Mapping cell-to-tissue graphs across human placenta histology whole slide images using deep learning with HAPPY.

Accurate placenta pathology assessment is essential for managing maternal and newborn health, but the placenta's heterogeneity and temporal variability pose challenges for histology analysis. To address this issue, we developed the 'Histology Analysis Pipeline.PY' (HAPPY), a deep learning hierarchical method for quantifying the variability of cells and micro-anatomical tissue structures across placenta histology whole slide images. HAPPY differs from patch-based features or segmentation approaches by following an interpretable biological hierarchy, representing cells and cellular communities within tissues at a single-cell resolution across whole slide images. We present a set of quantitative metrics from healthy term placentas as a baseline for future assessments of placenta health and we show how these metrics deviate in placentas with clinically significant placental infarction. HAPPY's cell and tissue predictions closely replicate those from independent clinical experts and placental biology literature.

Gradual dosing of ursodeoxycholic acid in mothers with intrahepatic cholestasis of pregnancy may improve composite neonatal outcome.

INTRODUCTION AND OBJECTIVES: Intrahepatic cholestasis of pregnancy (ICP) is often accompanied by fetal and maternal complications. MATERIALS AND METHODS: Retrospective review of the clinical course of women with ICP and their neonates treated at our medical center over a 10-year period. Special attention was paid to the maternal and neonatal response to 2 different modes of ursodeoxycholic acid (UDCA) administration. RESULTS: Neonates of mothers with high total bile acid levels had a poorer composite neonatal outcome. Twenty-seven women who presented at an advanced stage of their pregnancies did not receive UDCA. UDCA was administered in 2 modes: either a full dose at admission (76 women) or a gradually increasing dose until the desired dosage was reached (25 women). The mean gestational age at delivery for the 94 neonates that were exposed to full UDCA dose was the lowest (36±2.3 weeks for the full dose, 37±1.4 weeks for the 30 neonates from the gradually increasing dose, 38±1.6 weeks for the 29 neonates from the no treatment group, p<0.001). The group of neonates that were exposed to full UDCA dose had the highest rate of unfavorable composite neonatal outcome (53% for full dose, 30% for gradually increasing dose, 24% for the no treatment group, p=0.006). CONCLUSIONS: Compared to the administration of a full UDCA dose, the administration of a gradually increasing dose of UDCA may be associated with a greater gestational age at delivery and fewer events of unfavorable composite neonatal outcomes. These novel findings should be retested prospectively in a large cohort of patients.

Women's attitudes towards disclosure of genetic information in pregnancy with varying levels of penetrance.

BACKGROUND: Chromosomal-microarray-analysis (CMA) may reveal susceptibility-loci (SL) of varied penetrance for autism-spectrum-disorder (ASD) and other neurodevelopmental conditions. Attitudes of women/parents to disclosure of SL during pregnancy are understudied. METHODS: A multiple-choice questionnaire was distributed to postpartum women. Data were collected on women's interest to receive prenatal genetic information with various levels of penetrance. RESULTS: Women's (n = 941) disclosure choices were dependent on the magnitude of risk: approximately 70% supported disclosure of either full or 40% penetrance, 53% supported disclosure at a 20% risk threshold, and 40% supported disclosure at 10% or less. Although most women supported, rejected or were indecisive about disclosure consistently across all risk levels, nearly one-quarter (24%) varied their responses based on penetrance, and this was associated with religiosity, education, parity and concern about fetal health (p-values <0.04). Among those who varied their choices, the risk threshold was lower among secular women (20%) than among ultraorthodox women (40%). In a multivariable analysis, ultraorthodox women were much less likely to vary their choices on ASD disclosure compared with secular women (aOR = 0.37, p < 0.001). CONCLUSION: Women's attitudes toward disclosure are influenced by the level of risk and their individual characteristics. We therefore encourage engaging women/couples in disclosure decisions regarding uncertain and probabilistic results from prenatal genomic tests.

Postpartum women's attitudes to disclosure of adult-onset conditions in pregnancy.

