Risk factors associated with post-hemorrhagic hydrocephalus among very low birth weight infants of 24-28 weeks gestation.

OBJECTIVE: Post-hemorrhagic hydrocephalus (PHH) is associated with morbidity and mortality among very low birth weight (VLBW) infants. This study aimed to determine risk factors for PHH among VLBW infants with peri-intraventricular hemorrhage (PIVH). STUDY DESIGN: This is a population-based cohort of VLBW infants of 24 to 28 weeks gestation, born in Israel from 1995 to 2012. Infants in whom a brain ultrasound was not performed before 28 days or with major congenital malformations were excluded. Univariate and multivariable analyses identified risk factors associated with PHH. RESULTS: The final study cohort comprised 2811 infants with grade 2 or higher PIVH, of whom 610 (21.7%) developed PHH. PHH was independently associated with PIVH severity, with bilateral grade 3 PIVH and PIVH grade 3 and contralateral grade 4 having the highest risks (odds ratio (OR) 12.2, 95% confidence interval (CI) 8.56 to 17.4 and OR 13.7, 95% CI 9.4 to 20.1, respectively). Unilateral grade 3 or 4 PIVH's had moderately increased risks of PHH (OR 3.50, 95% CI 2.26 to 5.42 and OR 3.79, 95% CI 2.35 to 6.12, respectively). PHH was independently associated with increasing gestational age (GA) and with neonatal morbidities including patent ductus arteriosus (OR 1.47, 95% CI 1.15 to 1.88 if medically treated and OR 3.01, 95% CI 2.11 to 4.29 if surgically treated), sepsis (OR 1.79, 95% CI 1.44 to 2.22) and necrotizing enterocolitis (OR 1.60, 95% CI 1.18 to 2.17). CONCLUSIONS: Among VLBW infants with PIVH, PHH was independently associated with PIVH severity group, increasing GA and acute neonatal morbidities. Unilateral grade 3 or 4 PIVH was associated with a moderate risk of developing PHH compared with bilateral severe hemorrhages.

Potential application of the consistency approach for vaccine potency testing.

The Consistency Approach offers the possibility of reducing the number of animals used for a potency test. However, it is critical to assess the effect that such reduction may have on assay performance. Consistency of production, sometimes referred to as consistency of manufacture or manufacturing, is an old concept implicit in regulation, which aims to ensure the uninterrupted release of safe and effective products. Consistency of manufacture can be described in terms of process capability, or the ability of a process to produce output within specification limits. For example, the standard method for potency testing of inactivated rabies vaccines is a multiple-dilution vaccination challenge test in mice that gives a quantitative, although highly variable estimate. On the other hand, a single-dilution test that does not give a quantitative estimate, but rather shows if the vaccine meets the specification has been proposed. This simplified test can lead to a considerable reduction in the number of animals used. However, traditional indices of process capability assume that the output population (potency values) is normally distributed, which clearly is not the case for the simplified approach. Appropriate computation of capability indices for the latter case will require special statistical considerations.

Long-term outcome following selective serotonin reuptake inhibitor induced neonatal abstinence syndrome.

OBJECTIVE: To assess the long-term neurodevelopment of children exposed in utero to selective serotonin reuptake inhibitors (SSRIs) that developed a neonatal abstinence syndrome (NAS). STUDY DESIGN: Neurodevelopmental evaluation was performed at the age of 2 to 6 years. Children who developed NAS were compared with those who did not using univariate and logistic regression analyses. RESULT: Thirty children with NAS and 52 without NAS participated in the study. Both groups were similar in mean cognitive ability (106.9±14.0 vs 100.5±14.6, P=0.12) and developmental scores (98.9±11.4 vs 95.7±9.9, P=0.21). However, there was a trend towards small head circumference in the NAS group (20 vs 6%, P=0.068). NAS was associated with an increased risk of social-behavior abnormalities (odds ratio (OR) 3.03, 95% confidence interval (CI) 1.07 to 8.60, P=0.04) and advanced maternal age (OR 1.12, 95% CI 1.00 to 1.25, P=0.04). CONCLUSION: Infants who developed NAS had normal cognitive ability, but were at an increased risk for social-behavioral abnormalities. Follow-up evaluation of symptomatic neonates should be considered.

Comparability of ELISA and toxin neutralization to measure immunogenicity of Protective Antigen in mice, as part of a potency test for anthrax vaccines.

