Potential Impact of a Pregnant Woman's Microbiota on the Development of Fetal Heart Defects: A Review of the Literature.

Developments in medicine and biology in recent decades have led to a significant increase in our knowledge of the complex interactions between the microbiota and human health. In the context of perinatal medicine and neonatology, particular attention is being paid to the potential impact of the maternal microbiota on fetal development. Among the many aspects of this relationship, the question of the impact of dysbiosis on the development of fetal heart defects is an important one. In this article, we present an analysis of recent research and scientific evidence on the relationship between a pregnant woman's microbiota and the development of fetal heart defects. We also discuss potential intervention strategies, including the role of probiotics and diet in optimising the maternal microbiota.

Cytomegalovirus Infection in Pregnancy Prevention and Treatment Options: A Systematic Review and Meta-Analysis.

OBJECTIVES: Cytomegalovirus (CMV) infection is a significant health concern affecting numerous expectant mothers across the globe. CMV is the leading cause of health problems and developmental delays among infected infants. Notably, this study examines CMV infection in pregnancy, its management, prevention mechanisms, and treatment options. METHODS: Specifically, information from the Cochrane Library, PUBMED, Wiley Online, Science Direct, and Taylor Francis databases were reviewed along with additional records identified through the register, the Google Scholar search engine. Based on the search, 21 articles were identified for systematic review. RESULTS: A total of six randomized controlled trials (RCTs) were utilized for a meta-analytic review. As heterogeneity was substantial, the random effects model was used for meta-analysis. Utilizing the random-effects model, the restricted maximum likelihood (REML) approach, the estimate of effect size (d = -0.479, 95% CI = -0.977 to 0.019, p = 0.060) suggests the results are not statistically significant, so it cannot be inferred that the prevention methods used were effective, despite an inverse relationship between treatment and number of infected cases. The findings indicated that several techniques are used to prevent, diagnose, and manage CMV infection during pregnancy, including proper hygiene, ultrasound examination (US), magnetic resonance imaging (MRI), amniocentesis, viremia, hyperimmunoglobulin (HIG), and valacyclovir (VACV). CONCLUSIONS: The current review has significant implications for addressing CMV infection in pregnancy. Specifically, it provides valuable findings on contemporary management interventions to prevent and treat CMV infection among expectant mothers. Therefore, it allows relevant stakeholders to address these critical health concerns and understand the effectiveness of the proposed prevention and treatment options.

Impact of Prenatal and Postnatal Diagnosis on Parents: Psychosocial and Economic Aspects Related to Congenital Heart Defects in Children.

Congenital heart defects (CHD) are defects detected both prenatally and after birth. They are the most common congenital defects. Despite advances in diagnosis and treatment, CHD remain an important cause of morbidity and mortality in newborns, which has a great impact on economic aspects. It is crucial to provide a holistic approach to the care of children with CHD, including regular cardiac check-ups, appropriate drug treatment, surgical or cardiac interventions as needed, rehabilitation, psychological support, and education for patients and their families. Parents experience a variety of psychological problems. This article summarizes the influence of CHD in the psychological and economic areas.

Small prenatal diameter of the ascending aorta is associated with increased mortality risk in neonates with congenital diaphragmatic hernia.

Introduction: The aim of this study was to evaluate whether selected prenatal markers obtained from fetal echocardiography can predict postnatal outcome in congenital diaphragmatic hernia (CDH) patients. We also aimed to verify the prognostic value of lung-to-head ratio (LHR). Material and methods: The study group included 29 fetuses with CDH. We analyzed potentially prognostic parameters measured using fetal echocardiography and fetal ultrasound. The assessed parameters were compared between the group of patients with CDH who survived to discharge (n = 21) and the subset of patients who died before discharge from hospital (n = 8). Results: In survivors, mean z-score for ascending aorta (AAo) diameter was 0.23 ±0.98 vs. - 1.82 ±1.04 in patients who died (t-test, p = 0.0015). In survivors, the main pulmonary artery/ascending aorta ratio was 1.22 ±0.17 vs. 1.46 ±0.21 in patients who died (t-test, p = 0.017). In survivors, the LHR was 1.81 ±0.96 vs. 0.95 ±0.6 in patients who died (t-test, p = 0.019). In survivors, the observed to expected LHR was 57 ±30% vs 30 ±18% in patients who died (t-test, p = 0.018). Conclusions: Narrowing of the ascending aorta in CDH fetuses is a poor prognostic factor associated with increased mortality in neonates. Our study also confirmed the prognostic value of LHR.