BACKGROUND: Advanced prenatal genomic technologies can identify risks for adult-onset (AO) conditions in the fetus, challenging the traditional purpose of prenatal testing. Professional guidelines commonly support disclosure of high-penetrance AO actionable conditions, yet attitudes of women/parents to these findings and factors affecting their attitudes are understudied. METHODS: We explored 941 (77% response rate) postpartum women's attitudes towards receiving prenatal genetic information, and associations of sociodemographic, medical and psychological characteristics with their choices, focusing on AO conditions. RESULTS: Women largely support the disclosure of actionable AO findings (58.4%), in line with professional guidelines. A third of the women also supported the disclosure of non-actionable AO conditions. Stronger religious observance (p < 0.001) and higher psychological distress (p = 0.024) were associated with decreased interest in receiving actionable AO conditions, whereas higher concern for fetal health yielded increased interest (p = 0.032). Attitudes towards disclosure were strongly associated with women's perceived benefit of such information for their own, partner's, and future child's health. Termination of pregnancy based on such information received very little support. CONCLUSION: In-light of the demonstrated understanding of nuanced genetic information and the observed diversity in attitudes, a culturally competent opt-in/out policy could be considered. If full-disclosure is practiced, support should be provided to those expressing higher levels of distress.

Baseline Cystic fibrosis disease severity has an adverse impact on pregnancy and infant outcomes, but does not impact disease progression.

BACKGROUND: With increasing longevity and quality of life in adults with Cystic fibrosis (CF), growing maternity rates are reported. Women with severe CF are becoming pregnant, with unpredictable maternal and fetal outcomes. AIM: To determine how baseline disease severity, pancreatic insufficiency (PI) and Pseudomonas aeruginosa (PA) infection affect fertility, the pregnancy course, delivery, neonatal outcome, and subsequent disease progression. METHODS: A multicenter-retrospective cohort study. Data on patients that had been pregnant between 1986-2018 was collected from ten CF centers worldwide. Disease severity [mild or moderate-severe (mod-sev)] was defined according to forced expiratory volume % predicted in 1 second (FEV1) and body mass index (BMI). Three time periods were compared, 12 months prior to conception, the pregnancy itself and the 12 months thereafter. RESULTS: Data was available on 171 pregnancies in 128 patients aged 18-45 years; 55.1% with mod-sev disease, 43.1% with PI and 40.3% with PA. Women with mod-sev disease had more CF-related complications during and after pregnancy and delivered more preterm newborns. However, FEV1 and BMI decline were no different between the mild and mod-sev groups. A more rapid decline in FEV1 was observed during pregnancy in PI and PA infected patients, though stabilizing thereafter. PI was associated with increased risk for small for gestational age infants. CONCLUSION: Baseline disease severity, PA infection and PI have an adverse impact on infant outcomes, but do not impact significantly on disease progression during and after pregnancy. Consequently, pregnancies in severe CF patients can have a good prognosis.

Are Paula method exercises effective for gastrointestinal reactivation post-elective cesarean delivery? Randomized controlled trial.

AIM: To examine the effectiveness of the Paula Method exercises in comparison to standard care on resumption of gastrointestinal (GI) activity in women postelective caesarean delivery (CD). DESIGN: Randomized controlled trial on a postpartum unit of a university medical centre. METHODS: Sixty-four women following elective CD performed under regional anaesthesia were recruited between 2 February-3 July 2018. Participants were randomized into two groups: The Paula Method exercise group (intervention group) and the control group. Women in the intervention group performed circular muscle exercises according to the Paula Method and received standard care, while those in the control group were treated only with standard care. Time to first bowel sounds, passage of first flatus and first defecation after CD were measured. RESULTS: A significant difference was found in the time to passage of first flatus, in favour of the intervention group (24.07 [6.85] hours versus 39.07 [10.37] hours; p < .001). No significant differences between the groups were found for other main outcome measures. CONCLUSION: Paula Method exercises post CD can serve as natural and convenient alternative to the standard, conservative treatment to promote resumption of GI activity. IMPACT: CD can be associated with postoperative ineffective peristalsis that can lead to a paralytic ileus. Since standard methods are not sufficient for all women, there is a need for alternative modalities to accelerate the resumption of bowel functioning. In the Paula Method exercise group, time to first flatus passage occurred significantly sooner compared with the control group. Time to first defecation was earlier in the Paula Method exercise group but this difference did not reach statistical significance. Along with gum chewing, Paula Method exercises can be part of a simple and inexpensive GI activation strategy post CD. Further research should be performed using these exercises post other operative procedures.

