Mannose-binding protein in preterm infants: developmental profile and clinical significance

Abstract

SUMMARYThe aim of this study was to determine the developmental profile of mannose-binding protein (MBP) in preterm infants. MBP was measured in 885 longitudinally collected serum samples from 168 preterm infants, and 63 were genotyped with respect to the codon 54 mutation in the MBP gene. MBP level/codon 54 genotyping were also determined on the cord blood of 146/123 term infants and 138/123 adults, respectively. The best cut-off values of MBP for dividing preterm, term infants and adults into iow" and "high' M BP groups were 400 ng/ml (55 low, 113 high), 700 ng/ml (35 low, 111 high) and 750 ng/ml (33 low. 105 high), respectively, by achieving the least number of misclassifications according to the codon 54 mutation. The relative risk of the Mow" groups for presence of the codon 54 mutation compared with 'high" groups were 42 4, 67-9 and 22-9 for preterm, term infants and adults, respectively (PKO 00001). The gestational age and birth weight of the 'low* (n = 55) and 'high" (n= 113) MBP groups of the 168 preterm infants were 29 5 ± 2 8 weeks, 305±2-8 weeks (/'-003) and 1230±3I7g, I277±289g (/' = 035). respectively. The mean MBP levels of these two groups of preterm infants were different (P<OOOI) at all ages measured. Asa whole group, the MBP level rose from a mean of 500 ng/ml at 25 weeks gestation to 1700ng/ml at 20 weeks post full-term. The mortality rates of 'low' and 'high' MBP groups of preterm infants were 22% and 12%, respectively (/* -0113). This difference in mortality was due to gestational age and birth weight standard deviation score (SDS) after adjusting for length of gestation and gender (/* = 0 0001) rather than to low MBP levels (/* = 0 65). MBP levels were not related to birthweight SDS score (P = 0 26). The meanis.d. MBP levels for preterm, term infants and adults without the codon 54 mutation were 1225 ±701 ng/ml (n = 45), 2064 ± 829 ng/ml (H^88) and 2473 ± 1395ng/ml (/i = 95), respectively; the corresponding values for those with the codon 54 mutation were 130 ±275 ng/ml {n= 18), 533 ±665 ng/ml (/; = 35)and 330±225ng/ ml (« -28), respectively. Intra-uterine growth retardation in preterm infants does not influence MBP levels. For those without the codon 54 mutation, there is a significant difference in MBP level between the three age groups. For those with the codon 54 mutation, there is a significant difference between preterm and term infants, but not between term infants and adults. We conclude that there is a maturation in MBP levels for preterm infants, and that a moderately low MBP phcnotype does not affect survival. We cannot exclude an effect of profoundly reduced MBP levels (characteristic of individuals homozygous for the codon 54 mutation), since no such preterm infant was identified in this study.

Low Serum Levels of Mannose Binding Lectin Are a Risk Factor for Neonatal Sepsis

“…In neonates, MBL levels are related to GA and increase after birth in term and preterm infants (21,22,26). This maturational pattern has been confirmed by our study: 53% of our neonates with a GA Ͻ32 wk had serum MBL levels on admission Ͻ0.7 g/mL compared with only 33% of those with a higher GA (p ϭ 0.005).…”

Serum mannose-binding lectin (MBL) gene polymorphism and low MBL levels are associated with neonatal sepsis and pneumonia

“…CONS were also found to be the most common blood stream infection pathogen in NICU and no relationship was established between low-MBL producing genotypes and nosocomial infection risk. 32 Similarly, CONS were the primary causative pathogen in our sepsis group, which was followed by fungi and gram-negative pathogens. As MBL binds poorly to CONS, complement activation through MBL binding is not effective; and therefore, MBL may not be protective in CONS infections.…”

“…16,28,32 Lau et al 32 studied MBL levels in 885 longitudinally collected serum samples from 168 preterm infants and 63 were genotyped for codon 54 mutation in MBL gene. They found that for infants with codon 54 mutation, there was a significant difference between preterm and term infants.…”

Mannose-Binding Lectin Gene Polymorphism and Early Neonatal Outcome in Preterm Infants

“…In recent years several studies have elaborated the relationship between the innate immune system and infections in newborn infants. From these studies it is obvious that MBL levels are influenced by the genotype of the infant as in adults [11,21,22] .…”

“…This can be explained by the fact that all patients, even the cases with codon 54 polymorphism, have an increase in MBL levels after the first few days of life [21] . The maturational pattern of MBL levels which are related to gestational age and increase with time in term and preterm neonates could also account for our results.…”