Gestation In Women Research Articles

Timing of Delivery in Intrahepatic Cholestasis of Pregnancy With Total Bile Acids ≥100 µmol/L: A Decision Analysis [38N

INTRODUCTION: Our study models the trade-off between preterm neonatal morbidity and stillbirth for women with intrahepatic cholestasis of pregnancy (ICP) with total bile acids ≥100 µmol/L in order to determine the optimal gestational age for delivery. METHODS: A decision analytic model was created to compare the outcomes of delivery at 33 through 40 weeks gestation in women with total bile acids (TBA) ≥100 µmol/L. Baseline risks of stillbirth and spontaneous delivery were derived from the literature and adjusted for peak TBA. It was assumed that betamethasone was given within 48 hours of all planned preterm deliveries and before a percentage of spontaneous ones. We assumed a population of 10,000 women with ICP and calculated total quality-adjusted life years (QALYs) for each strategy, taking into account both maternal and neonatal perspectives. Univariate sensitivity analysis was performed for all variables to test the robustness of the model. RESULTS: In women with peak TBA ≥100 µmol/L, delivery at 34 weeks maximized QALYs. Compared to delivery at 36 weeks, it resulted in 1302.4 more QALYs, 98.2 fewer stillbirths, and 21 more cases of cerebral palsy in our theoretical cohort of 10,000 women. Sensitivity analysis demonstrated that when the relative risk of stillbirth given TBA ≥100 µmol/L fell from a baseline of 30.5 to below 26.2, delivery at 35 weeks became optimal. Monte Carlo analysis demonstrated that when variation was incorporated into the model, delivery at 34 weeks was the dominant strategy 45% of the time. CONCLUSION: In women with ICP with TBA ≥100 µmol/L, delivery at 34 weeks maximizes QALYs.

Features of the content of homocysteine and thyroid hormones in pregnant women with uterine myoma

The purpose and objectives of the study is to assess the effect of hyperhomocysteinemia on the first trimester of gestation in women with uterine myoma. Relevance. Biochemical and hormonal changes that occur in the myometrium and the body of a woman as a whole, without preventing the onset of pregnancy, can have a significant effect on the formation of the chorion and the clinical course of the gestational process, provoking complications such as miscarriage. Material and research methods. To achieve this goal, we examined 182 pregnant women, of which the main group was 98 pregnant women with a verified diagnosis of uterine fibroids, which took place before gestation, but did not prevent pregnancy. The comparison group included 84 pregnant women without anamnestic indications of gynecological pathology and signs of fetoplacental insufficiency. Results. We made an attempt to highlight the features of the content of homocysteine and thyroid hormones in pregnant women with uterine myoma and the influence of these indicators on the onset of gestation. Considering the results obtained, we indicate that pregnant women with uterine fibroids and without a tumor had significant differences in individual values. Conclusions. In women with benign tumors of the uterus that are pregnant, the most common conditions in the first trimester are mild anemia and genital tract bleeding. Half of the observed pregnant women with uterine myoma have hyperhomocysteinemia and, in some of them, subclinical hypothyroidism. This must be considered when preparing for the pregnancy of these women.

SMFM Statement: Use of 17-alpha hydroxyprogesterone caproate for prevention of recurrent preterm birth

In late 2019, results from the Progestin's Role in Optimizing Neonatal Gestation (PROLONG) trial were published showing no benefit of weekly injections of 17-alpha hydroxyprogesterone caproate (17-)HPC) from 16-20 weeks of gestation in women with a history of a singleton PTB in reducing the rates of subsequent PTB and neonatal morbidity. The Society for Maternal-Fetal Medicine believes that the differences in these results from the earlier Meis, et al trial, which did show a benefit of 17-OHPC in reducing the rate of spontaneous PTB (sPTB), may be at least partially explained by differences in study populations. SMFM concludes that it is reasonable for providers to use 17-OHPC in women with a profile more representative of the very-high-risk population reported in the Meis trial. For all women at risk of recurrent sPTB, the risk/benefit discussion should incorporate a shared decision-making approach, taking into account the lack of short-term safety concerns but uncertainty regarding benefit.

Balloon Mitral Valvotomy in Gestational Women with Symptomatic Mitral Stenosis

Background: Rheumatic valvular heart disease, commonly mitral stenosis, complicate 1% of pregnancies. Balloon mitral valvuloplasty (BMV) is an established treatment of rheumatic mitral stenosis. Aim of the study was to assess the safety and efficacy of Balloon mitral valvuloplasty in pregnant women with severe mitral stenosis.
 Materials and Methods: 66 patients who failed to respond to medical therapy undergoing BMV during pregnancy were analysed in this retrospective study. Mitral valve area (MVA), transmitral Mean valve gradient (MVG), and mitral regurgitation (MR), Pulmonary artery pressure (PAP) were assessed before and 24 hours after the procedure by transthoracic echocardiography. Patients were followed up to one month post BMV and neonates were monitored for the adverse effect of radiation. 
 Results: Mitral valve area increased from 0.83 ± 0.13 cm2 to 1.38 ± 0.29 cm2 (P = 0.007). Mean gradient mitral valve gradient decreased from 15.5 ± 7.4 mmHg to 3.36 ± 2.36 mmHg (P = 0.001). Pulmonary artery pressure decreased from 65.24 ± 17.9 to 50.45 ± 15.33 (P = 0.012). No maternal death, intrauterine growth restriction was observed.
 Conclusion: Balloon mitral valvuloplasty has favourable immediate good outcomes for mothers and newborns.