Cervical dilation at the time of epidural catheter insertion is not associated with the degree of prolongation of the first or second stages of labor, or the rate of instrumental vaginal delivery.

INTRODUCTION: Epidural analgesia (EA) is an established option for efficient intrapartum analgesia. Meta-analyses have shown that EA differentially affects the first stage of labor but prolongs the second. The question of EA timing remains open. We aimed to investigate whether EA prolongs delivery in total and whether the EA administration timing vis-à-vis cervical dilation at catheter insertion is associated with a modulation of its effects on the duration of the first and second stages, as well as the rate of instrumental vaginal delivery in primiparas and multiparas. MATERIAL AND METHODS: A retrospective electronic medical records-based study of 18 870 singleton term deliveries occurring in our institution from 2003 to 2015. Cervical dilation was determined within a half-hour of EA administration. We examined whether cervical dilation at EA administration correlated with the duration of the first and/or second stage, with the rate of prolonged second stage, and with the rate of interventional delivery. The study group was stratified to 10 subgroups defined by 1-cm intervals of cervical dilation at EA administration. Logistic regression modeling was applied to analyze the association between EA timing and rate of instrumental delivery while controlling for possible confounders. RESULTS: In primiparas, receiving EA correlated with longer medians of active first stage (+51 minutes; P < .001) and second stage (+55 minutes; P < .001). In multiparas, median increases in active first stage (+43 minutes; P < .001) and second stage (+8 minutes; P < .001) were noted. The timing of EA, vis-à-vis cervical dilation (1-10 cm) was not associated with a substantial modulation of these effects. Logistic regression showed that cervical dilation at EA was not associated with a higher instrumental vaginal delivery rate. CONCLUSIONS: Epidural analgesia prolonged the first and second stages of labor vs no epidural. Having EA was associated with a higher instrumental delivery rate but not with higher rates of maternal or neonatal complications, in primi- and multiparas. Importantly, the timing of EA, vis-à-vis cervical dilation, was not associated with substantial changes in the duration of labor stages or the instrumental delivery rate. Thus, EA may be offered early in the first stage of labor.

Timing of staples and dressing removal after cesarean delivery (the SCARR study).

OBJECTIVE: To investigate optimal timing of dressing and staples removal after cesarean delivery (CD). METHODS: This prospective clustered clinical trial enrolled women undergoing CD between January 1, 2013, and October 31, 2014, at Hadassah-Hebrew University Hospital, Jerusalem. Women were assigned to one of five clusters differing in timing of dressing and staples removal. We assessed scar healing at 6 weeks. RESULTS: 920 women completed telephone questionnaires. Wound healing did not differ significantly among the clusters: the healing complication rate was 21% in the control group (n=46) and ranged from 18% to 26% (n=27-50) in clusters two to five (P=0.49). More healing complications were observed in women with a body mass index (BMI) of more than 35 kg/m2 versus 35 kg/m2 or less (P=0.016), urgent versus elective CD (P=0.013), preterm premature rupture of the membranes (PPROM) versus intact membranes (P=0.016), and chorioamnionitis at delivery versus no chorioamnionitis (P=0.001). 586 (64%) women underwent physician assessment at staples removal and at 6 weeks post CD. CONCLUSIONS: Timing of dressing and staples removal has no effect on CD scar healing in low- and high-risk parturients. A BMI of more than 35 kg/m2 , urgent CD, PPROM, and chorioamnionitis were associated with mal-healing, regardless of cluster. Clinicaltrials.gov: NCT01724255.

Castor oil for induction of labor in post-date pregnancies: A randomized controlled trial.

