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The effective treatment of malaria can be very complex: Plasmodium parasites develop in multiple stages within a complex life cycle between mosquitoes as vectors and vertebrates as hosts. For the full and effective elimination of parasites, an effective drug should be active against the earliest stages of the Plasmodium infection: liver stages (reduce the progress of the infection), blood stages (cure the clinical symptoms), and gametocytes (inhibit the transmission cycle). Towards this goal, here we report the design, the synthetic methodology, and the characterization of novel hybrid agents with combined activity against Plasmodium liver stages and blood stages and gametocytes. The divergent synthetic approach allows the access to differently linked primaquine-chloroquine hybrid templates in up to eight steps.

Objective: To determine whether maternal features affect the accuracy of sonographic estimated fetal weight (SEFW) by evaluating the consistency of the systematic error of SEFW with regards to the birth weight (BW) in two consecutive pregnancies of the same gravida., Methods: The cohort included women with SEFW within 1 week of delivery (32-42 weeks' gestation) in two consecutive singleton pregnancies from 2007 to 2012. The systematic error was calculated as (SEFW - BW)/BW × 100 and expressed as a percentage of the BW., Results: A total of 636 pregnancies (318 gravidas) were eligible for analysis. The BW and SEFW were correlated in both first examined (r = 0.873, p < 0.001) and consecutive (r = 0.843, p < 0.001) pregnancies. There was a significant difference in mean systematic error between first examined and consecutive pregnancies (3.13 ± 8.95 vs. 0.34 ± 8.75%, p < 0.001), with a very weak correlation between the two (r = 0.135, p = 0.16). Nulliparity or multiparity at the first examined pregnancy was not found to be a significant factor, and in both groups the error was higher in the first examined pregnancy. There were no significant differences between parturients with a minor (10% and below) or major (>10%) difference in the systematic error between the two pregnancies., Conclusion: The systematic error between the SEFW and BW in two consecutive pregnancies is inconsistent, suggesting that it is unaffected by maternal biometric features., (© 2014 S. Karger AG, Basel.)

Objective: Limited data exist regarding uterine contraction intensity prior to membrane rupture. Using a novel technique of electrical uterine myography (EUM) we aimed to determine which factors affect myometrial activity during active phase of labor., Methods: EUM was prospectively measured in 37 women with singleton pregnancy at term during the active phase of labor until membranes' rupture. EUM was measured using non-invasive nine channels recorder with an EMG amplifier and three-dimensional position sensor. Uterine electrical activity was quantified with the EUM-index, defined as the mean electrical activity of the uterine muscle over a period of 10 min and measured in units of micro-Joule (microwatt per second [mW/s])., Results: The mean EUM-index at the first 10 min of the measurement was 3.3 ± 0.6 mW/s. In a stepwise linear regression model accounting potential confounders EUM was significantly affected by cervical dilatation (p = 0.005), maternal age (p = 0.04) and previous cesarean delivery status (p = 0.02). In a repeated measurement assessment of non-parametric Fridman's test for all subjects who had at least 10 continuouss EUM measurements, there was a significant increase in electrical uterine activity as labor progressed (p = 0.01)., Conclusion: Electrical uterine activity during the active phase of labor prior to rupture of membranes is affected by maternal age, previous cesarean delivery status and cervical dilatation. Moreover, electrical uterine activity is enhanced throughout labor.

Objective: We aimed to determine the incidence and risk factors for retained placenta immediately after vaginal delivery in a single, university-affiliated tertiary center., Methods: A case-control study. Women who delivered vaginally and diagnosed with suspected retained placenta were compared to control group of women with spontaneous vaginal delivery with spontaneous non-complicated placental separation between the years 2007 and 2012. Eligibility was limited to singleton fetuses in vertex presentation with no history of more than one cesarean section, stillbirth or major fetal anomaly., Results: Overall, 33,925 women delivered vaginally, of them, 491 (1.4%) underwent revision of uterine cavity due to suspected retained placenta. Women with retained placenta were characterized by a higher rate of previous cesarean section (OR 1.71, 95% CI 1.23-2.36), previous abortions, lower parity (OR 0.79, 95% CI 0.68-0.91), lower gestational age at delivery. Hypertensive disorders, oligohydramnios and labor and delivery interventions as induction of labor (OR 1.84, 95% CI 1.30-2.59), neuro-axial analgesia (OR 1.60, 95% CI 1.27-2.00) and vacuum delivery (OR 1.89, 95% CI 1.48-2.41) were independently associated with uterine revision for retained placenta., Conclusion: Risk factors for manual revision due to retained placenta can be recognized. This data should be taken into consideration in the assessment of women immediately after delivery.

Objective: Prostaglandin E2 (PGE2-Dinoprostone) is accepted for both ripening of the cervix and induction of labor. As conflicting data exist concerning the efficiency and safety of different treatment modalities, we aimed to compare slow-release vaginal insert PGE2 with serial vaginal tablets of PGE2 for cervical ripening and induction of labor., Methods: A retrospective cohort study comparing all pregnancies who underwent induction of labor by either a single slow-release vaginal insert of 10 mg PGE2 (study group) to a historical control group of women who were treated with serial administration of 3 mg vaginal PGE2 tablets in a 2:1 ratio, matched by parity., Results: Overall, 639 women were enrolled (213 treated with PGE2 tablets and 426 with slow-release vaginal inserts). Vaginal insert was associated with shorter initiation-to-ripening interval (12.4 ± 7.7 versus 18.6 ± 15.2 h, p < 0.001) and a higher rate of delivery within 24 h (61.5 versus 51.6%, p = 0.018). Vaginal insert was associated with an increased rate of tachysystole (8.0 versus 3.1%, p < 0.01); however, the rates of cesarean section or operative delivery due to non-reassuring fetal heart rate (NRFHR) were similar. On multivariable analysis, slow-release vaginal insert was independently associated with a higher rate of delivery within 24 h (OR 1.50, 95% CI 1.04-2.18)., Conclusion: Slow-release PGE2 vaginal insert achieves cervical ripening and subsequently delivery over a shorter time period than PGE2 tablets, without increasing uterine hyperstimulation rate.

Background: In the last three decades, systemic methotrexate (MTX) has become widely accepted as the primary treatment for unruptured tubal pregnancy. This has prompted investigations into the use of MTX in the management of interstitial pregnancy., Aim: To determine the effectiveness of methotrexate for treatment of interstitial pregnancy., Methods: We retrospectively reviewed 17 haemodynamically stable women admitted to our tertiary, university-affiliated medical centre with an intact interstitial pregnancy from January 2003 through February 2013. First-line treatment consisted of intramuscular MTX 1 mg/kg/day x4 alternating with folinic acid 0.1 mg/kg or, in cases of low beta-human chorionic gonadotropin (β-hCG) and no embryonic pole, one dose of 50 mg/m(2) body surface area. Uterine artery MTX injection was administered on the ipsilateral side of the pregnancy followed by uterine artery embolisation as second-line treatment. Failure criteria were <15% decrease in β-hCG or sonographic evidence of pregnancy development. Second-line failures were referred for surgery., Results: Twelve women (70.5%) underwent successful first-line treatment and 5 (29.5%) required second-line treatment. Baseline characteristics were similar except for a higher rate of two previous ectopic pregnancies in the first-line failures (80% versus 8.3%, P = 0.01). Two women eventually required surgery, both with two previous ectopic pregnancies. Of the three women with fetal cardiac activity on admission, two had successful first-line treatment and one required surgery., Conclusion: Systemic MTX is effective for treatment of intact interstitial pregnancy in haemodynamically stable women. The success rate is increased with uterine artery MTX injection as second-line treatment., (© 2014 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Purpose: As conflicting data exist concerning the implications of isolated oligohydramnios on pregnancy outcome at term, we aimed to assess this association in low-risk pregnancies., Methods: A retrospective cohort study of term pregnancies with sonographic finding of isolated oligohydramnios (amniotic fluid index (AFI) <5 cm) between 2007 and 2012. Outcome was compared to a control group of pregnancies with normal AFI (5-25 cm). Pregnancies complicated by thrombophilia, hypertension, diabetes, deviant fetal growth or chromosomal/structural abnormalities were excluded. Composite adverse outcome included CS/operative delivery due to non-reassuring heart rate (NRFHR), low Apgar score, umbilical artery pH < 7.10, neonatal intensive care admission, meconium aspiration syndrome, intubation or hypoxic-ischemic encephalopathy., Results: Overall, 987 pregnancies complicated by isolated oligohydramnios were compared to 22,280 low-risk pregnancies with normal AFI. Isolated oligohydramnios was associated with a higher rate of induction of labor (27.7 vs. 3.7 %, p < 0.001), CS due to NRFHR (2.3 vs. 1.1 %, p < 0.01) and composite adverse outcome (9.7 vs. 7.1 %, p < 0.01). However, after adjusting for potential confounders as induction of labor and nulliparity using multivariable logistic regression analysis, isolated oligohydramnios was not found to be independently associated with increased risk for composite adverse outcome (OR 1.01, 95 % CI 0.80-1.27, p = 0.93)., Conclusion: Isolated oligohydramnios at term by itself is not associated with increased obstetrical morbidity.

