Biomarkers in newborns with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia.

PURPOSE: The aim of the presented study was to evaluate the differences between selected biochemical markers in infants with moderate or severe hypoxic-ischemic encephalopathy (HIE) and their impact on patient prognosis. METHODS: A total of 57 cooled newborns were divided into groups according to Sarnat staging of HIE (A, moderate vs. B, severe). The differences between groups were evaluated depending on the mode of delivery, pregnancy and labor complications, gestational age at birth, birth weight, and Apgar score at 1.3 and 5 min. The differences in biochemical biomarkers of HIE (pH, base excess, serum lactate) as well as biomarkers of hepatic injury (aspartate transaminase, (AST), alanine transaminase (ALT), prothrombin time (PT), and activated partial thromboplastin time (APTT)), kidney failure (creatinine, urea), myocardial injury (troponin T (TnT)), levels of fibrinogen, and platelet counts were also examined. Univariate Kaplan-Meier method was used for survival analyses. RESULTS: The biomarker levels in severe HIE newborns compared with moderate were as follows: pH (7.10 vs. 6.99), serum lactate (22.50 vs. 17.00 mg/dL), AST (109.50 vs. 270.55 IU/L), ALT (27.30 vs. 108.05 IU/L), PT (17.00 vs. 44.20 s), APTT (47.75 vs. 47.90 s), TnT (0.22 vs. 0.85 ng/mL), creatinine (0.68 vs. 1.15 mg/dL), urea (44.55 vs. 73.30 mg/dL), and fibrinogen (1.65 vs. 1.90 mg/dL). Survival analyses showed significantly reduced survival for severe HIE infants (75%) vs. moderate HIE (100%). CONCLUSION: In conclusion, the severity of HIE can be evaluated based on selected markers; however, their levels do not correspond with future prognosis of newborns.

Role of Fibronectin-1 polymorphism genes with the pathogenesis of intraventricular hemorrhage in preterm infants.

BACKGROUND/INTRODUCTION: Intraventricular hemorrhage (IVH) is a dangerous complication facing a significant proportion of preterm infants. It is multifactorial in nature, and an observed fibronectin deficiency in the germinal matrix basal lamina is among the most prominent factors that influence such rupture. Better understanding of the FN1 gene polymorphisms and their role in IVH may further clarify the presence of a genetic susceptibility of certain babies to this complication. The aim of this study was to assess if 5 single nucleotide polymorphisms of the fibronectin gene may be linked to an increased incidence of IVH. MATERIAL AND METHODS: The study included 108 infants born between 24 and 32 weeks of gestation. IVH was diagnosed using cranial ultrasound performed on the 1st,3rd, and 7th day after birth and classified according to Papile et al. IVH classification. The 5 FN1 gene polymorphisms assessed in the study were the following: rs3796123; rs1968510; rs10202709; rs6725958; and rs35343655. RESULTS: IVH developed in 51 (47.2%) out of the 108 preterm infants. This includes, 18 (35.3%) with stage I IVH, 19 (37.3%) with stage II, 11 (21.6%) with stage III, and 3 (5.9%) with stage IV IVH. Incidence of IVH was higher in infants with lower APGAR scores, low gestational age, and low birthweight. Analysis showed that IVH stage II to IV was approximately seven times more likely to occur in infants with the genotype TT FN1 rs10202709 (OR 7237 (1046-79.59; p = 0,044)). No other significant association was found with the rest of the polymorphisms. CONCLUSION: The results of our study indicate a sevenfold increased genetic susceptibility to IVH in preterm infants with the TT FN1 rs10202709 gene polymorphism. The fibronectin gene polymorphism may therefore be of crucial importance as a genetic risk factor for IVH in preterm infants. Further studies are warranted.

Inflammation-associated gene polymorphisms and clinical variables in the incidence and progression of retinopathy of prematurity.