ПЕРЕБІГ ЗАГРОЗИ ПЕРЕРИВАННЯ ВАГІТНОСТІ ПРИ РІЗНИХ ТИПАХ ХРОНІЧНИХ ГАСТРИТІВ

Переривання вагітності – одна з важливих медико-соціальних проблем в усьому світі. Функціонально-морфологічні зміни в статевій сфері, які супроводжують нормальний ріст і розвиток плода при фізіологічній вагітності обумовлюють в різній мірі участь інших органів і систем материнського організму, сприяють зміні процесів обміну і підтримці гомеостазу в нових умовах для збереження вагітності. Розлади моторики шлунково-кишкового тракту можуть бути провідним патогенетичним чинником, що сприяє розвитку багатьох поширених гастроентерологічних розладів. Під час вагітності відзначається зниження перистальтичної активності кишечника, що може відігравати патогенетичну роль при вагітності як чинника, що призводить до зниження моторно-евакуаторної функції кишечника і, в свою чергу, здійснювати негативний вплив на перебіг вагітності. Метою дослідження було визначення особливостей клінічного перебігу загрози переривання в ранні терміни гестації у жінок з різними типами хронічних гастритів для оптимізації тактики ведення вагітності. Обстежено 67 вагітних із загрозою переривання в терміни 8-12 тижнів гестації, які становили 2 групи: 1 група- 35(52,2%) жінок з хронічними гастритами та 2 група – 32(47,8%) пацієнтки, які не мали гастритів. На початок вагітності всі жінки з хронічними гастритами були в стадії ремісії. Для визначення ролі моторно-евакуаторної функції ШКТ у розвитку загрози переривання у вагітних з гастритами проведена порівняльна оцінка частоти і виразності проявів даного ускладнення в ранні терміни за провідними клінічними ознаками: больовий синдром, кров’янисті виділення, наявність ретрохоріальної гематоми в поєднанні з основними гастроентерологічними проявами (блювання, закрепи) моторно-евакуаторної функції ШКТ при різних типах гастритів. Підтвердження типу гастриту проводилося за визначенням рівня базальної секреції гастрину 17 (G-17) в сироватці крові на тлі стимулюючого тесту. Результати оброблені методами математичного і статистичного аналізу з визначенням середніх величин (М ± m), критерія Стьюдента та показника достовірності (статистично достовірними вважали різницю р ˂ 0,05).Результати. Всі обстежені жінки знаходились в репродуктивному віці, середній вік вагітних в групах не мав статистичної різниці. Аналіз частоти клінічних проявів загрози переривання показав, що серед пацієнток 1 групи 35(100%) мали больову симптоматику, 30(85,7%) – кров’яністі виділення та 10(28,6%) – ретрохоріальну гематому, в 2 групі –відповідно: 32(100%), 12 (37,5%), 5(15,6%). Оцінка інтенсивності симптомів загрози переривання показала, що найчастіше відмічався помірний рівень болю при всіх типах гастритів Слабка інтенсивність мала місце при нормоацидному стані у жінок як 1групи (11,4%), так і 2 групи (9,4%). Сильний за інтенсивністю біль відмічали 2,9% вагітних 1 групи з гіперацидним станом та 3,1% жінок 2 групи з гіпоацидним станом. Аналіз характеру та інтенсивності кров’янистих виділень показав, що у жінок 1 групи при всіх типах гастритів були мажучі виділення: при гіперацидному типі у 11,4%, нормоацидному – 20,0% та гіпоацидному типі – у 11,4%.У жінок 2 групи мажучі виділення відмічені в 9,4% пацієнток з нормоацидним станом. Наявність помірних кров’янистих виділень була значно високою (в 7,4 рази вище) при гіперацидному стані у вагітних 1 групи в порівнянні з 2 групою. Ретрохоріальні гематоми реєструвались у вагітних 1 групи і становили 14,3% у пацієнток з гіперацидним типом, 5,7% - при нормоацидному типі і 8,6% - при гіпоацидному типі. Наявність ретрохоріальних гематом в 2,5 рази була вищою при гіперацидному гастриті в порівнянні з жінками з нормоацидним та в 1,7 рази вищою в порівнянні з гіпоацидним гастритом. Оцінка частоти поєднаних клінічних проявів функціональних захворювань ШКТ у вагітних із загрозою переривання вагітності показала, що прояви тільки загрози переривання спостерігались у 65,6% вагітних без гастритів, серед вагітних з гастритами їх відсоток становив лише 5,7%. Різні варіанти поєднаних клінічних проявів функціональних розладів ШКТ і загрози переривання суттєво переважали у жінок з хронічними гастритами: загроза переривання і блювання вагітних в 3 рази, загроза, блювання і закрепи – в 4,3 рази, загроза переривання і закрепи – в 1,6 рази. Найчастіше відмічено поєднання загрози переривання і блювоти вагітних при гіперацидному стані у жінок 1 групи (в 2,7 разів частіше ніж у жінок 2 групи). Варіант співвідношення загрози переривання, блювання вагітних та закрепів при гіперацидному стані в 3,6 разів частіше зустрічався серед жінок 1 групи, ніж 2 групи. Варіант загрози переривання із закрепами реєструвався у 17,1% жінок 1 групи при гіперацидному стані, що було в 2,7 разів частіше, ніж у жінок 2 групи. Найчастіше клінічні прояви загрози переривання і функціональні розлади ШКТ проявлялись в вагітних з хронічними гастритами при гіперацидному стані. Висновки. В клінічному перебігу загрози переривання вагітності важливу роль відіграє дисфункція моторно-евакуаторної діяльності ШКТ в залежності від типу хронічного гастриту, опосередкованого різною кислотоутворюючою функцією шлунку, що свідчить про необхідність оптимізації лікувальної тактики загрози переривання у вагітних з різними типами гастритів.

