Prenatal and Neonatal Pulmonary Thrombosis as a Potential Complication of SARS-CoV-2 Infection in Late Pregnancy.

Neonatal venous thrombosis is a rare condition that can be iatrogenic or occur due to viral infections or genetic mutations. Thromboembolic complications are also commonly observed as a result of SARS-CoV-2 infections. They can affect pediatric patients, especially the ones suffering from multisystem inflammatory syndrome in children (MIS-C) or multisystem inflammatory syndrome in neonates (MIS-N). The question remains whether the maternal SARS-CoV-2 infection during pregnancy can lead to thromboembolic complications in fetuses and neonates. We report on a patient born with an embolism in the arterial duct, left pulmonary artery, and pulmonary trunk, who presented several characteristic features of MIS-N, suspecting that the cause might have been the maternal SARS-CoV2 infection in late pregnancy. Multiple genetic and laboratory tests were performed. The neonate presented only with a positive result of IgG antibodies against SARS-CoV-2. He was treated with low molecular weight heparin. Subsequent echocardiographic tests showed that the embolism dissolved. More research is necessary to evaluate the possible neonatal complications of maternal SARS-CoV-2 infection.

A 646C > G (rs41423247) polymorphism of the glucocorticoid receptor as a risk factor for hyperglycaemia diagnosed in pregnancy-data from an observational study.

AIM: Hyperglycaemia diagnosed in pregnancy (HiP) is a serious and frequent complication of pregnancy, increasing the risk for adverse maternal and neonatal outcomes. Investigate whether allelic variations of the glucocorticoid receptor are related to an increased risk of HiP. METHOD: The following polymorphisms of the glucocorticoid receptor (GR) were investigated in the cohort study of N = 197 pregnant women with HiP and N = 133 normoglycemic pregnant controls: 646C > G (rs41423247), N363S (rs6195), ER23/22EK (rs6190, rs6189). RESULTS: A GG variant of the rs41423247 polymorphism was associated with a significantly higher risk for HiP: OR 1.94 (1.18; 3.18), p = 0.009. The relationship remained significant after controlling for maternal age and prepregnancy BMI: OR 3.09 (1.25; 7.64), p = 0.014. CONCLUSIONS: The allelic GG variant of the 646C > G (rs41423247) polymorphism is associated with an increased risk for hyperglycaemia in pregnancy.

The effects of a physical exercise program on fetal well-being and intrauterine safety.

OBJECTIVES: The aim of this study was to evaluate the effects of a supervised physical exercise program on fetal well-being and intrauterine safety. Physical activity is recommended for healthy pregnant women. However, constant evaluation of fetal condition and development is recommended to ensure the safety of the exercise program. MATERIAL AND METHODS: Randomized control trial study design. Sixty-six healthy pregnant women (age 24-35) with singleton gestation were randomly assigned to either an exercise group (EG, n = 34) or a non-active control group (CG, n = 32). The exercise program included 81 sessions (moderate intensity, 3 times per week, 50-60 min/session from weeks 13 to weeks 40/41 of pregnancy). Fetal well-being was assessed in weeks 32 and 37 of pregnancy. The cerebroplacental ratio (CPR) was calculated to evaluate the safety of the exercise program for the fetus. RESULTS: The differences in the CPR ratio measurements between EG and CG groups in week 37 (p < 0.05) were observed. The increase in the CPR ratio was also shown in week 37 of pregnancy in comparison to week 32 (p < 0.01). Moreover, maternal heart rate was significantly lower in the exercise group as measured at 37 weeks (p < 0.05). CONCLUSIONS: The results of this study confirm that regular and supervised exercise program throughout pregnancy does not affect fetal well-being and is safe for the fetus. Additionally, regular physical activity improves maternal physical fitness and cardiac efficiency which might aid at preparing pregnant women for natural labor.

The role of visfatin in pathogenesis of gestational diabetes (GDM).

Gestational diabetes (GDM) is defined as a glucose intolerance of varying severity with onset or first recognition during pregnancy. Two major metabolic disorders: insulin resistance and ß-cells dysfunction, play currently major role in pathogenesis of GDM. Adipose tissue is an organ involved in production of adipokines, which have various influence on metabolism of glucose and lipids. Visfatin is an adipokine mainly produced and secreted by the fat tissue. It exerts an insulin-like effect by binding to the insulin receptor-1 and have hypoglycemic effect. Visfatin appears to be an important factor in the pathophysiology of GDM. The aim of this article is to review the literature concerning the relationship between the adipokine mentioned above and GDM, and to clarify its role in the pathophysiology of GDM.

