Single nucleotide polymorphisms (SNPs) localised to the promoter region of the FCN2 gene are known to influence the concentration of ficolin-2 in human serum and therefore potentially have clinical ...associations. We investigated the relationships between SNPs at positions −986 (A > G), −602 (G > A), −64 (A > C) and −4 (A > G) and clinical complications in 501 preterms. Major alleles at positions −986 and −64 and A/A homozygosity for both polymorphisms were less frequent among babies with very low birthweight (VLBW, ≤1500 g) compared with the reference group (OR = 0.24, p = 0.0029; and OR = 0.49, p = 0.024, respectively for A/A genotypes). A lower frequency of G/G homozygosity at position −4 was associated with gestational age <33 weeks and VLBW (OR = 0.38, p = 0.047; and OR = 0.07, p = 0.0034, respectively). The AGAG haplotype was protective for VLBW (OR = 0.6, p = 0.0369), whilst the GGCA haplotype had the opposite effect (OR = 2.95, p = 0.0249). The latter association was independent of gestational age. The AGAG/GGAA diplotype favoured both shorter gestational age and VLBW (OR = 1.82, p = 0.0234 and OR = 1.95, p = 0.0434, respectively). In contrast, AGAG homozygosity was protective for lower body mass (OR = 0.09, p = 0.0155). Our data demonstrate that some FCN2 variants associated with relatively low ficolin-2 increase the risk of VLBW and suggest that ficolin-2 is an important factor for fetal development/intrauterine growth.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The aim of the study was to analyse a panel of 11 sphingolipids in plasma and three blood fractions (platelet-poor plasma, platelets and red blood cells) of women with mild preeclampsia.
We recruited ...21 women between 25-40 weeks gestation with diagnosed mild preeclampsia to the study group and 36 healthy women with uncomplicated pregnancies, who corresponded with the study group according to gestational age, to the control group. To assess the concentration of 11 sphingolipids in the blood plasma and blood fractions, we used ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC/MS/MS).
We showed a significant increase in the concentration of eight sphingolipids in the plasma of women with preeclampsia in comparison to the control group: Sph (p = 0.0032), S1P (p = 0.0289), C20-Cer (p < 0.0001), C18-Cer (p < 0.0001), C16-Cer (p = 0.012), C18:1-Cer (p = 0.003), C22-Cer (p = 0.0071), and C24:1-Cer (p = 0.0085).
We showed that selected sphingolipids, especially C20-Cer and C18-Cer, are totally new factors in the pathomechanism of PE and that these bioactive lipids may play an important role in apoptosis and autophagy.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: There is a growing body of epidemiologic literature reporting associations between atmospheric pollutants and reproductive outcomes, particularly birth weight and gestational duration. ...Objectives: The objectives of our international workshop were to discuss the current evidence, to identify the strengths and weaknesses of published epidemiologic studies, and to suggest future directions for research. Discussion: Participants identified promising exposure assessment tools, including exposure models with fine spatial and temporal resolution that take into account time-activity patterns. More knowledge on factors correlated with exposure to air pollution, such as other environmental pollutants with similar temporal variations, and assessment of nutritional factors possibly influencing birth outcomes would help evaluate importance of residual confounding. Participants proposed a list of points to report in future publications on this topic to facilitate research syntheses. Nested case-control studies analyzed using two-phase statistical techniques and development of cohorts with extensive information on pregnancy behaviors and biological samples are promising study designs. Issues related to the identification of critical exposure windows and potential biological mechanisms through which air pollutants may lead to intrauterine growth restriction and premature birth were reviewed. Conclusions: To make progress, this research field needs input from toxicology, exposure assessment, and clinical research, especially to aid in the identification and exposure assessment of feto-toxic agents in ambient air, in the development of early markers of adverse reproductive outcomes, and of relevant biological pathways. In particular, additional research using animal models would help better delineate the biological mechanisms underpinning the associations reported in human studies.
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BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Ficolin-2 is a serum pattern recognition molecule, involved in complement activation
the lectin pathway. This study aimed to investigate the association of ficolin-2 concentration in cord blood serum ...with complications related to premature birth.
546 premature neonates were included. The concentration of ficolin-2 in cord blood serum was determined by a sandwich TRIFMA method.
genetic variants were analysed with RFLP-PCR, allele-specific PCR, Sanger sequencing or allelic discrimination using TaqMan probes method.