Circulating Delta-like homolog 1 (DLK1) at 36 weeks is correlated with birthweight and is of placental origin

IntroductionRecently, Delta-like homolog 1 (DLK1) was identified as a potential marker of small-for-gestational-age (SGA; <10th centile) fetuses; mouse studies suggest reduced levels may represent a fetal stress signal. We sought to measure DLK1 in a large independent cohort of maternal blood samples, correlate levels with measures of placental insufficiency and assess whether DLK1 might be placental derived. MethodsThe Fetal Longitudinal Assessment of Growth (FLAG) study was a prospective blood collection from 2000 women. We assessed a case-control cohort at 28 and 36 weeks from the first 1000 FLAG women, before validating changes in the entire second 1000. A subgroup of FLAG participants underwent ultrasound examinations, and 137 neonates, body composition assessment (PEAPOD). DLK1 secretion was assessed from human placentas ex vivo. ResultsCirculating DLK1 was significantly reduced at 28 and 36 weeks’ gestation in women destined to deliver a SGA fetus and associated with birthweight centile (n = 999, p < 0.0001), and placental weight (n = 96, p = 0.0064). Ex vivo, DLK1 was abundantly released from human placenta and significantly reduced under hypoxia (n = 7, p < 0.05). We found no relationship between circulating DLK1 and estimated fetal weight, cerebroplacental ratio, uterine artery or umbilical artery pulsatility index. Nor was there a relationship between DLK1 and neonatal fat or lean mass (n = 137). ConclusionWe confirmed circulating DLK1 is reduced at both 28 and 36 weeks’ gestation preceding delivery of a SGA infant, shown that it is not significantly associated with clinical measures of placental insufficiency, and provide new data demonstrating it may be placenta-derived in humans.

Hematology Profile Analysis and Birth Weight in Preeclampsia

Preeclampsia is a specific syndrome in pregnancy that occur after 20 weeks gestation in women who were previously normotensive. Hypertension in pregnancy caused complications in cardiovascular, hematology, endocrine, metabolic and regional blood flow accompanied by disorders of various organs, resulting in an increase of hemoconcentration in haemoglobin. The purpose of this study was to analyze the hematology profile and birth weight in preeclampsia. the design of this study was cross sectional with a sample of 40 respondents, consisting of 20 preeclampsia women and 20 women normal pregnancy. The hematology profile assessed was haemoglobin levels, hematocrit levels, platelet levels and blood sedimentation rates. The results showed haemoglobin levels, hematocrit levels, platelet level and blood sedimentation rates in both groups were not significantly difference with p value in each category was 0,110; 0,163; 0,686 and 0,983 (p value &gt;0,05). Thus this study concludes that the hematological profile and birth weight in preeclampsia and normal pregnancies are the same.