Objective: To determine whether the predictive accuracy of sonographic cervical length (CL) for preterm delivery (PTD) in women with threatened preterm labor (PTL) is related to gestational age (GA) at presentation., Study Design: A retrospective cohort study of all women with singleton pregnancies who presented with PTL at less than 34 + 0 weeks and underwent sonographic measurement of CL in a tertiary medical center between 2007 and 2012. The predictive accuracy of CL for PTD was stratified by GA at presentation., Results: Overall, 1077 women who presented with PTL have had sonographic measurement of CL and met the study inclusion criteria. Of those, 223 (20.7%) presented at 24 + 0-26 + 6 weeks (group 1), 274 (25.4%) at 27 + 0-29 + 6 weeks (group 2), 283 (26.3%) at 30 + 0-31 + 6 weeks (group 3), and 297 (27.6%) at 32 + 0-33 + 6 weeks (group 4). The overall performance CL as a predictive test for PTD was similar in the 4 GA groups, as reflected by the similar degree of correlation between CL with the examination to delivery interval (r = 0.27, r = 0.26, r = 0.28, and r = 0.29, respectively, P = .8), the similar area under the receiver-operator characteristic curve (0.641-0.690, 0.631-0.698, 0.643-0.654, and 0.678-0.698, respectively, P = .7), and a similar decrease in the risk of PTD of 5-10% for each additional millimeter of CL. The optimal cutoff of CL, however, was affected by GA at presentation, so that a higher cutoff of CL was needed to achieve a target negative predictive value for delivery within 14 days from presentation for women who presented later in pregnancy. The optimal thresholds to maximize the negative predictive value for delivery within 14 days were 36 mm, 32.5 mm, 24 mm and 20.5 mm for women who presented at 32 + 0 to 33 + 6 weeks, 30 + 0 to 31 + 6 weeks, 27 + 0 to 29 + 6 weeks and 24 + 0 to 26 + 6, respectively., Conclusion: CL has modest predictive accuracy in women with threatened PTL, regardless of GA at presentation. However, the optimal cutoff of CL for the purpose of clinical decision making in women with PTL needs to be adjusted based on GA at presentation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To determine the effectiveness and safety of uterine artery methotrexate (MTX) infusion and embolization combined with systemic MTX for treatment of non-tubal ectopic pregnancy., Study Design: We retrospectively reviewed the electronic files of all women admitted to a single tertiary, university-affiliated medical center with a diagnosis of non-tubal (cervical, interstitial or cesarean section scar) ectopic pregnancy, who were treated by a combination of uterine artery MTX infusion and embolization and systemic MTX between January 2001 and March 2014. The treatment protocol included a total of 4 MTX injections in doses of 1 mg/kg/day every other day (days 1, 3, 5, 7 of the protocol) alternating with folinic acid 0.1 mg/kg (days 2, 4, 6, 8). The first or second MTX dose was administered by transcatheter intra-arterial injection during the embolization procedure just before injecting Gelfoam for bilateral uterine artery occlusion, and the remaining doses were given intramuscularly., Results: During the study period, 25 women underwent uterine artery infusion and embolization combined with systemic MTX treatment for non-tubal ectopic pregnancy. Ten of the pregnancies were cervical, 9 were interstitial, and 6 were cesarean scar pregnancies. Mean gestational age and beta-human chorionic gonadotropin (β-HCG) level at admission were 68.6±12.9 days and 14,179 (range 436-61596) IU/L, respectively. Treatment was successful in 24 patients (96%) with mean β-HCG resolution time of 52.6 (6-147) days. Mild immediate side effects were reported including 8 cases (32%) of abdominal discomfort, 3 cases (12%) of groin or leg pain and 3 cases (12%) of puncture-site local skin infection. No serious immediate side effects such as internal vascular bleeding, sepsis or early liver or renal failure were observed. Among 12 women who stated that they tried to conceive and were more than a year from the treatment, 10 (83.3%) had subsequent pregnancy., Conclusion: A combination of uterine artery MTX infusion and embolization with systemic MTX seems to be an effective and safe treatment for non-tubal ectopic pregnancies in women who try to conceive., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: To determine the accuracy and the delay in diagnosis of presumed acute appendicitis in pregnancy., Methods: Pregnant women undergoing appendectomy for presumed acute appendicitis were compared to non-pregnant age-matched women in a 3:1 ratio undergoing appendectomy in a tertiary medical center from 2001 to 2012., Results: Out of 1618 women who underwent appendectomy during the study period, 81 (4.2%) were pregnant who were compared to 243 age-matched non-pregnant women. There was a significantly shorter interval between admission to the hospital and surgery and shorter surgery length (10.2 versuss 15.7 h, 1.2 ± 0.4 versus 1.4 ± 0.5 h, respectively, p < 0.001) in the pregnant group with similar rates of negative appendectomy (19.8% versus 21.8%, respectively, p = 0.86). The positive and negative predictive values of ultrasonography (US) for the diagnosis of acute appendicitis were 88.2% and 100%, and 92.9% and 57.1%, among the pregnant and the non-pregnant group, respectively. In multivariate analysis, early gestational age was found to be independently associated with higher rate of accurate US results (OR = 0.92, 95% CI 0.85-0.99, p = 0.39)., Conclusion: Pregnant women undergoing appendectomy have shorter admission to surgery interval and surgical length with similar negative appendectomy rates compared to non-pregnant women. Ultrasound is an accurate tool for the diagnosis of acute appendicitis during pregnancy, especially during early gestation.