New Ideas for the Prevention and Treatment of Preeclampsia and Their Molecular Inspirations.

Preeclampsia (PE) is a pregnancy-specific disorder affecting 4-10% of all expectant women. It greatly increases the risk of maternal and foetal death. Although the main symptoms generally appear after week 20 of gestation, scientific studies indicate that the mechanism underpinning PE is initiated at the beginning of gestation. It is known that the pathomechanism of preeclampsia is strongly related to inflammation and oxidative stress, which influence placentation and provoke endothelial dysfunction in the mother. However, as of yet, no "key players" regulating all these processes have been discovered. This might be why current therapeutic strategies intended for prevention or treatment are not fully effective, and the only effective method to stop the disease is the premature induction of delivery, mostly by caesarean section. Therefore, there is a need for further research into new pharmacological strategies for the treatment and prevention of preeclampsia. This review presents new preventive methods and therapies for PE not yet recommended by obstetrical and gynaecological societies. As many of these therapies are in preclinical studies or under evaluation in clinical trials, this paper reports the molecular targets of the tested agents or methods.

The Predictive Value of the CSA Index in the Prenatal Diagnosis of Aortic Coarctation in Ultrasound Examination Performed during the Second Trimester.

BACKGROUND: Aortic coarctation (CoA) is the fourth most common congenital heart defect (8-10%) which occurs at a frequency of about 20-60/100,000 births. Only 22.3% of all cases appears to be diagnosed during the second trimester of pregnancy. Since the detection of prenatal aortic coarctations is very low, every effort should be made to change this situation. According to the authors of this study, the CSAi (carotid to subclavian artery index) could serve as a reliable indicator. MATERIAL AND METHODS: Ninety-six fetuses from healthy, single, pregnancies, with good ultrasound visualization between 18 and 27.5 weeks of gestation, and twenty-three fetuses suspected of aortic coarctation (postnatally confirmed) were included in this study. Our first aim was to compare the current most common method of prenatal CoA diagnosis based on the measurement of the aortic z-score in the aortic isthmus using the method suggested by us-CSAi. RESULTS: Logistic regression coefficients for z-score and CSAi were analyzed as predictors of coarctation occurrence. It appears that 39.4% of coarctation occurrence can be predicted on the basis of the z-score, and 93.5% on the basis of the CSAi. The cut-off value for CSAi in the study group was 0.81 (sensitivity: 95.7%, specificity 99%). Based on the ROC curve analysis, the cut-off value for the carotid to subclavian distance (mm) was determined; the risk of coarctation increased above this value. Based on the Gini index (0.867), this value was set at 2.55 (sensitivity 82.6%, specificity 93.7%). CONCLUSIONS: CSAi measurement is currently the most sensitive method for aortic coarctation detection. For the purpose of our study, this method was applied in diagnostics in the second trimester of pregnancy. This method is easy, reproducible and should be widely introduced into everyday echocardiographic diagnostics of coarctation to minimize the risk of error.

Ultrasonographic Signs of Cytomegalovirus Infection in the Fetus-A Systematic Review of the Literature.