837: Large-for-gestational-age as a marker for adverse perinatal outcomes in pregnancy complicated by gestational diabetes mellitus

We sought to examine the strength of large-for-gestational-age (LGA) measuring neonates as a marker for adverse perinatal outcomes associated with poor glycemic control in women with gestational diabetes mellitus (GDM). A retrospective cohort study of 141,670 women in California with singleton, vertex, non-anomalous gestations was performed in order to assess prevalence of adverse perinatal outcomes in GDM with LGA neonates. LGA was defined as birth weight greater than or equal to the 90th percentile for a given gestational age. Maternal outcomes examined included preeclampsia, post-partum hemorrhage (PPH) and chorioamnionitis. Neonatal outcomes examined included respiratory distress syndrome (RDS), hypoglycemia, jaundice and intrauterine fetal demise (IUFD). Confounding variables including pre-gestational diabetes mellitus were controlled for and a p-value of less than 0.05 was considered statistically significant. Overall, LGA gestation in women with GDM was a reliable marker for an increased risk of perinatal complications (Table 1). Statistically significant increased complications included neonatal RDS (2.64% vs 1.77% p=0.001), hypoglycemia (1.06% vs 0.05% p< 0.001), jaundice (21.52% vs 19.18% p=0.003), IUFD (0.49% vs 0.14% p< 0.001), PPH (4.07% vs 2.95% p=0.001) and a decreased risk of chorioamnionitis (1.87% vs 2.68% p=0.014). Most notably, the risk of IUFD (Figure 1) and RDS steadily increase as the size of the fetus increases proportional to gestational age. Maternal complications were less statistically significant in the extremes of LGA. Large-for-gestational-age measurements in women with GDM are reliable markers for adverse perinatal outcomes. Of particular concern is the risks of IUFD and RDS, which decidedly increase with LGA centile greater than 90th. Women should be counseled about these risks and providers prepared to give additional respiratory support to neonates at delivery.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Prophylaxis of placental insufficiency and other complications of gestation in women with diseases associated with endothelial dysfunction

The pathogenesis of placental insufficiency and other complications of gestation is associated with vascular endothelial dysfunction. Glycocalyx covering the endothelium plays a fundamental role in coagulation and fibrinolysis. The presence of low molecular weight glycosaminoglycans in glycocalyx has a protective effect. The proven clinical efficacy of sulodexide to correct vascular endothelial dysfunction, prevent placental insufficiency and other pregnancy complications makes it a promising tool for use in obstetric practice among patients with chronic diseases (arterial hypertension, diabetes, obesity, etc.), autoimmune pathology, thrombophilia and related pregnancy complications (gestational diabetes, hypertension in pregnant women, pre-eclampsia, recurrent miscarriage, fetal growth retardation).

Association Between First-Trimester Subchorionic Hematomas and Adverse Pregnancy Outcomes After 20 Weeks of Gestation in Singleton Pregnancies.

To assess the association of first-trimester subchorionic hematomas with pregnancy outcomes after 20 weeks of gestation in women with singleton pregnancies. We conducted a retrospective cohort study of all women with singleton pregnancies presenting for prenatal care before 14 weeks of gestation over a 3-year period at a single obstetric practice. All patients underwent routine first-trimester ultrasound examinations. We compared rates of adverse pregnancy outcomes at more than 20 weeks of gestation in women with and without a subchorionic hematoma on the initial ultrasound examination, excluding women with pregnancy loss before 20 weeks of gestation. From January 2015 to December 2017, a total of 2,172 women met the inclusion criteria for the study, 389 (17.9%) of whom had a subchorionic hematoma (mean largest diameter 2.1±1.4 cm). Women with subchorionic hematomas had their first ultrasound examination at earlier gestational ages (8 5/7 vs 9 6/7 weeks, P<.001) and were more likely to have vaginal bleeding at the time of the ultrasound examination (31.9% vs 7.9%, P<.001). Maternal age, race, use of in vitro fertilization, body mass index, and medical comorbidities did not differ between the groups. On univariable analysis, subchorionic hematoma was not associated with any pregnancy outcomes at more than 20 weeks of gestation, including gestational age at delivery, preterm birth, birth weight, birth weight less than the 10th percentile for gestational age, gestational hypertension, preeclampsia, placental abruption, intrauterine fetal death at more than 20 weeks of gestation, cesarean delivery, blood transfusion, and antepartum admissions. On regression analysis including subchorionic hematoma, vaginal bleeding, and gestational age at ultrasound examination, vaginal bleeding was independently associated with preterm birth at less than 37 weeks of gestation and birth weight less than the 10th percentile. Subchorionic hematoma was not independently associated with pregnancy outcomes. This study had 80% power to detect a 5% absolute difference in the frequency of preterm birth; that is, from 10% to 15%. In singleton pregnancies, a first-trimester subchorionic hematoma is not associated with adverse pregnancy outcomes at more than 20 weeks of gestation.