Complexities of lethal challenge models have prompted the investigation of immunogenicity assays as potency tests of anthrax vaccines. An ELISA and a lethal toxin neutralization assay (TNA) were used to measure antibody response to Protective Antigen (PA) in mice immunized once with either a commercial or a recombinant PA (rPA) vaccine formulated in-house. Even though ELISA and TNA results showed correlation, ELISA results may not be able to accurately predict TNA results in this single immunization model.

Mortality of full-term infants during the first month of life in a tertiary care hospital.

OBJECTIVE: The neonatal mortality rate is disproportionately influenced by preterm infants and does not reflect the rate in full-term infants. Our objectives were to estimate the full-term neonatal mortality rate and to identify causes of death in full-term infants during the first month of life. STUDY DESIGN: A retrospective study of full-term infant deaths during a 6-year period from 2000 to 2005, in a tertiary medical center. RESULT: During the study period there were 44,703 full-term births and 31 deaths, representing a mortality rate of 0.69 per 1,000 live births. The main cause of death was congenital anomalies (64.5%), specifically cardiac anomalies. Other causes were chromosomal anomalies or syndromes (12.9%), labor complications (12.9%), infections (3.2%), congenital diseases (3.2%) and metabolic disorders (3.2%). CONCLUSION: The mortality rate of full-term infants may be lower than previous estimates. Efforts aimed at decreasing mortality among full-term infants should focus on prenatal diagnosis.

A comparison of the effect of vitamin A on cytokine secretion by mononuclear cells of preterm newborns and adults.

BACKGROUND: For a long time vitamin A has been known to be essential for immune defense of the organism and protection against infections. Vitamin A deficiency in children is associated with morbidity and mortality from infectious diseases which could be prevented and even alleviated by vitamin A supplementation. Moreover, this vitamin is involved in the modulation of immunological and inflammatory responses by regulation of cytokine production. The aim of the study was to compare the in vitro effect of vitamin A on the production of pro-inflammatory (IL-1beta and IL-6) and anti-inflammatory (IL-1 receptor antagonist (ra) and IL-10) cytokines, as well as IL-2 and IFNgamma by cord blood mononuclear cells (CBMC) of preterm newborns to that of peripheral blood mononuclear cells (PBMC) from adults. METHODS: Mononuclear cells (MC) from individuals of the two age groups were incubated with vitamin A (retinyl palmitate) at various concentrations in the presence of phytohemagglutinin for IL-2 and IFNgamma production or LPS for IL-1beta, IL-1ra, IL-6 and IL-10 secretion. The level of the cytokines in the supernatants was tested by ELISA. RESULTS: Vitamin A exerted an in vitro inhibitory effect on the production of the anti-inflammatory cytokine IL-1ra by MC of preterm newborns and adults, but did not affect the secretion of the pro-inflammatory cytokines IL-1beta, IL-6 and IFNgamma. Vitamin A caused inhibition of IL-10 secretion by cells from adults, but it did not significantly affect this function in cells from newborns except when high unphysiological doses were applied. In addition vitamin A stimulated the secretion of IL-2 by cells isolated from adults but had no effect on those derived from premature neonates. CONCLUSIONS: The results indicate that vitamin A may affect the immune function of premature infants via inhibition of IL-1ra secretion. It is suggested that the beneficial effect of vitamin A on the clinical course of bronchopulmonary dysplasia (BPD) may be due to the reduced production of anti-inflammatory cytokines by neonatal CBMC. This may indicate the importance of the pro-inflammatory cytokines in the management of severe lung diseases and BPD.

Bronchopulmonary dysplasia in very low birth weight infants is associated with prolonged hospital stay.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is associated with prolonged hospital length of stay (LOS) and delayed discharge home. OBJECTIVES: To evaluate the association between BPD and LOS and to assess the contribution of concomitant major morbidities on LOS among infants with BPD. STUDY DESIGN: A population-based observational study of very low birth weight (VLBW) infants born from 1995 through 2003. Multivariate analyses, adjusted for perinatal variables, assessed the association between BPD and concomitant morbidities on LOS. RESULTS: Of 10 134 survivors, 1926 (19.0%) had BPD. The adjusted LOS for infants with and without BPD was 84.1 days (95% CI, 82.8, 85.6) and 58.1 days (95% CI, 57.2, 59.0), respectively. Addition of a single concomitant morbidity increased mean LOS by 4 to 13 days. CONCLUSIONS: BPD is a major cause of increased length of hospitalization among VLBW infants. Preventive or therapeutic modalities are required to reduce the significant burden of this condition.