BACKGROUND: congenital cytomegalovirus (cCMV) infection during pregnancy is a significant risk factor for fetal and neonatal morbidity and mortality. CMV detection is based on the traditional ultrasound (US) and MRI (magnetic resonance) approach. METHODS: the present review used the PRISMA protocol for identification of studies associated with CMV infection and sonographic analysis. Various search terms were created using keywords which were used to identify references from Medline, Pubmed, PsycInfo, Scopus and Web of Science. RESULTS: sonographic analysis of the cCMV infection identified several of the key features associated with fetuses. The presence of abnormal patterns of periventricular echogenicity, ventriculomegaly and intraparenchymal calcifications is indicative of CMV infection in the fetus. Hyperechogenic bowels were seen frequently. These results correlate well with MRI data, especially when targeted transvaginal fetal neurosonography was carried out. CONCLUSIONS: ultrasonography is a reliable indicator of fetal anomalies, due to cCMV. Fetal brain and organ changes are conclusive indications of infection, but many of the ultrasonographic signs of fetal abnormality could be due to any viral infections; thus, further research is needed to demarcate CMV infection from others, based on the ultrasonographic approach. CMV infection should always be an indication for targeted fetal neurosonography, optimally by the transvaginal approach.

Emergency cerclage using double-level versus single-level suture in the management of cervical insufficiency (Cervical Occlusion double-level Stitch Application, COSA): study protocol for a multicentre, non-blinded, randomised controlled trial.

INTRODUCTION: Cervical insufficiency accounts for 15% of recurrent pregnancy losses between 16 and 28 weeks of gestation. The aim of the study is to verify the effectiveness of emergency double-level cerclage with vaginal progesterone in cervical insufficiency treatment in terms of the prevention of preterm delivery before 34 weeks of gestation. METHODS AND ANALYSIS: This trial is a multicentre, non-blinded, randomised study with 1:1 allocation ratio. The study is conducted at tertiary perinatal care departments in Poland. It will include patients with cervical insufficiency with the fetal membranes visible in the open cervical canal or protruding into the vagina between 16+0 and 23+6 weeks of pregnancy. They will be randomised into two arms: emergency single-level cerclage with vaginal progesterone or double-level cerclage with vaginal progesterone. All will be administered antibiotics and indomethacin. The primary outcome is the rate of deliveries below 34+0 weeks of gestation, while secondary outcomes include gestational age at delivery, neonatal outcomes, maternal outcomes according to the Core Outcome Set for Evaluation of Interventions to Prevent Preterm Birth and cerclage procedure complications. The planned number of participants according to the power analysis is 78. ETHICS AND DISSEMINATION: The study protocol was written in accordance with the Standard Protocol Items: Recommendations for Interventional Trials statement. It was created according to the requirements of the Declaration of Helsinki for Medical Research involving Human Subject. Ethical approval was obtained from the Ethics Committee of the Centre of Postgraduate Medical Education (no. 1/2022). The study protocol was approved and published by ClinicalTrials.gov (posted on 24 February 2022). All participants gave a written informed consent. After completion of the study its results will be published in a peer-reviewed English language journal. TRIAL REGISTRATION: NCT05268640.

Assessment of fetal thymus size and BMI in pregnant women with diabetes.

OBJECTIVES: The purpose of this study is to demonstrate whether diabetes during pregnancy affects the development of the fetal immune system. The background: evaluation of potential complications in diabetic pregnancy. The objective is evaluation of the significance of a new ultrasound method of thymus size in pregnancies complicated by diabetes. MATERIAL AND METHODS: The analysis was performed with the use of IBM SPSS Statistics 25.0 software. The Mann-Whitney U test was used for comparison of two groups, i.e., diabetic pregnancies and non-diabetic pregnancies, whereas Kruskal-Wallis H test was used to compare multiple groups. A linear regression model was used to determine the correlation between the type of diabetes and fetal thymus size as well as between maternal body mass index (BMI) and fetal thymus size. The significance level α was set at 0.05. RESULTS: A comparison between diabetic and non-diabetic pregnancies was made with the use of Kruskal-Wallis H test. The compared groups included women without gestational diabetes, with pre-gestational diabetes, gestational diabetes managed by diet and gestational diabetes treated with insulin and diet. The analysis revealed significant differences between the compared groups, H (3) = 23.06; p < 0.001; ƞ2 = 0.04. The additional post hoc Dunn's test with Bonferroni correction of the significance level was used to explore specific differences between group means. The results of this detailed analysis indicated that foetuses of diabetic mothers treated with diet had smaller thymus than foetuses of non-diabetic mothers (p = 0.001). Linear regression analysis was used to establish whether maternal BMI (defined as the body mass divided by the square of the body height and expressed in units of kg/m²) affects fetal thymus size. The analysis found no correlation between maternal BMI divided into the following categories: 18.5-24.99 normal weight, 25-29.99 overweight, 30.00-34.99 obese class I, 35.00-39.99 obese class II and ≥ 40.00 very severely obese, and fetal thymus size, b = -1.82; SE = 2.17; t = -0.84; p = 0.405; R2 < 0.01. CONCLUSIONS: Thymus size is statistically smaller in foetuses of diabetic mothers when compared to healthy controls. Overweighted and obese pregnancy is not a factor affecting fetal thymus size.

Association of Single Nucleotide Polymorphisms from Angiogenesis-Related Genes, ANGPT2, TLR2 and TLR9, with Spontaneous Preterm Labor.

In this study, we hypothesized that the changes localized at angiopoietin-2 (ANGPT2), granulocyte-macrophage colony-stimulating factor (CSF2), fms-related tyrosine kinase 1 (FLT1) and toll-like receptor (TLR) 2, TLR6 and TLR9 genes were associated with spontaneous preterm labor (PTL), as well as with possible genetic alterations on PTL-related coagulation. This case-control genetic association study aimed to identify single nucleotide polymorphisms (SNPs) for the aforementioned genes, which are correlated with genetic risk or protection against PTL in Polish women. The study was conducted in 320 patients treated between 2016 and 2020, including 160 women with PTL and 160 term controls in labor. We found that ANGPT2 rs3020221 AA homozygotes were significantly less common in PTL cases than in controls, especially after adjusting for activated partial thromboplastin time (APTT) and platelet (PLT) parameters. TC heterozygotes for TLR2 rs3804099 were associated with PTL after correcting for anemia, vaginal bleeding, and history of threatened miscarriage or PTL. TC and CC genotypes in TLR9 rs187084 were significantly less common in women with PTL, compared to the controls, after adjusting for bleeding and gestational diabetes. For the first time, it was shown that three polymorphisms-ANGPT2 rs3020221, TLR2 rs3804099 and TLR9 rs187084 -were significantly associated with PTL, adjusted by pregnancy development influencing factors.

Sonographic measurement of the fetal pancreas in women with gestational diabetes.

Introduction: Maternal glycemic state is positively correlated with fetal insulin secretion. Randomized control studies have shown that treatment during pregnancy inhibits to some degree this glycemic effect. Our study aimed to assess fetal pancreas size in a population of treated mothers with gestational diabetes. Material and methods: A cross-sectional, prospective observational study was conducted. Pregnant women at 19-36 weeks of gestation with pre-gestational diabetes receiving insulin therapy or with gestational diabetes receiving either insulin or oral hypoglycemic therapy were recruited. The fetal pancreas circumference was measured and compared to the normal reference range. The Z score of the difference between measured and normal predicted mean pancreas circumference, the regression analysis throughout pregnancy, and the correlation between estimated fetal weight centile and pancreas circumference were calculated. Results: Ninety-one women who had gestational diabetes and thirty-four women who had pre-gestational diabetes were included in the study. For both groups, fetal pancreas circumference correlated significantly with abdominal circumference, estimated fetal weight and gestational age. The mean Z score between the predicted pancreas circumference in the group of women diagnosed with gestational diabetes and the predicted pancreas circumference in a normal population peaked at around 24 weeks of gestation (1.1) and decreased gradually afterward to a value of zero at 37 weeks. The mean Z score between the predicted pancreas circumference in the group of women with pre-gestational diabetes and the predicted pancreas circumference in a normal population constantly decreased with duration of pregnancy. It was positive until the 25th week of gestation and then presented negative values towards the term. Conclusions: The presented preliminary data suggest a possible correlation between glycemic control treatment, pancreas size, and gestational age.

Rs868058 in the Homeobox Gene HLX Contributes to Early-Onset Fetal Growth Restriction.

Fetal growth restriction (FGR) is a condition that characterizes fetuses as too small for their gestational age, with an estimated fetal weight (EFW) below the 10th percentile and abnormal Doppler parameters and/or with EFW below the 3rd percentile. We designed our study to demonstrate the contribution of single nucleotide polymorphisms (SNPs) from DLX3 (rs11656951, rs2278163, and rs10459948), HLX (rs2184658, and 868058), ANGPT2 (−35 G > C), and ITGAV (rs3911238, and rs3768777) genes in maternal blood in FGR. A cohort of 380 women with singleton pregnancies consisted of 190 pregnancies with FGR and 190 healthy full-term controls. A comparison of the pregnancies with an early-onset FGR and healthy subjects showed that the AT heterozygotes in HLX rs868058 were significantly associated with an approximately two-fold increase in disease risk (p ≤ 0.050). The AT heterozygotes in rs868058 were significantly more frequent in the cases with early-onset FGR than in late-onset FGR in the overdominant model (OR 2.08 95% CI 1.11−3.89, p = 0.022), and after being adjusted by anemia, in the codominant model (OR 2.45 95% CI 1.23−4.90, p = 0.034). In conclusion, the heterozygous AT genotype in HLX rs868058 can be considered a significant risk factor for the development of early-onset FGR, regardless of adverse pregnancy outcomes in women.

Establishing Reference Ranges for Aldosterone, Renin and Aldosterone-to-Renin Ratio for Women in the Third-Trimester of Pregnancy.

OBJECTIVE: Diagnosis of primary hyperaldosteronism in pregnancy is complicated due to lack of reference ranges for aldosterone, renin and aldosterone-to-renin ratio. We have endeavoured to establish third-trimester reference ranges for the above-mentioned parameters. DESIGN & PATIENTS: We performed postural tests for aldosterone and renin (chemiluminescence immunoassay Liason® DiaSorin Inc., Italy) in 70 healthy pregnant women (age 30.53±4.51 years), at 32.38±4.25 weeks of gestation and in 22 non-pregnant healthy women (age 33.08±8.72 years). RESULTS: Aldosterone reference ranges were 6.51-73.97 ng/dl and 12.33-86.38 ng/dl, for supine and upright positions, respectively and that for renin were 6.25-59.36 µIU/ml and 11.12-82.55 µIU/ml, respectively. Aldosterone and renin concentrations were higher in an upright position (p=0.000459 and p=0.00011, respectively). In contrast, aldosterone-to-renin ratio was not affected by posture (i. e. 0.497-3.084 ng/dl/µIU/ml versus 0.457-3.06 ng/dl/µIU/ml, p=0.12), but was higher (p=0.00081) than in non-pregnant controls. In comparison to manufacturer-provided non-pregnant reference range, supine aldosterone concentrations increased by 556% (lower cut-off) and 313% (upper cut-off), while upright aldosterone concentrations increased by 558% (lower cut-off) and 244% (upper cut-off). The reference range for supine renin concentrations increased by 223% (lower cut-off) and 48.7% (upper cut-off), while upright renin concentrations increased by 253% (lower cut-off) and 79% (upper cut-off). CONCLUSIONS: There is an upward shift in aldosterone and renin reference ranges in the third-trimester of pregnancy accompanied by an increase in an aldosterone-to-renin ratio, that is not influenced by posture. It remains to be established whether the aldosterone-to-renin ratio may be used as a screening tool for primary hyperaldosteronism in pregnancy.

