Effects of oral probiotic supplementation on gut Lactobacillus and Bifidobacterium populations and the clinical status of low-birth-weight preterm neonates: a multicenter randomized, double-blind, placebo-controlled trial.

AIM: Probiotic bacteria administered directly after birth to preterm neonates may improve gastrointestinal function and may reduce the incidence of late-onset sepsis, which is a frequent complication in this group. PURPOSE: The main objective of this study was to evaluate whether a new probiotic bacterial mixture of Lactobacillus rhamnosus KL53A and Bifidobacterium breve PB04 given to preterm, low-birth-weight neonates would influence composition of their gut microbiota and sepsis rates. PATIENTS AND METHODS: This study was a multicenter, randomized, double-blind, placebo-controlled trial conducted in clinical centers of neonatal care in Poland. A probiotic or placebo preparation was given twice daily to 181 preterm low-birth-weight neonates who were eligible for enteral feeding between July 2012 and July 2013. The probiotic was given to 90 neonates, while placebo was given to 91 neonates. The gut microbiota was monitored by microbiological analysis of stool samples. Sepsis episodes were detected on the basis of clinical and laboratory findings and confirmed by blood cultures. RESULTS: Tested probiotic administration resulted in continuous increase of the Lactobacillus and Bifidobacterium counts in the gut microbiota. The applied tested strains successfully colonized the neonates gut since they were present in over 90% of stool samples, which was confirmed by molecular analysis. Regardless of the study group (probiotic or placebo), B. breve colonization correlated with lower staphylococcal sepsis incidence, which was irrespective of whether probiotics were given. No sepsis case caused by strains included in study probiotic was recorded. CONCLUSION: Appropriately selected and characterized probiotic bacteria may be safely given to preterm neonates to normalize their distorted gut microbiota and may contribute to lower staphylococcal sepsis rates.

Components of the lectin pathway of complement activation in paediatric patients of intensive care units.

Infections are a major cause of childhood mortality. We investigated components of the lectin pathway of complement activation in the context of sepsis at both genetic and protein levels in neonates, infants and older children. Major components of the lectin pathway and two genes for Toll-like receptors were studied in 87 neonates with confirmed sepsis and compared with 40 babies with infections who did not develop sepsis (disease controls) and 273 infection-free neonatal controls. A second cohort comprised 47 older children with sepsis and 87 controls. Low MBL-conferring genotypes (LXA/O+O/O) were more frequent in sepsis patients than in healthy controls but no significant differences in the frequency of SNPs of other lectin pathway genes (FCN1, FCN2, FCN3, MASP1/3, MASP2) or TLR receptor genes (TLR2, TLR4) were found. One case of primary MASP-2 deficiency was found among healthy pre-terms and one neonate suffering from SIRS was heterozygous for the rare FCN1 gene mutation, +6658 G>A. Generally, sepsis was associated with low serum MBL and low ficolin-2 concentrations on admission. Among neonates, ficolin-1 and MASP-2 levels were elevated in sepsis relative to healthy, but not disease, controls. Unlike neonates, ficolin-3 and MASP-2 levels were lower in older patients than in healthy controls while no difference was found for ficolin-1. With the possible exception of MBL, inherited lectin pathway insufficiencies do not seem to predispose to sepsis, rather changes in protein concentrations reflect alterations in disease course.

Late-onset bloodstream infections of Very-Low-Birth-Weight infants: data from the Polish Neonatology Surveillance Network in 2009-2011.

