T-cell immunoglobulin mucin-3 and galectin-9 levels in peripheral blood mononuclear cells predict fetal acidemia in twin pregnancies.

Purposes: The pH in the umbilical artery at delivery provides information on the fetal environment and is related to postnatal outcomes. The ability to predict fetal acidemia at delivery would improve clinical management and neonatal well-being. We hypothesized that an alteration in maternal immunity would accompany placental changes that precede a decrease in pH in the fetal circulation in twin gestations.Methods: Peripheral blood mononuclear cells (PBMCs), obtained from 86 women with twin pregnancies, were lysed and assayed for concentrations of T-cell immunoglobulin mucin domain 3 (Tim-3) and galectin-9 (gal-9) by ELISA. Tim-3-gal-9 interaction is a primary mechanism promoting immune suppression. At delivery, the pH of arterial cord blood was determined.Results: In eight women (9.3%), the pH in the placental arteries from both twins was <7.15, indicating fetal acidosis. In the remaining 78 women the arterial pH was ≥7.15 in both twins. The median Tim-3 level was 361 pg/ml when arterial pH was <7.15 and 199 pg/ml when pH was ≥7.15 (p = .003). Similarly, gal-9 was 31.2 versus 12.4 ng/ml when pH was <7.15 or ≥7.15, respectively (p = .001). A Tim-3 concentration >260 pg/ml predicted arterial pH <7.15 with a sensitivity of 87.5%, specificity of 79.5% and negative predictive value of 98.4%. A gal-9 level >18.4 predicted arterial pH <7.15 with a sensitivity of 100%, specificity of 73.8% and a negative predictive value of 100%.Conclusion: We conclude that elevations in Tim-3 and gal-9 in PBMCs during gestation predict the subsequent occurrence of a pH <7.15 in the fetal arteries at delivery in twin gestations.

Influence of assisted reproductive technologies on maternal and neonatal outcomes in early preterm deliveries.

INTRODUCTION: Compared to spontaneous conception (SC), pregnancies conceived through assisted reproductive technologies (ART) carry worse pregnancy and neonatal outcomes. Evidences focused on preterm births are limited. Early preterm delivery is a critical situation for medical management and parental counselling. The aim of this study was to analyze if ART procedures influenced pregnancy and neonatal outcomes in singleton pregnancies with early preterm delivery. MATERIAL AND METHODS: This was a retrospective case control study. The population consisted of all consecutive early preterm deliveries occurred at Careggi University Hospital in Florence (Italy) between 2010 and 2017. Cases were considered patients who conceived though ART, including intra cytoplasmic sperm injection (ICSI), in vitro fertilization and embryo transfer (IVF-ET), intra uterine insemination (IUI) and ovarian stimulation. Controls were patients who conceived in the natural way. Main outcomes of the study were: birth weight, umbilical artery pH, Apgar score at 1 and 5 min, gestational age at delivery and mode of delivery. Secondary outcomes were: spontaneous preterm labor initiation, gestational diabetes mellitus, intrauterine growth restriction (IUGR), cholestasis of pregnancy, intra uterine fetal demise (IUFD), placenta previa, fetal malformations, pregnancy induced hypertensive (PIH) disorders (gestational hypertension, preeclampsia and hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome) and postpartum hysterectomy. Shapiro-Wilk test was used to check the normality of the data; Mann-Whitney test was used to compare two continuous variables not-normally distributed. Multiple and binomial logistic regression analyses were used to adjust the results of the statistical analysis for potential confounding factors. The analysis for the main outcomes was performed for all deliveries and then repeated for spontaneous deliveries, separately. RESULTS: Seventy-one patients had ART and 640 SC. We found no differences in birthweight, umbilical artery pH, Apgar at 1 and 5 min and gestational age at delivery between ART and SC groups. C-section rate, placenta previa and PIH disorders were higher in the ART group. The higher prevalence of C-sections in the ART group was not statistically significant after adjusting for age and parity in the whole population but resulted significantly different when analyzing the subgroup of patients with spontaneous initiation of labor. CONCLUSIONS: Fetal outcomes seem to be equal between ART and SC in early preterm neonates ; C-section rate and pregnancy complications such as placenta previa and PIH disorders seem to be higher in the ART group. These information should be part of the family counselling in these cases. We suggest that clinicians, after management of preterm delivery had been properly addressed, should not apply different management in ART compared to SC pregnancies.