Spread of vaccine-derived poliovirus from a paralytic case in an immunodeficient child: an insight into the natural evolution of oral polio vaccine.

Sabin strains used in the manufacture of oral polio vaccine (OPV) replicate in the human organism and can give rise to vaccine-derived polioviruses. The increased neurovirulence of vaccine derivatives has been known since the beginning of OPV use, but their ability to establish circulation in communities has been recognized only recently during the latest stages of the polio eradication campaign. This important observation called for studies of their emergence and evolution as well as extensive surveillance to determine the scope of this phenomenon. Here, we present the results of a study of vaccine-derived isolates from an immunocompromised poliomyelitis patient, the contacts, and the local sewage. All isolates were identified as closely related and slightly evolved vaccine derivatives with a recombinant type 2/type 1 genome. The strains also shared several amino acid substitutions including a mutation in the VP1 protein that was previously shown to be associated with the loss of attenuation. Another mutation in the VP3 protein resulted in altered immunological properties of the isolates, possibly facilitating virus spread in immunized populations. The patterns and rates of the accumulation of synonymous mutations in isolates collected from the patient over the extended period of excretion suggest either a substantially nonuniform rate of mutagenesis throughout the genome, or, more likely, the strains may have been intratypic recombinants between coevolving derivatives with different degrees of divergence from the vaccine parent. This study provides insight into the early stages of the establishment of circulation by runaway vaccine strains.

Risk factors associated with candidaemia in the neonatal intensive care unit: a case-control study.

The incidence of candidaemia is steadily increasing in neonatal intensive care units (NICUs). Several neonatal risk factors for candidaemia have been identified, however, the number of cases in controlled studies is small and knowledge concerning maternal and perinatal risk factors is limited. The present study attempted to identify modifiable, independent maternal, perinatal and neonatal risk factors for candidaemia using a retrospective case-control study in the NICU of a tertiary-care paediatric medical centre. The study group consisted of 56 neonates admitted to the NICU between 1996 and 2000 who acquired candidaemia. The control group comprised the first infant admitted immediately after each study infant matched for gestational age (+/-10 days) and birthweight (+/-200 g). Potential maternal, perinatal and neonatal risk factors were compared between the groups using statistical methods and analysed by univariate and multivariate stepwise logistic regression models. The independent risk factors found to be significantly associated with increased risk of candidaemia were duration of ventilation and presence of bacteraemia before candidaemia. Maternal steroids had a significant protective effect. The positive predictive value using these three parameters was 78.38%. Maximizing in-utero steroid treatment in high-risk pregnancies, minimizing the days of mechanical ventilation and investment of efforts in prevention of bacteraemia may help to reduce the incidence of candidaemia in the NICU.

Nitric oxide levels in preterm and term infants and in premature infants with bacteremia.

OBJECTIVE: To determine the serum nitric oxide levels in healthy neonates and in infants with bacteremia. METHODS: We performed a prospective study in a tertiary neonatal intensive care unit. The serum nitric oxide levels were measured in all infants at birth (basal) and in the infected neonates also on the first 2 days of bacteremia. RESULTS: Thirty-three neonates (10 term, 23 preterm) were included. Eleven preterm infants (mean gestational age 27 weeks) had bacteremia. The main blood culture isolates included coagulase-negative staphylococci (n=4), Klebsiella pneumoniae (n=3), and Escherichia coli (n=3). The serum nitric oxide levels increased during infection in 10 infants (p <0.008). The mean nitric oxide level before infection was 44 microM and during infection 96 microM (p=0.008). In the healthy babies, the mean nitric oxide level was 26 microM in those with a gestational age <27 weeks, 44 microM in those born between 28 and 36 weeks of gestation, and 63 microM in term infants. CONCLUSIONS: Bacteremic preterm infants produce significantly higher amounts of nitric oxide. The basal nitric oxide levels at birth may be correlated with gestational age.

Effect of radiant warmer on transepidermal water loss (TEWL) and skin hydration in preterm infants.