Features of pregnancy course in women with chemoresistant tuberculosis (a literature review)

Tuberculosis is a global cause of morbidity among women of reproductive age, constituting a serious maternal and perinatal risk in both developed and developing countries. Tuberculosis is the third highest cause of death in women of reproductive age. At the same time, the frequency of diagnosing a specific process in pregnant women and pregnancy in women with tuberculosis is almost the same. Today, against this background, the treatment of chemoresistant tuberculosis (CR-TB) in pregnant women remains controversial. The purpose. To conduct a review of current literature sources in order to determine the characteristics of gestation in women with CR-TB, which will assist clinicians in the management of such patients. Results . In pregnant women, extrapulmonary and pulmonary forms of tuberculosis incidence are almost the same. Chest X-ray examination in pregnant women should not be avoided, since the radiation risk for the fetus is insignificant when the abdominal cavity shielding. In women with tuberculosis, childbirth occurs on average at the 38th week of pregnancy, and premature labor is associated with tuberculosis progression. In pregnant women with tuberculosis, the incidence of chorioamnionitis, gestosis, premature birth, anemia, pneumonia, maternal and perinatal mortality is higher than in pregnant women without tuberculosis. Newborns have an increased risk of a premature birth, congenital tuberculosis, intrauterine growth retardation, congenital abnormalities, and distress syndrome. A high frequency of these pathologies in pregnant women and newborns largely depends on tuberculosis progression, chemoresistance of mycobacterium tuberculosis and the adequacy of anti-mycobacterial therapy. Untreated CR-TB is associated with higher maternal mortality, an increased risk of vertical transmission of tuberculosis, spontaneous miscarriage, intrauterine growth restriction, premature birth, increased neonatal mortality. Breastfeeding is possible if there is a sputum culture conversion in mother. The risk of toxic reactions to anti-tuberculosis drugs in breastfed infants is low and may be minimized if a mother with tuberculosis takes medications immediately after breastfeeding. Medical indications for artificial termination of pregnancy at 12–22 weeks’ gestation are severe forms of tuberculosis: disseminated, progressive, chemoresistant, with severe complications. Conclusions . Considering the analysis of the literature, all pregnant women should be prescribed treatment for CR-TB with second-line anti-tuberculosis drugs based on the drug sensitivity test starting from the second trimester (if a patient is HIV-negative or not in a critical state) with the exception of drugs such as amikacin, streptomycin, prothionamide and ethionamide. A timely and adequate anti-mycobacterial therapy is the key to successful pregnancy outcome. Pregnancy follow-up among women with CR-TB should be based on an interdisciplinary approach including a team of physicians such as a tuberculosis specialist, obstetrician, neonatologist, and public health expert.

The effect of postoperative vaginal progesterone in ultrasound-indicated cerclage to prevent preterm birth

Objectives To compare pregnancy outcomes according to the use of postoperative vaginal progesterone in patients who underwent ultrasound-indicated cerclage. Methods This was a retrospective cohort study of 86 consecutive asymptomatic singleton pregnancies who had undergone cerclage because of incidentally found short cervical length under 20 mm through transvaginal ultrasound between 16°/7 and 246/7 weeks’ gestational age. Outcomes were compared according to the use of vaginal progesterone after cerclage. Primary outcome measure was preterm delivery < 34 weeks of gestation. Results (1) The frequency of preterm delivery < 34 weeks of gestation was significantly lower in patients with postoperative vaginal progesterone than those without (2.2 versus 18.4%, p = .021); (2) the median gestational age at delivery in the postoperative vaginal progesterone group was significantly longer than the control group (38.3 weeks (interquartile range, 37.5–39.1 weeks) versus 37.3 weeks (interquartile range 33.9–38.6 weeks), p = .020); (3) Multivariable logistic regression analysis demonstrated the use of vaginal progesterone after cerclage was found to be independently associated with decrease in preterm delivery before 34 weeks (Odds ratio 0.10; 95% confidence interval, 0.01–0.93) and 37 weeks (Odds ratio 0.24; 95% confidence interval, 0.07–0.85). Conclusions The use of vaginal progesterone was associated with lower rates of preterm birth before 34 and 37 weeks of gestation in women who underwent ultrasound-indicated cerclage placement.

OBSESTRIC AND PERINATAL OUTCOMES OF PRETERM LABOR IN WOMEN LIVING WITH HIV

The objective of the present study is to reveal characteristics of the course of gestation and perinatal outcomes of preterm, labor associated with human immunodeficiency viral infection. Materials and methods. Retrospective case control study with the participation of 76 pregnant HIV-positive women with preterm labor (main group) and their 76 newborns was held. Comparison group consisted of 198 pregnant women without HIV-infection and their 198 newborns. HIV-infection verification was conducted in accordance with the standard procedure regulated by the Order of the Ministry of Health of the Russian Federation. Results. Antenatal chemoprophylaxis with antiretroviral drugs was used in 92,1% of infected patients. In the vast majority of cases (89,4%) the therapy was conducted with the combination of drugs: Combivir (zidovudine 300 mg + lamivudine 150 mg) taken 1 tablet twice daily combined with Kaletra (lopinavir 200 mg + ritonavir 25 mg) taken 2 tablets twice daily. Initiation of ART vary depending on the HIV infection date: in the first trimester of pregnancy, 48,9% of pregnant were intended to treat, in the second trimester — 36,2%, in the third — 6,4%. 7,9 patients did not receive treatment. Intranatal chemoprophylaxis of prevention of mother-to-child transmission was held in 69 (90,8%) HIV-infected patients. HIV-infection was detected in 2 (2,6%) newborns from mothers who did not receive etiotropic treatment. Common complications of gestation under HIV-infection include anemia (61,8%) and intrauterine growth retardation (34,2%), during labor — meconium in the amniotic fluid (31,6%). Respiratory distress syndrome occurred in 6 (7,6%) newborns, cerebral ischemia was diagnosed in 86,8% of newborns, respiratory distress — in 7,9%. Respiratory distress prophylaxis was conducted in 46% cases only. Conclusion. The course of gestation in women living with HIV with preterm labor was complicated by iron-deficiency anemia, intrauterine growth retardation, meconium in the amniotic fluid; cerebral ischaemia and respiratory distress syndrome most commonly occurred in newborns.