Maternal steroid therapy for fetuses with immune-mediated complete atrioventricular block: a systematic review and meta-analysis.

INTRODUCTION: To explore the effect of maternal fluorinated steroid therapy on fetuses affected by immune-mediated complete atrio-ventricular block (CAVB) in utero. MATERIAL AND METHODS: Pubmed, Embase, Cinahl, and ClinicalTrials.gov databases were searched. Only studies reporting the outcome of fetuses with immune CAVB diagnosed on prenatal ultrasound without any cardiac malformations and treated with fluorinated steroids compared to those not treated were included. The primary outcome observed was the regression of CAVB; secondary outcomes were need for pacemaker insertion, overall mortality, defined as the occurrence of either intrauterine (IUD) or neonatal (NND) death, IUD, NND, termination of pregnancy (TOP). Furthermore, we assessed the occurrence of all these outcomes in hydropic fetuses compared to those without hydrops at diagnosis. Meta-analyses of proportions using random effect model and meta-analyses using individual data random-effect logistic regression were used to combine data. RESULTS: Eight studies (162 fetuses) were included. The rate of regression was 3.0% (95%CI 0.2-9.1) in fetuses treated and 4.3% (95%CI 0.4-11.8) in those not treated, with no difference between the two groups (odds ratio (OR): 0.9, 95%CI 0.1-15.1). Pacemaker at birth was required in 71.5% (95%CI 56.0-84.7) of fetuses-treated and 57.8% (95%CI 40.3-74.3) of those not treated (OR: 9, 95%CI 0.4-3.4). There was no difference in the overall mortality rate (OR: 0.5, 95%CI 0.9-2.7) between the two groups; in hydropic fetuses, mortality occurred in 76.2% (95%CI 48.0-95.5) of the treated and in 23.8% (95%CI 1.2-62.3) of the untreated group, while in those without hydrops the corresponding figures were 8.9% (95%CI 2.0-20.3) and 12% (95%CI 8.7-42.2), respectively. Improvement or resolution of hydrops during pregnancy occurred in 76.2% (95%CI 48.0-95.5) of cases treated and in 23.3% (95%CI 1.2-62.3) of those nontreated with fluorinated steroids. CONCLUSIONS: The findings from this systematic review do not suggest a potential positive contribution of antenatal steroid therapy in improving the outcome of fetuses with immune CAVB.

Latent Syphilis Infection in Pregnancy: An Ultrasound Diagnosed Case of Penicillin Treatment Failure.

We report a case of early latent syphilis (reactive serologic tests without clinical evidence of disease within 24 months from the onset of the infection) in pregnancy. Despite an appropriate maternal treatment with benzathine penicillin G, sonographic signs of fetal syphilis were detected. Follow-up scans, in addiction to serial serological tests, have allowed the identification of fetal infection and therefore the failure of antibiotic therapy. We highlight the importance of ultrasound in suspecting fetal infection and in evaluation of the fetal response after penicillin treatment.

Evaluation of sexual function in women with deep infiltrating endometriosis.