BACKGROUND: Late-Onset Bloodstream Infections (LO-BSI) continue to be one of the most important complications associated with hospitalization of infants born with very low birth weight (VLBW). The aims of this study were to assess the epidemiology of LO-BSI together with the risk factors and the distribution of causative pathogens at six Polish neonatal intensive care units that participated in the Polish Neonatology Surveillance Network from January 1, 2009 to December 31, 2011. METHODS: The surveillance covered 1,695 infants whose birth weights were <1501 grams (VLBW) in whom LO-BSI was diagnosed >72 hours after delivery. Case LO-BSI patients were defined according to NeoKISS. RESULTS: Four hundred twenty seven episodes of LO-BSI were diagnosed with a frequency of 25.3% and an incidence density of 6.7/1000 patient-days (pds). Results of our multivariate analysis demonstrated that surgical procedures and lower gestational age were significantly associated with the risk of LO-BSI. Intravascular catheters were used in infants with LO-BSI significantly more frequently and/or for longer duration: Central venous cathters (CVC) (OR 1.29) and Peripheral venous catheters (PVC) (OR 2.8), as well as, the total duration of total parenteral nutrition (13 vs. 29 days; OR 1.81). Occurrence of LO-BSI was significantly associated with increased the length of mechanical ventilation (MV) (OR 2.65) or the continuous positive airway pressure (CPAP) (OR 2.51), as well as, the duration of antibiotic use (OR 2.98). The occurrence of more than one infection was observed frequently (OR 9.2) with VLBW with LO-BSI. Microorganisms isolated in infants with LO-BSI were dominated by Gram-positive cocci, and predominantly by coagulase-negative staphylococci (62.5%). CONCLUSIONS: Independent risk factor for LO-BSI in VLBV infants are: low gestational age and requirement for surgery. The incidence rates of LO-BSI especially CVC-BSI were higher in the Polish NICUs surveillance than those of other national networks, similar to the central- and peripheral utilization ratio.

Necrotising enterocolitis in preterm infants: epidemiology and antibiotic consumption in the Polish neonatology network neonatal intensive care units in 2009.

UNLABELLED: The aim of this study was to describe the epidemiology of necrotising enterocolitis (NEC), antibiotic consumption and the usefulness of microbiological tests in very low birth weight (VLBW) Polish newborns. METHODS: Prospective surveillance was performed in the year 2009 by local infection control teams. The study covered 910 infants hospitalized in six Polish neonatal intensive care units. Two kinds of indicators were used for the description of antibiotic usage: the duration of treatment (days of treatment, DOTs) and the defined daily dose (DDD). RESULTS: NEC incidence was 8.7% and fatality rate was 19%. Chorioamnionitis, late gestational age and low birth weight were identified as risk factors for NEC. Catheterization, mechanical ventilation and other selected procedures were used considerably longer in newborns with NEC than in the remaining neonates. Total usage of antibiotics reached 2.9 DDDs or 1.437 days; the average use of drugs per case of NEC amounted to 0.47 DDD or 23.2 DOTs. The level of antibiotic usage was analysed with correlation to microbiological tests performed and it was non-significantly greater in the group of children with NEC in whom the tests were performed. CONCLUSIONS: A high risk of developing NEC is closely associated with VLBW and with inflammation of the amnion during labour. We observed no relationship between the consumption of antibiotics in neonates with NEC and positive results of microbiological testing indicating sepsis accompanying NEC or gut colonization with pathogens.

[Epidemiology of infections in very low birth weight infants. Polish Neonatology Network research]. / Epidemiologia Zakazen Noworodkówz Bardzo Mala Masa Urodzeniowa.badania Polskiej Sieci Neonatologicznej.

AIM OF STUDY: 1. prospective record of infections; 2. prevention of nosocomial infections by providing current data about infections, which are significant for making therapeutic decisions. MATERIAL AND METHODS: Recorded infections: early-onset sepsis (congenital), late-onset sepsis (acquired in hospital), necrotising enterocolitis (NEC), pneumonia. Infections were diagnosed and qualified on the basis of definitions of infections based on the National Nosocomial Infections Surveillance (NNIS) criteria, developed by CDC, USA, including modifications of German Neo-KISS programme. Infection control was realised as a part of common research project of "Polish Neonatology Network", appointed by the decision of the Minister of Science and Higher Education no. 669/E-215/BWSN- 0180/2008 dated 20.05.2008 r. The study was conducted by 6 Polish neonatology units, Microbiology Chair of Jagiellonian University Collegium Medicum and Institute of Theoretical and Applied Computer Science. Infants with birth weight lower than 1500 g were qualified for the study. RESULTS: Between 1.01.2009 and 31.12.2009, 910 patients were registered, i.e. 19.1% of VLBW infants born in that period. The conducted analysis showed significant differences between centres in gestational age, birth weight, hospitalisation, use of invasive procedures, antibiotics and parenteral feeding. Cumulative morbidity rate was 68.5% total. Blood infection (sepsis) was the most commonly observed type of infection: 268 cases - 43.1% of all recorded forms of infection. Pneumonia was diagnosed in 242 cases, 38.8% total. NEC constituted 12.7% studied infections (79 cases). Apart from NEC, the risk of other forms of infection differed between centres. Dominant etiologic factor of all infections were Gram-positive cocci, which constituted 565 isolated microorganisms. Among them coagulase-negative staphylococci (CNS) were the most common (41.7%), while Staphylococcus aureus was fourth most frequent etiologic factor of infections (6.3% total). CONCLUSIONS: 1. Introduction of unified definition and criteria for diagnosing infections and the use of morbidity rates enables comparative analysis of epidemiology of infections in neonatal intensive care units. 2. Due to significant differences observed between prophylactic and therapeutic procedures in various units, it is essential to propose Polish recommendations regarding control over etiology of infections and use of invasive procedures, such as intravenous catheters and ventilation. 3. It is essential to undertake action leading to fully rational antibiotic therapy, because overuse of antibiotics leads to bacterial resistance and increases incidence of infections.

Infections reported in newborns with very low birth weight who required surgical treatment. Data from the Polish Neonatology Surveillance Network.

AIM: To determine the risk of various forms of infections appearing in very low birth weight newborns (VLBW) during the period of 30 days after surgical treatment in hospitals which have perinatal care departments with neonatal intensive care units that form the Polish Neonatology Surveillance Network (PNSN). MATERIAL AND METHODS: Continuous prospective monitoring of infections was carried out from January 1st to December 31st 2009 in six neonatal intensive care units which form the Polish Neonatal Surveillance Network. (PNSN). 910 newborns with very low birth weight (VLBW) were included in the study programme. 91 (10%) of this group underwent 118 surgical interventions. 12 newborns needed two or more surgeries. The most common procedure was the closure of persistent ductus artesiosus (PDA) and photocoagulation of vascular damage in the eye fundus. RESULTS: In the period of 30 days after surgery the following were diagnosed: in 3 newborns - necrotizing enterocolitis (NEC), in 22 newborns - sepsis (BSI) and in 54 newborns - pneumonia (PNEU). Symptoms of BSI and PNEU were on average observed on the 10th day after surgical intervention, while in the case of NEC on the 17th day. The highest incidence of infection (148.4%) was observed after PDA closure and in connection with introducing a drain into the pleural cavity through the intercostal space. The incidence of PN EU (37.3%) was twice as high as the incidence of BSI (18.6%). Surgical procedure was a factor significantly increasing the risk of infection and morbidity (RR 2.1, P<001) In our investigations there was no case of the local infection of a surgical site. 11 newborns died (mortality was 12.1%). The most common bacterial strains found in our investigation were coagulase-negative Staphylococcus and Escherichia Coli. CONCLUSIONS: Taking into consideration the fact that surgical procedure in VLBW-newborns significantly increases the risk of pneumonia and to a minor degree the risk of NEC and BSI, further detailed investigation in the field of perisurgical epidemiology is needed in order to elaborate a more deeply oriented and more effective strategy of infection prevention in the group of VLBW newborns.

The relationship between FCN2 genotypes and serum ficolin-2 (L-ficolin) protein concentrations from a large cohort of neonates.