Prenatal exposure to neurotoxic metals and micronutrients and neurodevelopmental outcomes in early school age children from Poland.

Exposure to environmental factors, such as neurotoxic metals and micronutrients, during critical periods of development can contribute to long-term consequences in offspring's health, including neurodevelopmental outcomes. The aim of this study was to evaluate the association between simultaneous prenatal exposure to metals [lead (Pb), cadmium (Cd), mercury (Hg)] and micronutrients [selenium (Se), zinc (Zn), copper (Cu)] and neurodevelopmental outcomes in school-age children from the Polish Mother and Child Cohort (REPRO_PL). Metals and micronutrients concentrations were measured in cord blood (Pb, Cd, Se, Zn, Cu) and in maternal hair (Hg) collected during the 3rd trimester of pregnancy. Behavioral and emotional problems, as well as children's cognitive and psychomotor development, were assessed in 436 school-age children using the Strengths and Difficulties Questionnaire (SDQ, filled in by the mothers) and the Polish adaptation of the Intelligence and Development Scales (IDS, administered by trained psychologists). Multivariate regression models were applied after imputation of missing values, using two approaches: (i) a joint analysis taking into account all metals and micronutrients simultaneously, and (ii) an ExWAS study (single-exposure model). In the SDQ, Hyperactivity/Inattention problems and Total difficulties were associated with higher Hg concentrations in maternal hair (0.18, 95% CI: 0.05; 0.3; and 0.14, 95% CI: 0.01; 0.3, respectively), whereas Emotional symptoms were inversely associated with Se and Zn levels in cord blood (-0.13, 95% CI: -0.3; 0.004; and -0.10, 95% CI: -0.2; 0.02, respectively). In the IDS, cord blood Pb levels were found to be negatively associated with Fluid and Crystallized IQ (-0.12, 95% CI: -0.3; 0.02; and -0.14, 95% CI: -0.3; 0.007, respectively) as well as Mathematical skills (-0.15, 95% CI: -0.3; 0.01). The current research has been able to simultaneously assess the exposure to various interacting chemicals during the prenatal period. We demonstrate that prenatal co-exposures to Pb, Hg, Zn and Se have long-term influences on the neuropsychological outcome of school-age children.

High prevalence of early (1st trimester) gestational diabetes mellitus in Polish women is accompanied by marked insulin resistance - comparison to PCOS model.

INTRODUCTION: Both pregnancy and polycystic ovary syndrome (PCOS) constitute insulin-resistant states that are associated with an increased prevalence of glucose intolerance. Some women demonstrate significant insulin resistance (IR) and develop gestational diabetes (GDM) even in the 1st trimester. We compared surrogate IR indices in 1st-trimester pregnant women and in women with PCOS (Rotterdam consensus criteria). MATERIAL AND METHODS: We performed a 75-g oral glucose tolerance test (OGTT) with insulin measurements in 106 healthy 1st-trimester pregnant women at 9.9 ± 2.6 weeks of gestation and in 418 women with PCOS. We assessed IR (HOMA-IR, QUICKI, Matsuda, Belfiore, and Stumvoll indices) as well as the prevalence of GDM according to the International Association of Diabetes and Pregnancy Study Groups (IADSPG) and World Health Organization (WHO) (1999) criteria. RESULTS: Despite having a slightly lower BMI (p = 0.027), pregnant women had either similar (QUICKI, Belfiore index, Stumvoll0-120 min) or greater IR than women with PCOS (e.g. HOMA-IR 3.85 ± 6.11 vs. 2.64 ± 2.04, p = 0.002), while only the Matsuda index demonstrated less IR in pregnant women (p = 0.003). The correlation between IR indices in pregnant women showed marked variability, ranging from r = 0.334 (HOMA-IR vs. Belfiore index) to r = -1.0 (HOMA-IR vs. QUICKI, p < 0.001). This was accompanied by a high prevalence of GDM (14.2% and 9.4%, IADPSG and WHO criteria, respectively). Women with GDM diagnosed according to IADPSG criteria demonstrated greater IR than pregnant women without GDM. In women with GDM diagnosed according to WHO (1999) criteria these differences were visible only for OGTT-derived IR indices (Belfiore, Matsuda, and Stumvoll0-120 index). CONCLUSIONS: Depending on the choice of IR indices, healthy 1st-trimester pregnant women demonstrate either similar or greater IR than women with PCOS, and this is accompanied by a high prevalence of early GDM. It remains to be established whether GDM screening should be performed in the 1st trimester.