Cord blood serum ficolin-2 concentration correlated positively with Apgar score and inversely with the length of hospitalisation and stay at Neonatal Intensive Care Unit (NICU). Multivariate logistic regression analysis indicated that low ficolin-2 increased the possibility of respiratory distress syndrome (RDS) diagnosis OR=2.05, 95% CI (1.24-3.37), p=0.005. Median ficolin-2 concentration was significantly lower in neonates with RDS than in premature babies without this complication, irrespective of
gene polymorphisms localised to promoter and 3'untranslated regions: for patients born <33 GA: 1471 ng/ml
2115 ng/ml (p=0.0003), and for patients born ≥33 GA 1610 ng/ml
. 2081 ng/ml (p=0.012). Ficolin-2 level was also significantly lower in neonates requiring intubation in the delivery room (1461 ng/ml
1938 ng/ml, p=0.023) and inversely correlated weakly with the duration of respiratory support (R=-0.154, p<0.001). Interestingly, in the neonates born at GA <33, ficolin-2 concentration permitted differentiation of those with/without RDS AUC=0.712, 95% CI (0.612-0.817), p<0.001 and effective separation of babies with mild RDS from those with moderate/severe form of the disease AUC=0.807, 95% CI (0.644-0.97), p=0.0002.
Low cord serum ficolin-2 concentration (especially in neonates born at GA <33 weeks) is associated with a higher risk of developing moderate/severe RDS, requiring respiratory support and intensive care.
•The third trimester placenta expressed all genes encoding RIG-I-like receptors.•The RIG-I and MDA5 expression increased in VSV-infected explants.•The activation of RIG-I/MDA5 by VSV resulted in ...enhanced IFN-β secretion in tissues.•CMV infection had no effect on cytokine production.
A viral infection is detected through germline-encoded pattern-recognition receptors (PRRs) leading to the production of interferons (IFNs) and proinflammatory cytokines. The objective of this study was to investigate the expression of retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) in response to viral infection and the selected cytokine responses in the human term placenta. Placental villi and decidual explants were infected with human cytomegalovirus (CMV) or vesicular stomatitis virus (VSV) and cultured ex vivo to study viral infection. To evaluate DDX58 (RIG-I), IFIH1 (MDA5), and DHX58 (LGP2) expression, quantitative real-time PCR (qRT-PCR) was used. The expression of RLRs was detected by Western blotting. Cytokine and chemokine production, as well as RLR protein levels, were quantified using ELISA. The increased expression of both RIG-I and MDA5 and the enhanced secretion of IFN-ß were observed in response to VSV infection compared to mock-infected tissues. CMV infection resulted in higher transcript levels of DDX58 and IFIH1, while no changes in the cytokine production were observed. Our results indicate that RIG-I and MDA5 are specifically expressed in chorionic villi and deciduae in response to VSV infection. These findings suggest that RLRs may play a key role in pathogen recognition and the immune response against intrauterine viral transmission.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Ficolin-2 is regarded as an important innate immunity factor endowed with both lectin (carbohydrate recognition) qualities and ability to induce complement activation. The aim of this study was to ...investigate the association of the
3'-untranslated region (3'UTR) polymorphisms with ficolin-2 expression and perinatal complications in preterm neonates. The sequencing analysis allowed us to identify six 3'UTR polymorphisms with minor allele frequency (MAF) >1%: rs4521835, rs73664188, rs11103564, rs11103565, rs6537958 and rs6537959. Except for rs4521835, all adhered to Hardy-Weinberg expectations. Moreover, rs6537958 and rs6537959 were shown to be in perfect linkage disequilibrium (LD) with nine other genetic polymorphisms: rs7040372, rs7046516, rs747422, rs7847431, rs6537957, rs6537960, rs6537962, rs11462298 and rs7860507 together stretched on a distance of 1242 bp and very high LD with rs11103565. The 3'UTR region was shown to bind nuclear extract proteins. The polymorphisms at rs4521835 and rs73664188 were found to influence serum ficolin-2 concentration significantly. All polymorphisms identified create (together with exon 8 polymorphism, rs7851696) two haplotype blocks. Among 49 diplotypes (D1-D49) created from rs7851696 (G>T), rs4521835 (T>G), rs73664188 (T>C), rs11103564 (T>C), rs11103565 (G>A) and rs6537959 (T>A), twenty two occurred with frequency >1%. Two diplotypes: D13 (GTTTGT/GGTCGT) and D10 (GTTTGT/GGTCGA), were significantly more frequent among preterm neonates with early onset of infection and pneumonia, compared with newborns with no infectious complications (OR 2.69 and 2.81, respectively; both p<0.05). The minor (C) allele at rs73664188 was associated with an increased risk of very low (≤1500 g) birthweight (OR=1.95, p=0.042) but was associated with the opposite effect at rs11103564 (OR=0.11, p=0.005).