The human FCN2 gene codes for ficolin-2 (L-ficolin), a major pattern recognition molecule and activator of the lectin pathway of complement. Seven single nucleotide polymorphisms of this gene were investigated in a large series of cord blood DNA samples. Mutations from the majority to the minority alleles at -602, -4 and +6359 were associated with an increase, while mutations at -986, -557, -64 and +6424 were associated with a decrease, in protein concentration. Full (7 loci) genotypes were obtained for 1229 unrelated neonates, 12 sets of twin siblings and one set of triplets. Forty-four separate genotypes were detected. Four genotypes accounted for more than half the unrelated neonates, and >90% had one of the 12 commonest genotypes. Genotypes were associated with significant differences in mean serum ficolin-2, but the intra-genotype concentration ranges were large and greater than the inter-genotype differences. Consequently, there were no associations between genotypes and low birthweight babies or perinatal infections, and only a weak relationship with preterm deliveries, despite all three adverse pregnancy features being significantly associated with serum ficolin-2 protein. FCN2 genotyping may be of value in clinical studies, but not as a substitute for total serum ficolin-2 protein measurement.

Enterobacteriaceae infections of very low birth weight infants in Polish neonatal intensive care units: resistance and cross-transmission.

BACKGROUND: The aims of our study were analysis of the occurrence of infections by members of the Enterobacteriaceae family in 6 Polish neonatal intensive care units in 2009, their drug resistance, the epidemiology of extended-spectrum ß-lactamase (ESBL)-producing strains and the possibility of using modern tools of microbiology diagnosis in infection control, especially for the reduction of antimicrobial resistance. METHODS: A prospective surveillance covered 910 newborns. Case patients were defined as neonates with very low birth weight who had clinical signs of septicemia, pneumonia or necrotizing enterocolitis. Early-onset infection was defined as infection diagnosed within 3 days after delivery. RESULTS: The incidence of Enterobacteriaceae infections was 2.6/1000 patient-days. The risk of Enterobacteriaceae pneumonia increased with the length of hospitalization (P = 0.0356). The most common pathogen was Escherichia coli (12.4% of all strains, in early-onset infection 18.5%) and Klebsiella spp. (9.1% of all). The ESBL phenotype was found in 37% of isolates, of which 89.3% were producing CTX-M-type, 70.2% TEM-type and 8.5% SHV-type. Epidemic clones were detected in the 2 studied neonatal intensive care units: 6 of the 9 ESBL-positive Enterobacter cloacae and 16 of the 18 ESBL-positive Klebsiella pneumoniae strains were classified into 1 epidemic clone, which showed resistance to penicillin without inhibitors, amoxycillin/clavulanic acid, cephalosporins, aztreoname, aminoglycosides and trimethoprim/sulfamethoxazole. CONCLUSIONS: Enterobacteriaceae bacilli are a significant problem in neonatal intensive care units, especially in early-onset infection and for long hospitalized very low birth weight infants. The observed high drug resistance was in large part related to the dominance of epidemic strains as a result of horizontal transmission. The best way to reduce drug resistance would be adequate procedures of isolation and hand hygiene.

[Antibiotic consumption and its costs of purchase in Polish neonatology networks units]. / Zuzycie antybiotyków i koszty ich zakupu w oddzialach Polskiej sieci neonatologicznej.

