The association of mannose-binding lectin 2 polymorphisms with outcome in very low birth weight infants

<div><p>Objectives</p><p>Studies on the influence of mannose-binding lectin (MBL) deficiency on infection susceptibility in preterm infants have yielded controversial results. We investigated the association of genotype-based MBL levels with outcome in very-low-birth weight infants (VLBWI).</p><p>Methods</p><p>We genotyped 3 genetic variants of MBL2 (rs1800450, rs1800451, rs5030737) in 6878 VLBWI. MBL plasma levels were categorized as normal (wild type, A/A), low (heterozygotes, A/O) or undetectable (homozygotes, O/O). Primary outcome was the effect of genotype-based MBL2 levels on blood-culture proven and clinical sepsis during primary stay in hospital. We also evaluated burden of infection within 24 months after discharge.</p><p>Results</p><p>We found no association between MBL levels and sepsis risk in the whole cohort. Infants without measurable MBL levels born between 32 0/7 to 36 6/7 weeks of gestation, however, had a higher rate of Gram-negative sepsis than infants with normal or reduced MBL levels. In a follow-up investigation at 24 months (n = 1070 infants), infants without measurable MBL levels suffered more frequently from stomatitis and urinary tract infection.</p><p>Conclusions</p><p>In a large cohort of VLBWI MBL2 deficiency had no major impact on infection risk unless children were born between 32 0/7 and 36 6/7 weeks of gestation.</p></div

Mean outcome distribution according to genotype and phenotype.

*<p>Surgery for necrotizing enterocolitis.</p

Infection risk according to MBL levels in gestational age group 22 0/7–27 6/7 weeks of gestation.

<p>Infection risk according to MBL levels in gestational age group 22 0/7–27 6/7 weeks of gestation.</p

Episodes of herpes stomatitis and bacterial urinary tract infection in the first 24 months of life.

<p>The mean±SD number of episodes of episodes of stomatitis and urinary tract infection (UTI) are based on parents’ responses to the KIGGS questionnaire at 24 months of age. Data are described according to genotype-based MBL levels. Infants without measurable MBL levels had a higher rate of herpes stomatitis as compared to infants with normal MBL levels (p = 0.004) and low MBL levels (p = 0.02) and a higher frequency of bacterial UTI as compared to infants with normal MBL levels (p = 0.03, Mann-Whitney U-test).</p

Episodes of infections in the first 24 months of life according to genotype-based MBL levels.

<p>Episodes of infections in the first 24 months of life according to genotype-based MBL levels.</p

Frequency of MBL2 polymorphisms in the European cohort and number of genotyped infants (PCR + Genome-Wide Association Study).

<p>Frequency of MBL2 polymorphisms in the European cohort and number of genotyped infants (PCR + Genome-Wide Association Study).</p

Hypertrophy and hypotrophy and clinical data in German vlbw infant population.

<p>Hypertrophy and hypotrophy and clinical data in German vlbw infant population.</p

Clinical characteristics of VLBW cohort according to genotype-based MBL levels.

<p>Clinical characteristics of VLBW cohort according to genotype-based MBL levels.</p

Multivariable logistic regression analysis for mortality and morbidities including well known-risk factors.

<p>Multivariable logistic regression analysis for mortality and morbidities including well known-risk factors.</p

Clinical characteristics of VLBW cohort categorized according to PPROM.

<p>p-values are derived from Fisher´s exact test or Mann-Whitney-U-test if indicated (*)</p><p>Clinical characteristics of VLBW cohort categorized according to PPROM.</p