An observational study of the risk of neonatal macrosomia, and early gestational diabetes associated with selected candidate genes for type 2 diabetes mellitus polymorphisms in women with gestational diabetes mellitus.

OBJECTIVES: 1) to analyse the prevalence of selected candidate genes for type 2 diabetes mellitus polymorphisms (IRS1 G972R; ENPP1 K121Q; ADRB3 W64R) among women with gestational diabetes; and 2) to investigate any association between variants of these genes and risk of neonatal macrosomia. MATERIAL AND METHODS: We conducted a prospective observational study of a group of women (N = 140) in singleton pregnancies who delivered at term. Characteristics of the study group at enrolment: age: 32.0 ± 4.9 years; GA: 26.6 ± 7.5 weeks; HbA1c: 5.6 ± 0.6%; fasting blood glucose: 102.3 ± 16.3 mg/dL; insulin treatment (G2DM): 65.7%; chronic hypertension: 11.4%; gestational hypertension: 17.9%; preeclampsia: 1.4%; birth weight: 3590 ± 540 g; birth weight ≥ 4000 g (macrosomia): 18.6%; caesarean section: 44.3%; and female newborns: 57.1%. RESULTS: The maternal metabolic characteristics at the time of booking did not differ between polymorphisms. Macrosomia was insignificantly more frequent in females (22.5%) than in males (13.3%) (p = 0.193). Only maternal height and body weight at the time of booking significantly predicted birth weight (R = 0.27, p = 0.007; R = 0.25, p = 0.005, respectively). IRS1 G972R GR and ENPP1 K121Q KQ polymorphisms were associated with an insignificantly increased risk for macrosomia. Carriers of the heterozygotic variant of the IRS 1 gene were significantly more likely to be diagnosed with GDM/DiP in the first trimester: OR 5.2, 95% CI: 1.4; 19.2; p = 0.014. CONCLUSIONS: 1) having similar metabolic characteristics, carriers of specific variants of T2DM candidate genes might be at increased risk of delivery of macrosomic newborns; 2) any association between genetic variants and macrosomia in this population might be gender-specific; and 3) allelic variation in the IRS1 gene is associated with early GDM/DiP.

Ballantyne Syndrome (Mirror Syndrome) associated with severe non-immune fetal hydrops--a case report.

OBJECTIVES: The aim of the study was to present a case of rapidly progressing non-immune fetal hydrops (NIHF) of unknown etiology in a normal-karyotype fetus, accompanied by severe maternal edema, anemia, and hypoproteinemia. After the differential diagnosis, Ballantyne Syndrome (BS, Mirror Syndrome) was diagnosed. MATERIAL AND METHODS: We present a case of a 31-year-old multipara at 22/24 weeks of pregnancy presenting severe symptoms of non-immune fetal hydrops: subcutaneous edema, hydrothorax, ascites and placental edema associated with maternal edema, anemia and hypoproteinemia. After cardiovascular infectious, immune and morphological causes were excluded, amniocentesis was performed and confirmed normal female 46, XX karyotype. Since 22 weeks of pregnancy increasing maternal edema and anemia were observed. No hematological, cardiac or nephrological causes of this condition were found. RESULTS: At 24 weeks of pregnancy intrauterine fetal demise was diagnosed and surgical evacuation (cesarean section) of the fetus was performed. Resolution of maternal edema, anemia, and hypoproteinemia was observed shortly after the delivery. CONCLUSIONS: Based on our findings, it seems safe to conclude that BS may develop in pregnancy complicated by NIHF of unknown origin.

[The impact of metabolic control on uteroplacental circulation parameters in pregnancies complicated by gestational hypertension and/or preeclampsia in pregnant women with pregestational diabetes]. / Wplyw wyrównania metabolicznego na parametry krazenia maciczno-lozyskowego w ciazy powiklanej nadcisnieniem ciazowym i stanem przedrzucawkowym u ciezarnych z cukrzyca przedciazowa.