AIM: The study presents the results of the analysis of antibiotic consumption and its direct costs in selected neonatal units. MATERIAL AND METHODS: Data were collected retrospectively (the year 2007) in five hospitals, during the pilot phase of the Polish Neonatal Network . Antibiotic consumption was assessed using the Defined Daily Dose (DDD). The costs were assessed as the costs of purchase of one DDD. RESULTS: The study included 11 922 children hospitalized in the period from 1.01 to 31.12.2007. In this group, 731 infants have birth weight < 1500 grams (from 2.2% to 64.2% in individual units, median--7.3%). The mean consumption of antibacterial drugs was 48.52 DDD/1 000 person-days (P-D) of stay among the entire study population (median--42,52), and varied from 23.13 to 85.82 DDD/1,000 P-D. However, this difference has not been statistically significant. The most commonly used group of antibiotics were beta-lactams--in four out of five units the percentage of its usage ranged from 48.71% to 74.67%. Next group were aminoglicosides--in one unit its usage reached 56.97% and in other ranged from 5.01% to 22.53%. Glycopeptides and macrolides were also used in every unit of the studied group. The usage of glycopeptides ranged from 1.7% to 10.81% and of macrolides from 1.32% to 15.71%. Different kinds of antibiotics were used occasionally. The differences of costs of purchase of one DDD between hospitals were greater and varied from 17,64 PLN/ DDD to 84,58 PLN/ DDD (average costs). A considerable range of costs index values was also noted for different groups of antibiotics. The costs of purchase of one DDD of beta-lactams varied from 19.54 PLN/ DDD to 68.35 PLN/ DDD; for aminoglicosides the cost varied from 4.61 PLN/ DDD to 122.9 PLN/ DDD, for glycopeptides--from 31.40 PLN/ DDD to 283.13 PLN/ DDD and in case of macrolides: from 12.05 PLN/ DDD to 90.77 PLN/ DDD. This differentiation of the cost of purchasing a single defined daily dose, taking into account the specific groups of antibiotics, did not have the characteristics of statistical significance. CONCLUSIONS: As expected, the antibiotic regimens in the studied wards were similar. This is due to a homogeneous population of hospitalized patients. However, the differences of costs of purchase of antibiotics observed in the study, indicate the considerable variety of the treatment patterns in Polish neonatology units and the need to develop and implement recommendations of effective pharmacotherapy for patients in intensive neonatal care units and the implementation of a unified model of infections surveillance.

[Perinatal transmission of Chlamydia trachomatis and its complication in preterm infants]. / Czestosc perinatalnej transmisji Chlamydia trachomatis i powiklania z nia zwiazane u noworodków przedwczesnie urodzonych.

INTRODUCTION: Chlamydia trachomatis is the most common agent of sexually transmitted infections. In pregnant women it can cause premature delivery. In newborns the clinical manifestation are pneumonia and conjunctivitis. AIM: The aim of the study was to estimate the perinatal transmission of Chlamydia trachomatis and the prevalence of neonatal complications. MATERIAL AND METHODS: The study included 82 mothers with delivery < 34 weeks of gestation and 100 of their newborns. All patients were hospitalized at the Poznan University of Medical Sciences Gynecology and Obstetrics Hospital between 2004 and 2009. Polymerase chain reaction (PCR) method in AMPLICOR CT/NG test was used for the detection of Chlamydia trachomatis infection. RESULTS: Chlamydia trachomatis was identified in 8 pregnant women among 82 tested patients (10%) and in 6 neonates. Perinatal transmission was 75%. All infected infants developed respiratory disorders. Five of them needed respiratory support such as nCPAP or mechanical ventilation. Three newborns presented apneic spells. CONCLUSIONS: Asymptomatic chlamydial infection is frequently detected in women with preterm delivery. There is high risk of perinatal transmission of the infection from the mother to the newborn, which leads to perinatal complications such as neonatal pneumonia which in preterm infants can develop just after the delivery and give rise to life-threatening respiratory disorders.

Early-onset infections of very-low-birth-weight infants in Polish neonatal intensive care units.

