A rare case of a live abdominal pregnancy in a woman with subsequent gestation in utero.

This report concerns now 40-year-old healthy woman who was born alive and healthy from an ectopic pregnancy in the abdominal cavity, with placental localization on the omentum. This was a historical case report 40 years ago, as at that time doctors had little information about similar case in the world. Even today, in the era of modern medicine, we find only rare cases where a child developed outside the uterine cavity is born healthy and without developmental deformities. The mother subsequently had a normal intrauterine pregnancy 2 years later, ending with a caesarean section and the birth of a healthy boy.

Proactive approach at the limits of viability improves the short-term outcome of neonates born after 23 weeks' gestation.

OBJECTIVE: The aim of this single-center study was to identify factors that affect the short-term outcome of newborns delivered around the limits of viability. METHODS: A group of 137 pregnant women who gave birth between 22+0/7 and 25+6/7 weeks of gestation was retrospectively studied. The center supports a proactive approach to infants around the limits of viability. Perinatal and neonatal characteristics were obtained and statistically evaluated. RESULTS: A total of 166 live-born infants were enrolled during a 6-year period; 162 (97.6%) of them were admitted to the neonatal intensive care unit (ICU) and 119 (73.5%) survived until discharge. The decrease in neonatal mortality was associated with an advanced gestational age (P<0.001) and a completed course of corticosteroids (P=0.002). Neonatal morbidities were common among infants of all gestational ages. The incidence of severe intraventricular hemorrhage significantly depended on gestational age (P<0.001) and a completed course of corticosteroids (P=0.002). Survival without severe neonatal morbidities was 39.5% and occurred mostly after 24+0/7 weeks of gestation. CONCLUSION: The short-term outcome of newborns delivered around the limits of viability is mostly affected by gestational age and antenatal corticosteroid treatment. A consistently proactive approach improves the survival of infants at the limits of viability. This is most pronounced in cases where the delivery is delayed beyond 24 completed gestational weeks.

A Comprehensive Evaluation of Steroid Metabolism in Women with Intrahepatic Cholestasis of Pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is a common liver disorder, mostly occurring in the third trimester. ICP is defined as an elevation of serum bile acids, typically accompanied by pruritus and elevated activities of liver aminotransferases. ICP is caused by impaired biliary lipid secretion, in which endogenous steroids may play a key role. Although ICP is benign for the pregnant woman, it may be harmful for the fetus. We evaluated the differences between maternal circulating steroids measured by RIA (17-hydroxypregnenolone and its sulfate, 17-hydroxyprogesterone, and cortisol) and GC-MS (additional steroids), hepatic aminotransferases and bilirubin in women with ICP (n = 15, total bile acids (TBA) >8 µM) and corresponding controls (n = 17). An age-adjusted linear model, receiver-operating characteristics (ROC), and multivariate regression (a method of orthogonal projections to latent structure, OPLS) were used for data evaluation. While aminotransferases, conjugates of pregnanediols, 17-hydroxypregnenolone and 5ß-androstane-3α,17ß-diol were higher in ICP patients, 20α-dihydropregnenolone, 16α-hydroxy-steroids, sulfated 17-oxo-C19-steroids, and 5ß-reduced steroids were lower. The OPLS model including steroids measured by GC-MS and RIA showed 93.3% sensitivity and 100% specificity, while the model including steroids measured by GC-MS in a single sample aliquot showed 93.3% sensitivity and 94.1% specificity. A composite index including ratios of sulfated 3α/ß-hydroxy-5α/ß-androstane-17-ones to conjugated 5α/ß-pregnane-3α/ß, 20α-diols discriminated with 93.3% specificity and 81.3% sensitivity (ROC analysis). These new data demonstrating altered steroidogenesis in ICP patients offer more detailed pathophysiological insights into the role of steroids in the development of ICP.

Diagnostic and prognostic value of presepsin in preterm deliveries.