INTRODUCTION: The influence of deep infiltrating endometriosis (DIE) on sexual function has been poorly studied. The aim of this study was to evaluate the impact of DIE on sexual function by administering questionnaires to women. METHODS: Women with a clinical and ultrasound diagnosis of DIE and histological confirmation of endometriosis were included in the study. In interview, women were asked to rate five pain symptoms, dysmenorrhea, dyspareunia, dyschezia, dysuria and Cronic Pelvic Pain (CPP), on a visual analogue scale (VAS), and sexual function was assessed using the Female Sexual Function Index (FSFI). RESULTS: A total of 170 women with DIE were identified. A VAS score of 7 or more was taken to indicate that a symptom was 'severe'. Dysmenorrhea was reported to be severe by 66.5% of the sample, dyspareunia by 41.8%, dyschezia by 32.4% and dysuria by 6.5%. Mean FSFI scores did not differ significantly between women with and without endometriosis lesions at particular sites, except for rectovaginal nodules, which were found to be associated with more impaired sexual activity and sexual function. CONCLUSIONS: Women with DIE had significant impairment of sexual activity when a partial or total infiltration of the rectovaginal septum occurred. Particular attention should be given to women with this kind of lesion.

US trends in abortion and preterm birth.

BACKGROUND: A recent large meta-analysis concluded that prior surgical abortion was an independent risk factor for spontaneous preterm birth (PTB), while they found no significant correlation between PTB and medical abortion. OBJECTIVE: To evaluate the potential impact of changes in US abortion rates and practices on US incidence of PTB rate. STUDY DESIGN: This was an epidemiologic analysis of legal abortion and PTB data in the USA from 2003 to 2012. Birth data (annual total birth, annual number and incidence of PTB, defined as PTB <37 weeks) are from National Vital Statistics Reports from the National Center for Health Statistics, Center of Disease Control and Prevention (CDC). Abortion data were collected using Abortion Surveillance provided by the CDC. Abortion incidence was reported overall, and by type: surgical, medical method and procedures reported as "other" such as intrauterine instillation and hysterectomy/hysterotomy. To test for the trend of abortion and of PTB over time, we used the chi-squared test for trend. The primary outcome of our study was the correlation trend analysis between abortion rate and PTB rate. Pearson correlation test was used. A two-tailed p value of 0.05 or less was considered significant. RESULTS: From 2003 to 2012 there were 41 206 315 births in USA, of which 5 042 982 (12.2%) were <37 weeks. The PTB rate declined significantly from 12.3% in 2003 to 11.5% in 2012 (p value test for trend <.04). Out of the 6 122 649 legal abortions, reported by type of procedure, performed from 2003 to 2012 in USA, 5 132 789 were surgical abortion (82.8%) and 860 288 (14.0%) were medical. Chi-squared test for trend showed that the rate of surgical abortion significantly decreased from 88.9 to 78.0% (p < .01) while the rate of medical abortion significantly increased from 7.9 to 21.9% (p < .01) from 2003 to 2012, respectively. The rate of PTB was correlated with the rate of medical abortion (p = .01) and of surgical abortion (p = .02) over time. The higher the surgical abortion rate, the higher the incidence of PTB (Pearson correlation 0.712); the higher the medical abortion rate, the lower the incidence of PTB (Pearson correlation -0.731). CONCLUSION: Recent changes in abortion practices may be associated with the current decrease in US incidence of PTB. Further study on the effect of surgical versus medical abortion is warranted regarding a possible effect on the incidence of PTB.