INTRODUCTION: A growing body of evidence shows that genetics plays a vital role in the development and progression of retinopathy of prematurity (ROP). Perinatal inflammation is also considered an important risk factor of ROP. Therefore, understanding the interplay of genetics and susceptibility to inflammation might shed light on the pathogenesis of ROP and make its screening and treatment more effective in preventing visual impairment in premature infants. MATERIAL AND METHODS: This study investigated the correlation of inflammation-associated gene polymorphisms: IL-1ß +3953 C>T, IL-1RN VNTR 86 bp, IL-6 -174 G>C, IL-6 -596 G>A, and TNF-α -308 G>A as well as demographic and clinical characteristics of ROP in preterm infants (n = 90). RESULTS: Our results demonstrate that IL-1RN rs2234663 1/1 genotype prevails in infants with ROP that regresses without intervention, when compared to those requiring laser photocoagulation/anti-VEGF injection (p = 0.031). Genotype 2/2 of IL-1RN occurs more frequently in children with severe ROP (28.6%) than in the group in which ROP regressed spontaneously (4.0%). The analysis revealed also differences between the genotypes of IL-1RN in ROP patients with intrauterine infection and in patients who had ROP without intrauterine infection; however, this was not statistically significant. Other studied polymorphisms were not associated with ROP development or its progression. CONCLUSIONS: These results suggest that different genotypes of IL-1RN might have an impact on the course of ROP. Genotype 2/2 of IL-1RN gene may predispose to ROP progression.

Candidate gene analysis in pathogenesis of surgically and non-surgically treated necrotizing enterocolitis in preterm infants.

Necrotizing enterocolitis (NEC) is one of the most severe and unpredictable complications of prematurity. There are two possible mechanisms involved in the pathogenesis of NEC: individual inflammatory response and impaired blood flow in mesenteric vessels with secondary ischemia of the intestine. The aim of this study was to evaluate the possible relationship between polymorphisms: Il-1ß 3953C>T, Il-6 -174G>C and -596G>A, TNFα -308G>A, and 86 bp variable number tandem repeat polymorphism of interleukin-1 receptor antagonist (Il-1RN VNTR 86 bp) and three polymorphisms that may participate in arteries tension regulation and in consequence in intestine blood flow impairment: eNOS (894G>T and -786T>C) and END-1 (5665G>T) and NEC in 100 infants born from singleton pregnancy, before 32 + 0 weeks of gestation, exposed to antenatal steroids therapy, and without congenital abnormalities. In study population, 22 (22%) newborns developed NEC. Surgery-requiring NEC was present in 7 children. Statistical analysis showed 20-fold higher prevalence of NEC in infants with the genotype TT [OR 20 (3.71-208.7); p = 0.0004] of eNOS 894G>T gene polymorphism. There was a higher prevalence of allele C carriers of eNOS 786T>C in patients with surgery-requiring NEC [OR 4.881 (1.33-21.99); p = 0.013]. Our investigation did not confirm any significant prevalence for NEC development in another studied genotypes/alleles. This study confirms the significant role of polymorphisms that play role in intestine blood flow. Identifying gene variants that increase the risk for NEC development may be useful in screening infants with inherent vulnerability and creating strategies for individualized care.

The significance of polymorphisms in genes encoding Il-1ß, Il-6, TNFα, and Il-1RN in the pathogenesis of intraventricular hemorrhage in preterm infants.

INTRODUCTION: Intraventricular hemorrhage (IVH) is a significant morbidity seen in very low birth weight infants. Genes related to inflammation may be risk factors for IVH. MATERIAL AND METHODS: We examined five polymorphisms for an association with IVH in 100 preterm infants born from singleton pregnancy, before 32 + 0 weeks of gestation, exposed to antenatal steroid therapy, and without congenital abnormalities. These polymorphisms include interleukin-1ß 3953 C>T, interleukin-6 -174G>C and -596G>A, tumor necrosis factor -308 G>A, and 86 bp variable number tandem repeat polymorphism of interleukin-1 receptor antagonist (Il -1RN 86 bp VNTR). RESULTS: In our study population, 45 (45%) infants developed IVH, including 15 (33.33%) with stage 1, 19 (42.22%) with stage 2, 8 (17.77%) with stage 3, and 3 (6.66%) with stage 4. In contrast to the previously published data, the prevalence of IVH did not vary between infants with different IL-6 and TNFα alleles and genotypes. Our novel investigations in Il-1 +3953 C>T and Il-1RN 86 bp VNTR polymorphism did not show any significant link between those alleles or genotypes and IVH. CONCLUSIONS: IVH is a significant problem for preterm infants. In addition to little progress in preventing IVH in preterm babies, substantial research that are focused on understanding the etiology, mechanism and risk factors for IVH are imperative. In the era of personalized medicine, identification of genetic risk factors creates opportunities to generate preventative strategies. Further studies should be performed to confirm the role of genetic factors in etiology and pathogenesis of IVH.

