Scotland (20.3%) than Australia (16.6%) (relative risk 1.22, 95% CI 1.08 to 1.39, p = 0.002). In a post hoc analysis, neonatal mortality was also higher in England and Wales than in Australia.
CONCLUSIONS—Study 1: outcome was better in the Australian NICUs. Study 2: perinatal outcome was better in Australia. Both results may be consistent, at least in part, with differences in the organisation and implementation of neonatal care.



This paper presents the first systematic survey of both threshold and suprathreshold visual function in very low birth weight premature infants without retinal or cerebral pathology at 5 to 7 months' corrected age.

Purpose.

Preterm infants are at high risk of visual and neural developmental deficits. However, the development of visual cortical function in preterm infants with no retinal or neurologic morbidity has not been well defined. To determine whether premature birth itself alters visual cortical function, swept parameter visual evoked potential (sVEP) responses of healthy preterm infants were compared with those of term infants.

Methods.

Fifty-two term infants and 58 very low birth weight (VLBW) infants without significant retinopathy of prematurity or neurologic morbidities were enrolled. Recruited VLBW infants were between 26 and 33 weeks of gestational age, with birth weights of less than 1500 g. Spatial frequency, contrast, and vernier offset sweep VEP tuning functions were measured at 5 to 7 months' corrected age. Acuity and contrast thresholds were derived by extrapolating the tuning functions to 0 amplitude. These thresholds and suprathreshold response amplitudes were compared between groups.

Results.

Preterm infants showed increased thresholds (indicating decreased sensitivity to visual stimuli) and reductions in amplitudes for all three measures. These changes in cortical responsiveness were larger in the <30 weeks ' gestational age subgroup than in the ≥30 weeks' gestational age subgroup.

Conclusions.

Preterm infants with VLBW had measurable and significant changes in cortical responsiveness that were correlated with gestational age. These results suggest that premature birth in the absence of identifiable retinal or neurologic abnormalities has a significant effect on visual cortical sensitivity at 5 to 7 months' of corrected age and that gestational age is an important factor in visual development.

Background

Over the last two decades, improvements in medical care have been associated with a significant increase and better outcome of very preterm (VP, < 32 completed gestational weeks) and very low birth weight (VLBW, < 1500 g) infants. Only a few publications analyse changes of their short-term outcome in a geographically defined area over more than 10 years. We therefore aimed to investigate the net change of VP- and VLBW infants leaving the hospital without major complications.

Methods

Our population-based observational cohort study used the Minimal Neonatal Data Set, a database maintained by the Swiss Society of Neonatology including information of all VP- and VLBW infants. Perinatal characteristics, mortality and morbidity rates and the survival free of major complications were analysed and their temporal trends evaluated.

Results

In 1996, 2000, 2004, and 2008, a total number of 3090 infants were enrolled in the Network Database. At the same time the rate of VP- and VLBW neonates increased significantly from 0.87% in 1996 to 1.10% in 2008 (p < 0.001). The overall mortality remained stable by 13%, but the survival free of major complications increased from 66.9% to 71.7% (p < 0.01). The percentage of infants getting a full course of antenatal corticosteroids increased from 67.7% in 1996 to 91.4% in 2008 (p < 0.001). Surfactant was given more frequently (24.8% in 1996 compared to 40.1% in 2008, p < 0.001) and the frequency of mechanical ventilation remained stable by about 43%. However, the use of CPAP therapy increased considerably from 43% to 73.2% (p < 0.001). Some of the typical neonatal pathologies like bronchopulmonary dysplasia, necrotising enterocolitis and intraventricular haemorrhage decreased significantly (p ≤ 0.02) whereas others like patent ductus arteriosus and respiratory distress syndrome increased (p < 0.001).

Conclusions

Over the 12-year observation period, the number of VP- and VLBW infants increased significantly. An unchanged overall mortality rate and an increase of survivors free of major complication resulted in a considerable net gain in infants with potentially good outcome.

Introduction

Streptococcus pneumoniae infection may result in invasive pneumococcal disease (IPD), such as bacteremia, meningitis and bacteremic pneumonia, or in non-IPD, such as pneumonia, sinusitis and otitis media. In June 2001, a heptavalent pneumococcal conjugate vaccine (PCV7) (Prevnar, Wyeth Pharmaceuticals, Canada) was approved for use in children in Canada. The objective of the present paper is to review S pneumoniae-induced disease incidence and vaccine recommendations in Canadian infants and children younger than five years of age. Particular attention is given to the expected benefits of vaccination in Canada based on postmarketing data and economic modelling.

Methods

Searches were performed on PubMed and Web of Science databases and specific Canadian journals using the key words 'pneumococc*', 'vaccine', 'conjugate', 'infant' and 'Canadian'.

Results and Discussion

PCV7 appears to be safe and effective against IPD and non-IPD in children younger than five years of age and, more importantly, in children younger than two years of age (who are at highest risk for IPD). An examination of postmarketing data showed a reduction in incidence of pneumococcal disease in age groups that were vaccinated and in older age groups, indicating the likelihood of herd protection. Concurrently, there was a reduction in the occurrence of antimicrobial-resistant isolates.

Conclusions

The results from the present review suggest that PCV7 is currently benefiting Canadian children and society by lowering S pneumoniae-associated disease. Additional gains from herd protection and further reductions in antimicrobial resistance will be achieved as more Canadian children younger than five years of age are routinely vaccinated with PCV7.

Background

Calprotectin is a cytosolic component of neutrophils. Fecal calprotectin (FC) level is a useful marker for exacerbation of inflammatory bowel disease in children. FC may be a useful marker for necrotizing enterocolitis (NEC).

Objective

To determine normal baseline levels of FC and observe dynamic changes of FC levels over the first postnatal month in very low birth weight (VLBW) infants.

Methods

FC levels of 14 VLBW infants (gestational age 23–30 weeks, birth weight ≤1,500 g) were serially measured in the first postnatal month. Demographics, feeding regimens, antibiotic use, laboratory and x-ray results, and maternal information were recorded. We assessed how FC levels changed over time, varied with nutritional source and differed between sick versus well infants.

Results

FC levels were not related to gestational age or feedings regimen. FC levels tended to decrease with increasing age (p = 0.121) and feeding volumes (p = 0.179). FC levels differed between ‘well’ and ‘sick’ infants (122.8 ± 98.9 vs. 380.4 ± 246.3 μg/g stool, p < 0.001). FC >350 μg/g stool was noted with signs of gastrointestinal injury, such as bloody stool and bowel perforation. FC levels decreased after initiation of treatments in sick infants who recovered.

Conclusions

FC levels may be a marker for early diagnosis and resolution of gastrointestinal illnesses in VLBW infants. Its utility for early diagnosis and assessment of resolution of NEC should be studied in a larger cohort of VLBW infants.