Exercise during pregnancy and risk of preterm birth in overweight and obese women: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: The incidence of overweight and obesity in pregnancy has risen significantly in the last decades. Overweight and obesity have been shown to increase the risk for some adverse obstetric outcomes. Lifestyle interventions, such as diet, physical activity and behavior changes, may reduce these risks by promoting weight loss and/or preventing excessive weight gain. The possible impact of exercise on the risk of preterm birth (PTB) in overweight or obese women is controversial. Therefore, the aim of our study was to evaluate the effect of exercise on the risk of PTB in overweight or obese pregnant women. MATERIAL AND METHODS: MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID and Cochrane Library were searched from their inception to November 2016. This meta-analysis included only randomized controlled trials (RCTs) of pregnant women assigned or not assigned before 25 weeks to an aerobic exercise regimen. Types of participants included overweight or obese (mean body mass index ≥25 kg/m2 ) women with singleton pregnancies without any contraindication to physical activity. The summary measures were reported as relative risk (RR) or as mean difference (MD) with 95% confidence intervals (CI). The primary outcome was the incidence of PTB <37 weeks. RESULTS: Nine trials including 1502 overweight or obese singleton gestations were analyzed. Overweight and obese women who were randomized in early pregnancy to aerobic exercise for about 30-60 min three to seven times per week had a lower percentage of PTB <37 weeks (RR 0.62, 95% CI 0.41-0.95) compared with controls. The incidence of gestational age at delivery (MD 0.09 week, 95% CI -0.18 to 0.24) and cesarean delivery (RR 0.93, 95% CI 0.77-1.10) were similar in both groups. Women in the exercise group had a lower incidence of gestational diabetes mellitus (RR 0.61, 95% CI 0.41-0.90) compared with controls. No differences in birthweight (MD 16.91 g, 95% CI -89.33 to 123.19), low birthweight (RR 0.58, 95% CI 0.25-1.34), macrosomia (RR 0.92, 95% CI 0.72-1.18) and stillbirth (RR 2.13, 95% CI 0.22-20.4) between the exercise group and controls were found. CONCLUSIONS: Overweight and obese women with singleton pregnancy can be counseled that, compared with being more sedentary, aerobic exercise for about 30-60 min three to seven times per week during pregnancy is associated with a reduction in the incidence of PTB. Aerobic exercise in overweight and obese pregnant women is also associated with a significant prevention of gestational diabetes mellitus, and should therefore be encouraged.

Exercise during pregnancy in normal-weight women and risk of preterm birth: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Preterm birth is the major cause of perinatal mortality in the United States. In the past, pregnant women have been recommended to not exercise because of presumed risks of preterm birth. Physical activity has been theoretically related to preterm birth because it increases the release of catecholamines, especially norepinephrine, which might stimulate myometrial activity. Conversely, exercise may reduce the risk of preterm birth by other mechanisms such as decreased oxidative stress or improved placenta vascularization. Therefore, the safety of exercise regarding preterm birth and its effects on gestational age at delivery remain controversial. OBJECTIVE: The objective of the study was to evaluate the effects of exercise during pregnancy on the risk of preterm birth. DATA SOURCES: MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID, and Cochrane Library were searched from the inception of each database to April 2016. STUDY DESIGN: Selection criteria included only randomized clinical trials of pregnant women randomized before 23 weeks to an aerobic exercise regimen or not. Types of participants included women of normal weight with uncomplicated, singleton pregnancies without any obstetric contraindication to physical activity. The summary measures were reported as relative risk or as mean difference with 95% confidence intervals. The primary outcome was the incidence of preterm birth <37 weeks. TABULATION, INTEGRATION, AND RESULTS: Of the 2059 women included in the meta-analysis, 1022 (49.6%) were randomized to the exercise group and 1037 (50.4%) to the control group. Aerobic exercise lasted about 35-90 minutes 3-4 times per week. Women who were randomized to aerobic exercise had a similar incidence of preterm birth of <37 weeks (4.5% vs 4.4%; relative risk, 1.01, 95% confidence interval, 0.68-1.50) and a similar mean gestational age at delivery (mean difference, 0.05 week, 95% confidence interval, -0.07 to 0.17) compared with controls. Women in the exercise group had a significantly higher incidence of vaginal delivery (73.6% vs 67.5%; relative risk, 1.09, 95% confidence interval, 1.04-1.15) and a significantly lower incidence of cesarean delivery (17.9% vs 22%; relative risk, 0.82, 95% confidence interval, 0.69-0.97) compared with controls. The incidence of operative vaginal delivery (12.9% vs 16.5%; relative risk, 0.78, 95% confidence interval, 0.61-1.01) was similar in both groups. Women in the exercise group had a significantly lower incidence of gestational diabetes mellitus (2.9% vs 5.6%; relative risk, 0.51, 95% confidence interval, 0.31-0.82) and a significantly lower incidence of hypertensive disorders (1.0% vs 5.6%; relative risk, 0.21, 95% confidence interval, 0.09-0.45) compared with controls. No differences in low birthweight (5.2% vs 4.7%; relative risk, 1.11, 95% confidence interval, 0.72-1.73) and mean birthweight (mean difference, -10.46 g, 95% confidence interval, -47.10 to 26.21) between the exercise group and controls were found. CONCLUSION: Aerobic exercise for 35-90 minutes 3-4 times per week during pregnancy can be safely performed by normal-weight women with singleton, uncomplicated gestations because this is not associated with an increased risk of preterm birth or with a reduction in mean gestational age at delivery. Exercise was associated with a significantly higher incidence of vaginal delivery and a significantly lower incidence of cesarean delivery, with a significantly lower incidence of gestational diabetes mellitus and hypertensive disorders and therefore should be encouraged.