The lynch pin between theory and practice: A unique model for supporting students in the clinical setting

Spontaneous preterm birth is the endpoint of multiple different pathophysiological pathways. Fetal growth restriction, assessed by serial ultrasonic fetal biometry, has been shown to predict both preterm and early-term spontaneous labor. The soluble fms-like tyrosine kinase-1 to placental growth factor ratio is predictive of early-term spontaneous labor, but its association with spontaneous preterm birth is unclear.This study aimed to determine whether maternal serum levels of soluble fms-like tyrosine kinase-1, placental growth factor, and the soluble fms-like tyrosine kinase-1: placental growth factor ratio at 20 and 28 weeks’ gestation, and the rate of change in these biomarkers between 20 and 28 weeks were predictive of risk of spontaneous preterm birth.The biomarkers were measured in maternal serum at 20- and 28-weeks’ gestation in women recruited to a prospective cohort of unselected nulliparous women as part of the Pregnancy Outcome Prediction study in Cambridge, United Kingdom. The risk of spontaneous preterm birth was assessed using Cox regression and competing-risks regression. Associations from Cox regression were quantified by the adjusted hazard ratio for a 1 standard deviation higher level of a given biomarker or a 1 standard deviation increase in the marker between 20 and 28 weeks’ gestation. A previously identified risk factor, slow femur length growth, was used as an additional predictor of spontaneous preterm birth for the purpose of risk stratification.Of the 3763 participants in the analysis, 95 (2.5%) had spontaneous preterm birth and 54 (1.4%) had medically indicated preterm birth. At 20 weeks’ gestation, higher levels of soluble fms-like tyrosine kinase-1 and the soluble fms-like tyrosine kinase-1:placental growth factor ratio were associated with reduced risk of spontaneous preterm birth (adjusted hazard ratio [95% confidence interval], 0.75 [0.61–0.92]; P=.006 and 0.71 [0.59–0.87]; P=.0009, respectively). At 28 weeks’ gestation, there was no association between either soluble fms-like tyrosine kinase-1 or placental growth factor and the risk of spontaneous preterm birth, but there was a U-shaped relation with the soluble fms-like tyrosine kinase-1:placental growth factor ratio. However, when the biomarkers were quantified as the rate of increase between 20 and 28 weeks’ gestation, there were strong positive associations between spontaneous preterm birth and rate of increase in soluble fms-like tyrosine kinase-1 (1.36 [1.13–1.63]; P=.001) and the soluble fms-like tyrosine kinase-1:placental growth factor ratio (1.50 [1.30–1.73]; P<.0001), and a strong negative association with the rate of increase in placental growth factor (0.71 [0.61–0.82]; P<.0001). Women who were in the highest decile of increase in the soluble fms-like tyrosine kinase-1:placental growth factor ratio and the lowest decile of femur length growth between 20 and 28 weeks’ gestation had approximately 9-fold risk of spontaneous preterm birth (9.27 [4.21–20.37]; P<.0001). Competing-risks regression yielded similar results.Changing levels of soluble fms-like tyrosine kinase-1 and placental growth factor are indicative of placental dysfunction and are strongly associated with the risk of spontaneous preterm birth, especially when combined with slower fetal femur length growth.

1391-P: Longitudinal Changes of Plasma Sphingomyelins during Gestation in Women With and Without Type 1 Diabetes and Preeclampsia