The role of FV 1691G>A, FII 20210G>A mutations and MTHFR 677C>T; 1298A>C and 103G>T FXIII gene polymorphisms in pathogenesis of intraventricular hemorrhage in infants born before 32 weeks of gestation.

BACKGROUND: Congenital thrombophilia is associated with an increased intraventricular hemorrhage (IVH) risk among newborns, but it may also play a protective role. The role of genetic polymorphisms involved in the coagulation pathway of IVH pathogenesis is probably a consequence of an increased risk of thrombosis in the fine blood vessels in the germinal matrix region. MATERIAL AND METHODS: The aim of this study was to evaluate the possible relationship between Factor V (FV) 1691G>A, Factor II (FII) 20210G>A mutations and methylenetetrahydrofolate reductase (MTHFR) 677C>T; 1298A>C and Factor XIII (FXIII) 103G>T gene polymorphisms and the occurrence of IVH in 100 infants born from 24 + 0 to 32 + 0 weeks of gestation, born from singleton pregnancy, before 32 + 0 weeks of gestation, exposed to antenatal steroid therapy, and without congenital abnormalities. RESULTS: IVH developed 45 (45%) infants, including 15 (33.33%) diagnosed with IVH stage I, 20 (42.22%) with stage II, 8 (17.77%) with stage III, and 3 (6.66%) with stage IV. Analysis showed a prevalence 4.5 times higher of IVH stages II to IV in infants with the genotype CC (OR 4511 (1147-17.75); p = 0.026) of MTHFR 1298A>C gene polymorphism. Our investigation did not confirm any significant prevalence of IVH development in other studied mutations/polymorphisms. CONCLUSIONS: This study confirmed that the MTHFR 1298A>C polymorphism is associated with the risk of IVH. IVH is a significant problem for preterm infants. In addition to little progress in preventing IVH in preterm babies, substantial research that is focused on understanding the etiology, mechanism, and risk factors for IVH is imperative. In the era of personalized medicine, identification of genetic risk factors creates opportunities to generate preventative strategies.

The significance of IL-1ß +3953C>T, IL-6 -174G>C and -596G>A, TNF-α -308G>A gene polymorphisms and 86 bp variable number tandem repeat polymorphism of IL-1RN in bronchopulmonary dysplasia in infants born before 32 weeks of gestation.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects primarily preterm infants. Genetic factors are also taken into consideration in the pathogenesis of BPD. Genetic predispositions to higher production of inflammation mediators seem to be crucial. MATERIAL AND METHODS: The aim of this study was to evaluate the possible relationship between polymorphisms: interleukin-1ß +3953 C>T, interleukin-6 -174 G>C and -596 G>A, tumour necrosis factor -308 G>A and interleukin-1RN VNTR 86bp and the occurrence of BPD in a population of 100 preterm infants born from singleton pregnancy, before 32+0 weeks of gestation, exposed to antenatal steroids therapy, and without congenital abnormalities. RESULTS: In the study population BPD was diagnosed in 36 (36%) newborns. Among the studied polymorphisms we found the higher prevalence for BPD developing of the following genotypes: 1/2 (OR 1.842 [0.673-5.025] and 2/2 IL-1RN (OR 1.75 [0.418-6.908] 86bpVNTR; GC (2.222 [0.658-8.706]) and CC IL-6 -174G>C (1.6 [0.315-8.314]) and GA (2.753 [0.828-10.64]) and AA (1.5 [0.275-8.067] IL-6 -596G>A), GA 1.509 (0.515-4.301) TNF-α -308G>A. However, these finding were not statistically significant. CONCLUSIONS: Genetic factors are undeniably involved in the pathogenesis of BPD. In the times of individualised therapy finding genes responsible for BPD might allow the development of new treatment strategies. A new way of specific therapy could ensure the reduction of complications connected with BPD and treatment costs.

Intraventricular hemorrhage in neonates born before 32 weeks of gestation-retrospective analysis of risk factors.

INTRODUCTION: Intraventricular hemorrhage (IVH) affects 15-20 % of babies born before 32 weeks of pregnancy. A lot of risk factors of developing IVH are known. The making appropriate recommendations for dealing with infant born less than 32 weeks of gestation aimed at reducing the incidence of IVH is still needed. The study aim was to determine the incidence and analyze risk factors of IVH stage 3 and 4 in infants born before 32 + 0 weeks of pregnancy. METHODS: The retrospective analysis of 267 preterm babies (24 to 32 weeks of gestation) hospitalized in 2011-2013 at Department of Neonatology, Poznan University of Medical Sciences was performed. The diagnosis of IVH was confirmed by ultrasound scans according to Papille criteria. Stage 3 and 4 of IVH was confirmed in 14 (25 %) newborns from 23 to 24 weeks of gestation; 21 (37.5 %) from 25 to 26 weeks of gestation; 11 (19.6 %) from 27 to 28 weeks of gestation; 9 (16.1 %) from 29 to 30 weeks of gestation; and 1 (1.8 %) from 31 to 32 weeks of gestation. RESULT: The incidence of IVH stage 3 and 4 was higher in children: with less use of AST (OR 1.27; 0.62-2.61), born out of third-level hospitals (OR 2.25; 1.23-4.08), born with asphyxia (OR 3.46; 1.8-6.64), with acidosis treated with NaHCO3 (OR 6.67; 3.78-11.75), those who in the first days of life were treated for hypotension (OR 9.92; 5.12-19.21). CONCLUSION: No or uncompleted antenatal steroid therapy increased probability for development of severe intraventricular hemorrhage. Antenatal steroids therapy should be promoted among women at risk of a premature delivery. Hypotension therapy with catecholamines and acidosis with sodium hydrogen carbonate should be carefully considered. The use of appropriate prophylaxis of perinatal (antenatal steroids therapy women at risk of preterm birth, limiting the indications for the use of catecholamines for hypotension treatment and sodium hydrogen carbonate for acidosis therapy, limitation of preterm deliveries outside tertiary referral centeres) significantly reduces the incidence of intraventricular hemorrhage stage 3 and 4. The significance of intraventricular hemorrhage creates a need to carry out periodical analysis, at regional level, concerning its incidence, causes and effects to improve local treatment outcomes by identifying further courses of action.

The incidence of severe intraventricular hemorrhage based on retrospective analysis of 35939 full-term newborns-report of two cases and review of literature.

INTRODUCTION: Intraventricular hemorrhage (IVH) is mostly documented in premature infants, and the younger the gestational age, the more often it occurs. IVH is very rarely reported in full-term neonates. CASE REPORT: Retrospective analysis was performed in 35939 full-term neonates, who were born in the Clinical Hospital of Gynecology and Obstetrics at the University of Medical Sciences in Poznan. Clinical data were retrieved from their medical records. We report a case series of 2 term newborns, who developed severe IVH grade 3 and 4 with no evidence of asphyxia, neuroinfection, TORCH infections, coagulation disorders and trombocytopenia, metabolic disorders, arteriovenous malformations, and selected genetic abnormalities (factor V Leiden 1601G > A polymorphism and MTHFR 677C > T; 1298A > C polymorphisms). IVH in both cases was complicated by posthemorrhagic hydrocephalus treated with decompressive lumbar punctures and next ventriculoperitoneal shunt placement. CONCLUSIONS: In conclusion, several factors influence the predisposition for severe IVH in term neonates. Perinatal period complicated by fetal distress, birth trauma, and severe asphyxia should be taken into account. However, it is possible that etiopathogenesis cannot be defined clearly as in our cases. Cranial ultrasounds in a specific group of term newborns (taking into account risk factors for IVH) should be widely recommended.