AIM: The objective of this study was to investigate the incidence, causes, the risk factors, etiologic agents and the outcomes of early-onset infections (EOIs) in very-low-birth-weight newborns in Polish neonatal intensive care units. METHODS: Continuous prospective infection surveillance conducted during 2009 at 6 Polish neonatal intensive care units and included 910 newborns whose birth weight was lower than 1500 g. Infections were defined according to the Gastmeier's criteria. EOIs were diagnosed <3 days after delivery. RESULTS: The frequency of early-onset septicemia (EOS) was 7.0% and of early-onset pneumonia (EO-pneumonia) 8.6%. The factors significantly increasing the risk of EOS were low gestational age, small birth weight, low score in the Clinical Risk Index for Babies and Apgar score as well as maternal chorioamnionitis. The perinatal prophylaxis did not have an influence on the occurrence of EOS. The factors considerably increasing the risk of EO-pneumonia were low scores in the Clinical Risk Index for Babies and Apgar scores, a low gestational age and bacterial vaginosis in the child's mother during pregnancy. The most important etiologic organisms were Gram-positive cocci (39.7% of all the infections, 47.8% in EOS), Streptococcus agalactiae (20% of the EOS), Gram-negative bacilli (33.3% isolates), yeast-like fungi (isolated in 7.9% of cases) and atypical bacteria (22% of the cases of EO-pneumonia). CONCLUSIONS: The observed frequency of EOS did not differ from the one described in the literature, whereas the frequency of EO-pneumonia was higher. The bacterial etiologies suggest the vertical transmission of the pathogens and a close relationship between the observed EOIs with maternal environment. The applied perinatal antibiotic prophylaxis was ineffective.

H-ficolin (ficolin-3) concentrations and FCN3 gene polymorphism in neonates.

Serum H-ficolin (ficolin-3) concentrations (n=613) and FCN3 genotypes (n=529) from a large group of neonates are presented. Both pre-term deliveries and low birthweight (independently of gestational age) were significantly associated with low H-ficolin concentrations but not with heterozygosity for the FCN3 1637delC frameshift mutation. The presence of the variant allele, however, apparently influenced the protein level. No association of FCN3 gene heterozygosity or relative functional H-ficolin insufficiency (determined as serum level ≤8.6 µg/ml) with perinatal infections was found. One premature newborn, with confirmed infection caused by Streptococcus agalactiae, was H-ficolin-deficient (FCN3 variant homozygote, no detectable protein). We present what is only the fourth case report of total H-ficolin deficiency in the world literature. This neonate was however previously found to be mannan-binding lectin (MBL) as well as MBL-associated serine protease-2 (MASP-2) deficient and also had low serum L-ficolin.

[Recommendations of prophylaxis of vitamin D deficiency in Poland (2009)]. / Zalecenia dotyczace profilaktyki niedoborów witaminy D w polsce (2009).

Adequate vitamin D intake and its status as well outdoor physical activity are important not only for normal bone development and Ca-P metabolism, but for optimal function of many organs and tissues throughout the body. Due to documented changes in dietary habits and physical activity level, both observed in growing children and adults, the prevalence of vitamin D insufficiency is continuously increasing. National Consultants and experts in this field established the Polish recommendations for prophylactic vitamin D supplementation in infants, toddlers, children and adolescents as well as in adults, including pregnant and lactating women based on current literature review. Taking into consideration pleyotropic vitamin D action and safety aspects serum 25-hydroxyvitamin D (25-OHD) level of 20-60 ng/ml (50-750 nmol/l) in children and 30-80 ng/ml (75-200 nmol/I) in adults is considered as optimal. Sunlight exposure inducing vitamin D production in the skin is main endogen source of vitamin D in the body but sunscreens may reduce skin synthesis by 90%. In Poland, skin synthesis is effective only from April to September so other sources of vitamin D such as diet and supplements play an important role. All newborns should be supplemented with 400 IU/d of vitamin D beginning from the first few days of life and continue during infancy. In formula fed infants vitamin D intake from the diet should be taken into account. In preterm infants higher total vitamin D intake (400-800 IU/day) is recommended till 40 weeks post conception. Total vitamin D intake in children and adolescents required from all sources (diet and/or supplements) should be 400 IU/d between October and March and throughout the whole year in case of inadequate vitamin D skin synthesis during the summer months. In overweight/obese children supplementation with higher dosage of vitamin D up to 800-1000 IU/d should be considered. Adults require 800-1000 IU/d of vitamin D. In pregnant and lactating women such supplementation is recommended in case of inadequate intake from diet and/or skin synthesis supplementation. Monitoring of serum 25-OHD level to define optimal dosage should be considered.