PROBLEM: To evaluate the association between serum presepsin (soluble CD14 antigen subtype, sCD14-ST) levels soon after the appearance of signs of preterm delivery and preterm delivery within 48 h, before the 34th and 37th gestational weeks and the possible additional value of concurrently evaluated ultrasound vaginal cervicometry with serum presepsin measurement. METHODOLOGY: A total of 60 females were included. Serum presepsin was measured by a chemiluminescent immunoassay. Sonographic evaluation of cervical length in all females was conducted by transvaginal ultrasound. RESULTS: Patients who delivered within 48 h after analysis showed significantly higher presepsin concentrations compared to females with later deliveries. Higher presepsin was proven also for deliveries before/after weeks 34 and 37. A combined finding of cervical length shortening below 18 mm and presepsin level increasing above 623.5 pg/mL could point to the significantly high risk of preterm delivery. CONCLUSION: Elevated maternal serum concentration of sCD14-ST could be an independent and relevant risk factor for preterm delivery.

Low levels of circulating T-regulatory lymphocytes and short cervical length are associated with preterm labor.

Recent discoveries suggest that T-regulatory lymphocytes (Treg) might play an important role in the pathophysiology of preterm labor. The aim of this study was to assess the relationship among the levels of maternal circulating Treg cells, uterine cervical length, and the risk of preterm labor. Sixty women with regular contractions and/or cervical incompetence at 24-32 weeks' gestation were recruited into a prospective study. Each patient underwent transvaginal ultrasound examination of the cervical length, and regulatory T cells were quantified in peripheral blood samples by flow cytometry. Patients with cervical incompetence were prescribed vaginal progesterone until birth. Measurements of Treg levels and cervical length correlated with the timing of labor. The risk of preterm labor happening within 48 h of testing was demonstrated to be almost 35 times higher (OR=35.21, CI 13.3; 214, p<0.001) in the group with simultaneously low Treg values (<0.031 × 10(9)/L) and a shortened uterine cervix (<17.5mm), compared with the situation where both of these values were normal. Similar results were found in predicting preterm delivery before 34 weeks, or between 34 and 37 weeks. A statistically nonsignificant trend toward increased cervical length and increased Treg count was noted in the women on progesterone treatment. We show for the first time that the combined assessment of Treg cell count and cervical length is a much better predictor of preterm delivery than either parameter used on its own. This combined approach may offer clinical application in patients who present with risk factors for preterm labor.

Receptor for advanced glycation end products (RAGE) and glyoxalase I gene polymorphisms in pathological pregnancy.

OBJECTIVES: The aim of the study was to analyze polymorphisms of receptor for advanced glycation end products (RAGE) gene, and glyoxalase I gene and soluble RAGE, sRAGE, in physiological and pathological pregnancy. DESIGN AND METHODS: Polymorphisms of RAGE gene (-429 T/C, -374 T/A, 557 G/A, 2184 A/G) and glyoxalase I gene (A419C) and sRAGE serum levels were determined in 284 women with pathological and physiological pregnancy. RESULTS: No differences in distribution of genotype and allelic frequencies of studied polymorphisms were found. GA genotype of RAGE 557 G/A polymorphism (known as Gly82Ser) is associated with lower sRAGE serum levels in healthy pregnant women compared to GG genotype (483 ± 104 vs. 692 ± 262 pg/mL, p=0.008). sRAGE correlates negatively with ALT in patients with pregnancy intrahepatic cholestasis (r=-0.536, p=0.05). CONCLUSIONS: We did not show any association of RAGE and glyoxalase I gene polymorphisms with pathological pregnancy, however further studies are needed to confirm the results.

Association of pregnancy-associated plasma protein A polymorphism with preeclampsia - a pilot study.

OBJECTIVES: The aim of the study was to investigate genetic and biochemical background of PAPP-A (pregnancy-associated plasma protein A) in patients with risk pregnancies. DESIGN AND METHODS: Five PAPP-A gene polymorphisms and PAPP-A maternal serum levels were studied together in 165 women in third trimester pregnancies complicated with threatening preterm labor (n=98), preeclampsia (n=35), intrauterine growth restriction (n=34) and ICP (intrahepatic cholestasis of pregnancy) (n=15). 114 healthy pregnant women served as controls. RESULTS: Preeclamptic patients had significantly higher frequency of TT genotype of Cys327Cys polymorphism compared to controls (p<0.01). Patients with ICP had increased serum levels of PAPP-A compared to controls and correlation analysis showed significant relationship between PAPP-A and CRP (C-reactive protein) in the patients with intrauterine growth restriction (r=0.49, p=0.007). CONCLUSION: Our study indicates the association of TT genotype of Cys327Cys polymorphism of the PAPP-A gene with preeclampsia. However, further study with larger groups of preeclamptic patients is needed to confirm our results.

Low maternal serum matrix metalloproteinase (MMP)-2 concentrations are associated with preterm labor and fetal inflammatory response.

OBJECTIVES: to assess the relationship between maternal and umbilical serum concentrations of matrix metalloproteinases (MMP)-2,8,9, the soluble receptor for advanced glycation end products (sRAGE) and IL-10 and premature delivery and fetal inflammation. METHODS: maternal serum levels of MMPs, sRAGE, IL-10 and C-reactive protein (CRP) were determined in 67 women with preterm labor and in 38 healthy pregnant women of similar gestational age (GA). In the group with preterm labor we also determined umbilical concentrations of MMPs, IL-6 and sRAGE. The group with preterm labor was additionally divided based on the presence of funisitis and elevations of fetal umbilical IL-6 concentrations. RESULTS: maternal serum levels of MMP-2 and sRAGE were significantly lower in women with preterm labor compared to women with normal pregnancy. Additionally, within the group of women with preterm labor, maternal serum MMP-2 concentrations were significantly lower in the subgroup with funisitis and in the subgroup with elevated umbilical concentration of IL-6. CONCLUSION: our results demonstrate significantly different serum concentrations of MMP-2 and sRAGE in women with preterm labor compared to healthy pregnant patients of the same GA.

Soluble receptor for advanced glycation end products in physiological and pathological pregnancy.

OBJECTIVE: The receptor for advanced glycation end products, RAGE, has been implicated in pathogenesis of many diseases. Soluble RAGE, sRAGE, extracellular domain of RAGE, is new biomarker. The aim of the study was to determine sRAGE levels in physiological pregnancy and their changes in pregnancies complicated by preterm labor or preeclampsia. DESIGN AND METHODS: Serum levels of sRAGE were determined in 79 healthy pregnant women, 42 pregnant women in preterm labor or with preeclampsia and 24 non-pregnant controls. RESULTS: sRAGE serum levels are decreased in physiological pregnancy compared to healthy non-pregnant controls (p<0.001). Serum sRAGE concentrations are higher in the 2nd trimester of physiological pregnancy, compared to the 1st and 3rd trimesters of pregnancy (p<0.001). sRAGE levels in women with preterm labor are decreased (p<0.05) and correlate negatively with the leukocyte count (r=-0.47, p<0.05). In women with preeclampsia, sRAGE is elevated (p<0.05) and correlates with serum creatinine concentration (r=0.54, p<0.05) and with uric acid concentration (r=0.51, p<0.05). CONCLUSION: Our results clearly demonstrate significant differences in serum sRAGE levels in physiological pregnancy and in pathological states in pregnancy, however, further studies are required demonstrate the usefulness and significance of sRAGE.

Detection of feto-maternal infection/inflammation by the soluble receptor for advanced glycation end products (sRAGE): results of a pilot study.

OBJECTIVE: The receptor for advanced glycation end products, RAGE, plays an important role in the pathogenesis of several diseases. sRAGE, soluble receptor for advanced glycation end products, is an inhibitor of the pathological effect mediated via RAGE. The aim of this study was to assess the usefulness of measuring sRAGE concentration in pregnant women with threatening preterm labor. METHODS: Serum levels of sRAGE, interleukin-6 (IL-6) and routine markers of inflammation were determined in 46 pregnant women with threatening preterm labor, 35 healthy pregnant women and 15 non-pregnant controls. RESULTS: Serum levels of sRAGE in healthy pregnant women were significantly lower than in non-pregnant controls (669+/-296 vs. 1929+/-727 pg/mL, P<0.05). Women with threatening preterm birth had a significantly higher concentration of serum sRAGE in comparison with healthy pregnant women (819+/-329 pg/mL vs. 669+/-296 pg/mL, P<0.05). Conversely, patients with PPROM had significantly lower levels of sRAGE compared with patients with threatening premature labor (600+/-324 pg/mL, P<0.05). sRAGE correlated negatively with leukocyte counts (r=-0.325, P<0.05). CONCLUSIONS: sRAGE might be a new and promising marker of premature labor, especially with the symptoms of PPROM.

Conducting labor in women with previous caesarean section in a low gestational week. A prospective case-controlled study.

AIMS: To assess whether vaginal labor after a previous caesarean section in a low gestational week performed by means of a high placed U-section technique could be recommended by obstetricians as a sufficiently safe method of choice for pregnant women. METHODS: Of 309 pregnant women with a history of a high placed U-section, 166 (53.7%) met the criteria for the subsequent vaginal delivery and agreed with it. In 78%, vaginal labor started spontaneously and in 22% it was induced due to postterm pregnancy or preterm rupture of membranes. RESULTS: Vaginal labor was successful in 72.3% of women. Deliveries after spontaneous onset of uterine contractions (80%) were considerably more successful. In the group of women with induced labor, the success rate was below 50%. Uterine rupture was not encountered in the study group. CONCLUSIONS: Vaginal labor after a previous high placed U-section is a sufficiently safe method of choice for selected groups of pregnant women, but it has to be mentioned that selecting criteria can only minimize and not entirely exclude the risk of uterine rupture.

Neuroactive pregnanolone isomers during pregnancy.

The pregnanolone isomers (PI) allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one), isopregnanolone (3beta-hydroxy-5alpha-pregnan-20-one), epipregnanolone (3beta-hydroxy-5beta-pregnan-20-one), progesterone, and estradiol were measured in 138 pregnant women. The sampling was carried out from the first through the 10th month of pregnancy. Gas chromatography-mass spectrometry analysis and RIA were used for the measurement of steroid levels. The ratios of individual PI were similar to those found previously around parturition: about 25:10:7:1 for allopregnanolone, pregnanolone, isopregnanolone, and epipregnanolone, respectively. All the PI showed a significant increase during pregnancy, which was more pronounced in the 3alpha-steroids. The results indicated changing ratios between 3alpha- and 3beta-PI and between 5alpha- and 5beta-PI throughout pregnancy. The constant allopregnanolone/isopregnanolone ratio found through pregnancy weakened the hypothesis of the role of isopregnanolone in the onset of parturition. The ratio of estradiol (stimulating uterine activity) to 5alpha-PI and epipregnanolone exhibited significant changes during pregnancy in favor of estradiol up to the sixth or seventh month, in contrast to the constant estradiol/pregnanolone ratio. A pregnancy-stabilizing role of pregnanolone, counterbalancing the stimulating effect of estradiol on the onset of parturition, was suggested.

Fetal anemia, thrombocytopenia, dilated umbilical vein, and cardiomegaly due to a voluminous placental chorioangioma. A case report.

We report a case of voluminous placental chorioangioma diagnosed by ultrasound and color Doppler imaging during the 20th week of pregnancy. The size of the tumor was enlarging progressively (up to 10 cm in the 32nd week), and during this time the signs of fetal intrauterine volume overload and blood cell consumption, such as cardiomegaly, umbilical vein dilation, hydramnios, anemia, and thrombocytopenia, were observed. In the 32nd week of pregnancy, the signs of uteroplacental insufficiency and fetal hypoxia appeared; therefore, the pregnancy was terminated by cesarean section, and a female infant weighing 1,870 g was delivered. She was discharged, fully recovered, after 48 days. Histopathological examination of the placental tumor showed a benign, vascular-type chorioangioma.