OBJECTIVE: To evaluate the effect of radiant warmers on skin barrier function in preterm infants. METHODOLOGY: Transepidermal water loss (TEWL) and stratum corneum hydration were measured in 30 preterm infants (birth weight 825 to 2220 g) in seven body areas: forehead, upper back, cubital fossa, palms, soles, abdomen, and inguinal region. Measurements were performed under radiant warmer and incubator conditions. Each patient served as his/her control. RESULTS: TEWL was significantly higher in the radiant warmer compared to the incubator condition in only two areas: forehead and back. The overall mean difference in percentage TEWL between the conditions was 15%. Stratum corneum hydration was not affected by the radiant warmer. CONCLUSIONS: The use of radiant warmers does not significantly decrease barrier function in the preterm infant.

Disinfection with 10% povidone-iodine versus 0.5% chlorhexidine gluconate in 70% isopropanol in the neonatal intensive care unit.

AIM: The finding that 10% povidone-iodine skin disinfectant may compromise thyroid function in premature infants prompted its replacement with 0.5% chlorhexidine gluconate solution in 70% isopropanol. The objective of this study was to compare the incidence rates of true infection and contamination associated with the use of these two disinfectants in the neonatal intensive care unit. METHODS: The study population comprised two cohorts of infants admitted to our neonatal intensive care unit: 1) in 1992-1993 when only 10% povidone-iodine was used as a skin disinfectant, and 2) in 1995-1996 when only 0.5% chlorhexidine gluconate solution in 70% isopropanol was used. A retrospective chart review was conducted to determine whether all documented positive blood, CSF and suprapubic aspirate cultures indicated true infection or contamination. True infection was defined as clinical symptoms and/or laboratory abnormalities suggestive of sepsis, with positive blood, CSF or suprapubic aspirate cultures. RESULTS: 1146 infants were admitted during the study periods, 507 during the first period and 639 during the second. In the early group, 17.6% of infants had major malformations, 72.0% were premature and 25.2% had weights of < 1500 g. Corresponding percentages for the latter group were 16.0%, 80.6% and 32.9%, respectively. No statistically significant differences were found between the two research periods in rate of infants with positive blood cultures, true infections, or contamination. CONCLUSION: The use of 0.5% chlorhexidine gluconate solution in 70% isopropanol as a skin disinfectant is justified in neonatal intensive care units because it is not associated with an increased incidence of infections as opposed to 10% povidone-iodine and is devoid of detrimental effects.

Association between IL-1ra gene polymorphism and premature delivery.

IL-1 receptor antagonist (IL-1ra) gene polymorphism was examined in 95 Israeli preterm newborns and compared to that of adult volunteers. The genotype was determined using PCR amplification of the variable region of intron 2 of the IL-1ra gene. The IL-1raA1 allele was found to be predominant in the two groups. However, a significant higher frequency of IL-1raA2 allele was found in preterm newborns. The difference was mainly due to higher proportion of homozygous for IL-1raA2 in the preterm neonates (19%) as compared with adults (7%). No such association could be demonstrated between IL-1raA2 allele and severe sepsis in preterm newborns. The frequency of IL-1raA2 allele among preterms with a septic episode did not differ significantly from that found in newborns without sepsis. The results suggest an association between the IL-1ra genotype and the incidence of premature delivery.

Keratometry measurements in preterm and full term newborn infants.

AIM: To evaluate the relation between postconceptional age and birth weight with keratometric values in preterm and full term infants. METHODS: A prospective cross sectional study was performed. The cohort included 99 infants (198 eyes) admitted to the Neonatal and Neonatal Intensive Care Units at Schneider Children's Medical Center of Israel from February to September 2002. Keratometry in the horizontal and vertical meridians was performed in both eyes of each infant by two ophthalmologists using an autokeratometer. The results were evaluated according to: postconceptual age (<32 weeks, 32-36 weeks, >36 weeks) and birth weight (<1500 g, 1501-2500 g, >2501 g). RESULTS: Corneal curvature measurements decreased progressively with both postconceptual age and birth weight. At <32 weeks, mean (standard deviation) readings were 63.3 (3.2) diopters (D) for the horizontal meridian and 57.3 (2.6) D for the vertical meridian; corresponding values at >36 weeks were 54.0 (3.0) D and 50.7 (2.4) D. In the <1500 g group, mean (SD) readings were 61.3 (3.9) D for the horizontal meridian and 56.0 (2.9) D for the vertical meridian; corresponding values in the >2501 g group were 51.3 (2.1) D and 48.6 (1.8) D. CONCLUSIONS: There is an inverse relation of horizontal and vertical keratometric values with both postconceptional age and birth weight. Highest readings were noted in the babies with the lowest birth weight and youngest postconceptional age. The decrease in corneal dioptric power to normal values is linear and is apparently part of the normal ocular maturation.