[Prophylaxis of vitamin D deficiency--Polish recommendations 2009]. / Polskie zalecenia dotyczace profilaktyki niedoborów witaminy D--2009.

Appropriate state procurement system for vitamin D is important not only for the proper functioning of the skeletal, maintaining calcium and phosphorus homeostasis, but also for a number of other organs and tissues in our body. In connection with the change in lifestyle including dietary habits change, the widespread use of UV filters and less outdoor activity, observed an increase in the percentage of vitamin D deficiency, both in population and developmental age and adults. Based on the results of recent scientific research team of experts provides recommendations for preventive Polish supply of vitamin D in infants, children, adolescents and adults, including pregnant women and nursing mothers.

[Prophylaxis of vitamin D deficiency--Polish recommendation 2009]. / Stanowisko Zespolu Ekspertów. Polskie zalecenia dotyczace profilaktyki niedoborów witaminy D - 2009.

Adequate vitamin D intake and its status are important not only for bone health and Ca-P metabolism, but for optimal function of many organs and tissues throughout the body. Due to documented changes in dietary habits and physical activity level, both observed in growing children and adults, the prevalence of vitamin D insufficiency is continuously increasing. Basing on current literature review and opinions of National Consultants and experts in the field, polish recommendations for prophylactic vitamin D supplementation in infants, toddlers, children and adolescents as well as in adults, including pregnant and lactating women have been established.

Long-term effects of diabetes during pregnancy on the offspring.

BACKGROUND: Many epidemiological and experimental studies have proven that some adult diseases might have their origin in fetal life. It has been also hypothesized that intra-uterine environment in pregnancy complicated with diabetes might influence the development of obesity, type 2 diabetes, and cardiovascular diseases in the offspring. OBJECTIVES: To assess glucose metabolism, insulin secretion, and prevalence of obesity in the offspring of mothers with pregestational diabetes mellitus (PGDM) and gestational diabetes mellitus (GDM) and to evaluate the relationship between maternal metabolic control during pregnancy and metabolic disturbances in children. SUBJECTS: Children of mothers with PGDM (n = 43) and GDM (n = 34) were examined at 4-9 yr of age and compared with the control group (n = 108; metabolic parameters available for n = 29). METHODS: The incidence of overweight and obesity, impaired glucose tolerance, and insulin resistance were analyzed based on anthropometric and biochemical measurements. Statistical analysis was performed with statistica package. RESULTS: In children of GDM mothers, body mass index z-score (0.81 +/- 1.01 vs. -0.04 +/- 1.42 PGDM vs. 0.07 +/- 1.28 control group) and insulin resistance indices (homeostasis model assessment index - insulin resistance 1.112 vs. 0.943 PGDM vs. 0.749 control group) were significantly higher than in other groups. Obesity and insulin resistance were also most frequent in GDM group [not significant (NS)]. In addition, we observed the relationship between maternal hemoglobin A1c and mean glycemia in perinatal period and insulin resistance in children. There was not such correlation for the class of maternal diabetes. CONCLUSION: Children born to mothers with gestational diabetes seem to be at risk for obesity and metabolic disturbances.

Mannan-binding lectin-associated serine protease-2 (MASP-2) in a large cohort of neonates and its clinical associations.