OBJECTIVES: The aim of the study was to evaluated the impact of metabolic control in pregnant women with PGDM on uteroplacental circulation parameters during pregnancy. MATERIAL AND METHODS: The study group included 141 pregnant women divided into 3 subgroups: PE + GH group (n = 16)--woman suffering from PGDM, with superimposed PE or GH, the PGDM group (n = 84)--women suffering from PGDM without hypertension, and the control group--41 healthy women in uncomplicated pregnancy. All participants were monitored for metabolic control and uteroplacental circulation parameters during pregnancy. The survey was completed after the data from the perinatal period were collected. RESULTS: The differences between the uterine artery pulsatility index (Pi UtA) in the first trimester of pregnancy expressed as a multiple of the median (MoM), were not statistically significant between the groups (p ≥ 0.42). Also, no statistically significant differences were observed between the groups Pi UtA in the second (p ≥ 0.33) and third trimester of pregnancy (p = 1.0). The rate of fetal growth was comparable in all groups. Infant birth weight percentile in the study groups did not differ statistically (p ≥ 0.15). CONCLUSIONS: Tight metabolic control during pregnancy in women suffering from PGDM allows to obtain blood flow in the uteroplacental circulation which is comparable to their healthy pregnant peers.

Concentrations of eNOS, VEGF, ACE and PlGF in maternal blood as predictors of impaired fetal growth in pregnancy complicated by gestational hypertension/preeclampsia.

OBJECTIVES: To investigate into an association between circulating levels of vascular factors (VF: ACE, eNOS, PlGF and VEGF) and impaired fetal growth measured as a small for gestational age newborn (SGA) in women with gestational hypertension/preeclampsia. METHODS: A prospective observational trial in 46 patients in singleton pregnancies. Concentrations of VF were compared between participants who delivered SGA versus non-SGA newborns. RESULTS: only low levels of ACE were associated with significantly increased risk for SGA (for a cut-off value, LR: 1.4-3.6). CONCLUSIONS: Circulating levels of VF are not sufficient predictors of SGA in pregnancies complicated by gestational hypertension/preeclampsia.

Maternal serum placental growth factor and fetal SGA in pregnancy complicated by type 1 diabetes mellitus.

AIM: To analyze the role of maternal placental growth factor (PlGF) in the prediction of small for gestational age (SGA) birth weight in pregnancy complicated by type 1 diabetes mellitus (T1DM). METHODS: A prospective observational study on 59 normotensive T1DM pregnant women, assessing maternal PlGF concentrations between the 10th-14th and 22nd-25th weeks of gestation. RESULTS: Number of SGA vs. non-SGA newborns was 11 (18.6%) vs. 48 (81.4%), respectively. First trimester PlGF serum concentrations (pg/mL) were similar between SGA vs. non-SGA groups [data given as median (interquartile range)]: 65.5 (35.58-159.20) vs. 68.23 (11.59-150.03), respectively; P=0.44. A trend for lower PlGF concentrations was observed in the second trimester in the SGA vs. non-SGA group: 63.34 (12.79-119.16) vs. 116.75 (33.93-235.82); P=0.07. In the SGA group, PlGF concentrations did not differ between the first and the second trimester: 65.5 (35.58-159.20) vs. 63.34 (12.79-119.16), respectively; P=0.36. In the non-SGA group, PlGF concentrations were significantly higher at the gestational age of 22-25 weeks compared to 10-14 weeks [116.75 (33.93-235.82) vs. 68.23 (11.59-150.03); P=0.03). CONCLUSIONS: Decreased PlGF serum concentration in mid-pregnancy, as well as a lack of physiological increase in PlGF levels between early and mid-gestation, may precede development of SGA in women with T1DM.

[The influence of single nucleotide polymorphisms of endothelial nitric oxide synthase and angiotensin-converting enzyme on the course of pregnancy complicated by type 1 diabetes]. / Wplyw polimorfizmów pojedynczych nukleotydów (SNP) sródblonkowej syntazy tlenku azotu (eNOS) oraz konwertazy angiotensyny (ACE) na przebieg ciazy powiklanej cukrzyca typu 1.