Neonatologists are using much less dexamethasone.

Two historical cohorts (1993-1994 and 2001) of preterm infants ventilated for respiratory distress syndrome were compared. Dexamethasone administration fell from 22% to 6%. Chronic lung disease in survivors rose slightly from 13% to 17%, and mortality fell from 21% to 15% (other causes). The effect of restriction of dexamethasone use on chronic lung disease and mortality remains to be seen.

Faecal elastase 1 levels in premature and full term infants.

BACKGROUND: Determination of faecal elastase 1 (FE1) is a simple, relatively inexpensive, non-invasive, highly specific and sensitive test for determining pancreatic function. Secretion of pancreatic enzymes varies during infancy, but there are almost no specific data on the ontogeny of elastase 1 in human babies. AIM: To study FE1 levels in preterm and term babies, and to determine the possible effect of gestational and postconceptual age on these levels. METHODS: Serial stool samples were collected and tested for FE1 level from 77 premature and full term infants. FE1 levels were determined by a commercially available enzyme linked immunosorbent assay (ELISA) kit. RESULTS: A total of 232 stool samples were collected from 77 neonates. The FE1 level measured in the first stool sample (meconium) was below normal (200 micro g/g stool) in all samples regardless of gestational age. Sixty three neonates had at least two samples tested for FE1 level. The mean (SD) level of FE1 in sample 1 was 45.9 (51.1) micro g/g stool and was significantly (p < 0.001) lower than in sample 2 (243.0 (164.9) micro g/g stool). The lower the gestational age of the newborn, the more time it took for FE1 to reach normal levels. CONCLUSIONS: FE1 levels in meconium are low, and studies in meconium should be avoided if pancreatic sufficiency is to be determined. FE1 reaches normal levels by day 3 in term newborns and by 2 weeks in infants born before 28 weeks gestation. Normal levels are reached sooner in infants of more advanced gestational age who start enteral feeding earlier.

Comparative outcome study between triplet and singleton preterm newborns.

AIM: To evaluate the outcome of triplet versus singleton preterm newborns. METHODS: The study population included 64 sets of preterm triplet (gestational age 25-34 wk) and 64 singleton controls. Data on prenatal and perinatal findings, neonatal complications, duration of hospitalization, and neonatal mortality were collected by chart review. RESULTS: Mothers of triplets were more likely to receive prenatal tocolytic treatment and more antenatal steroids for foetal lung maturation, and to be delivered by caesarean section. No differences were found between the groups in perinatal parameters (cord pH, Apgar score, respiratory support after birth), respiratory parameters (severity of acute and chronic lung disease, use and duration of oxygen treatment and assisted ventilation), or neonatal complications (patent ductus arteriosus, intraventricular haemorrhage, periventricular leukomalacia, necrotizing enterocolitis, retinopathy of prematurity, meningitis, sepsis and jaundice). This was also true for duration of hospitalization and neonatal mortality. No differences were recorded by birth order among the triplets for any of these parameters. CONCLUSION: The study indicates that good prenatal care can lead to a good outcome for preterm triplets, close to that of preterm singleton infants. Families and physicians should consider this information when foetal reduction is offered.

Indomethacin and ibuprofen effect on IL-1ra production by mononuclear cells of preterm newborns and adults.

The in vitro effect of indomethacin (IM) and ibuprofen (IB) on the production of the interleukin-1 receptor antagonist (IL-1ra) by cord blood mononuclear cells (CBMC) from preterm newborns was compared to that of peripheral blood mononuclear cells (PBMC) from adults. Mononuclear cells (MC) were incubated with lipopolysaccharide (LPS) in the absence or presence of various concentrations of IM and IB. The level of IL-1ra in the supernatants was tested by ELISA. The results showed a lower ability of MC from preterm newborns to produce IL-1ra as compared with adult cells, supporting the assumption of neonatal immune cell immaturity. IM at pharmacological concentrations caused inhibition of IL-1ra secretion by PBMC from adults whereas IB suppressed the secretion of IL-1ra at higher concentrations only. At the same concentrations neither drug had an in vitro effect on the production of IL-1ra by CBMC of preterm newborns. In conclusion, the lower ability of CBMC of preterm newborns to produce IL-1ra in response to LPS and the absence of an IM and IB effect on the secretion of this cytokine by these cells as compared with PBMC of adults, suggest an underdevelopment of the immune response in preterm newborns.