One collectin (mannan-binding lectin, MBL) and three ficolins (M-ficolin/ficolin-1, L-ficolin/ficolin-2 and H-ficolin/ficolin-3) share the capability to activate complement via the lectin pathway. This property depends on the ability of these lectins to form complexes with MBL-associated serine proteases (MASPs), particularly MASP-2. We report the results of an investigation of cord blood MASP-2 concentrations in a large, ethnically homogeneous cohort (n=1788) of neonates. The median value of MASP-2 in cord sera was determined to be 93 ng/ml (range <25-812). Serum MASP-2 concentrations correlated with gestational age and birthweight and were significantly lower in premature babies and other pre-term babies compared with term babies. Neonates with MASP-2 concentrations below 42 ng/ml were deemed to be MASP-2 deficient. That group had a shorter mean gestational age and a higher incidence of premature and low birthweight babies, but not of perinatal infections when compared with the others. Indeed, there was a trend towards higher MASP-2 concentrations amongst babies with infections. Among 362 samples tested for the D120G single nucleotide polymorphism (SNP) of the MASP2 gene, no homozygote for that mutation was found. Heterozygosity for this allele significantly influenced the protein concentration, but not the lectin pathway of complement activity (MBL-MASP-2 complex activity). Moreover, no association of this SNP was apparent with prematurity, low birthweight or perinatal infections.

Mannan-binding lectin genotypes and genotype-phenotype relationships in a large cohort of Polish neonates.

Circulating mannan (or mannose)-binding lectin (MBL) is genetically determined. Low MBL concentrations are associated with certain point mutations in the human MBL2 gene. Here we report the full MBL2 genotypes of 1800 Polish neonates and relate individual genotypes to serum MBL and MBL-dependent activity of the lectin pathway of complement activation. The seven acknowledged common haplotypes were found, plus the uncommon LYPD haplotype, combining to form 33 genotypes in this population. As expected, a strong correlation existed between genotypes and serum MBL or lectin pathway activity, and the latter two entities correlated strongly with each other. However, serum MBL values varied up to greater than 90-fold within genotypes. Unexpectedly, higher lectin pathway activity was found in association with the P allele relative to the Q allele. These data from a large cohort of neonates, representing an ethnically homogenous population, suggest that the current knowledge of the genetics of MBL2 is inadequate to predict serum MBL concentration and MBL-dependent lectin pathway activity in individual subjects.

Two factors of the lectin pathway of complement, l-ficolin and mannan-binding lectin, and their associations with prematurity, low birthweight and infections in a large cohort of Polish neonates.

Ficolins and one collectin, mannan-binding lectin (MBL), are the only factors known to activate the lectin pathway (LP) of complement. There is considerable circumstantial evidence that MBL insufficiency can increase susceptibility to various infections and influence the course of several non-infectious diseases complicated by infections. Much less information is available concerning l-ficolin. We report the results of a prospective study to investigate any association between either MBL deficiency or l-ficolin deficiency with prematurity, low birthweight or perinatal infections in a large cohort of Polish neonates, representing an ethnically homogenous population (n=1832). Cord blood samples were analysed to determine mbl-2 gene variants, MBL concentrations and MBL-MASP-2 complex activities (MBL-dependent lectin pathway activity) as well as l-ficolin levels. Median concentrations of l-ficolin and MBL were 2500 and 1124 ng/ml, respectively, while median LP activity was 272 mU/ml. After genotyping, 60.6% of babies were mbl-2 A/A, 35.4% were A/O and 4% were O/O genotypes. We found relative l-ficolin deficiency to be associated with prematurity, low birthweight and infections. l-Ficolin concentration correlated with gestational age and with birthweight, independently of gestational age. Preterm deliveries (<38 weeks) occurred more frequently among neonates with low LP activity but not with those having low serum MBL levels. Similarly, no association of serum MBL deficiency with low birthweight was found, but there was a correlation between LP activity and birthweight. Genotypes conferring very low serum MBL concentrations were associated with perinatal infections, and high-MBL-conferring genotypes were associated with prematurity. Our findings suggest that l-ficolin participates in host defence during the perinatal period and constitute the first evidence that relative l-ficolin deficiency may contribute to the adverse consequences of prematurity. Some similar trends were found with facets of MBL deficiency, but the observed relationships were weaker and less consistent.