Objective: To compare pregnancy outcome between deliveries complicated by new onset of meconium during labor following prior evidence of clear amniotic fluid and labors in which meconium was present to begin with., Methods: A retrospective cohort study of all singleton term (≥37 + 0 weeks) deliveries complicated by intrapartum meconium-stained amniotic fluid in a tertiary referral medical center during the year 2012. Outcome was compared between deliveries with new onset of meconium during labor following prior evidence of clear amniotic fluid (secondary meconium group) and those in which meconium was already evident at the time of membranes rupture (primary meconium group)., Results: Of the 9167 deliveries during the study period, 694 were eligible for the study group. Of these, 537 were complicated by primary meconium and 157 by secondary meconium. Only secondary meconium, but not primary meconium, was independently associated with an increased risk of operative vaginal delivery (OVD) and adverse neonatal outcome. Pregnancies complicated by secondary meconium were independently associated with a higher rate of OVD (28.0% versus 11.4%, p < 0.001), POP position of the fetal head (6.4% versus 2.6%, p = 0.02), and adverse neonatal outcome (17.2% versus 8.9%, p = 0.003)., Conclusion: Secondary meconium is associated with a higher rate of adverse obstetrical and neonatal outcome compared with primary meconium.

Objective: To assess pregnancy outcome among women with hyperemesis gravidarum (HEG) with and without total parenteral nutrition (TPN) support., Study Design: A retrospective study of all pregnant women with singleton pregnancies who were hospitalized due to HEG between 1997 and 2011. Pregnancy outcome was compared with a control group without HEG matched by maternal age and parity in a 3:1 ratio., Results: Overall 599 women were admitted during the study period with the diagnosis of HEG and subsequently delivered in our center. Of those, 122 (20.4%) received TPN support. Women in the HEG group were characterized by a higher rate of severe preeclampsia (1.3% versus 0.5%, p = 0.04), and a higher rate of preterm delivery at less than 37 and 34 weeks (10.9% versus 6.9%, p < 0.001 and 4.7% versus 1.6%, p < 0.001, respectively). Neonates in the HEG group were characterized by a lower birth weight (3074 ± 456 g versus 3248 ± 543 g, p < 0.001), higher rate of birth weight < 10th percentile (12.7% versus 6.8%, p < 0.001), and a higher rate of neonatal morbidity (8.7% versus 3.8%, p < 0.001). These associations persisted after adjustment for potential confounders, and were of most notable among women with HEG who did not receive TPN support., Conclusion: HEG is an independent risk factor for adverse pregnancy outcome. TPN support during early pregnancy is associated with a decreased risk for perinatal morbidity.

Objective: Data regarding the association between isolated single umbilical artery (SUA) and pregnancy outcome are inconsistent and mainly address the risk of pregnancy complications. Thus, we aimed to focus on the association between isolated SUA, and labor and delivery., Methods: We conducted a case-control study of all singleton pregnancies diagnosed with isolated SUA (no known chromosomal/structural anomalies/fetal growth restriction) attempting vaginal delivery. Obstetric and neonatal outcome was compared with that of a control group of pregnancies with a three-vessel cord in a 1:2 ratio matched by parity. Composite adverse outcome included the following: Cesarean section (CS) and/or operative delivery due to non-reassuring fetal heart rate (NRFHR), prolonged neonatal admission, low Apgar score and umbilical artery pH < 7.2., Results: Out of 34 196 deliveries, 162 (0.5%) were diagnosed with SUA, and 91 (0.27%) were diagnosed with isolated SUA. Isolated SUA was associated with a higher rate of CS due to NRFHR (5.5% vs 1%, p = 0.02), small for gestational age (SGA) (14.3% vs 4.9%, p = 0.009), lower birth weight, and a higher rate of composite adverse outcome (20.9% vs 8.8%, p = 0.005). On multivariable analysis, isolated SUA was independently associated with an increased risk for composite adverse outcome (OR 2.34, 95% CI 1.05-5.21)., Conclusion: Isolated SUA is associated with increased risk for CS due to NRFHR and increased rate of SGA., (© 2014 John Wiley & Sons, Ltd.)