AIM: to study the frequency of genetic variants of eNOS and ACE polimorphism and their possible influence on the course of diabetic pregnancy and perinatal outcome. MATERIAL AND METHODS: 107 pregnant women with type 1 diabetes, treated at the Department of Obstetrics and Women's Diseases between 2008-2011, were enrolled into the study. Ninety six (90%) of the patients delivered at term. All women were treated with intensive insulin therapy Glucose control was performed by means of self-monitoring with glucometers. The target fasting glucose levels were below 90 mg/dl (5.0 mmol/l) and postprandial below 120 mg/dl (6.7 mmol/I). DNA for the analysis of polimorphisms was extracted from the leukocytes. Afterwards, the number of specific eNOS and ACE genotypes was calculated and the subgroups of alleles of these two genes were created. RESULTS: Subjects with heterozygote genotype eNOS GT and ACE ID constituted the largest group of patients (24/22%); the smallest group presented eNOS TT (ACE II, ID, DD) genotype (8/8% of the whole studied group). Next, selected genotypes were analyzed in relation to the metabolic status, duration of diabetes and perinatal outcome. RESULTS: Our results enabled us to conclude that, despite identical treatment of all gravidas, diabetic patients with eNOS TT polimorphism presented with the highest body weight, and the strongest lipid and glucose disturbances, what probably resulted in marosomic neonatal weight. CONCLUSIONS: The eNOS and ACE genetic variants may affect the course of a diabetic pregnancy in terms of metabolic control and perinatal outcome.

Multiple daily injections of insulin versus continuous subcutaneous insulin infusion for pregnant women with type 1 diabetes.

AIMS: The aim was to evaluate the outcome of pregnancies with type 1 diabetes (T1DM) treated from the first trimester with continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI). METHODS: In a retrospective, observational study, we matched 64 CSII patients for age, age at onset and duration of diabetes and HbA1c in the first trimester with 64 MDI pregnancies. We analysed carbohydrate metabolism, insulin requirements, development of PIH, progression of retinopathy and fetal outcome. RESULTS: In CSII group, we found a significantly smaller insulin requirement both at the beginning of pregnancy and before delivery, significant decrease in HbA1c levels and significantly smaller number of hypoglycaemic episodes in the second trimester and significantly more hyperglycaemic episodes in the first trimester. In both groups, maternal, fetal and perinatal outcomes were similar and the number of hypo- and hyperglycaemic episodes decreased throughout pregnancy. CONCLUSION: Continuous subcutaneous insulin infusion (CSII) treatment in pregnant women with type 1 diabetes is associated with a reduced number of hypoglycaemia and decreased insulin requirement. We noted no difference in perinatal outcome comparing women on multiple insulin injections with those on continuous insulin infusion.

[The influence of metabolic parameters on fetal development weight in women with type 1 diabetes and homozygotic variant in -2548 G/A of leptin gene and its 668 A/G receptor polymorphism]. / Wplyw czynników metabolicznych na wzrastanie plodu u ciezarnych z cukrzyca typu 1 oraz wariantem homozygotycznym polimorfizmu -2548 G/A genu leptyny i 668 A/G receptora leptyny.

INTRODUCTION: Leptin, as many other hormones and metabolic factors, may play a role in fetal development in pregnancy complicated by type 1 diabetes. Different genetic variants in leptin gene and leptin gene receptor may have influence on leptin synthesis in the course of pregnancy and metabolic state of the mother. AIM: To assess the possible influence of metabolic factors on fetal weight in type 1 diabetic subjects with homozygotic variants in leptin gene (-2548 G/A) and leptin gene receptor (668 G/A). METHODS: 30 diabetic and homozygotic subjects (out of 100 diabetic subjects) were qualified to the study Genotyping was performed by PCR-RFLR The following factors were assessed: glycemia, leptin concentration, glycated hemoglobin, lipid profile (total cholesterol, LDL, HDL, triglycerides), maternal body weight. Multiple regression models were developed and ROC curves were used in the analysis. RESULTS: Mean fetal weight in the analyzed group was 3600 g. The following parameters were found to have influence on fetal weight: I trimester leptin (R2-0.80741288, p < 0.05), I trimester glycemia (R2-0.80741288, p < 0.05), III trimester glycemia (R2-0.80741288, p < 0.05), I trimester HbA1C (R2-0.80741288, p < 0.05), III trimester LDL (R2 = 0.63192254, p < 0.05). Moreover the influence of LDL and maternal BMI (R2-0.81869348, p < 0.05) was found. ROC curve analysis revealed the influence of I trimester leptin--AUC 0.62; sensitivity 0.75; specificity 0.5; cut-off 28.127 ng/ml, III trimester HbA1C AUC 0.66; sensitivity 0.23; specificity 0.91; cut-off 7.9%, III trimester mothers weight AUC 0.63; sensitivity 0.25; specificity 0.93; cut-off 98 kg. CONCLUSION: Apart from well-known metabolic factors influencing fetal weight, I trimester leptin concentration was found to have an impact on fetal growth.