Role of selected cytokines in the etiopathogenesis of intraventricular hemorrhage in preterm newborns.

Proinflammatory cytokines are essential mediators and indicators of an inflammatory process occurring in the body. Their physiological role is to stimulate the immune response, yet their excessive propagation and interaction with cells outside the immune system may be linked to the risk of organ damage. This is specifically important in the case of immature tissues of fetuses and prematurely born infants. Analysis of the concentrations of specific cytokines in different compartments makes it possible to assess the risk of premature birth, preterm rupture of the membranes, and to determine an existing intrauterine infection. The purpose of this paper is to summarize the existing research concerning the relationships between the concentrations of specific proinflammatory cytokines in different compartments (maternal blood serum, amniotic fluid, umbilical cord blood, arterial and venous blood, and cerebrospinal fluid of the newborn) and the risk of intraventricular hemorrhage (IVH) and the degree of its severity. The paper takes also into account the assessment of the usefulness of cytokines as biomarkers for IVH and its complications (posthemorrhagic hydrocephalus, white matter injury).

Perinatal outcome according to chorionicity in twins - a Polish multicenter study.

OBJECTIVES: The aim of the study was to analyze the perinatal outcome of twin gestations and estimate the influence of chorionicity on the outcome in a large cohort of twin pregnancies in Poland. MATERIAL AND METHODS: A retrospective analysis of 465 twin deliveries in 6 Polish centers in 2012 was conducted. Baseline characteristics, the course of pregnancy and labor, as well as the neonatal outcome were analyzed in the study group and according to chorionicity. RESULTS: A total of 356 twin pregnancies were dichorionic (DC group) (76.6%), and 109 were monochorionic (MC group) (23.4%). There were no differences in the occurrence of pregnancy complications according to chorionicity, except for IUGR of at least one fetus (MC 43.1% vs. DC 34.6%; p = 0.003). 66.5% of the women delivered preterm, significantly more in the MC group (78% vs. 62.9%; p = 0.004). Cesarean delivery was performed in 432 patients (92.9%). Mean neonatal birthweight was statistically lower in the MC group (2074 g vs. 2370 g; p < 0.001). Perinatal mortality of at least one twin was 4.3% (2.8% in the DC group vs. 9.2% in the MC group; p = 0.004). Neonatal complications, including NICU admission, respiratory disorders, and infections requiring antibiotic therapy, were significantly more often observed among the MC twins. CONCLUSIONS: The overall perinatal outcome in the presented subpopulation of Polish twins and its dependence on cho-rionicity is similar to the reports in the literature. Nevertheless, the rates of preterm and cesarean deliveries remain higher. It seems that proper counselling of pregnant women and education of obstetricians may result in reduction of these rates.

Late prematurity in twins: a Polish multicenter study.

The study aimed at investigating the impact of late prematurity (LPT) on neonatal outcome in twins and neonatal morbidity and mortality within LPT with regard to the completed weeks of gestation. The study was conducted in six tertiary obstetric departments from different provinces of Poland (Warsaw, Lublin, Poznan, Wroclaw, Bytom). It included 465 twin deliveries in the above centers in 2012. A comparative analysis of maternal factors, the course of pregnancy and delivery and neonatal outcome between LPT (34 + 0-36 + 6 weeks of gestation) and term groups (completed 37 weeks) was performed. The neonatal outcome included short-term morbidities. The analysis of neonatal complication rates according to completed gestational weeks was carried out. Out of 465 twin deliveries 213 (44.8%) were LPT and 156 (33.55%) were term. There were no neonatal deaths among LPT and term twins. One-third of LPT newborns suffered from respiratory disorders or required antibiotics, 40% had jaundice requiring phototherapy, and 30% were admitted to NICU. The analysis of neonatal morbidity with regard to each gestational week at delivery showed that most analyzed complications occurred less frequently with the advancing gestational age, especially respiratory disorders and NICU admissions. The only two factors with significant influence on neonatal morbidity rate were neonatal birth weight (OR = 0.43, 95% CI = 0.2-0.9, p = .02) and gestational age at delivery (OR = 0.62, 95% CI = 0.5-0.8, p < .01). LPT have a higher risk of neonatal morbidity than term twins. Gestational age and neonatal birth weight seem to play a crucial role in neonatal outcome in twins.

Hearing Impairment in Infants with Hypoxic Ischemic Encephalopathy Treated with Hypothermia.

Therapeutic hypothermia acts as the standard of care for infants with moderate to severe hypoxic ischemic encephalopathy (HIE). A proportion of neonates who undergo hypothermia due to HIE have shown to develop various degrees of hearing impairment. Analyzing and identifying infants at high risk of developing hearing difficulties is fundamental for early intervention of such auditory complications. The aim was to assess clinical factors in the development of hearing impairment following therapeutic hypothermia in HIE infants. A retrospective analysis was performed on infants hospitalized in our neonatology department in Poznan University of Medical Sciences, Poland. All infants experienced moderate to severe HIE, and were treated with therapeutic hypothermia. Risk factors for hearing impairment were identified in all infants included in the study. Clinical data during hospital stay and follow-up hearing status were analyzed. A total of 87 HIE infants were included in the study. Seventy-six infants (40 male and 36 female) had otoacoustic emission (OAE) examination following birth, of which 14 (18.4%) demonstrated abnormal (positive) results. Infants with abnormal OAE results had significantly lower blood pH (6.86 ± 0.16, p = 0.001) and base excess (BE) (-22.46 ± 2.59, p = 0.006). Of the 49 infants who returned for follow-up assessment, 4 (8.2%) were diagnosed with sensorineural bilateral hearing impairment (1 infant, mild [<40 dB], 2 moderate [41-70 dB], and 1 profound [>90 dB]). The biochemical analysis following birth revealed significantly lower umbilical BE levels (-23.90 ± 4.99, p = 0.041) and higher lactate levels (160.67 ± 4.93, p = 0.019) in the infants with eventual sensorineural hearing deficit. Infants with moderate or severe HIE are at risk of delayed onset hearing loss. Diligent efforts to monitor auditory status are required, even if early screening results for hearing are insignificant. Exploring biochemical parameters, such as lactate, BE, and blood pH, can prove beneficial in identifying HIE infants at risk of developing a hearing impairment.

Variable outcome in quintuplets pregnancy based on obstetric care.

The incidence of multiple pregnancies has increased dramatically over the last few years in developed countries, largely attributed to delayed childbearing and the increasing use of assisted reproduction technologies and ovulation inducing hormones. Relatively few countries have population-based statistics covering birth statistics. Of those that do, the numbers of quintuplet pregnancies rose sharply in the nineties while, at the same time, their delivery rates decreased greatly because of the use of fetal reduction. Fetal reduction is not possible or legal in some countries, Poland being one of them, and therefore obstetricians are faced with the challenges of quintuplet deliveries. Conservative treatment and management is difficult, and outcomes often vary greatly. Despite this, expert care provided at tertiary care centers can positively influence outcomes. The objective of this article is to present different care options and their consequences in two illustrative cases, as well as to establish a set of obstetric care and management goals that would allow prolongation of the gestation time. Quintuplet pregnancy is rare but poses relevant clinical problems to both the obstetrician and the neonatologist. It should be managed with close cooperation between all concerned. Due to the extreme and invariable risk of premature delivery associated with quintuplet pregnancies, we recommend early diagnosis, adequate prenatal care at one tertiary medical center, routine hospitalization and bed rest, repeated ante partum ultrasound surveillance with tests of fetal well-being, tocolytic therapy at first signs of the risk of premature labor, and specialized neonatology care after delivery.