Objective: To evaluate uterine activity during the third stage of labor and compare it to that observed in the second stage of labor., Study Design: Uterine electric activity was prospectively measured using electrical uterine myography (EUM) in 44 women with singleton pregnancy at term during the final 30 min of the second stage and throughout the third stage of labor. Results are reported using a scoring index of 1-5 mWS (micro-Watt-Second). Patients were stratified into two groups based on the duration of the third stage (<15 min and >=15 min), Results: The mean durations of the second and third stages were 51.9 ± 63.5 and 15.4 ± 7.5 minutes, respectively. During the third stage, uterine activity (contractions peaks) was similar to that observed during the second stage of labor (3.43 ± 0.64 mWS versus 3.42 ± 0.57 mWS, p = 0.8). No correlation was found between the duration of the third stage and EUM measurements during the third (p = 0.9) or the second (p = 0.2) stages of labor. No association was found between EUM measurements during the third stage and parity, maternal age, fetal weight, duration of labor, gestational age, gravity or BMI. The rate of oxytocin use during the second stage and EUM measurements during the second or third stage did not differ among women with short versus long duration of the third stage., Conclusion: Uterine activity during the third stage is comparable and as intense as that occurring during the second stage. Third stage length cannot be predicted by contraction intensity during the second or third stage of labor.

Purpose of Review: To address the recent evidence regarding the association between hyperglycemia during pregnancy and adverse short-term and long-term outcome for both mothers and offspring., Recent Findings: Recent data suggest a relationship between hyperglycemia during pregnancy and adverse short-term fetal outcomes, mainly those associated with excessive fetal growth. The degree of hyperglycemia plays an important role in risk stratification. Moreover, the long-term effect of hyperglycemia during pregnancy is expressed mainly as cardiometabolic morbidity and increased risk for the development of metabolic syndrome both maternal and in early adolescence. Alternation in DNA methylation and gene expression of metabolic pathways were found in association with hyperglycemia in utero, supporting the 'developmental origins of disease' hypothesis., Summary: The effect of hyperglycemia on the early life metabolic environment may contribute to the subsequent risk of cardiovascular or metabolic morbidity later in life. It is also a sign of future maternal metabolic alternation. Several future randomized trials, hopefully will help to determine if early intervention could decrease the risk for gestational diabetes and whether long term adverse outcome are preventable and importantly the association with degree of maternal hyperglycemia in pregnancy and future morbidity.

Objective: To investigate the effect of prostaglandin E2 (PGE2) on electrical uterine activity using a novel uterine muscle electromyography device in patients undergoing induction of labor., Study Design: Electrical uterine myography (EUM) was prospectively measured using a noninvasive nine channels recorder in 31 women undergoing induction of labor with vaginal PGE2 tablets. Women were monitored before and up to 12 hours after vaginal PGE2 application. EUM index was defined as mean electrical activity of the uterine muscle over a period of 10 minutes measured in units of microjoule (µJ, µWs)., Results: The EUM index was not increased significantly during the first 2 hours following PGE2 application (overall increase of 5.3 ± 60.1%, p = 0.7). Peak EUM activity was observed during 2 to 8 hours following PGE2 application, which represented a statistically significant increase compared with the EUM index before PGE2 application (3.3 ± 0.5 µJ vs. 2.5 ± 0.95 µJ, p = 0.01), and with the EUM index 0 to 2 hours following PGE2 application (3.3 ± 0.5 µJ vs. 2.3 ± 0.9 µJ, p = 0.004)., Conclusion: The data suggests that in women undergoing labor induction with PGE2, uterine activity peaks 2 to 8 hours following PGE2 application. This information may provide more insight into the mechanism of PGE2 action., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To compare perioperative and pregnancy outcome between women undergoing laparoscopic appendectomy and those undergoing open appendectomy during pregnancy for presumed acute appendicitis., Methods: A retrospective cohort study of all women undergoing appendectomy during pregnancy in a tertiary referral medical center from 2000 to 2009. Outcome was compared between those undergoing laparoscopic appendectomy and those undergoing open appendectomy., Results: Overall, 83,510 deliveries occurred during the study period, 85 (0.10%) were eligible for the study group. Of these, 26 (31%) had a laparoscopic appendectomy and 59 (69%) had an open appendectomy. No significant difference was found in the general, delivery and neonatal outcome characteristics between the two groups. There was a significant difference in the mean gestational age at surgery between laparoscopic appendectomy and the open appendectomy groups (14.6 versus 19.3 weeks respectively, p = 0.009). Post-operative complications (fever >38.0 °C or the presence of uterine contractions) rate was higher in the open appendectomy compared to the laparoscopic appendectomy group (25.5% versus 3.8%, respectively, p = 0.009)., Conclusion: Laparoscopic appendectomy appears to be a safe procedure for presumed acute appendicitis during pregnancy with less post-operative complications as compared to open appendectomy.