Preeclampsia (PE), a major cause of maternal and fetal morbidity and mortality worldwide, has significantly higher incidence in women with type 1 diabetes mellitus (T1DM) than in nondiabetic populations (∼20% vs. 5%, respectively). Sphingolipids are key signaling molecules, and have many roles in the structure and regulation of cellular functions. Sphingomyelin (SM) is the most abundant sphingolipid in plasma lipoproteins. There is evidence that altered SM metabolism may contribute to cardiovascular and renal complications in diabetes. We aimed to determine whether plasma concentrations of 12 SM species were associated with PE in T1DM in a prospective study of pregnancy of 23 T1DM women who developed PE and 24 T1DM who remained normotensive. Additionally, 19 normotensive nondiabetic pregnant women were included for reference. All subjects were free of microalbuminuria and hypertension at enrolment, and all visits (12, 22, 32 weeks’ gestation) preceded clinical PE onset. Results: There were no cross-sectional differences in total SM, or in any individual SM species, between diabetic women with and without PE, or between normotensive women with and without diabetes at any stage of gestation. With advancing gestation in all groups, C18-SM, C18:1-SM, C20-SM, C20:1-SM, C22-SM, C22:1-SM, C24-SM, and C24:1-SM increased (all p&amp;lt;0.001). LDL- and VLDL-cholesterol also increased, while HDL-cholesterol did not change. In contrast, C14-SM, C16-SM, C26-SM and C26:1-SM decreased (all p&amp;lt;0.001). There were no correlations between any SM species and conventional lipid profiles. Conclusions: With advancing gestation, plasma concentrations of most SM species increased, as did LDL and VLDL; however, two long-chain and two very long-chain SM species decreased. Although there were no differences in SM according to diabetes or PE status at any time point, further studies should address the significance of differential changes of SM species during pregnancy. Disclosure C.B. Kelly: None. S.M. Hammad: None. R.L. Klein: None. M.F. Lopes-Virella: None. M.J. Leyva: None. J. Yu: None. A.J. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. A.J. Nankervis: None. K.F. Hanssen: None. S.K. Garg: Advisory Panel; Self; Eli Lilly and Company, Roche Pharma, Sanofi-Aventis, Zealand Pharma A/S. Research Support; Self; Eli Lilly and Company, WebMD. J.A. Scardo: None. C.E. Aston: None. T. Lyons: None. Funding JDRF; Novo Nordisk; National Institutes of Health

Role Of Uterine Artery Doppler For Prediction Of Fetal Outcome In Preeclamptic Patients

Objective: The aim of this prospective observational study is to assess the accuracy of Doppler indices of uterine artery during the third trimester in predicting poor fetal outcome in women with preeclampsia. Methods: Study design: Cohort observational study among women with preeclampsia. Study setting: One hundred cases who were at 32 to 40 weeks of gestation with preeclampsia(from March 2017 to March 2018) attended antenatal clinic and emergency room at obstetrics and gynecology department, faculty of medicine, Sohag University Hospital. Ultrasound was performed at the fetal care unit at Sohag University Hospital. Results: This observational cross-sectional study was designed to assess Doppler indices of uterine artery as predictor of neonatal outcomes among women with preeclampsia.A total of 100 pregnant women with preeclampsia were recruited in the study Conclusion: We recommend adding mean uterine artery Doppler indices to routine antepartum fetal surveillance from 32 weeks gestation for women with preeclampsia as there is a strong correlation between it and poor neonatal outcomes.

Role Of Middle Cerebral Artery / Umbilical Artery Pusatility Index Ratio (cerebro-placental ratio CPR) For Prediction Of Fetal Outcome In Preeclamptic Patients

Objective: The aim of this prospective observational study is to assess the accuracy of Doppler indices of umbilical and middle cerebral especially fetal middle cerebral artery/umbilical artery pulsatility index ratio during the third trimester in predicting acidemia and low Apgar score at 5 minutes after birth in neonates of women with preeclampsia. To provide basis for use of Doppler tests in directing treatment protocol for preeclamptic patients. Methods: Study design: Cohort observational study among women with preeclampsia. Study setting: One hundred cases who were at 32 to 40 weeks of gestation with preeclampsia(from March 2017 to March 2018) attended antenatal clinic and emergency room at obstetrics and gynecology department, faculty of medicine, Sohag University Hospital. Ultrasound was performed at fetal care unit at Sohag University Hospital. Results: This observational cross-sectional study was designed to assess Doppler indices of umbilical artery as predictor of neonatal outcomes among women with preeclampsia.A total 100 pregnant women with preeclampsia were recruited in the study Conclusion: We recommend adding MCA (PI)/ UA (PI) ratio to routine antepartum fetal surveillance from 32 weeks gestation for women with preeclampsia as there is a strong correlation between it and poor neonatal outcomes.

Evaluation of the effect of antenatal betamethasone on neonatal respiratory morbidity in early-term elective cesarean