Hepatitis B vaccination: long-term follow-up of the immune response of preterm infants and comparison of two vaccination protocols.

BACKGROUND: We conducted a 3-year follow-up study of long-term antibody persistence following vaccination of low-risk preterm infants with recombinant hepatitis B vaccine (HBV). Two three-dose protocols were compared: vaccination beginning within 24 h of birth to initial vaccination delayed until a weight of 2,000 g was reached. SUBJECTS AND METHODS: The study population included 136 children, divided into three groups: children born prematurely (< or = 35 weeks, n = 57), children born at term (> or = 37 weeks, n = 39), both groups receiving the first dose of HBV within 24 h of birth, and children born prematurely (< or = 35 weeks, n = 40), who received the first dose of HBV when a weight of 2,000 g was reached. All infants received the second hepatitis vaccination 1 month after the first, and the third dose 6 months after the first. Hepatitis B surface antibody (AntiHBs) was measured at an age of 3-3.5 years (at least 2.5 years after completion of the three-dose HBV series). An AntiHBs level of > or = 10 IU/l was considered positive. RESULTS: At 3-3.5 years of age, a higher percentage of the premature-delayed vaccination group had a positive AntiHBs level (92.5%) compared to both the premature (54.4%, p < 0.001) and full-term groups (71.8%, p < 0.05) vaccinated soon after birth. The premature-delayed vaccination group also had a significantly higher geometric mean concentration (GMC) (119 vs 14.2 IU/l, p < 0.001 and 119 vs 32.7 IU/l, p < 0.005, respectively). CONCLUSION: Delaying vaccination of premature infants against hepatitis B until a weight of 2,000 g was reached resulted in both a significantly higher percentage of children with positive antibody levels and a significantly higher GMC at 3-3.5 years of age as compared to early-vaccinated preterm and full-term infants. The known short-term advantage of delayed vaccination of preterm infants was shown to persist for at least the first 3 years of life.

Deposition of whole blood platelets on extracellular matrix under flow conditions in preterm infants.

BACKGROUND: A previous study showed greater adhesion by platelets of healthy full term infants to subendothelial extracellular matrix (ECM) under flow conditions compared with healthy adult platelets. AIM: To investigate the adhesion and aggregation of platelets from preterm infants on ECM under defined shear conditions. METHODS: In vitro platelet function was investigated in 106 preterm infants, 74 full term infants, and 26 healthy adults. Blood samples were obtained from all infants within 24 hours of birth, and weekly until discharge from preterm infants only. Citrated whole blood was placed in ECM precoated tissue culture plates and subjected to shear stress (1300 s-1) for two minutes using a rotating Teflon cone. Platelet adhesion (surface coverage) and aggregation (average size) to ECM were assayed using an image analyser. Assays for von Willebrand factor (vWF) antigen, ristocetin cofactor, and vWF collagen-binding activity were performed on samples from an additional 70 preterm infants, 23 healthy full term infants, and 24 healthy adults. Preterm infants with hyaline membrane disease (HMD) were analysed separately in both cohorts. RESULTS: Platelets from preterm infants displayed significantly less platelet adhesion than those from full term infants but similar aggregation and levels of vWF antigen, ristocetin cofactor, and collagen binding activity. Mean surface coverage was 22.0 (8.4)% for preterm infants with HMD, 28.7 (8.0)% for healthy preterm infants, and 35.7 (7.9)% for full term infants. Surface coverage in the preterm infants correlated with gestational age during the first 24 hours only, and did not reach full term levels during 10 weeks of follow up. CONCLUSION: Platelet adhesion to ECM is significantly poorer in preterm than in full term infants, and poorer in preterm infants with HMD than in healthy preterm infants. Intrinsic platelet properties rather than the concentration or activity of vWF may be responsible for this difference.