Endothelial dysfunction is considered an important prognostic factor in atherosclerosis. To determine the long-term association of brachial artery flow-mediated dilation (FMD) and adverse cardiovascular (CV) events in healthy subjects, we prospectively assessed brachial FMD in 618 consecutive healthy subjects with no apparent heart disease, 387 men (63%), and mean age 54 ± 11 years. After overnight fasting and discontinuation of all medications for ≥12 hours, FMD was assessed using high-resolution linear array ultrasound. Subjects were divided into 2 groups: FMD ≤11.3% (n = 309) and >11.3% (n = 309), where 11.3% is the median FMD, and were comparable regarding CV risk factors, lipoproteins, fasting glucose, C-reactive protein, concomitant medications, and Framingham 10-year risk score. In a mean clinical follow-up of 4.6 ± 1.8 years, the composite CV events (all-cause mortality, nonfatal myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting, and percutaneous coronary interventions) were significantly more common in subjects with FMD ≤11.3% rather than >11.3% (15.2% vs 1.2%, p = 0.0001, respectively). Univariate analysis demonstrated that the median FMD significantly predicted CV events (odds ratio 2.78, 95% CI 1.35 to 5.71, p <0.001). Multivariate analysis, controlling for traditional CV risk factors, demonstrated that median FMD was the best independent predictor of long-term CV adverse events (odds ratio 2.93, 95% CI 1.28 to 6.68, p <0.001). In conclusion, brachial artery median FMD independently predicts long-term adverse CV events in healthy subjects with no apparent heart disease in addition to those derived from traditional risk factor assessment., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To compare the performance of the 50 g glucose challenge test (GCT) and the 100 g oral glucose tolerance test (OGTT) in twin versus singleton pregnancies., Methods: A retrospective study of all women who underwent a GCT (24-28 weeks) and delivered in a single tertiary medical center (2001-2012). The performance of the GCT and the OGTT tests were compared between twin and singleton pregnancies., Results: The results of the GCT were available for 14 797 women, of whom 14 268 were singleton and 529 were twin pregnancies. Women in the twins group were characterized by a higher mean GCT result (104.7 ± 28 versus 98.5 ± 25, p < 0.001), a higher rate of GCT > 130 mg/dl (20.2% versus 11.8%, p < 0.001) or GCT >140 mg/dl (13.8% versus 9.6%, p = 0.001). The positive prediction value (PPV) for a GCT >140 mg/dl was significantly lower in the twins group for the prediction of either ≥1 abnormal values (21.1% versus 33.8%, p = 0.03) or ≥2 abnormal values (12.7% versus 23.0%, p = 0.04) in the OGTT. Twin pregnancy was independently associated with an increased risk for a GCT result >130 mg/dl [odds ratio (OR) = 2.2, 95% confidence interval (CI) 1.7-2.7] or >140 mg/dl (OR = 1.9, 95% CI 1.5-2.5) even after adjustment for maternal age, parity and fetal sex., Conclusion: The 50 g GCT appears to be associated with a higher false positive rate and a lower positive predictive value in twin compared with singleton pregnancies.

Objective: To assess the risk of recurrence of third- and fourth-degree perineal tears (34DPT) and to determine whether previous 34DPT is an independent risk factor for 34DPT in subsequent deliveries., Method: The study group included all women who had a vaginal delivery complicated by 34DPT (2000-2012, N = 356) and subsequently delivered again in the same medical center (N = 204). The rate of recurrence of 34DPT was compared with a control group of women who had a previous vaginal delivery not complicated by 34DPT (N = 58 581) and had a subsequent delivery in the same time period (N = 23 045)., Results: Women in the past-34DPT group had a higher rate of CS (18.6% versus 10.1%, p < 0.001), fetal head in occiput-posterior position (POP; 2.5% versus 0.7%, p = 0.004) and mediolateral episiotomy (25.5% versus 19.4%, p = 0.03). Women in the past-34DPT group had a higher rate of 34DPT in the subsequent delivery (2.0% versus 0.3%, p < 0.001). The rate of recurrence of 34DPT was considerably higher among women with past fourth-degree tear versus women with past third-degree tear (22.2% versus 1.0%, p < 0.001). 34DPT in previous pregnancy is independently associated with increased risk of 34DPT in subsequent delivery (OR = 4.6, 95%-CI 1.3-15.3)., Conclusion: Women who experienced 34DPT in their previous pregnancy have an increased risk for recurrence of 34DPT in subsequent pregnancy, especially in cases of past fourth-degree tears.

Objective: To assess the predictive role of ultrasonographic cervical length for preterm delivery in women with threatened preterm labor., Methods: A retrospective cohort study of women with singleton pregnancies who presented with preterm labor before 34 weeks of gestation and underwent ultrasonographic measurement of cervical length in a tertiary medical center. Women with cervical cerclage, cervical dilatation greater than 3 cm at presentation, and pregnancies complicated by placental abruption, clinical chorioamnionitis, stillbirth, or major fetal anomalies were excluded. The predictive accuracy of cervical length for preterm delivery was analyzed using both fixed thresholds and outcome-specific thresholds, which are associated with a detection rate of 90%, false-positive rate of 10%, or the inflexion point of the receiver operator characteristic curve., Results: Between 2007 and 2012, 1,077 women presented with preterm labor and met the study criteria. The correlation between cervical length and the time interval to delivery was significant but weak (r=0.293, P<.001). Cervical length was independently associated with the risk of preterm delivery at less than 37, 35, and 32 weeks of gestation and within 14 and 7 days from presentation (a 4-7% decrease in the risk for each additional millimeter of cervical length) as well as with the time interval between presentation and delivery (each additional 2 mm was associated with an increase of 1 day). Overall, the accuracy of cervical length in predicting preterm delivery was relatively poor., Conclusion: Although cervical length is an independent predictor of preterm delivery in women with preterm labor, its predictive accuracy as a single measure is relatively limited., Level of Evidence: : II.

Objective: To determine whether the incidence, severity and effects of hyperemesis gravidarum (HEG) are related to fetal gender., Method: A retrospective study of all pregnant women who were admitted with the diagnosis of HEG between 1994 and 2008 (N = 545). The association between fetal gender and pregnancy outcome in pregnancies complicated by HEG was compared to that of a control group of women with singleton pregnancies matched by maternal age and parity in a 3:1 ratio (N = 1635)., Results: Women with HEG with a female fetus were younger (28.2 ± 4.8y versus 29.5 ± 5.5y, p = 0.003), were admitted earlier in pregnancy for HEG (admission < 10w: 62.3% versus 53.4%, p = 0.04), and were more likely to require TPN support (35.6% versus 26.9%, p = 0.03) compared to women with HEG having a male fetus. Compared to controls, women with HEG were more likely to have a female rather than a male fetus (odds ratio (OR) = 1.20) although this difference reached statistical significance only for the subgroup of women with HEG who were admitted prior to 10 weeks of gestation (OR = 1.40, 95%-confidence interval (CI) 1.03-1.70) or who required TPN support (OR = 1.593, 95% CI 1.15-2.0263). The presence of a male fetus in pregnancies complicated by HEG was associated with an increased risk for preterm delivery (OR = 0.49, 95% CI 0.27-0.87), and composite neonatal morbidity (OR = 0.38, 95% CI 0.20-0.74)., Conclusion: Although HEG appears to be more common and more severe in the presence of a female fetus, male fetuses appear to be more susceptible to the adverse effects of HEG on pregnancy outcome.

Objective: To determine risk factors and to quantify the risk of cesarean section (CS) associated with labor induction., Method: A prospective controlled study of women admitted for labor induction with PGE2 in a single tertiary medical center. Outcome was compared with women who presented with spontaneous onset of delivery., Results: The induction group were characterized by a higher body mass index (BMI), lower Bishop score and a higher cervical length at presentation compared with controls. Labor induction with PGE2 was associated with increased risk of CS (14.8% versus 4.5%, p = 0.02). This association persists after adjustment for potential confounders including Bishop score at presentation (OR = 2.9, 95% CI 1.03-11.8). The risk of CS was especially high for nulliparous (24.4% versus 5.1%, p = 0.02), overweight (21.2% versus 3.7%, p = 0.047), induction at <40 weeks of gestation (22.2% versus 2.2%, p = 0.004), in Bishop score <4 (18.2% versus 4.5%, p = 0.03), cervical length >25 mm (19.2% versus 4.5%, p = 0.005), or intact membranes (25.0% versus 4.5%, p = 0.02) at presentation., Conclusions: Labor induction with PGE2 is associated with increased risk of CS. These data should be taken into consideration when deciding on labor induction, especially in the absence of clear medical indication.