[Thanatoforic dysplasia--case report]. / Dysplazja tanatoforyczna u plodu--opis przypadku.

The case report presents a prenatal diagnosis of a fetus with thanatophoric dysplasia. Characteristic features in this syndrome are: extremely short limbs with curved thigh bones, narrow chest, enlarged abdomen, prominent forehead, dysmorphic face, macrocephaly polihydramnion. The malformation results from the mutation in fibroblast growth factor receptor gene (FGFR-3) which is located in chromosome 4. TD is considered to be an autosomal dominant but most cases are caused by new mutations in the FGFR-3 gene. The prognosis in this malformation is extremely poor. The article presents ultrasound and additional investigations which might be useful in differential diagnosis.

Leptin gene, leptin gene receptor polymorphisms and body weight in pregnant women with type 1 diabetes mellitus.

UNLABELLED: Leptin, as well as many other hormones, may play an important role in the pathogenesis of obesity. Several genetic variants of both leptin and its receptor genes may influence human body weight AIM: To investigate the role of leptin gene polymorphism promotion region (-2548G/A) and leptin gene receptor polymorphism (668 A/G) in regulation of body weight in the group of women with type 1 diabetes (PGDM-1). METHODS: 78 PGDM-1 first trimester pregnant women were qualified for the study group (SG). They were divided into normal and overweight subgroups, based on pre-pregnancy BMI. Control group (CG) consisted of first trimester healthy pregnant women with normal pre-pregnancy body weight Genetic variants of leptin gene and its receptor were analyzed with the help of PCR-RFLP assays. In the SG, the following metabolic parameters were estimated: MBG, HbA1c, insulin dose, LDL, HDL, T-CHOL, triglycerids, creatinine, creatinine clearance and blood pressure. RESULTS: A tendency for the majority of homozygous A and G variants in LEP -2548 G/A and LEPR 668 A/G was found in overweight and obese patients, in comparison to normal-weight subjects. No specific differences in selected first trimester metabolic parameters were found in relation to patients' genotypes in the diabetic group.

[The (-2548G/A) polymorphism of leptin gene in women with gestational hypertension and preeclampsia]. / Polimorfizm (-2548G/A) genu leptyny u kobiet z nadcisnieniem ciazowym oraz preeklampsja.

INTRODUCTION: Leptin is a polypeptide hormone (167 amino acids, molecular weight of about 16kDa), synthesized mainly in white adipose tissue. The hormone plays an important role in regulation of hunger and satiety processes, in metabolism of carbohydrates and fats, development of cardio-vascular diseases and obesity. The occurrence of the increased level of leptin in pregnant women with hypertension, especially in women with preeclampsia, has also been brought to our attention. In recent years it has been suggested that the presence of different variants of leptin and leptin receptor genes may modify the leptin level in serum, and, in this way, influence an increased risk of obstetric complications, such as preeclampsia or eclampsia. MATERIALS AND METHODS: We have analyzed a group of 103 hypertensive pregnant women--61 women with gestational hypertension (GH) and 42 women with preeclampsia (PE). The control group consisted of 113 healthy pregnant women who have been investigated. Gestational hypertension and preeclampsia were recognized with the help of and assessed according to the ACOG criteria. The (-2548G/A) polymorphism was determined using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP). RESULTS: In our study, a higher frequency of mutated AA genotype in GH group and PE groups (21.31% and 21.43% respectively vs. 16.81% in the controls) and the overrepresentation of mutated A allele in both analyzed groups (47.54% and 45.24% respectively vs. 41.59% in the controls) have been observed, without statistically significant differences. CONCLUSIONS: The overrepresentation of AA genotypes and higher frequency of mutated A allele of (-2548G/A) polymorphism of leptin gene in GH and PE groups might indicate its possible contribution in gestational hypertension and preeclampsia.

[Leptin, leptin gene, leptin gene receptor polymorphisms and pregnancy]. / Leptyna, polimorfizmy genu leptyny i jej receptora a ciaza.

The article presents information about leptin as the major metabolic hormone. The structure, localization of the hormone and its receptor have been described focusing on maturation and fertility processes. Several polymorphisms of leptin gene and its receptor have been described as potential developmental factors of pregnancy complications such as diabetes mellitus or pregnancy induced hypertension.