Vitamin D receptor (VDR) is expressed in the placenta and tissues related to the immune system occurrence of various variants of VDR may modify the effects of vitamin D on pregnancy. The aim of this ...study was to evaluate the association between the parturients' Apa1, Taq1, and Bsm1 polymorphisms of the VDR and their combinations and the risk of preterm birth in the Polish population.
Determination of polymorphism for VDR was assayed using the RT-PCR method. 199 Caucasian women at childbirth were qualified:100 patients who had a spontaneous preterm birth and 99 patients who had a term birth.
Three separate genotypes of the Apa1, Taq1, and Bsm1 polymorphisms were detected. No significant differences in the frequency of particular genotypes in the compared groups were found. Some of the genotype combinations were significantly more frequent in the preterm group - the bb/AA/TT genotype (28.0% vs. 10.1%; p = 0.0013) and the BB/aa/tt genotype (14.0% vs. 4.04% p = 0.0277). The Bb/AA/Tt and the BB/Aa/tt genotypes were found only in the control group (16.1% and 7.0% of patients, respectively). The bb/aa/TT was significantly more frequent in the control group (2.0% vs. 11.1%; p = 0,0207). Two genotype combinations reduced the risk of preterm birth - the Bb/AA/Tt genotype by 94% (OR = 0.43, 95% CI: 0.002-0.885, p = 0.041) and the BB/Aa/tt genotype by 98% (OR = 0.029, 95% CI: 0.001-0.838, p = 0.039).
Our result suggests that there may be a relationship between certain VDR genotype combinations and the risk of preterm birth. Further research is needed in order to substantiate this finding.
Short cervical length (SCL) should be defined as cervical length (CL) less than 25 mm between 18 and 22 weeks of gestation. This definition of SCL is fully applicable for singleton pregnancies but is ...not entirely correct for twin pregnancies. So far there are no explicit guidelines on the treatment of twin pregnancy with SCL. The use of progesterone in the treatment of SCL and preterm birth (PTB) prophylaxis is one of the interventions recommended by the Polish Ministry of Health for cervical shortening in singleton pregnancies. In twin pregnancies attention should be paid to the potential benefits of using vaginal progesterone in reduction of neonatal mortality and incidence of neonatal complications in a group of patients with twin pregnancies and CL less than 25 mm or below the 10th percentile for the gestational age, measured between 18 and 22 weeks of gestation. It is still difficult to identify the benefits of using pessaries in the prevention of PTB in twin pregnancies. The usage of pessaries appears to be beneficial only in selected subpopulations of patients with asymptomatic CL less than 25 mm or 10th percentile for gestational age. The use of cervical cerclage in PTB prevention in twin pregnancies is limited to cases where the external cervical dilation is >1 cm and.
We present a rare case of a complication after pessary insertion during pregnancy due to short cervix. A woman in the 35th week of gestation was admitted to the Department of Perinatology due to ...preterm labor. The patient's history revealed cervical pessary insertion during the 29th week of pregnancy due to a cervix of 18 mm in length. Because of threatened preterm labor, the pessary was removed. After pessary removal, a rupture of the cervix was diagnosed. Because of active labor and cervical rupture, a cesarean section was performed and a healthy newborn was delivered. After cesarean section the cervical rupture was sutured. Five days after the operation, the patient underwent surgery again due to a necrotically changed part of the cervix. This part of the cervix was removed. We present this case to emphasize that cervical pessaries can cause serious complications during pregnancy. Clinicians should take this into consideration before qualifying patients for pessary insertion.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK