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Artikel in mehreren Sprachen: Deutsch und Englisch Aim: This revised guideline was coordinated by the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (OEGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). It aims to improve the prediction, prevention, and management of preterm birth, based on evidence from the current literature, the experience of members of the guidelines commission, and the viewpoint of self-help organizations. Methods: The members of the contributing professional societies and organizations developed recommendations and statements based on international literature. The recommendations and statements were presented and adopted using a formal process (structured consensus conferences with neutral moderation, written Delphi vote). Recommendations: Part 1 of this short version of the guideline presents statements and recommendations on the epidemiology, etiology, prediction, and primary and secondary prevention of preterm birth. Ziel: Überarbeitete Leitlinie der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG), der Österreichischen Gesellschaft für Gynäkologie und Geburtshilfe (OEGGG) und der Schweizerischen Gesellschaft für Gynäkologie und Geburtshilfe (SGGG). Ziel der Leitlinie ist es, die Prädiktion, die Prävention und das Management der Frühgeburt anhand der aktuellen Literatur, der Erfahrung der Mitglieder der Leitlinienkommission einschließlich der Sicht der Selbsthilfe evidenzbasiert zu verbessern. Methoden: Anhand der internationalen Literatur entwickelten die Mitglieder der beteiligten Fachgesellschaften und Organisationen zahlreiche Empfehlungen und Statements. Diese wurden in einem formalen Prozess (strukturierte Konsensuskonferenzen mit neutraler Moderation, schriftliche Delphi-Abstimmung) verabschiedet. Empfehlungen: Der Teil 1 dieser Kurzversion der Leitlinie zeigt Statements und Empfehlungen zur Epidemiologie, Ätiologie, der Prädiktion sowie der primären und sekundären Prävention der Frühgeburt.

Background: Pancreatic stone protein (PSP) is a biochemical serum marker that contains levels that are elevated in various inflammatory and infectious diseases. The role of PSP in the diagnosis of these diseases seems to be more important compared to clinically established biochemical serum markers in discriminating the severity of the same diseases. Standard values for PSP in pregnant women in relation to gestational age have been reported recently. Additionally, increased PSP levels have been observed to be associated with renal dysfunction in pregnant women. The aim of this study is to evaluate the diagnostic role of PSP in pregnancy-related diseases, such as pre-eclampsia (PE), hemolysis-elevated liver enzymes, and low platelet (HELLP) syndrome. In addition, the study aims to assess its diagnostic role in inflammation-triggered diseases as preterm premature rupture of membranes (PPROM) or COVID-19-positive pregnant women. Materials and Methods: In this single-centred prospective study performed at a tertiary university hospital between 2013 and 2021, we included 152 pregnant women who were diagnosed with either PE, HELLP syndrome, or PPROM. In December 2020, in the context of the COVID-19 pandemic, the Independent Ethics Committee (IEC) approved an amendment to the study protocol. Depending on the underlying disease, single or serial-serum PSP measurements were assessed. These PSP values were compared to PSP levels of women with normal pregnancies. Results: Pregnant women diagnosed with pre-eclampsia or HELLP syndrome had significantly increased PSP values (mean 9.8 ng/mL, SD 2.6) compared to healthy singleton pregnant women (mean 7.9 ng/mL, SD 2.6, p ≤ 0.001). There was no difference in serum PSP in pregnant women with PPROM compared to women with uncomplicated singleton pregnancies (mean in PPROM: 7.9 ng/mL; SD 2.9 versus mean in healthy pregnancies: 7.9 ng/mL; SD 2.6, p = 0.98). Furthermore, no difference in the PSP values in women with or without intra-amniotic infection was observed (infection: mean 7.9 ng/mL; SD 2.8 versus no infection: mean 7.8 ng/mL; SD 3, p = 0.85). The mean value of PSP in COVID-19-infected women during pregnancy (8.5 ng/mL, SD 2.3) was comparable to healthy singleton pregnancies (mean 7.9 ng/mL, SD 2.6), p = 0.24. Conclusions: The novel serum biomarker PSP is significantly upregulated in pregnant women with pre-eclampsia and HELLP syndrome. Our observations call for the further evaluation of PSP in randomized controlled clinical trials to demonstrate the actual role of PSP in pregnancy-related diseases and whether it may provide new approaches for the management and discrimination of the severity of these gestational conditions.

Artikel in mehreren Sprachen: Englisch und Deutsch Aim: The revision of this guideline was coordinated by the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (OEGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of the guideline is to improve the prediction, prevention and management of preterm birth based on evidence from the current literature, the experience of members of the guidelines commission, and the viewpoint of self-help organizations. Methods: The members of the contributing professional societies and organizations developed recommendations and statements based on international literature. The recommendations and statements were presented and adopted using a formal process (structured consensus conferences with neutral moderation, written Delphi vote). Recommendations Part 2 of this short version of the guideline presents statements and recommendations on the tertiary prevention of preterm birth and the management of preterm premature rupture of membranes. Ziel: Überarbeitete Leitlinie der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG), der Österreichischen Gesellschaft für Gynäkologie und Geburtshilfe (OEGGG) und der Schweizerischen Gesellschaft für Gynäkologie und Geburtshilfe (SGGG). Ziel der Leitlinie ist es, die Prädiktion, die Prävention und das Management der Frühgeburt anhand der aktuellen Literatur, der Erfahrung der Mitglieder der Leitlinienkommission einschließlich der Sicht der Selbsthilfe evidenzbasiert zu verbessern. Methoden: Anhand der internationalen Literatur entwickelten die Mitglieder der beteiligten Fachgesellschaften und Organisationen zahlreiche Empfehlungen und Statements. Diese wurden in einem formalen Prozess (strukturierte Konsensuskonferenzen mit neutraler Moderation, schriftliche Delphi-Abstimmung) verabschiedet. Empfehlungen: Der Teil 2 dieser Kurzversion der Leitlinie zeigt Statements und Empfehlungen zur tertiären Prävention der Frühgeburt sowie zum Management des frühen vorzeitigen Blasensprungs.

Objectives: to study the levels of the total, phosphorylated p65-subunit of the nuclear factor NF-kB, activity of p65 and the relation with the level and ratio of T-helpers type I and II in pregnant women with placental dysfunction and different clinical types of the course of preterm labor (with preterm premature rupture of membranes (pPROM) and without it).Materials and methods. The case-control study included 60 pregnant women: 40 women with placental disorders and spontaneous premature labor in the period of 24–34 weeks (group I – 20 women with premature labor and timely discharge of amniotic fluid, group II – 20 women with pPROM) and 20 women of the control group (CG) with normal timely delivery in the head position of a fetus without complications.The value of the total NF-kB p65 subunit and its phosphorylated fraction was determined in all women using ELISA in placenta lysates. On this basis the p65 subunit activity was calculated; number of T-helper I (Th1) and T-helper II (Th2) was determined using flow cytometry in a whole blood sample, with afterward calculation of the Th1/Th2 ratio.Results. Elevated levels of total p65 and its phosphorylated fraction were found in women with placental dysfunction (p < 0.01 in groups I and II compared with CG), as well as the activity p65 (p < 0.01 in group I, p = 0.04 in group II compared with CG). The difference in the Th1 value and the Th1/Th2 ratio was significantly higher in both groups (p < 0.01 in group I, p = 0.03 in group II for Th1; p < 0.01 in both groups for Th1/Th2), the number of Th2 differed significantly only in group I (p < 0.01 compared with CG). A strong positive correlation between p65 activity and Th1/Th2 was also established (r = 0.8).Conclusions. Obtained data indicates the increased NF-kB p65-subunit activity in women with placental disorders and spontaneous premature labor without pPROM, which is impact on the increase of the Th1/Th2 ratio due to the Th1 increase. This mechanism might be considered to be the leading cause of the premature birth in this group of pregnant women. However, for women with the preterm labor activity with pPROM, the difference with GC has a lower level of significance, which may indicate the existence of another leading mechanism for the initiation of premature labor in this group., Мета дослідження: вивчити рівні загальної, фосфорильованої р65-субодиниці ядерного чинника NF-kB, її активність і зв’язок із кількістю та співвідношенням Т-хелперів І та ІІ типу у вагітних із плацентарними порушеннями й різними клінічними типами перебігу передчасної пологової діяльності (з передчасним розривом плодових оболонок (ПРПО) і без нього).Матеріали та методи. До дослідження типу «випадок-контроль» увійшли 60 вагітних: 40 жінок із плацентарними порушеннями й розвитком спонтанної передчасної пологової діяльності на терміні 24–34 тижні (група І – 20 жінок із передчасними пологами та своєчасним відходженням вод, група ІІ – 20 жінок із ПРПО) та 20 жінок групи контролю (ГК) з нормальними терміновими пологами в головному передлежанні плода без ускладнень. У всіх жінок досліджували кількість загальної р65-субодиниці ядерного чинника NF-kB та фосфорильованої її фракції імуноферментним методом ELISA в лізатах плаценти. На основі цього обчислювали показник активності вказаного білка; кількість Т-хелперів 1-го (Тh1) і 2-го типів (Тh2) досліджували шляхом проточної цитометрії у зразку цільної крові, визначаючи співвідношення обох типів Т-хелперів і зв’язок з активністю р-65 NF-kB. Результати. У жінок із плацентарною дисфункцією виявлено підвищені рівні загального р65 і його фосфорильованої фракції (р < 0,01 у І та ІІ групах при порівнянні з ГК), а також показника активності р65 у плаценті (р < 0,01 у групі І, р = 0,04 у групі ІІ при порівнянні з ГК). Різниця концентрації Тh1 та співвідношення Th1/Th2 були достовірно вищими в обох групах (р < 0,01 у І групі, р = 0,03 у ІІ групі для Th1; р < 0,01 в обох групах для Th1/Th2 ), кількість Тh2 достовірно відрізнялася лише у групі І (р < 0,01 ІІ при порівнянні з ГК). Виявлено сильний позитивний кореляційний зв’язок активності р65 та Th1/Th2 (r = 0,8).Висновки. Отримані результати свідчать про існування підвищеної активності р-65 NF-kB у жінок із плацентарними порушеннями й розвитком спонтанної передчасної пологової діяльності без ПРПО, що впливає на зсув співвідношення Th1/Th2 у бік зростання за рахунок підвищення фракції Тh1 та, найімовірніше, є основним механізмом розвитку передчасних пологів у цієї групи вагітних. Однак для жінок із розвитком передчасної пологової діяльності з ПРПО різниця з ГК має нижчий рівень значущості, що може свідчити про існування в них іншого провідного механізму ініціації передчасних пологів.

Purpose: The aim of this study was to evaluate the effect of gestational age (GA) at the time of fetoscopic laser photocoagulation (FLP) for severe twin–twin transfusion syndrome (TTTS) on perinatal outcomes in a single center in Taiwan. Materials and methods: Severe TTTS was defined as a diagnosis of TTTS before a GA of 26 weeks. Consecutive cases of severe TTTS treated at our hospital with FLP between October 2005 and September 2022 were included. The evaluated perinatal outcomes were preterm premature rupture of membranes (PPROM) within 21 days of FLP, survival 28 days after delivery, GA at delivery, and neonatal brain sonographic imaging findings within 1 month of delivery. Results: We included 197 severe TTTS cases; the mean GA at the time of FLP was 20.6 weeks. After the cases were divided into cases of FLP at early (below 20 weeks) and late GAs (more than 20 weeks), the early-GA group was discovered to be associated with a deeper maximum vertical pocket in the recipient twin, a higher rate of PPROM development within 21 days of FLP, and lower rates of survival of one or both twins. In the cases of stage I TTTS, the rate of PPROM within 21 days of FLP was higher in the group that underwent FLP at an early GA than in the group that underwent FLP at a late GA (50% (3/6) vs. 0% (0/24), respectively, p = 0.005). Logistic regression analysis revealed that the GA at the time of FLP and the cervical length before FLP is implemented are significantly associated with the survival of one twin and the incidence of PPROM development within 21 days of FLP. The GA at the time of FLP, the cervical length before FLP, and TTTS being stage III TTTS were associated with the survival of both twins after FLP. Neonatal brain image anomalies were associated with GA at delivery. Conclusions: FLP being performed at an earlier GA is a risk factor for lower fetal survival and PPROM development within 21 days of FLP in cases of severe TTTS. Delaying FLP for cases involving stage I TTTS diagnosed at an early GA without risk factors, such as maternal symptoms, cardiac overload in the recipient twin, or a short cervical length, may be considered, but whether delaying FLP would improve surgical outcomes and, if so, how long the delay should be may need further trials to answer.

Purpose - to estimate the prognostic value of vitamin 25(OH)D levels and the expression of antimicrobial peptides (β-defensins 2) in maternal blood in predicting perinatal losses in preterm premature rupture of membranes (pPROM) up to 36 weeks of gestation. Materials and methods. A total of 109 women with singleton pregnancies complicated by pPROM at 23 to 36 weeks’ gestation and 20 women in the control group with intact membranes who subsequently gave birth to full-term infants were prospectively screened. A standard examination of pregnant women with pPROM was performed, and vitamin 25(OH)D levels and β-defensin 2 expression were examined by enzyme-linked immunoassay. Results. Correlation analysis revealed significant associations between the incidence of perinatal loss in preterm pregnancy complicated by pPROM, both with gestational age and maternal factors such as moderate anemia, serum vitamin 25(OH)D and β-defensins 2 expression, low coverage of preventive measures for neonatal respiratory distress syndrome. Conclusions. On the basis of the selected predictors, 3 multivariate logistic regression models were built, which allow to estimate the probability of perinatal losses in preterm pregnancy complicated by pPROM at the individual level with fairly high diagnostic efficiency - sensitivity (62.5-75.0%), specificity (100%), accuracy of the forecast (97.3-98.2%). The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors., Цель - оценить прогностическое значение уровня витамина 25(ОН)D и экспрессии антимикробных пептидов (β-дефензинов 2) в крови матери в прогнозировании перинатальных потерь при преждевременном разрыве плодных оболочек (ПРПО) до 36 недель беременности. Материалы и методы. Проспективно обследованы 109 женщин с одноплодной беременностью, осложненной ПРПО в сроке беременности 23-36 недель, и 20 женщин группы контроля с интактными плодными оболочками, у которых впоследствии родились доношенные дети. Проведено стандартное обследование беременных при ПРПО, а также исследование уровня витамина 25(ОН)D и экспрессии β-дефензинов 2 методом иммуноферментного анализа. Результаты. По данным корреляционного анализа установлены достоверные ассоциации между частотой перинатальных потерь при недоношенной беременности, осложненной ПРПО, как со сроками гестации, так и с такими материнскими факторами: анемия средней степени, уровень сывороточного витамина 25(ОН)D и экспрессии β-дефензинов 2, низкий уровень охвата профилактическими мероприятиями неонатального респираторного дистресс-синдрома. Выводы. На основе выделенных предикторов построены три модели многофакторной логистической регрессии, позволяющие на индивидуальном уровне оценить вероятность перинатальных потерь при недоношенной беременности, осложненной ПРПО, с достаточно высокими показателями диагностической эффективности - чувствительность (62,5-75,0%), специфичность (100%), точность прогноза (97,3-98,2%). Исследование выполнено в соответствии с принципами Хельсинкской декларации. Протокол исследования одобрен Локальным этическим комитетом указанного в работе учреждения. На проведение исследований получено информированное согласие женщин. Авторы заявляют об отсутствии конфликта интересов., Мета - оцінити прогностичне значення рівня вітаміну 25(ОН)D та експресії антимікробних пептидів (β-дефензинів 2) у крові матері в передбаченні перинатальних втрат при передчасному розриві плодових оболонок (ПРПО) до 36 тижнів вагітності. Матеріали та методи. Проспективно обстежено 109 жінок з одноплідною вагітністю, ускладненою ПРПО в термін вагітності 23-36 тижнів, і 20 жінок групи контролю з інтактними плодовими оболонками, у яких згодом народилися доношені діти. Проведено стандартне обстеження вагітних при ПРПО, а також дослідження рівня вітаміну 25(ОН)D та експресії β-дефензинів 2 методом імуноферментного аналізу. Результати. За даними кореляційного аналізу встановлено вірогідні асоціації між частотою перинатальних втрат при недоношеній вагітності, ускладненій ПРПО, як із термінами гестації, так і з такими материнськими факторами: анемія середнього ступеня, рівень сироваткового вітаміну 25(ОН)D та експресії β-дефензинів 2, низький рівень охоплення профілактичними заходами щодо неонатального респіраторного дистрес-синдрому. Висновки. На основі виділених предикторів побудовано три моделі багатофакторної логістичної регресії, які дають змогу на індивідуальному рівні оцінити ймовірність перинатальних втрат при недоношеній вагітності, ускладненій ПРПО, з досить високими показниками діагностичної ефективності - чутливість (62,5-75,0%), специфічність (100%), точність прогнозу (97,3-98,2%). Дослідження виконано відповідно до принципів Гельсінської декларації. Протокол дослідження схвалений Локальним етичним комітетом зазначеної в роботі установи. На проведення досліджень отримано інформовану згоду жінок. Автори заявляють про відсутність конфлікту інтересів.

Purpose Treatment of mid-trimester classic preterm premature rupture of membranes (PPROM) with systemic antibiotics has limited success in the prevention of chorioamnionitis, funisitis and fetal inflammatory response syndrome because of very low transplacental passage. Methods Here we report a case of PPROM at 18 weeks gestation with anhydramnion colonized by multi-resistant Escherichia coli (E. coli). A catheter system was implanted at 23/2nd weeks gestation, enabling long-term continuous lavage of the amniotic cavity with Amnion Flush Solution (100 ml/h combined with intraamniotic meropenem application). Results The patient gave birth to a preterm male infant at 28/3rd without any signs of infection. In a follow-up examination at 24 months, there was no neurological disturbance or developmental delay. Conclusion The classic PPROM with multi-resistant E. coli colonization could be treated with continuous amnioinfusion and meropenem.

Objective To explore the indications of prenatal antibiotic withdrawal and its correlation with maternal and infant outcomes of preterm premature rupture of membranes (PPROM) without infection. Methods Clinical data of 121 patients with PPROM between 24 and 33+6 gestational weeks expecting to prolong latency in our hospital between January 2015 and December 2019 were collected and retrospectively analyzed. According to having high risk factors for infection or not and maternal and infant outcomes, they were divided into group A (low-risk but without adverse outcome), group B (low-risk with adverse outcome), group C (high-risk but without adverse outcome) and group D (high-risk with adverse outcome). Univariate analysis and multivariate logistic regression analysis were performed for statistical analysis. Results The results of univariate analysis showed that there were statistical differences in procalcitonin (PCT), C-reactive protein (CRP) and hemeglobin (Hb) between group A and B at discontinuation of antibiotics (P < 0.05). Significant differences were seen in duration of antibiotics use, neutrophil-lymphocyte ratio (NLR) and CRP between group C and D at antibiotics discontinuation (P < 0.05). Multivariate analysis indicated that when antibiotics were discontinued, the low-risk groups had CRP (5~30 mg/L, >30 mg/L) increased and increased risk of adverse maternal and infant outcomes (OR=2.227, 95%CI: 0.689~7.205; OR=14.000, 95%CI: 1.471~133.233); while for the high-risk groups, CRP was elevated (5~30 mg/L, >30 mg/L) or short course of treatment (< 3 d), and the incidence of adverse maternal and child outcomes was increased (OR=1.508, 95%CI: 0.452~5.024; OR=14.278, 95%CI: 1.526~133.570; OR=4.045, 95%CI: 1.341~12.199). Conclusion CRP can be used to guide the use of antibiotics in PPROM patients. For those at high risk of infection, the duration of anti-infection therapy is associated with maternal and infant outcomes and should be maintained at least longer than 3 d.

The impact of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in pregnancy has yet to be determined. Some studies indicate that SARSCoV- 2 infection may be associated with a higher risk of adverse outcomes in pregnant women. Here, we performed a meta-analysis to estimate the frequency of intrauterine growth restriction (IUGR) and preterm premature rupture of the membranes (PPROM) in pregnant women with Coronavirus disease-2019 (COVID-19). A comprehensive search was performed in various databases, such as PubMed, Scopus, SciELO, MedRxiv, and Web of Science, to find all relevant studies published before 10 February 2021. Cross-sectional and consecutive case series reporting the pregnancy outcomes of COVID-19 were included. A total of 24 studies, including 8 studies on IUGR and 16 studies on PPROM, were selected. Pooled data showed that the frequencies of IUGR and PPROM in pregnant women with COVID-19 were 2.6% and 9.9%, respectively. Analyses stratified by ethnicity showed that the frequencies of IUGR in Asian and Caucasian COVID-19-infected pregnant women were 2.9% and 2.0%, respectively. Moreover, the frequencies of PPROM in Asian and Caucasian COVID-19-infected pregnant women were 10.2% and 5.8%, respectively. This meta-analysis showed that the frequencies of IUGR and PPROM in COVID-19-infected pregnant women were 2.6% and 9.9%, respectively. However, well-designed, large-scale and multicenter clinical studies are required to improve and validate these results.

The purpose - to evaluate the clinical status of newborns in women with pregnancy complicated by preterm premature rupture of membranes (pPROM) and its relationship with the course of pregnancy and childbirth, the duration of the latency period between pPROM and delivery (LP), as well as with the levels of vitamin 25(OH)D and the expression of antimicrobial peptides (β-defensins 2) in the mother’s blood. Materials and methods. The condition and morbidity of newborns with preterm birth due to pPROM have been carefully studied. The levels of vitamin 25(OH)D and the expression of antimicrobial peptides (β-defensins 2) in the blood serum of 109 women with singleton pregnancy complicated by pPROM at 23-36 weeks of gestation and 20 pregnant women of the control group with intact membranes, who subsequently gave birth to full-term babies, were studied by enzyme-linked immunosorbent assay. Results. No significant relationship between the condition of newborns and the duration of LP was found. Medical tactics of pregnancy management with pPROM led to the presence of a direct relationship between the prolongation of LP and the prevention of respiratory distress syndrome with dexamethasone/betamethasone (r=+0.36; p, Цель - оценить клинический статус новорожденных у женщин с недоношенной беременностью, осложненной преждевременным разрывом плодовых оболочек (ПРПО), и его связь с течением беременности и родов, длительностью безводного промежутка (БП), а также с уровнями витамина 25(ОН)D и экспрессии антимикробных пептидов (β-дефензинов 2) в крови матери. Материалы и методы. Тщательно изучены состояние и заболеваемость новорожденных при преждевременных родах вследствие ПРПО. При помощи иммуноферментного анализа исследованы уровни витамина 25(ОН)D и экспрессии антимикробных пептидов (ß-дефензинов 2) в сыворотке крови 109 женщин с одноплодной беременностью, осложненной ПРПО в сроки беременности 23-36 недель, и 20 беременных контрольной группы с интактными плодовыми оболочками, у которых потом родились доношенные дети. Результаты. Не выявлено достоверной связи между состоянием новорожденных и длительностью БП. Врачебная тактика ведения беременности с ПРПО обусловила наличие прямой связи между пролонгацией БП и профилактикой респираторного дистресс-синдрома дексаметазоном/бетаметазоном (r=+0,36; р, Мета - оцінити клінічний статус новонароджених у жінок із недоношеною вагітністю, ускладненою передчасним розривом плодових оболонок (ПРПО), та його зв’язок із перебігом вагітності та пологів, тривалістю безводного проміжку (БП), а також із рівнями вітаміну 25(ОН)D та експресії антимікробних пептидів (β-дефензинів 2) у крові матері. Матеріали та методи. Ретельно вивчено стан і захворюваність новонароджених при передчасних пологах унаслідок ПРПО. За допомогою імуноферментного аналізу проведено дослідження рівнів вітаміну 25(ОН)D та експресії антимікробних пептидів (β-дефензинів 2) у сироватці крові 109 жінок з одноплідною вагітністю, ускладненою ПРПО в терміни вагітності 23-36 тижнів, та 20 вагітних контрольної групи з інтактними плодовими оболонками, у яких згодом народилися доношені діти. Результати. Не виявлено достовірного зв’язку між станом новонароджених і тривалістю БП. Лікарська тактика ведення вагітності з ПРПО обумовила наявність прямого зв’язку між пролонгацією БП і профілактикою респіраторного дистрес-синдрому дексаметазоном/бетаметазоном (r=+0,36; р

Background. Preterm premature rupture of membranes (PPROM) is one of the main causes of perinatal morbidity and mortality. Associated oligohydramnios may further exacerbate the condition leading to intra-amniotic inflammation and adverse obstetric and perinatal outcomes in preterm labor.Aim of the research. To determine an impact of oligohydramnios on patients with preterm premature rupture of membranes.Materials and methods. We performed a retrospective analysis of two groups of patients with PPROM: 56 patients with oligohydramnios were included in the main group, 111 patients without oligohydramnios were included in the control group. The gestational age varied from 24+0 weeks to 33+6 weeks. Amniotic fluid index, endocervical culture, leukogram and neutrophil-to-lymphocyte ratio (NLR), serum procalcitonin and C-reactive protein levels were assessed in all participants.Results. We witnessed a plethora of consequences in the group of women with PPROM and oligohydramnios: shorter latent phase, higher incidence of clinical chorioamnionitis, antenatal fetal distress, higher levels of C-reactive protein, leukocytes, neutrophils and NLR, lower level of lymphocytes, and increased growth of potentially pathogenic cervical flora. Moreover, the patients with oligohydramnios demonstrated a significantly higher rate of cesarean delivery. The combination of PPROM and oligohydramnios also take a toll on the condition of the newborns: they have lower 5-minute Apgar score and higher prevalence of respiratory distress syndrome, congenital pneumonia, and necrotizing enterocolitis. Furthermore, newborns from the main group are more likely to be admitted to the neonatal intensive care unit, compared with newborns from the control group.Conclusion. Oligohydramnios in PPROM is associated with a dramatic rise of numerous complications affecting both the women and the newborns.

Objective: To investigate the severity of histologic chorioamnionitis /funisitis according to the indication for preterm delivery and their corresponding neonatal outcomes. Method: This study included 411 singleton women who delivered between 21+0 and 31+6 week of gestation due to preterm labor (PTL, n = 165), preterm premature rupture of membranes (PPROM, n = 202), or incompetent internal os of the cervix (IIOC, n = 44). The primary outcome measure was the rate of severe histological chorioamnionitis/funisitis. Secondary outcome measure was neonatal outcomes including neonatal and infant death, and neonatal composite morbidity. Results: The PPROM group demonstrated a higher rate of severe histological chorioamnionitis/funisitis compared to the PTL group (severe histological chorioamnionitis; PPROM, 66.3% vs. PTL, 49.1%, p = 0.001, severe funisitis; PPROM, 44.1% vs. PTL, 23.6%, p < 0.001) and this remained significant after multivariable analysis (severe histologic chorioamnionitis, OR 2.367, 95% CI 1.517–3.693; severe funisitis, OR 2.668, 95% CI 1.684–4.226). For neonatal outcomes only, a higher rate of patent ductus arteriosus was observed in the IIOC group compared to the PTL and PPROM groups (IIOC, 77.3% vs. PTL, 54.0% vs. PPROM, 54.0%, p = 0.043) and this remained significant after multivariable analysis. Conclusion: Indication of spontaneous preterm delivery might affect the placental inflammatory pathology and neonatal morbidity.

Chorioamnionitis is an acute inflammation of the foetal membranes and placenta. This infection is dangerous for women because it increases the risk of uterine atony and postpartum haemorrhage, endometritis, peritonitis and sepsis. This infection is dangerous to the neonate, because of the increased risk of foetal inflammatory response syndrome, pneumonia, meningitis, sepsis and death. There is still no universally accepted single method for diagnosing chorioamnionitis. Each year, more studies are being carried out to validate a test method that is suitable for the early diagnosis of chorioamnionitis, is quick and easy to perform, and that has a high specificity and sensitivity. The aim of this dissertation is to evaluate the role of inflammatory markers in maternal blood and non-invasively collected amniotic fluid, for the antenatal diagnosis of chorioamnionitis. It was found that NLR has higher diagnostic values than the assessment of leukocyte count and CRP in the diagnosis of histological chorioamnionitis. IL-6, TNF-α, MMP-8 and suPAR in non-invasively collected amniotic fluid are statistically significant diagnostic markers of histological chorioamnionitis. The best diagnostic value for histological chorioamnionitis have TNF-α and MMP-8. The optimal values of inflammatory markers of maternal blood and amniotic fluid for the diagnosis of chorioamnionitis have been determined: NLR – 5,97, CRP – 8,56 mg/l, IL-6 – 1 389,82 pg/ml, TNF-α – 21,17 pg/ml, MMP-8 – 172,53 ng/ml, suPAR – 30,08 mcg/ml. Evaluation of CRP with MMP-8 or TNF-α and NLR with MMP-8 showed a statistically significantly higher diagnostic values than evaluation of CRP or NLR alone. To improve the prediction of chorioamnionitis, it is recommended to assess inflammatory markers in the maternal blood and amniotic fluid together.

Amaç: Preterm erken membran rüptüründe (PPROM) ve preterm doğumda (PD) idrar yolu enfeksiyonunun olumsuz neonatal sonuçları ve doğum süresine ile arasındaki ilişkinin araştırılmasını amaçladık.Gereç ve Yöntem: 2008-2014 yılları arasında merkezimize başvuran 1033 gebe hastayı retrospektif olarak değerlendirdik. Çalışma grupları 446 PPROM ve 587 PD hastasından oluşuyordu. Bulgular: İdrar kültürü pozitif PPROM hastalarında transvajinal ultrasonografi ile ölçülen servikal uzunluk(OR = 0.806,) ve amniyon sıvısı indeksi (AFI), (OR = 0.961) ve idrar kültürü pozitif PD hastalarında sadece servikal uzunluk OR = 0.862 doğum süresinin yedi günden daha kısa olacağı ile ilişkili idi. Ayrıca idrar kültürü pozitif olan PPROM grubunda AFI’ nin (OR = 0.982) olumsuz neonatal sonuçlarla ilişkilendirileceğini belirledik.Sonuç: İdrar kültürü pozitif PPROM ve PD hastalarında olumsuz neonatal sonuçları ve doğum zamanını öngörmede AFI ve servikal uzunluk da kullanılabilir., urpose: We aimed to investigate the relationship between adverse neonatal outcomes and the time period of labor in between urinary tract infection in preterm premature rupture of membranes (PPROM) to preterm labor (PL). Materials and Methods: We evaluated a total number of 1033 pregnant patients who admitted to our center between 2008 and 2014, with retrospective analysis. Study groups consisted of 446 PPROM and 587 PL patients who had urine cultures. Results: We determined cervical lengths which were measured by transvaginal ultrasonography, with OR = 0.806 and amniotic fluid index (AFI), OR = 0.961 in PPROM group, which had positive urine culture, and also cervical length OR = 0.862 in PL group which had positive urine culture and to be associated with shorter than seven days of delivery. Additionally, we determined that only the AFI, with OR= 0.982, to be associated with adverse neonatal outcomes in the PPROM group, having positive urine culture. Conclusion: AFI and cervical length can also be used to predict adverse neonatal outcomes and time of delivery in urine culture positive PPROM and PL patients.

Objective: Given that many studies report on a limited spectrum of adverse events of transvaginal cervical cerclage for preventing preterm birth, but are not powered to draw conclusions about its safety, the objective of this study was to conduct a systematic review with pooled risk analyses of perioperative complications and compare characteristics on the basis of indication for cerclage in singleton pregnancies. Data Sources: Ovid MEDLINE, Ovid Embase, Web of Science, the Cochrane Central Register of Controlled Trials (CENTRAL), and the prospective trial registers ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform were searched from inception to April 2020. Study Eligibility Criteria: All randomized controlled trials and both retrospective and prospective observational cohort studies reporting about complications in history-indicated cerclage, ultrasound-indicated cerclage, or physical examination-indicated cerclage were eligible. Studies were included if they contained original data on the occurrence of adverse events during surgery or within 24 hours after surgery. Methods: The Cochrane risk of bias tool for randomized controlled trials and the Newcastle–Ottawa scale for cohort and case–control studies were used for the critical appraisal. The pooled risk assessment was conducted using meta and metafor packages in R (studio), version 4.0.3. Results: The search yielded 2328 potential studies; 3 randomized controlled trials, 3 prospective, and 38 retrospective cohort studies were included in the final analysis. Of the 4511 women with singleton gestations, 1561 (34.6%) underwent history-indicated cerclage, 1348 (29.9%) underwent ultrasound-indicated cerclage, and 1549 (33.3%) underwent physical examination-indicated cerclage. Most perioperative complications occurred in physical examination-indicated cerclage, especially hemorrhage (2.3%; 95% confidence interval, 0.0–7.6) and preterm premature rupture of membranes (2.5%; 95% confidence interval, 0.91–4.5). The fewest complications occurred in history-indicated cerclage, varying from 0.0% of preterm premature rupture of membranes (95% confidence interval, 0.0–1.7) to 0.9% of hemorrhage (95% confidence interval, 0.0–7.9). In ultrasound-indicated cerclage, the most common complication was hemorrhage (1.4%; 95% confidence interval, 0.0–4.1), followed by lacerations (0.6%; 95% confidence interval, 0.0–3.1) and preterm premature rupture of membranes (0.3%; 95% confidence interval, 0.0–0.8). Conclusion: The highest risk of perioperative complications was observed in physical examination-indicated cerclage in comparison with ultrasound- and history-indicated cerclage. However, the occurrence of complications is poorly documented in the published literature, as is the timing of the complications (ie, perioperative or later in pregnancy). There is an urgent need for uniform complication reporting policy in both cohort studies and randomized controlled trials on cerclage.

Preterm premature rupture of membranes (PPROM) interrupts normal lung development, resulting in neonatal respiratory morbidity. Although post-PPROM risks have been researched, only a few studies have investigated noninvasively obtained amniotic fluid (AF) to predict neonatal outcomes. In this study, we aimed to determine whether epidermal growth factor (EGF) in vaginally-collected AF is a significant predictor of neonatal respiratory outcomes after PPROM. We analyzed EGF in vaginally-obtained AF from 145 women with PPROM at 22–34 weeks of gestation. The following neonatal outcomes were included: respiratory distress syndrome, surfactant need, duration and type of respiratory support, and bronchopulmonary dysplasia. We found that EGF concentration was associated with gestational age, and its medians were lower in neonates with respiratory morbidities than unaffected ones. EGF concentrations gradually declined, the lowest being in the most clinically ill patients. EGF < 35 pg/mL significantly predicted the odds of severe respiratory outcomes. EGF in noninvasively collected AF may be a reliable predictor for respiratory outcomes of preterm neonates with PPROM before 34 weeks of gestation. The results of our study may have implications for further research both in noninvasive amniotic fluid analysis and the management of patients after PPROM.

Citrobacter koseri is a facultative anaerobic, motile, non-spore-forming Gram-negative bacillus, which belongs to the family of Enterobacteriaceae. Severe infections due to Citrobacter spp. have been reported in the urinary tract, respiratory airways, intra-abdominal organs, skin and soft tissue, eye, bone, bloodstream, and central nervous system. In newborns, C. koseri is a well-known cause of meningitis, cerebral abscesses, brain adhesions, encephalitis, and pneumocephalus. Infection can be acquired through vertical maternal transmission or horizontal hospital settings; however, in many cases, the source is unknown. Preterm premature rupture of membranes (PPROM), caused by C. koseri, has rarely been described. Herein, we describe a case of PPROM at 16 weeks and 3 days of gestation, leading to anhydramnios. The parents opted for legal termination of the pregnancy, as the prognosis was very poor. C. koseri was isolated postmortem from a placental subamniotic swab and parenchymal sample, as well as fetal blood and lung. To the best of our knowledge, this is the first case of early second-trimester PPROM in which C. koseri infection was demonstrated.

Background: Preterm premature rupture of membranes (PPROM) is associated with high neonatal morbidity and mortality. However, the influences of cesarean section (CS) on neonatal outcomes in preterm pregnancies complicated with PPROM are not well elucidated. The aim of this study was to investigate the influence of delivery modes on neonatal outcomes among pregnant women with PPROM. Methods: A retrospective cross-sectional study was conducted in 39 public hospitals in 14 cities in the mainland of China from January 1st, 2011 to December 31st, 2011. A total of 2756 singleton pregnancies complicated with PPROM were included. Adverse neonatal outcomes including early neonatal death, birth asphyxia, respiratory distress syndrome (RDS), pneumonia, infection, birth trauma, and 5-min/10-min Apgar scores were obtained from the hospital records. Binary variables and ordinal variables were respectively calculated by binary logistic regressions and ordinal regression. Numerical variables were compared by multiple linear regressions. Results: In total, 2756 newborns were involved in the analysis. Among them, 1166 newborns (42.31%) were delivered by CS and 1590 newborns belonged to vaginal delivery (VD) group. The CS proportion of PPROM obviously increased with the increase of gestational age (χ2 = 5.014, P = 0.025). Compared with CS group, VD was associated with a higher risk of total newborns mortality(odds ratio [OR], 2.38; 95% confidence interval [CI], 1.102–5.118; P = 0.027), and a lower level of pneumonia (OR, 0.32; 95% CI, 0.126–0.811; P = 0.016). However, after multivariable adjustment and stratification for gestational age, only pneumonia was significantly related with CS in 28 to 34 weeks group (OR, 0.34; 95% CI, 0.120–0.940; P = 0.038). There were no differences regarding to other adverse outcomes in the two groups, including neonatal mortality, birth asphyxia, Apgar scores, RDS, pneumonia, and sepsis. Conclusions: The proportion of CS of pregnant women with PPROM was very high in China. The mode of delivery does not affect neonatal outcomes of pregnancies complicated with PPROM. Key words: Preterm premature rupture of membranes; Cesarean section; Vaginal delivery; Perinatal outcomes

BACKGROUND: Preterm premature rupture of membranes is an obstetric complication which has adverse perinatal effects and long-term morbidity and mortality. There is no published outcome data in Rwanda. OBJECTIVES: To assess maternal and neonatal outcomes at 24 to 34 weeks gestational age with preterm premature rupture of membranes (PPROM). METHODS: Retrospective chart review of patients admitted with PPROM from 2011 to 2014 in the largest teaching hospital in Rwanda. Prospective data collection was performed in the last year (2015). Overall maternal and neonatal outcomes were documented as well as a comparison of neonatal outcomes stratified into 3 gestational age groups (24 to 28 weeks, 29 to 31 weeks and 32 to 34 weeks). RESULTS: The study group was 109 patients. The mean gestational age at PPROM and delivery were 28.9 ± 2.8 weeks and 30.0 ±2.8 weeks, respectively. The majority (62.4%) delivered within one week of PPROM. Chorioamnionitis was present in 9.2%, placenta abruption in 4.6% and the cesarean delivery rate was 42.2%. The overall perinatal death rate was 38.5% and neonatal mortality rate was 30.9%. Perinatal mortality was highest in the 24 to 28 weeks gestational age group (73.5%) and in infants weighing less than 1 kg (67.9%). CONCLUSION: PPROM in our setting carries significant maternal morbidity and high neonatal mortality below 28 weeks. Parents should be thoroughly counseled about potential adverse maternal complications and poor neonatal outcome and be involved in decision-making regarding cesarean delivery and intensive neonatal care.

The aim of this study was to assess the frequency and risk factors of Preterm birth (PB), depending on the mechanism of their occurrence in nulliparous women with singleton pregnancies. Methods and Results: This retrospective, population-based cohort study included 327 nulliparous women who gave birth at 22-37 weeks gestation. Three groups of women were formed: Group 1 included 32 women with spontaneous PB, Group 2 included 115 women with preterm premature rupture of membranes (PROM), and Group 3 included 180 women with medical indication for PB. The average age of the mothers for the whole group was 29.3±6.0 years. Depending on the gestational age, PB in 22-27 weeks occurred in 23(7.4%) cases, 28-33 weeks in 110(33.6%) cases, and 34-37 weeks in 194(59%) cases. In our cohort, the frequency of PB resulting from spontaneous PB, PROM or medical indication for PB was 9.8%, 35.2%, and 55%, respectively. The main risk factors for PB were preeclampsia of varying severity, placental abruption, placental insufficiency, and fetal growth retardation. The highest number of pregnancy complications was found in Group 3. Conclusion: PB in nulliparous women occurs more often in the period of 34-37 weeks, the main reason being medical indications (maternal or fetal). Attempts to analyze, interpret, and reduce the level of PB should be considered separately, depending on the mechanism of their occurrence.

An abdominal pregnancy is not a common occurrence reported sparsely in the literature. But what is even more uncommon is the finding of a dead and retained, supra hepatic, abdominal pregnancy co-existing with a live intrauterine pregnancy at different stages of development. This is an extremely rare case of a 22-year old multigravida, who presented with 6 months amenorrhoea, abdominal distension, and difficulty in breathing. She had a previous history of a preexisting advanced abdominal pregnancy diagnosed a year earlier which had not been delivered. Evaluations revealed a viable intra-uterine gestation at 24 weeks, co-existing with a non-viable, sub-diaphragmatic/supra-hepatic abdominal pregnancy at term. She had the macerated abdominal pregnancy delivered at laparotomy and the intra-uterine pregnancy was left to continue. She developed Preeclampsia and eventually had pre-term premature rupture of membranes PPROM at 28 weeks of gestation with a live birth of a female fetus that weighed 800 grammes. There have been very few reports on advanced abdominal pregnancy and even more rarely, human superfetation in multiple pregnancy, but not a report on an intrauterine conception with a pre-existing advanced, abdominal ectopic pregnancy until now. This report is thus the first of its kind. We report an extremely rare case of a woman conceiving an intrauterine pregnancy, carrying it to the age of viability in the presence of a previously conceived, undelivered, dead, advanced abdominal pregnancy., {"references":["Baffoe P, Fofie C, Gandau BN. Term abdominal pregnancy with healthy newborn: A case report. Ghana Med J [Internet]. 2011 Aug 23 [cited 2020 Aug 19];45(2). Available from: https://www.ajol.info/ index.php/gmj/article/view/68933"]}

Background Fibulin-1 is an extracellular matrix protein expressed at high levels in the placenta. Elevated circulating fibulin-1 have been observed in women with severe pre-eclampsia, whereas low levels have been found in the fetal membranes, prior to membrane rupture. The aim of the study was primarily to evaluate plasma fibulin-1 during expected normal pregnancy and delivery, and secondarily to explore fibulin-1 levels in women developing pre-eclampsia or preterm premature rupture of fetal membranes (PPROM). Methods From the historical longitudinal cohort originally consisting of 801 healthy Danish women with a singleton pregnancy, 128 women (632 samples) were selected. Of these, 107 women had normal pregnancies, nine experienced PPROM, and 12 pre-eclampsia. All samples were analyzed for fibulin-1, and levels were compared with blood donors. Differences in mean fibulin-1 between groups were estimated using a linear mixed model. Results The mean concentration of fibulin-1 in 120 blood donors was 15.7 µg/mL, (25th-75th-percentiles, 12.3–18.2), with no significant difference in groups stratified by gender or age. Compared to baseline levels in week 12–20, fibulin-1 levels increased significantly from week 29–34 (estimated difference, 5.6 µg/mL; standard error, 1.7; p p p = 0.002) and emergency (-5.6 µg/mL; 2.9; p = 0.05) cesarean section than after vaginal delivery (reference group). Women who developed PPROM had lower fibulin-1 levels throughout their pregnancies (-11.6 µg/mL; 4.2; p = 0.006). We did not observe a correlate between late pre-eclampsia and fibulin-1 (-0.2 µg/mL; 3.0; p = 0.9). Conclusions Fibulin-1 was above non-pregnant levels at week 12 and increased significantly throughout pregnancy. We observed an association between low levels of fibulin-1 and PPROM. Further studies are needed to examine if fibulin-1 could serve as biomarker for the risk of PPROM. However, its role in late preeclampsia is doubtful. Trial registration The study was conducted in accordance with the Declaration of Helsinki. The participants provided written informed consent, including storage for future use. The study was approved on July 18, 2005 by The Danish National Committee on Bioethics (No. KA 05065 and S-20,090,061) and the Danish Data Protection Agency.

Background: Culture-proven sepsis is the gold standard in early-onset neonatal sepsis diagnosis. Infants born ≤29 weeks gestation after preterm rupture of membranes in the years 2009–2015 were included in a retrospective cohort study performed at a level III fetal-maternal unit. The study aimed to compare culture-proven sepsis, clinical sepsis and positive laboratory biomarkers ≤72 h as predictors of mortality before discharge and the combined outcome of mortality or severe short-term morbidity (severe cerebral morbidity, bronchopulmonary dysplasia and retinopathy). Results: Of the 354 patients included, culture-proven sepsis, clinical sepsis and laboratory biomarkers were positive in 2.3%, 8.5% and 9.6%, respectively. The mortality rate was 37.5% for patients with culture-proven sepsis (3/8), 33.3% for patients with clinical sepsis (10/30) and 8.8% for patients with positive laboratory biomarkers (3/34), respectively. Mortality or severe morbidity occurred in 75.0% of patients with culture-proven sepsis (6/8), 80.0% of patients with clinical sepsis (24/30) and 44.1% of patients with positive laboratory biomarkers (15/34), respectively. Conclusion: In preterm infants after preterm rupture of membranes, clinical sepsis was almost four times more common and at least equally valuable in predicting mortality and mortality or severe morbidity compared to culture-proven sepsis.

Background Fibroids are present in approximately one in ten pregnancies and are inconsistently linked with preterm birth. We sought to determine the association between fibroids and preterm birth in a prospective cohort with standardized research ultrasounds for characterizing fibroids in early pregnancy while accounting for the clinical paths that precede preterm birth. Methods Participants who were pregnant or planning a pregnancy were recruited from communities in three states between 2000 and 2012. Members of this prospective cohort had a research ultrasound in the first trimester to establish pregnancy dating and to record detailed information about the presence, size, number, and location of fibroids. Baseline information from time of enrollment and a detailed first trimester interview contributed key information about candidate confounders. Birth outcomes, including clinical classification of type of preterm birth (preterm labor, preterm premature rupture of membranes, and medically indicated preterm birth) were cross-validated from participant report, labor and delivery records, and birth certificate data. Results Among 4,622 women with singleton pregnancies, 475 had at least one fibroid (10.3%) and 352 pregnancies resulted in preterm birth (7.6%). Prevalence of fibroids was similar for women with preterm and term births (10.2% vs. 10.3%). Fibroids were not associated with increased risk of preterm birth after taking into account confounding (risk ratio adjusted for race/ethnicity and maternal age, 0.88; 95% confidence interval, 0.62–1.24) nor any clinical subtype of preterm birth. No fibroid characteristic or combination of characteristics was associated with risk. Conclusions If fibroids increase risk of preterm birth, the effect is substantially smaller than previous estimates. Given lack of effect in a large population of women from the general population, rather than higher risk academic tertiary populations previously most studied, we encourage a reconsideration of the clinical impression that presence of fibroids is a major risk factor for preterm birth.

Contains fulltext : 237895.pdf (Publisher’s version ) (Open Access) BACKGROUND: Ovarian cancer risk in BRCA1 and BRCA2 mutation carriers has been shown to decrease with longer duration of oral contraceptive use. Although the effects of using oral contraceptives in the general population are well established (approximately 50% risk reduction in ovarian cancer), the estimated risk reduction in mutation carriers is much less precise because of potential bias and small sample sizes. In addition, only a few studies on oral contraceptive use have examined the associations of duration of use, time since last use, starting age, and calendar year of start with risk of ovarian cancer. OBJECTIVE: This study aimed to investigate in more detail the associations of various characteristics of oral contraceptive use and risk of ovarian cancer, to provide healthcare providers and carriers with better risk estimates. STUDY DESIGN: In this international retrospective study, ovarian cancer risk associations were assessed using oral contraceptives data on 3989 BRCA1 and 2445 BRCA2 mutation carriers. Age-dependent-weighted Cox regression analyses were stratified by study and birth cohort and included breast cancer diagnosis as a covariate. To minimize survival bias, analyses were left truncated at 5 years before baseline questionnaire. Separate analyses were conducted for each aspect of oral contraceptive use and in a multivariate analysis, including all these aspects. In addition, the analysis of duration of oral contraceptive use was stratified by recency of use. RESULTS: Oral contraceptives were less often used by mutation carriers who were diagnosed with ovarian cancer (ever use: 58.6% for BRCA1 and 53.5% BRCA2) than by unaffected carriers (ever use: 88.9% for BRCA1 and 80.7% for BRCA2). The median duration of use was 7 years for both BRCA1 and BRCA2 carriers who developed ovarian cancer and 9 and 8 years for unaffected BRCA1 and BRCA2 carriers with ovarian cancer, respectively. For BRCA1 mutation carriers, univariate analyses have shown that both a longer duration of oral contraceptive use and more recent oral contraceptive use were associated with a reduction in the risk of ovarian cancer. However, in multivariate analyses, including duration of use, age at first use, and time since last use, duration of oral contraceptive use proved to be the prominent protective factor (compared with 10 years [hazard ratio, 0.37; 95% confidence interval, 0.19-0.73]; P(trend)=.008). The inverse association between duration of use and ovarian cancer risk persisted for more than 15 years (duration of ≥10 years; BRCA1 15 years since last use [hazard ratio, 0.56; 95% confidence interval, 0.18-0.59]). Univariate results for BRCA2 mutation carriers were similar but were inconclusive because of limited sample size. CONCLUSION: For BRCA1 mutation carriers, longer duration of oral contraceptive use is associated with a greater reduction in ovarian cancer risk, and the protection is long term.

Obstetrical complications, often referred to as the "great obstetrical syndromes," are among the most common global causes of mortality and morbidity in young women and their infants. However, treatments for these syndromes are underdeveloped compared with other fields of medicine and are urgently needed. This current paucity of treatments for obstetrical complications is a reflection of the challenges of drug development in pregnancy. The appetite of pharmaceutical companies to invest in research for obstetrical syndromes is generally reduced by concerns for maternal, fetal, and infant safety, poor definition, and high-risk regulatory paths toward product approval. Notably, drug candidates require large investments for development with an unguaranteed return on investment. Furthermore, the discovery of promising drug candidates is hampered by a poor understanding of the pathophysiology of obstetrical syndromes and their uniqueness to human pregnancies. This limits translational extrapolation and de-risking strategies in preclinical studies, as available for other medical areas, compounded with limited fetal safety monitoring to capture early prenatal adverse reactions. In addition, the ethical review committees are reluctant to approve the inclusion of pregnant women in trials, and in the absence of regulatory guidance in obstetrics, clinical development programs are subject to unpredictable regulatory paths. To develop effective and safe drugs for pregnancy complications, substantial commitment, and investment in research for innovative therapies are needed in parallel with the creation of an enabling ethical, legislative, and guidance framework. Solutions are proposed to enable stakeholders to work with a common set of expectations to facilitate progress in this medical discipline. Addressing this significant unmet need to advance maternal and possibly perinatal health requires the involvement of all stakeholders and specifically patients, couples, and cli-nicians facing pregnancy complications in the dearth of appropriate therapies. This paper focused on the key pharmaceutical research and development challenges to achieve effective and safe treatments for obstetrical syndromes.

Background Diabetes mellitus is a leading cause of nephropathy and end-stage renal disease. However, diabetic nephropathy during pregnancy in patients with normal glomerular filtration rate and subsequent progression to end-stage renal disease has not been well studied. Cases This report presents two patients with poorly controlled type 1 diabetes mellitus who had diabetic nephropathy with preserved estimated glomerular filtration rate (Case 1: 117 mL/min/1.73m2; Case 2: 79 mL/min/1.73m2) and shared a similar clinical course, with glomerular filtration rates decreasing by approximately one-half during pregnancy and progression to end-stage renal disease within the first year postpartum. Both women had a long history of type 1 diabetes: 18 years and 24 years for case 1 and case 2 respectively. The first patient's course of pregnancy was complicated by difficult-to-control blood glucose and hypertension with subsequent preeclampsia. The second patient's course of pregnancy was complicated by difficult-to-control blood sugars and preterm labor resulting in classical cesarean delivery at 24 weeks. Both patients had renal biopsies shortly after delivery as their renal function continued to worsen postpartum. Both kidney biopsies demonstrated advanced diabetic nephropathy changes and ultimately required chronic renal replacement therapy within 7–9 months postpartum. Conclusion Comprehensive family planning discussions with women who have diabetic nephropathy should include the risks of renal disease progression, even in those patients with preserved renal function at the time of conception., Highlights • Diabetic nephropathy carries a high risk for renal disease progression. • Diabetics with nephropathy need counseling on risk of kidney disease progression. • Diabetic women should be started on kidney-protective medications postpartum.

INTRODUCTION: This study was conducted to evaluate soluble Toll-like receptor 2 (sTLR-2) and soluble Toll-like receptor 4 (sTLR-4) levels in vaginally obtained amniotic fluid and investigate their value in the prediction of histological chorioamnionitis (HCA). MATERIAL AND METHODS: This prospective case-control study included patients who had been diagnosed with preterm premature rupture of membranes before 34 weeks of gestation and were admitted to Vilnius University Hospital Santaros Klinikos. Free leaking amniotic fluid was obtained vaginally using a sterile speculum up to 48 hours before delivery. Amniotic fluid levels of sTLR-2 and sTLR-4 were determined using an enzyme linked immunosorbent assay. The diagnosis of chorioamnionitis was confirmed by histological examination of the placenta and membranes after delivery. RESULTS: The study included 156 patients, 65 with (HCA Group) and 91 without (non-HCA Group) HCA. No statistically significant differences were noted in the concentrations of sTLR-2 and sTLR-4 in vaginally obtained amniotic fluid between patients with and without HCA: the median sTLR-2 level was 0.09 ng/mL in HCA Group vs 0.1 ng/mL in non-HCA Group, and the median sTLR-4 level was 0.23 ng/mL in HCA Group vs 0.28 ng/mL in non-HCA Group (p > 0.05). A positive correlation between sTLR-2 and sTLR-4 levels was identified (rho = 0.57, p < 0.001), but no correlation was found between these markers and gestational age. CONCLUSIONS: Concentrations of sTLR-2 and sTLR-4 in vaginally obtained amniotic fluid do not reflect the presence of HCA in pregnancies complicated by preterm premature rupture of membranes before 34 weeks of gestation.

Objective Symmetrical peripheral gangrene (SPG) is an uncommon but important clinical syndrome. We present a case of acute chorioamnionitis complicated with SPG. Case report A 33-year-old female (gravida 5, para 2) was admitted with preterm premature rupture of membranes (PPROM) at 20 weeks and four days of gestation. She received cervical cerclage four days ago. Seven days after the diagnosis of PPROM, she developed fever, tachypnea and tachycardia. Termination of pregnancy was decided for clinical diagnosis of sepsis. After the abortus was born, gangrene change on the nose was noticed. Afterwards, this patient developed acrocyanosis of extremities. SPG developed following sepsis with intravascular disseminated coagulation (DIC). After intensive care, the patient underwent hyperbaric oxygen therapy and fasciectomy of the left forearm. Conclusion We suggest awareness of SPG associated with acute chorioamnionitis. Early recognition of SPG, multidisciplinary care, and treatment of its underlying conditions are the mainstays of management.

Preterm premature rupture of membranes and massive genital bleeding in the second trimester are serious obstetrical problems in pregnancy after trachelectomy. We had managed a twin post‐trachelectomy pregnancy by multiple strategies, and two healthy infants were delivered at 32+5 weeks, although the optimum management for such patients is unknown.

Even though assisted reproductive techniques represent one of the greatest achievements in modern medicine, the risk of preterm birth related to these pregnancies is about twice as high. This must be highlighted and further investigated to optimize the management of both mothers and newborns. The purpose of this study was to compare adverse pregnancy outcomes after assisted reproductive techniques (ART) and spontaneous conceptions, focusing on the incidence of preterm births (PTB) and distinguishing between iatrogenic and spontaneous events. This retrospective cohort study analyzed single births of one Italian hospital. The incidence of PTBs in ART pregnancies, divided into iatrogenic procedures, spontaneous preterm labors and preterm premature ruptures of the membranes (pPROMs), was compared with the non-ART control group. The incidence of other adverse pregnancy outcomes and the types of delivery were also reported and compared. Of the 11,769 single births included, 2.39% were conceived by ART. The incidence of PTBs was 4.74% for spontaneous pregnancies and 12.8% for ART pregnancies (aOR 1.93; 95% CI 1.29–2.88). The percentage of iatrogenic procedures was 27.78% in the ART-PTBs’ group and 30.88% in the non-ART-PTBs’ controls. ART pregnancies showed an increased incidence of pPROMs (6.40% versus 2.41%), preterm labors (2.85% versus 0.93%), hypertensive disorders of the pregnancy (8.19% versus 2.32%), placenta previa (3.20% versus 0.59%), cesarean sections (28.47% versus 16.27%) and vacuum extractions (10.32% versus 5.19%). Singleton ART pregnancies have a higher risk of PTB which is mostly linked to a higher incidence of pPROMs and spontaneous preterm labor. The concurrency of a demonstrated higher risk of hypertensive gestational disorders and placenta previa suggests that placental development plays an important role in the pathogenesis of PTB.

BACKGROUND: Preterm premature rupture of membranes (P-PROM) exerts a tremendous influence on pregnancy prognosis. Additionally, it is a major public health concern, as the cause of up to 40% of all preterm births. AIM: The objective of this study was to identify predictors of Caesarean Delivery in singleton pregnancies complicated by P-PROM. MATERIALS AND METHODS: This is a retrospective observational study of all consecutive singleton P-PROM deliveries (24-37 weeks) over an 18 months at a tertiary referral centre. Pertinent data was collected comprising demographics, obstetric history, pregnancy-associated pathology and delivery from electronic patient records. Univariate statistical analysis comprised Odds Ratio, 95% Confidence interval and Chi-square test with subsequent p-value with statistical significance set at p < 0.05. RESULTS: A total of 240 women delivered singletons following P-PROM over an 18-month period. Maternal age ranged between 12-41 years with an average age of 28 ± 6.27 years. Vaginal delivery (VD) was the predominant mode of delivery, accounting for 52.9% (n = 127) of deliveries. The following parameters were identified as predictors of Caesarean Section (CS) in P-PROM: vaginal infection (p = 0.04), previous CS (p < 0.0001), primiparity (p = 0.004), gravidity > 5 (p = 0.009), university education (p = 0.0006) and prenatal care (p < 0.0001). CONCLUSION: The advantage of CS over vaginal delivery is expedited delivery of the distressed fetus, while that of vaginal delivery entails avoiding postoperative morbidity. However, large multicentric randomised-controlled studies are needed to elucidate this dilemma definitively.

Objective A 7-day course of a penicillin (PCN) and macrolide is standard of care (SAR) in preterm premature rupture of membranes (PPROM). Data regarding alternative antibiotic regimens are limited. We sought to assess the impact of non-PCN regimens on neonatal outcomes. Study Design Secondary analysis of randomized controlled trial of antenatal magnesium sulfate. Singleton, nonanomalous pregnancies complicated by PPROM at > 24 weeks of gestation receiving the SAR were compared with women receiving a non-β-lactam regimen and a macrolide (NPCR). Primary outcome was a neonatal composite. Secondary outcomes included pregnancy latency, endometritis, and chorioamnionitis. Results A total of 949 women met inclusion criteria; 821(56%) received the SAR and 128(8.8%) received NPCR. Adjusted models did not demonstrate worse outcomes (AOR [adjusted odds ratio] = 0.50; 95% CI [confidence interval]: 0.22–1.11). Neonates receiving SAR were less likely to have bronchopulmonary dysplasia (BPD; p = 0.03) but more likely to have severe necrotizing enterocolitis (sNEC; p = 0.04). Risk for chorioamnionitis and median latency did not differ between groups but women receiving the SAR were less likely to get endometritis (AOR = 0.35; 95% CI: 0.14–0.91). Conclusions In this cohort, receiving NPCR in the setting of PPROM did not impact the overall risk of adverse neonatal outcomes or latency, but did increase the risk of endometritis. Alterations in individual neonatal morbidities suggest follow-up studies are needed.

Amaç: Erken membran rüptürü (EMR) preterm doğuma, neonatal morbiditelere ve mortaliteye sebep olabilir. Bu çalışmadaki amacımız EMR’nin, Aim: Premature rupture of membranes (PROM) can cause preterm birth, neonatal morbidity and mortality. In this study, we aim to examine the effect of PROM on the early prognosis of premature infants

Background We sought to determine whether lipopolysaccharide binding protein (LBP), pentraxin 3, resistin, and insulin-like growth factor binding protein (IGFBP)-3 in plasma and amniotic fluid (AF) can predict microbial invasion of the amniotic cavity (MIAC), intra-amniotic inflammation (IAI), and microbial-associated IAI in women with preterm premature rupture of membranes (PPROM). Methods This was a retrospective cohort study involving 168 singleton pregnant women with PPROM. AF obtained via amniocentesis was cultured and assayed for interleukin (IL)-6 to define IAI and for IL-8 to compare with AF biomarkers. Plasma samples were collected at the time of amniocentesis, and C-reactive protein (CRP) levels in serum were compared with plasma biomarkers. The stored plasma and AF samples were assayed for LBP, pentraxin 3 (PTX3), resistin, and IGFBP-3 by ELISA. Results Multivariate logistic regression analysis revealed that: 1) elevated plasma and AF levels of LBP were independently associated with increased risks of MIAC, IAI, and microbial-associated IAI; 2) elevated AF, but not plasma, PTX3, and resistin levels were independently associated with increased risks of MIAC, IAI, and microbial-associated IAI; 3) decreased IGFBP-3 levels in the plasma were independently associated with only IAI, whereas those in the AF were associated with only microbial-associated IAI. Among the tested biomarkers, AF PTX3 and resistin had the highest predictive performance for MIAC, IAI, and microbial-associated IAI (area under the curves [AUC] = 0.85–0.95), which is similar to the performance of AF IL-8. The AUCs of the plasma LBP and IGFBP-3 were similar to that of serum CRP with respect to IAI. Conclusion Maternal plasma LBP and IGFBP-3 are potential biomarkers for the non-invasive identification of IAI in women with PPROM, with a similar accuracy to the serum CRP level. AF LBP, PTX3, resistin, and IGFBP-3 may be involved in the intra-amniotic inflammatory responses in PPROM complicated by MIAC., Graphical Abstract

Background The neutrophil-lymphocyte ratio (NLR) is easily calculated blood test parameter, which can be used as marker to predict many inflammatory disorders. The aim of this study was to assess and compare the NLR in maternal blood with the white blood cell (WBC) count and C-reactive protein (CRP) concentration for the prediction of histological chorioamnionitis. Methods This was a case-control study of 137 woman with preterm premature rupture of membranes (PPROM) at a gestational age between 22+ 0 and 34+ 6 weeks. Blood samples, collected less than 48 h before delivery and at least 48 h after the administration of corticosteroids, were selected for the analysis. The NLR was calculated by dividing the number of neutrophils by the number of lymphocytes. Chorioamnionitis was diagnosed by the histopathological evaluation of placental membranes and chorionic plate. Results Patients with diagnosed histological chorioamnionitis (HCA) had significantly higher levels of WBC, CRP and NLR (p-value Conclusion NLR has a good predictive value for HCA and could be used as an additional diagnostic marker for predicting histological chorioamnionitis in cases with preterm premature rupture of membranes before 34 weeks of gestation.

Introdução: Ruptura prematura das membranas amnióticas pré-termo (RPMP) é responsável por cerca de 30% dos nascimentos prematuros, estando associada à grande morbimortalidade neonatal. O uso de antibióticos na conduta conservadora parece aumentar o tempo de latência entre a RPMP e o nascimento, assim como melhorar desfechos maternos e neonatais. O benefício a curto e longo prazo, e o esquema ideal de antibiótico ainda permanecem controversos. Esse estudo busca demonstrar que o uso de antibióticos na conduta conservadora reduz a taxa de nascimentos nas primeiras 48 horas após a RPMP, aumentando o tempo de latência entre a RPMP e o nascimento,. Método: estudo observacional, de coorte retrospectiva em gestantes com RPMP tratadas de forma conservadora no Hospital de Clínicas de Porto Alegre (HCPA), de janeiro de 2012 a dezembro de 2019. Para o grupo que utilizou antibiótico, o esquema utilizado foi Azitromicina e ampicilina por 48 horas, seguido de amoxicilina por 5 dias - completando 7 dias de tratamento. Resultados: 145 participantes, 107 não utilizaram antibiótico (grupo 1), 38 utilizaram antibiótico (grupo 2). A taxa de nascimento em 48 horas foi significativamente menor no grupo com antibiótico (36 {33,64%} na grupo 1, vs. 6 {16%} no grupo 2, p = 0,04). Conclusão: O uso desse esquema de antibióticos reduziu a taxa de nascimentos em 48 horas, aumentando o tempo de latência entre a RPMP e o nascimento, com potencial benefício clínico pelo aumento da janela farmacológica para ação corticoterapia, entre outros. Introduction: Preterm premature rupture of amniotic membranes (PPROM) is responsible for about 30% of premature births, being associated with great neonatal morbidity and mortality. The use of antibiotics in expectant management seems to increase the latency period between PPROM and birth, as well as improving maternal and neonatal outcomes. However, short and long term benefits, and the ideal antibiotics regimen remains controversial. This study seeks to demonstrate that the use of antibiotics in conservative management reduces the birth rate in the first 48 hours after PPROM, increasing the latency period between PPROM and birth. Methods: Observational, retrospective cohort study in pregnant women with PPROM treated conservatively at the Hospital de Clínicas de Porto Alegre (HCPA), from January 2012 to December 2019. For the group that used antibiotics, the scheme was Azithromycin and Ampicillin for 48 hours, followed by Amoxicillin for 5 days, completing 7 days of treatment. Results: 145 participants, of which 107 did not use antibiotics (group 1) and 38 used antibiotics (group 2). The 48-hour birth rate was significantly lower in the antibiotics group (33.6% in group 1 vs. 16% in group 2, p=0.04). Conclusion: The use of this antibiotics regimen reduced the birth rate in the first 48 hours, increasing the latency period between PPROM and birth, with potential clinical benefits due to the increase in the pharmacological window for corticosteroid action, among others.

Background: Preterm premature rupture of membranes (PPROM) is a complication responsible for a third of preterm births. Clinical management is initially hospital based, but homecare management is possible if patients are clinically stable 48 h after PPROM. This study set out to determine factors that are predictive of short latency (delivery &le, 7 days) exceeding 48 h after PPROM, enabling estimation of the prevalence of maternal and neonatal complications and comparison of maternal and fetal outcomes between inpatient and outpatient management. Method: This was a monocentric retrospective study conducted between 1 January 2010 and 28 February 2017 on all patients experiencing PPROM at 24 to 34 weeks + 6 days and who gave birth after 48 h. Maternal, obstetric, fetal, and neonatal variables were included in the data collected. The primary endpoint was latency, defined as the number of days between rupture of membranes and delivery. Results: 170 consecutive patients were analyzed. Short latency could be predicted by the need for tocolysis, a cervical length less than 25 mm at admission and the existence of anamnios. Outpatient follow-up was not found to lead to increased maternal morbidity or neonatal mortality. Conclusion: Our study highlights predictive factors of short latency exceeding 48 h after PPROM. Knowledge of these factors may provide justification for outpatient monitoring of patients presenting with a long cervix, absence of need for tocolysis and persistence of amniotic fluid and, thus, no risk factors after 48 h of admission.

IntroductionChorioamnionitis is one of the most important maternal complications in the expectant management of patients with preterm premature rupture of membranes (PPROM). Procalcitonin (proCT), the precursor of the hormone calcitonin, is used to differentiate bacterial infections from non-bacterial ones. The objective of the study was to determine the efficacy of maternal serum procalcitonin levels in the early prediction of chorioamnionitis in women with PPROM.Material and methodsThe study was conducted in 76 pregnant women hospitalized due to PPROM at the maternal-fetal medicine unit of a tertiary center in Istanbul. Patients were followed up with white blood cell (WBC), C-reactive protein (CRP) and proCT levels every 2 days. The values of investigated parameters were recorded at the diagnosis of PPROM and at the time of delivery. The maximum values during the follow-up period were also recorded.ResultsOut of the 76 patients with PPROM, 15 (19.73%) developed clinical chorioamnionitis. No significant difference could be detected in the gravidity, parity, duration of hospitalization and gestational week at diagnosis between those patients who developed clinical chorioamnionitis and those who did not. The WBC at the time of hospital admittance and before delivery, and CRP levels before delivery were statistically higher in the chorioamnionitis group (p < 0.05). No difference in the proCT levels could be detected either at the time of hospital admittance or before delivery between the two groups.ConclusionsMaternal proCT was not found to be predictive of chorioamnionitis. However, since there are reports in the literature that contradict these results, further studies are warranted to determine the true efficacy of proCT in the prediction of clinical chorioamnionitis.

To compare the type of management (active versus expectant) for preterm premature rupture of membranes (PPROM) between 34 and 36 + 6 weeks of gestation and the associated adverse perinatal outcomes in 2 tertiary hospitals in the southeast of Brazil. In the present retrospective cohort study, data were obtained by reviewing the medical records of patients admitted to two tertiary centers with different protocols for PPROM management. The participants were divided into two groups based on PPROM management: group I (active) and group II (expectant). For statistical analysis, the Student Of the 118 participants included, 78 underwent active (group I) and 40 expectant management (group II). Compared with group II, group I had significantly lower mean amniotic fluid index (5.5 versus 11.3 cm, There was no association between active versus expectant management in pregnant women with PPROM between 34 and 36 + 6 weeks of gestation and adverse perinatal outcomes. Comparar o tipo de manejo (ativo versus expectante) para ruptura prematura de membranas (PPROM, na sigla em inglês) entre 34 e 36 semanas e 6 dias de gestação e os resultados perinatais adversos relacionados, em 2 hospitais terciários do sudeste brasileiro. MéTODOS: No presente estudo de coorte retrospectivo, os dados foram obtidos através da revisão dos prontuários de gestantes internadas em dois centros terciários com protocolos diferentes para o seguimento da PPROM. As gestantes foram divididas em dois grupos com base no manejo da PPROM: grupo I (ativo) e grupo II (expectante). Para análise estatística, foram utilizados o teste t de Student, qui-quadrado e regressão logística binária. Das 118 gestantes incluídas, 78 foram submetidas a tratamento ativo (grupo I) e 40 a seguimento expectante (grupo II). Comparado ao grupo II, o grupo I apresentou índice de líquido amniótico médio significativamente menor (5,5 versus 11,3 cm

Purpose Early detection of infection is of supreme importance in obstetrics; however, during pregnancy it is not reliably predicted by standard laboratory tests. We aimed to determine if procalcitonin (PCT) is a reliable predictor of chorioamnionitis (CA) in women with premature rupture of membranes (PPROM). Methods An electronic search of Scopus, ISI, Medline, Embase, ClinicalTrials.gov and the Cochrane Library databases was performed using specifed key words. We examined all English and French reports on PCT measurement after admission for PPROM and considered: human studies published between 1990 and 2019; observational studies; and randomized controlled trials. A protocol was determined previously, registered at PROSPERO as CRD42019145464. The eligibility was independently assessed by two researchers and literature search yielded 590 studies; after revision of the titles and abstracts, 46 articles were identifed as potentially eligible; eight studies were included in the meta-analysis. Primary data synthesis was performed in Review Manager Version 5.3 and average sensitivity and specifcity was calculated using Midas, Stata. Results From the eight studies included, 335 participants with PPROM were enrolled. Our meta-analysis disclosed that PCT has a poor sensitivity (0.50; 95% CI 0.28–0.73) and a modest specifcity (0.72; 95% CI 0.51–0.87) in diagnosing CA. C-reactive protein (CRP) not only has better sensitivity (0.71; 95% CI 0.53–0.84), but also better specifcity (0.75; 95% CI 0.55–0.88), compared with the other infammatory parameters analyzed. Procalcitonin does not seems to be better than CRP in preterm rupture of membranes for chorioamnionitis diagnosis. F31D-D663-4EF2 | Anabela Mota Pinto info:eu-repo/semantics/publishedVersion

International audience; Preterm premature rupture of membranes (PPROM), defined as rupture of fetal membranes prior to 37 weeks of gestation, complicates approximately 2–4% of pregnancies and is responsible for 40% of all spontaneous preterm births. PPROM arises from complex pathophysiological pathways with a key actor: inflammation. Sterile inflammation is a feature of senescence-associated fetal membrane maturity. During specific steps of sterile inflammation, cells also release highly inflammatory damage-associated molecular pattern markers (DAMPs), such as high-mobility group box 1 (HMGB1) or S100A8/A9, known to link and activate the receptor for advanced glycation end products (RAGE). The objective of this study was to measure longitudinally during pregnancy concentrations of the soluble form of RAGE (sRAGE) and its main ligands (AGE, HMGB1, S100A8/A9) in blood specimens. We studied 246 pregnant women (82 with PPROM and 164 matched control pregnant women without complications) from a cohort of 7,866 pregnant women recruited in the first trimester and followed during pregnancy until delivery. sRAGE, AGE, HMGB1, and S100A8/A9 concentrations were measured in plasma and in serum-extracted extracellular vesicles from first trimester (T1), second trimester (T2), and delivery (D). In plasma, we observed, in both PPROM and control groups, (i) a significant increase of HMGB1 concentrations between T1 vs. T2, T1 vs. D, but not between T2 vs. D; (ii) a significant decrease of sRAGE concentrations between T1 and T2 and a significant increase between T2 and D; (iii) a significant decrease of AGE from T1 to D; (iv) no significant variation of S100A8/A9 between trimesters. In intergroup comparisons (PPROM vs. control group), there were no significant differences in time variation taking into account the matching effects. There was a correlation between plasma and serum-extracted extracellular vesicle concentrations of sRAGE, AGE, HMGB1, and S100A8/A9. Our results suggest that the rupture of fetal membranes (physiological or premature) is accompanied by a variation in plasma concentrations of sRAGE, HMGB1, and AGE. The study of RAGE and its main ligands in extracellular vesicles did not give additional insight into the pathophysiological process conducting to PPROM.

In approximately 8% of term births and 33% of pre-term births, the fetal membrane ruptures before delivery. In vitro studies of fetal membranes after delivery have suggested the series of events leading to rupture, but no in vivo studies have confirmed this model. In this study, we used a three-dimensional constructive interference in steady state sequence to examine the fetal membrane at the cervical internal os zone during pregnancy. 18 pregnant women with 1 ~ 3 longitudinal MRI scans were included in this study. In 14 women, the fetal membrane appeared normal and completely intact. In 4 women, we noted several fetal membrane abnormalities including cervical funneling, chorioamniotic separation, and chorion rupture. Our data support the in vitro model that the fetal membrane ruptures according to a sequence starting with the stretch of chorion and amnion, then the separation of amnion from chorion, next the rupture of chorion, and finally the rupture of amnion ruptures. These findings hold great promise to help to develop an in vivo magnetic resonance imaging marker that predicts early fetal membrane rupture.

Preterm premature rupture of membranes is a leading cause of preterm births. Cytokine induced matrix metalloproteinase1 and interleukin 8 production from amnion mesenchymal cells may contribute to fetal membrane weakening and rupture. Progestins inhibit inflammation induced fetal membrane weakening but their effect on the inflammatory response of amnion mesenchymal cells is unknown. This study was designed to determine the role of progesterone receptor membrane component 1 and the glucocorticoid receptor in mediating the effects of progestins on interleukin-1 induced matrix metalloproteinase 1 and interleukin-8 expression in human amnion mesenchymal cells. Primary amnion mesenchymal cells harvested from human fetal membranes were passaged once and treated with vehicle, progesterone or medroxyprogesterone acetate at 10-6 M for 1 h followed by stimulation with interleukin-1 at 1 ng/ml for 24h. Medroxyprogesterone acetate but not progesterone inhibited interleukin-1-induced interlukin-8 and matrix metalloproteinase 1 mRNA expression. In subsequent dose response studies, medroxyprogesterone acetate, but not progesterone, at doses of 10-6 to 10-8 M inhibited interleukin-1 induced interleukin-8 and matrix metalloproteinase 1 mRNA expression. We further demonstrated that inhibition of glucocorticoid receptor expression, but not progesterone receptor membrane component 1 knockdown with small interfering RNA transfection, resulted in a reversal in medroxyprogesterone acetate’s (10-7M) inhibition of interleukin-1- induced matrix metalloproteinase 1 mRNA expression and interleukin-8 mRNA expression and protein expression. Our findings demonstrate that medroxyprogesterone acetate exerts its anti-inflammatory effect primarily through the glucocorticoid receptor in human amnion mesenchymal cells. Modulation of glucocorticoid receptor signalling pathways maybe a useful therapeutic strategy for preventing inflammation induced fetal membrane weakening leading to preterm premature rupture of membranes.

Purpose: We aimed to investigate the relationship between adverse neonatal outcomes and the time period of labor in between urinary tract infection in preterm premature rupture of membranes (PPROM) to preterm labor (PL). Materials and Methods: We evaluated a total number of 1033 pregnant patients who admitted to our center between 2008 and 2014, with retrospective analysis. Study groups consisted of 446 PPROM and 587 PL patients who had urine cultures. Results: We determined cervical lengths which were measured by transvaginal ultrasonography, with OR = 0.806 and amniotic fluid index (AFI), OR = 0.961 in PPROM group, which had positive urine culture, and also cervical length OR = 0.862 in PL group which had positive urine culture and to be associated with shorter than seven days of delivery. Additionally, we determined that only the AFI, with OR = 0.982, to be associated with adverse neonatal outcomes in the PPROM group, having positive urine culture. Conclusion: AFI and cervical length can also be used to predict adverse neonatal outcomes and time of delivery in urine culture positive PPROM and PL patients. WOS:000522558800006

Background The reason for increased serum creatinine levels in preterm infants often remains unclear. We aimed to determine whether postnatal serum creatinine in preterm infants correlates with intake of amniotic fluid, represented by the amount of amniotic fluid after preterm premature rupture of membranes (PPROM). Methods 74 preterm infants with PPROM > 48 h duration were retrospectively studied. Postnatal creatinine concentration was determined at day 2–5, 10–17 and 26–33 of life and compared between infants with normal intrauterine amniotic volumes, oligohydramnios and anhydramnios. Results Mean gestational age of included patients was 29.7 weeks (range: 24.0–36.1 weeks) and mean birth weight was 1452 g (range: 560–2940 g). Serum creatinine concentration was similar at day 2–5 and day 10–17 of life between the three groups. We observed a significant decrease in creatinine concentration from day 2–5 to day 26–33 in infants with normal amniotic fluid volume and oligohydramnios (p = 0.0001 and p = 0.0071, respectively), but not in anhydramnios. On day 26–33 of life, infants with anhydramnios showed significantly higher creatinine levels compared to infants with normal amniotic fluid volume and oligohydramnios (p = 0.0211). Conclusion Postnatal serum creatinine of preterm infants at day 26–33 of life is elevated in infants with PPROM-induced anhydramnios, but not in oligohydramnios.

Aim. Investigation of the association between SNP genes of IL4 (rs2243250), IL10 (rs1800896 and rs1800872) and RLN2 (rs4742076 and rs3758239) and preterm premature rupture of membranes in 26–34 weeks of gestation in Zaporizhzhia population. Materials and methods. W e have investigated markers of cytokines genes in 50 women with PPROM in 26–34 weeks of gestation period and 50 pregnant women with physiological pregnancy and term labour without complications. The genotyping using TaqMan tests was done on amplifier CFX96™ Real-Time PCR Detection Systems (Bio-Rad Laboratories, Inc., USA. The combined effect of the studied locus of the analyzed genes on the appearance of PPROM, PTL in the population was initiated using the Multifactory Dimensionality Reduction (MDR) method (software MDR ver. 3.0.2). Results. The distribution of the rs2243250 gene polymorphism alleles of the IL4 gene of the main study group – TT homozygotes were determined in 4 % cases, CT heterozygotes were found in 22 %, CC homozygotes – in 74 % cases. We have got statistically significant differences of rs4742076 polymorphisms (TT, CT, and CC) of the RLN2 gene in the study groups. We also detected statistically significant differences in all the alleles of rs3758239 polymorphism (AA, GG and AG) of the gene RLN2 – χ 2 = 23.86, OR( AA ) = 12.57; 95 % CI: 3.68–42.98; OR( GG )= 0.08; 95 % CI: 0.02–0.27; and OR( AG )= 0.11; 95 % CI: 0.03–0.42, respectively, P < 0.05, indicating the reliability of the received prognostic markers. The nature of interlocal interaction between the genes is at the level of “independent effects” of influence (IL4-IL10 rs1800896 = -23.08 %, IL10 rs1800896 – IL10 rs1800872 = -19.94 %, IL10 rs1800872-IL-4 = -19.34 %). The percentage of entropy of the investigated polymorphism of each gene for the case-control status was 14.15 % for the IL4 gene, 23.08 % for the IL10 rs1800896 gene and 9.34 % for the IL10 rs1800872 gene. Conclusions. Combination of IL4 rs2243250, IL10 rs1800896 and rs1800872 supports the role for functional polymorphisms in immunoregulatory genes in the development of PPROM and PTL. Reliable clinical association of rs4742076 and rs3758239 gene RLN2 was established with the PPROM in 26–34 weeks’ gestation in Zaporizhzhia population.

Background: For the past two decades, studies have investigated the relationship between periodontal disease and adverse pregnancy outcomes such as pre-eclampsia, preterm birth, low birth weight and preterm premature rupture of membranes. Objectives: To determine the prevalence of periodontal disease and associated adverse pregnancy outcomes among women delivering at the Kilimanjaro Christian Medical Centre (KCMC). Methods: This cross-sectional study was based on the use of patients’ files, clinical examinations and oral interviews with mothers who delivered at the KCMC. Pregnant women with singleton babies (N=1117) who delivered at the KCMC were recruited for the study. Intra-oral examination was performed within five days of birth. The Community Periodontal Index was used to assess periodontal disease Results: The prevalence of periodontal disease was 14.2%. Periodontal disease was significantly associated with higher odds of pre-eclampsia [adjusted Odds Ratio 95% Confidence Interval (aOR=4.12;95%CI:2.20-7.90)], low birth weight (aOR=2.41;95%CI:1.34-4.33) and preterm birth (aOR=2.32;95%CI:1.33-4.27). There was no significant association between periodontal disease and preterm premature rupture of membranes (aORs 1.83;95%CI:0.75-4.21) and eclampsia (3.71;95%CI:0.80-17.13). Conclusion: Maternal periodontal disease is a potential independent risk indicator for pre-eclampsia, low birth weight, and preterm birth. Periodontal assessment and therapy should form part of the preventive antenatal care provided to women in developing countries. Keywords: Preterm birth; low birth weight; pre-eclampsia; eclampsia; preterm premature rupture of membranes; periodontal disease; periodontitis; cross-sectional studies.

Background Twin studies have revealed a significant contribution of the fetal genome to risk of preterm birth. Preterm premature rupture of membranes (PPROM) is the leading identifiable cause of preterm delivery. Infection and inflammation of the fetal membranes is commonly found associated with PPROM. Methods We carried out whole exome sequencing (WES) of genomic DNA from neonates born of African-American mothers whose pregnancies were complicated by PPROM (76) or were normal term pregnancies (N = 43) to identify mutations in 35 candidate genes involved in innate immunity and host defenses against microbes. Targeted genotyping of mutations in the candidates discovered by WES was conducted on an additional 188 PPROM cases and 175 controls. Results We identified rare heterozygous nonsense and frameshift mutations in several of the candidate genes, including CARD6, CARD8, DEFB1, FUT2, MBL2, NLP10, NLRP12, and NOD2. We discovered that some mutations (CARD6, DEFB1, FUT2, MBL2, NLRP10, NOD2) were present only in PPROM cases. Conclusions We conclude that rare damaging mutations in innate immunity and host defense genes, the majority being heterozygous, are more frequent in neonates born of pregnancies complicated by PPROM. These findings suggest that the risk of preterm birth in African-Americans may be conferred by mutations in multiple genes encoding proteins involved in dampening the innate immune response or protecting the host against microbial infection and microbial products.

Background: Preterm premature rupture of membrane (PPROM) can lead to serious consequences such as intrauterine infection, prolapse of the umbilical cord, and neonatal respiratory distress syndrome. Genital infection is a very important risk which closely related with PPROM. The preliminary study only made qualitative research on genital infection, but there was no deep and clear judgment about the effects of pathogenic bacteria. This study was to analyze the association of infections with PPROM in pregnant women in Shaanxi, China, and to establish Bayesian stepwise discriminant analysis to predict the incidence of PPROM. Methods: In training group, the 112 pregnant women with PPROM were enrolled in the case subgroup, and 108 normal pregnant women in the control subgroup using an unmatched case-control method. The sociodemographic characteristics of these participants were collected by face-to-face interviews. Vaginal excretions from each participant were sampled at 28–36+6 weeks of pregnancy using a sterile swab. DNA corresponding to Chlamydia trachomatis (CT), Ureaplasma urealyticum (UU), Candida albicans, group B streptococci (GBS), herpes simplex virus-1 (HSV-1), and HSV-2 were detected in each participant by real-time polymerase chain reaction. A model of Bayesian discriminant analysis was established and then verified by a multicenter validation group that included 500 participants in the case subgroup and 500 participants in the control subgroup from five different hospitals in the Shaanxi province, respectively. Results: The sociological characteristics were not significantly different between the case and control subgroups in both training and validation groups (all P > 0.05). In training group, the infection rates of UU (11.6% vs. 3.7%), CT (17.0% vs. 5.6%), and GBS (22.3% vs. 6.5%) showed statistically different between the case and control subgroups (all P < 0.05), log-transformed quantification of UU, CT, GBS, and HSV-2 showed statistically different between the case and control subgroups (P < 0.05). All etiological agents were introduced into the Bayesian stepwise discriminant model showed that UU, CT, and GBS infections were the main contributors to PPROM, with coefficients of 0.441, 3.347, and 4.126, respectively. The accuracy rates of the Bayesian stepwise discriminant analysis between the case and control subgroup were 84.1% and 86.8% in the training and validation groups, respectively. Conclusions: This study established a Bayesian stepwise discriminant model to predict the incidence of PPROM. The UU, CT, and GBS infections were discriminant factors for PPROM according to a Bayesian stepwise discriminant analysis. This model could provide a new method for the early predicting of PPROM in pregnant women.