Nomograms of the fetal thymus for clinical practice.

INTRODUCTION: The fetal thymus may be visualized using ultrasonography (USG) and is typically located in the mediastinum. In the past years, the size of the fetal thymus has served not only as a marker of genetic or heart defects but also as a predictive factor for intrauterine growth restriction, premature birth, preeclampsia, chorioamnionitis or even neonatal sepsis. MATERIAL AND METHODS: A total of 410 fetuses were qualified for the study. Fetuses with heart defects were excluded from the study. The fetal thymus was evaluated with ultrasonography between the 14th and 40th week of gestation. After obtaining a standard transverse view encompassing the three great vessels, thymus measurements were attempted, i.e. maximal transverse diameter, circumference and surface area. Linear regression was used for statistical analysis, yielding 3 models, each with a different dependent variable. The confidence interval for each model was set at 80% to aid the comparison with centile grid growth charts for neonates and children. The test was regarded as statistically significant when p < 0.05. RESULTS: From a total of 410 fetuses the thymus transverse diameter, circumference and area were successfully measured in 410, 320 and 330 cases, respectively. The probabilities are lower than 0.0005 for each model, which means that each model is quite statistically significant. CONCLUSIONS: The coverage of healthy thymus nomograms in the fetal population may be the basis for the identification of fetuses at risk of hypoplasia or thymic hyperplasia, which seems particularly important from the point of view of the detection of potential inborn immunological disorders.

Single Nucleotide Polymorphisms from CSF2, FLT1, TFPI and TLR9 Genes Are Associated with Prelabor Rupture of Membranes.

A prelabor rupture of membranes (PROM) and its subtypes, preterm PROM (pPROM) and term PROM (tPROM), are associated with disturbances in the hemostatic system and angiogenesis. This study was designed to demonstrate the role of single nucleotide polymorphisms (SNPs), localized in CSF2 (rs25881), FLT1 (rs722503), TFPI (C-399T) and TLR9 (rs352140) genes, in PROM. A population of 360 women with singleton pregnancy consisted of 180 PROM cases and 180 healthy controls. A single-SNP analysis showed a similar distribution of genotypes in the studied polymorphisms between the PROM or the pPROM women and the healthy controls. Double-SNP TT variants for CSF2 and FLT1 polymorphisms, CC variants for TLR9 and TFPI SNPs, TTC for CSF2, FLT1 and TLR9 polymorphisms, TTT for FLT1, TLR9 and TFPI SNPs and CCCC and TTTC complex variants for all tested SNPs correlated with an increased risk of PROM after adjusting for APTT, PLT parameters and/or pregnancy disorders. The TCT variants for the CSF2, FLT1 and TLR9 SNPs and the CCTC for the CSF2, FLT1, TLR9 and TFPI polymorphisms correlated with a reduced risk of PROM when corrected by PLT and APTT, respectively. We concluded that the polymorphisms of genes, involved in hemostasis and angiogenesis, contributed to PROM.