Organ Complications of Infants with Hypoxic Ischemic Encephalopathy Before Therapeutic Hypothermia.

Hypoxic ischemic encephalopathy (HIE) is a serious neurological complication that may develop in asphyxiated infants. Severity of encephalopathy may vary, and concurrent multiorgan dysfunctions are commonly observed. Analyzing the incidence of such complications according to severity of HIE, and how they correlate with each other, may shape clinical judgment and allow for early intervention. The study included a total of 57 HIE infants, in which 27/57 (47.37%) met Sarnat inclusion criteria for moderate stage II HIE (Group A) and 30/57 (52.63%) for severe stage III HIE (Group B). Both groups were assessed and compared for incidence of kidney dysfunction, liver dysfunction, coagulopathy, qualitative cardiac abnormalities, respiratory-related dysfunction, and bone marrow insufficiency/thrombocytopenia. All assessments were performed before initiation of therapeutic hypothermia. The complications were further assessed for the presence of correlations. Group B experienced significantly higher incidence of kidney dysfunction (A: 2/27 [7.4%] vs. B: 21/30 [70%], p < 0.001), liver dysfunction (A: 14/27 [51.8%] vs. B: 28/30 [93.3%], p < 0.001), and thrombocytopenia (A: 8/27 [29.6%] vs. B 21/30 [70%], p = 0.002) in our study group. Kidney dysfunction and bone marrow insufficiency showed the highest affiliation with other organ systems in both groups, correlating positively with each other as well as HIE severity, cardiac abnormalities, liver dysfunction, and infant death. A total of 8/57 (14%) infant deaths were observed, all originating from grade III severe HIE group (p = 0.003). Multiorgan dysfunction showed a significant difference between HIE severity (A: 12/27 [44.4%] vs. B: 28/30 [93.3%], p < 0.001). A positive correlation was obtained between multiorgan dysfunction, HIE severity, and infant death. Stage III HIE infants are more likely to experience abnormalities in the kidneys, liver, bone marrow as compared with stage II HIE infants. Correlations between organ complications are present, and should be taken into account during clinical assessment of HIE infants. The probability of mortality is higher in stage III HIE infants with observed multiorgan dysfunctions.

[The impact of premature rupture of membranes (PROM) on neonatal outcome]. / Wplyw przedwczesnego pekniecia blon plodowych (PROM) na stan noworodka.

OBJECTIVE: The aim of the following study was to evaluate the impact of premature rupture of membranes (PROM) on neonatal outcome, particularly on the incidence of intrauterine infections (IUI). MATERIAL AND METHODS: The study included 428 newborns, born after PROM and hospitalized in the Department of Neonatology at Poznan University of Medical Sciences in 2006. The influence of selected variables on the development of IUI and other complications was analyzed. RESULTS: IUI occurred in 124 newborns (29%). The odds ratio (OR) of IUI incidence increased with decreasing gestational age, birth weight and Apgar score, as well as with increasing duration of the time between PROM and birth, called the latency period. Logistic regression showed that IUI was significantly influenced by the latency period (OR=1.37; 95% CI: 1.10-1.71; p<0.01), gestational age (OR=2.29; 95% CI: 1.59-3.30; p<0.0001) and 5-minute Apgar score (OR=2.50; 95% CI: 1.57-3,98; p<0.001). The incidence of other complications such as prematurity respiratory distress syndrome, respiratory failure, intraventricular hemorrhage, and anemia increased with the duration of the latency period. Compared to uninfected infants, the infected ones were characterized by lower birth weight, lower gestational age, lower Apgar score and poorer laboratory results. CONCLUSIONS: Among neonates born from pregnancies complicated with PROM, the incidence of IUI is significantly influenced by the latency period, gestational age and 5-minute Apgar score. The incidence of other complications increases with the duration of the latency period. Prematurity is an important contributor to morbidity in this group of neonates.