Neuraxial analgesia to increase the success rate of external cephalic version: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: External cephalic version is a medical procedure in which the fetus is externally manipulated to assume the cephalic presentation. The use of neuraxial analgesia for facilitating the version has been evaluated in several randomized clinical trials, but its potential effects are still controversial. OBJECTIVE: The objective of the study was to evaluate the effectiveness of neuraxial analgesia as an intervention to increase the success rate of external cephalic version. DATA SOURCES: Searches were performed in electronic databases with the use of a combination of text words related to external cephalic version and neuraxial analgesia from the inception of each database to January 2016. STUDY ELIGIBILITY CRITERIA: We included all randomized clinical trials of women, with a gestational age ≥36 weeks and breech or transverse fetal presentation, undergoing external cephalic version who were randomized to neuraxial analgesia, including spinal, epidural, or combined spinal-epidural techniques (ie, intervention group) or to a control group (either intravenous analgesia or no treatment). STUDY APPRAISAL AND SYNTHESIS METHODS: The primary outcome was the successful external cephalic version. The summary measures were reported as relative risk or as mean differences with a 95% confidence interval. TABULATION, INTEGRATION, AND RESULTS: Nine randomized clinical trials (934 women) were included in this review. Women who received neuraxial analgesia had a significantly higher incidence of successful external cephalic version (58.4% vs 43.1%; relative risk, 1.44, 95% confidence interval, 1.27-1.64), cephalic presentation in labor (55.1% vs 40.2%; relative risk, 1.37, 95% confidence interval, 1.08-1.73), and vaginal delivery (54.0% vs 44.6%; relative risk, 1.21, 95% confidence interval, 1.04-1.41) compared with those who did not. Women who were randomized to the intervention group also had a significantly lower incidence of cesarean delivery (46.0% vs 55.3%; relative risk, 0.83, 95% confidence interval, 0.71-0.97), maternal discomfort (1.2% vs 9.3%; relative risk, 0.12, 95% confidence interval, 0.02-0.99), and lower pain, assessed by the visual analog scale pain score (mean difference, -4.52 points, 95% confidence interval, -5.35 to 3.69) compared with the control group. The incidences of emergency cesarean delivery (1.6% vs 2.5%; relative risk, 0.63, 95% confidence interval, 0.24-1.70), transient bradycardia (11.8% vs 8.3%; relative risk, 1.42, 95% confidence interval, 0.72-2.80), nonreassuring fetal testing, excluding transient bradycardia, after external cephalic version (6.9% vs 7.4%; relative risk, 0.93, 95% confidence interval, 0.53-1.64), and abruption placentae (0.4% vs 0.4%; relative risk, 1.01, 95% confidence interval, 0.06-16.1) were similar. CONCLUSION: Administration of neuraxial analgesia significantly increases the success rate of external cephalic version among women with malpresentation at term or late preterm, which then significantly increases the incidence of vaginal delivery.