Background: Compared with vaginal delivery, early-term cesarean section (CS) is associated with an increased risk of neonatal respiratory morbidity. Given the role of steroids in lung maturation in preterm labor, few studies have investigated their effects on early-term delivery. Therefore, this study aimed to investigate the effect of antenatal betamethasone on neonatal respiratory morbidity in early-term elective cesarean (37–38 weeks and 6 d).Methods: This randomized clinical trial was conducted in Mahdieh Hospital in Tehran in 2017. Women with single pregnancy who were candidates for planned elective CS in 37–38 weeks and 6 d of gestation were randomly assigned to either betamethasone group (intramuscular injection of 12 mg of betamethasone in two doses with an interval of 24 h from the 37th week of gestation) or control group (routine treatment). Then, neonatal respiratory morbidities, hospitalization in NICU, and its cause and duration were recorded and compared between the two groups.Results: Of all, 16 neonates (7%) suffered from one or more respiratory morbidities, and there was no significant difference between the betamethasone and control groups (six cases (6%) and 10 cases (9%), respectively, p = .299). There was also no significant difference between betamethasone and control groups in terms of the frequency of respiratory morbidities at the gestational age of 37 and 38 weeks (p > .05). Grunting, retraction, or nasal flaring was the most common respiratory morbidity that was observed in 13 neonates (6%). We observed the need for CPAP in three neonates (1%), respiratory distress syndrome (RDS) in three neonates (1%), transient tachypnea of the newborn (TTN) in two neonates (1%), need for resuscitation at birth in one neonate (0.5%), and apnea in one neonate (0.5%). There was no significant difference between the two groups in terms of respiratory morbidities (p > .05). A total of 17 neonates (8%) were admitted to NICU; the number of neonates admitted to NICU was significantly lower in betamethasone group than in the control group (three neonates (7.2%) and 14 neonates (12.7%), respectively, p = .005). Respiratory distress in 11 neonates (5%), sepsis in two neonates (1%), and other cases in four neonates (2%) were the main reasons for NICU admission. The prevalence of respiratory distress, as a cause for admission, was significantly lower in the betamethasone group (p = .005).Conclusion: The findings of this study showed that intramuscular injection of 12 mg of betamethasone in two doses, with an interval of 24 h, after 37 weeks of gestation in women undergoing early-term CS did not have a significant effect on respiratory morbidities in neonates. However, it decreased the frequency of admission to NICU, especially admission due to respiratory distress; it could indicate that the respiratory morbidities were less severe in betamethasone group than in the control group.

Prophylactic Measures in Early Recurrent Pregnancy Loss in Women with Polycystic Ovary Syndrome and Hyperhomocysteinemia

AbstractBackground: The Polycystic Ovary Syndrome (PCOS) is the commonest endocrine disturbance affecting women, several complications of pregnancy in women with Polycystic Ovary Syndrome (PCOS) including recurrent pregnancy loss, the exact mechanisms that may cause RPL in PCOS patients are obscure. Several etiologies have been proposed, hyperhomo-cysteinemia is a common finding in women with PCOS and was found to be associated with both RPL and PCOS.Aim of Study: Aim of the study is to evaluate prophylactic measures against early recurrent pregnancy loss before 20 weeks of gestation in women with polycystic ovary syndrome and hyperhomocysteinemia by either Low Dose Aspirin (LDA), LMWH or both.Patient and Methods: The present study was carried out on 120 pregnant women in reproductive period, their age ranged between 20 and 35 years. They were classified into three groups, group I treated with Low Dose Aspirin (LDA) (40), group II treated with low molecular weight heparin (40) and group III treated with low dose aspirin and low molecular weight heparin (40).Result: Hyperhomocysteinemia is a common finding in women with PCOS and was found to be associated with both RPL and PCOS. It was shown that combined treatment with aspirin and Low Molecular Weight Heparin (LMWH) in women with hyperhomocysteinemia improved successful pregnancy rates.Conclusion: The use of clexane or Clexane with LDA prevent early recurrent pregnancy loss in patients with PCOS and hyperhomocysteinemia better than LDA alone.

Analysis of GDF15 and IGFBP7 in Hyperemesis Gravidarum Support Causality.

Objective Hyperemesis gravidarum, severe nausea and vomiting in pregnancy, occurs in up to 2% of pregnancies and leads to significant weight loss, dehydration, electrolyte imbalance, and ketonuria. It is associated with both maternal and fetal morbidity. Familial aggregation studies and twin studies suggest a genetic component. In a recent GWAS, we showed that placentation, appetite, and cachexia genes GDF15 and IGFBP7 are linked to hyperemesis gravidarum (HG). The purpose of this study is to determine whether GDF15 and IGFBP7 are upregulated in HG patients. Methods We compared serum levels of GDF15 and IGFBP7 at 12 and 24 weeksʼ gestation in women hospitalized for HG, and two control groups, women with nausea and vomiting of pregnancy (NVP), and women with no NVP. Results We show GDF15 and IGFBP7 serum levels are significantly increased in women with HG at 12 weeksʼ gestation. Serum levels of hCG are not significantly different between cases and controls. At 24 weeks gestation, when symptoms have largely resolved, there is no difference in GDF15 and IGFBP7 serum levels between cases and controls. Conclusion This study supports GDF15 and IGFBP7 in the pathogenesis of HG and may be useful for prediction and diagnosis. The GDF15-GFRAL brainstem-activated pathway was recently identified and therapies to treat conditions of abnormal appetite are under intense investigation. Based on our findings, HG should be included.