Single nucleotide vitamin D receptor polymorphisms (FokI, BsmI, ApaI, and TaqI) in the pathogenesis of prematurity complications.

The vitamin D receptor (VDR), coded by the VDR gene, plays a pivotal role in executing cellular functions when bound by the active form of vitamin D. Gene polymorphisms in this receptor have been increasingly associated with a heightened state of vulnerability to certain diseases. However, limited data is available concerning the role of VDR gene polymorphisms in preterm infant complications. In 114 premature infants (< 32 weeks gestation) we analyze four single nucleotide VDR polymorphisms (rs2228570 (FokI), rs1544410 (BsmI), rs797532 (ApaI), rs731236 (TaqI)) for their association with respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC) and retinopathy of prematurity (ROP). The results show that BPD was almost four times more likely in infants with the genotype CC of ApaI (rs7975232) (OR 3.845; p = 0.038). While both BPD and NEC were 2.1 times more likely to occur in preterm infants with the allele C of ApaI (rs7975232) (respectively: OR 2.111 and OR 2.129, p < 0.05). The ApaI VDR polymorphism appears to influence incidence of BPD and NEC in preterm infants. Considering VDR polymorphisms in future genetic investigations, in preterm complications, may prove clinically relevant.

Airway concentrations of angiopoietin-1 and endostatin in ventilated extremely premature infants are decreased after funisitis and unbalanced with bronchopulmonary dysplasia/death.

A systemic inflammatory response of the fetus, reflected by histologic funisitis, is a risk factor for bronchopulmonary dysplasia (BPD). Impaired pulmonary angiogenesis accompanied by simplification and rarification of alveoli is a histologic hallmark of BPD. Angiopoietin-1 mediates vascular development, maturation, and stabilization. Endostatin mainly acts as an angiostatic factor. We hypothesized that funisitis was associated with changes of endostatin and angiopoietin-1 concentrations in the airways and that an imbalance between the factors might be associated with BPD or death. We measured concentrations of angiopoietin-1 and endostatin by enzyme-linked immunosorbent assay in tracheobronchial aspirate fluid samples of 42 ventilated preterm infants during postnatal days 1 through 15. The secretory component for IgA served as reference protein. A standardized histologic examination was used to distinguish three groups: chorioamnionitis, funisitis, and controls without inflammation. Concentrations of the mediators steadily decreased. Funisitis was associated with lower concentrations of both proteins, which might impair their physiologic activities in pulmonary angiogenesis. An increase of the ratio angiopoietin-1/endostatin until day 7 of life indicated a shift of the mediators potentially favoring angiogenesis. However, infants, who developed BPD or died, had a decreased ratio on days 1, 3, and 15, suggesting an imbalance toward inhibition of pulmonary angiogenesis.

Systemic fetal inflammation and reduced concentrations of macrophage migration inhibitory factor in tracheobronchial aspirate fluid of extremely premature infants.

OBJECTIVE: Macrophage migration inhibitory factor is a proinflammatory mediator of innate immunity, enhances cell growth, and plays a role in preterm delivery. We speculated that funisitis, reflecting fetal systemic inflammation, would be associated with higher concentrations of macrophage migration inhibitory factor in airways of extremely premature infants. STUDY DESIGN: We measured macrophage migration inhibitory factor by enzyme linked immunosorbent assay in tracheobronchial aspirate fluid of 35 ventilated infants less than 30 weeks' gestational age, throughout the first week of life. Three groups were distinguished histologically: chorioamnionitis, funisitis, and control. RESULTS: Unexpectedly, funisitis was associated with significantly decreased macrophage migration inhibitory factor in tracheobronchial aspirate fluid on day 1 (P < .01) and levels remained lower than in the chorioamnionitis group thereafter. For the 35 patients in total, macrophage migration inhibitory factor steadily declined. CONCLUSION: Decreased macrophage migration inhibitory factor concentrations in airways of extremely premature infants with systemic fetal inflammation early in life might predispose them to pulmonary infection and interfere with maturation of the lung, contributing to adverse pulmonary outcome.