Objective: The purpose of this study was to investigate the effect of atosiban (Tractocile; Ferring, Limhamn, Sweden), an oxytocin receptor antagonist, on uterine electrical activity in women with preterm labor and to determine whether this information can assist in the prediction of preterm delivery., Study Design: Uterine electrical activity was recorded prospectively in 21 women with preterm labor before and during treatment with Tractocile and, for purpose of comparison, in 4 pregnant women without uterine contractions to set the baseline of uterine electrical activity in a quiescent uterus. Uterine activity was recorded with a noninvasive, 9-channel recorder with an electromyography amplifier and a 3-dimensional position sensor with an automatic data analyzer. Uterine electrical activity was quantified by an electrical uterine monitor (EUM) and measured in microwatts per second (μW/s)., Results: The overall pre-Tractocile EUM index was 3.43 ± 0.58 μW/s, which was significantly higher than baseline uterine activity in women without preterm contractions (2.3 ± 0.11 μW/s; P = .001). During the administration of Tractocile, the EUM index gradually decreased in a relatively constant rate from 3.43 ± 0.58 μW/s to 2.56 ± 0.88 μW/s after 330 minutes of continuous therapy (P < .001). The peak effect of Tractocile was observed 4 hours after the initiation of treatment and was followed by a relative plateau. Women with a latency of <7 days from treatment to delivery were characterized by a distinct EUM-pattern in response to Tractocile, compared with women with a latency of ≥7 days (P < .001). A similar EUM-pattern after the administration of Tractocile was also observed for women who delivered at <37 weeks of gestation compared with the women who delivered at term., Conclusion: Tractocile reduces uterine electrical activity in women with preterm labor. This information can provide more insight into the effects of tocolytic agents and to aid in the risk stratification of preterm delivery in women with preterm contractions., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: To determine whether a low-GCT result is predictive of low birthweight and to identify the lower GCT threshold for prediction of fetal growth restriction., Methods: A retrospective cohort study of 12,899 women who underwent a GCT (24-28 weeks). Women with a low-GCT result (<10th percentile (70 mg/dL) were compared to women with normal-GCT result (70-140 mg/dL). ROC analysis was used to determine the optimal lower GCT threshold for the prediction of growth restriction., Results: Women in the low GCT had significant lower rates of cesarean delivery (18.7% versus 22.5%), shoulder dystocia (0.0% versus 0.3%), mean birthweight (3096 ± 576 versus 3163 ± 545) and birthweight percentile (49.1 ± 27.0 versus 53.1 ± 26.7) and significant higher rates of birthweight <2500 g (11.3% versus 8.5%), below the 10th percentile (8.3% versus 6.5%) and 3rd percentile (2.3% versus 1.4%). Low GCT was independently associated with an increased risk for birthweight <2500 g (OR = 1.6, 1.2-2.0), birthweight <10th percentile (OR = 1.3, 1.1-1.6), birthweight <3rd percentile (OR = 1.7, 1.2-2.5) and neonatal hypoglycemia (OR = 1.4, 1.02-2.0). The optimal GCT threshold for the prediction of birthweight <10th percentile was 88.5 mg/dL (sensitivity 48.5%, specificity 58.1%)., Conclusion: Low-GCT result is independently associated with low birthweight and can be used in combination with additional factors for the prediction of fetal growth restriction.

Objective: To characterize the response to labor induction with prostaglandin E2 (PGE2) and to identify risk factors for induction failure., Methods: A prospective controlled study of women admitted for labor induction with PGE2. Maternal characteristics, Bishop score and sonographic cervical length were documented at admission. The change in cervical characteristics and the emergence of uterine contractions following each application of PGE2 were analyzed., Results: Of the 88 women who were included in the study, 19 (21.6%) failed to response to PGE2. The following factors were independently associated with induction failure: nulliparity (odds ratio [OR] = 5.9, 95% confidence interval (CI): 1.2-30.2), pre-pregnancy body mass index >25 kg/m2 (OR = 5.4, 95% CI: 1.1-26.5), Bishop score <4 (OR = 2.3, 95% CI: 1.05-14.4), cervical length <25 mm (OR = 0.2, 95% CI: 0.1-0.8) and the development of uterine contractions in response to the first application of PGE2 (OR = 0.4, 95% CI: 0.1-0.93). Overall, most women required only one (60.9%) or two (85.5%) applications of PGE2 to achieve successful induction. The number of applications of PGE2 required to achieve successful induction was related to parity and cervical status at presentation., Conclusions: Overall, most women who eventually respond to PGE2 do so following the first two applications of PGE2, and the contribution of subsequent applications is relatively small and related to cervical status at admission.

Objective: To determine whether an abnormal 50-g glucose-challenge test (GCT) is independently associated with adverse pregnancy outcome., Methods: A retrospective study of women with abnormal GCT (>140 mg/dL) but normal subsequent 100-g oral glucose-tolerance test (OGTT). Pregnancy outcome was compared with that of women with normal GCT (<140 mg/dL)., Results: Of the 79,153 women delivered during the study period, the results of the GCT were available for 14,268. Of these, 809 (5.7%) had an abnormal GCT and normal OGTT and were eligible for the study group. An abnormal GCT was independently associated with an increased risk for macrosomia (odds ratio [OR] = 2.0, 95% CI: 1.5-2.7), large for gestational age (OR = 1.6, 95% CI: 1.3-2.0), cesarean section (OR = 1.3, 95% CI: 1.1-1.6), respiratory morbidity (OR = 1.6, 95% CI: 1.1-2.7) and neonatal hypoglycemia (OR = 1.8, 95% CI: 1.1-3.2). In contrast, an abnormal GCT was associated with decreased risk for preterm delivery at less than 37 weeks (OR = 0.7, 95% CI: 0.5-0.9) and 34 weeks (OR = 0.3, 95% CI: 0.1-0.6). The association between abnormal GCT and adverse pregnancy outcome was unrelated to the degree of GCT abnormality except for cases in which the GCT was extremely high (≥180 mg/dL)., Conclusion: Women with abnormal-GCT result are at increased risk for adverse pregnancy outcome even in the presence of a normal subsequent OGTT.