BACKGROUND: Castor oil is a substance used for labor induction in an inpatient setting. However, its efficacy as an agent for the induction of labor, for post-date pregnancies in an outpatient setup is unknown. OBJECTIVE: Efficacy of castor oil as an agent for the induction of labor, for post-date pregnancies in outpatient settings. METHODS: Eighty-one women with a low-risk post-date singleton pregnancy with a Bishop score≤7, without effective uterine contractions were randomized to the intervention, 60ml of castor oil, or the control, 60ml of sun-flower oil. The primary outcome was proportion of women entering the active phase of labor 24, 36, 48h after ingestion. Secondary outcomes included meconium stained amniotic fluid, abnormal fetal heart rate tracing, cesarean section rate, instrumental deliveries, birth weight, 5min Apgar score, chorioamnionitis, hypertensive complications, retained placenta, and post-partum hemorrhage. FINDINGS: Intervention and control groups included 38 and 43 women, respectively. No differences in baseline characteristics, except for age were noted. The observed interaction between castor oil and parity was significant (pinteraction=0.02). Multiparous women in the intervention group exhibited a significant beneficial effect on entering active labor within 24, 36 and 48h after castor oil consumption compared with the placebo (Hazard Ratio=2.93, p=0.048; Hazard Ratio=3.29, p=0.026; Hazard Ratio=2.78, p=0.042 respectively). This effect was not noted among primiparous women. No differences in rate of obstetric complications or adverse neonatal outcomes were noted. CONCLUSION: Castor oil is effective for labor induction, in post-date multiparous women in outpatient settings.

Association of Catastrophic Neonatal Outcomes With Increased Rate of Subsequent Cesarean Deliveries.

OBJECTIVE: To evaluate whether full-term deliveries resulting in neonates diagnosed with hypoxic-ischemic encephalopathy are associated with a significant increase in the rate of subsequent unscheduled cesarean deliveries. METHODS: We conducted a retrospective chart review study and examined all deliveries in the Department of Obstetrics and Gynecology at Hadassah University Hospital, Mt. Scopus campus, Jerusalem, Israel, during 2009-2014. We reviewed all cases of hypoxic-ischemic encephalopathy in singleton, term, liveborn neonates and identified seven such cases, three of which were attributed to obstetric mismanagement and four that were not. We measured the rate of unscheduled cesarean deliveries before and after the events and their respective hazard ratio. RESULTS: Before a mismanaged delivery resulting in hypoxic-ischemic encephalopathy, the baseline rate of unscheduled cesarean deliveries was approximately 80 unscheduled cesarean deliveries for every 1,000 deliveries. In the first 4 weeks immediately after each of the three identified cases, there was a significant increase in the rate of unscheduled cesarean deliveries by an additional 48 unscheduled cesarean deliveries per 1,000 deliveries (95% confidence interval [CI] 27-70/1,000). This increase was transient and lasted approximately 4 weeks. We estimated that each case was associated with approximately 17 additional unscheduled cesarean deliveries (95% CI 8-27). There was no increase in the rate of unscheduled cesarean deliveries in cases of hypoxic-ischemic encephalopathy that were not associated with mismanagement. CONCLUSION: The increase in the rate of unscheduled cesarean deliveries after a catastrophic neonatal outcome may result in short-term changes in obstetricians' risk evaluation.

Third- or Fourth-Degree Intrapartum Anal Sphincter Tears Are Associated With Levator Ani Avulsion in Primiparas.

OBJECTIVES: We evaluated primiparous women with clinically diagnosed third- and fourth-degree and anal sphincter tears, to evaluate the rate of levator ani muscle injury compared to primiparous women without sphincter tears. METHODS: Primiparous women delivering in our maternity ward with intrapartum diagnoses of third- or fourth-degree anal sphincter tears, repaired by the overlapping technique, were recruited to undergo 3-dimensional transperineal sonography of the pelvic floor anatomy, including the anterior and posterior compartments. Primiparas with uncomplicated vaginal deliveries were recruited as a comparison group. Patient files were examined, and maternal backgrounds and delivery and neonatal details were extracted for all patients. RESULTS: Ninety-four women with tears were recruited to the study group, and 464 women with normal vaginal deliveries constituted the comparison group. The groups differed significantly in the rates of levator ani defects: 38 of 94 women (40.4%) in the study group versus 75 of 464 (16.2%) in the comparison group (P < .001; odds ratio, 3.53; 95% confidence interval, 2.18-5.7). Neonatal head circumference differed significantly between the study and comparison groups: (mean ± SD, 34.5 ± 1.3 cm in the study group versus 33.9 ± 1.3 cm in the comparison group; P= .005), as did birth weight (3322 ± 430 g in the study group versus 3169 ± 458 g in the comparison group; P = .007). The groups did not differ in maternal age, gestational age at delivery, length of second stage of labor, and rates of epidural anesthesia, episiotomy, and vacuum extraction. CONCLUSIONS: Third- and fourth-degree intrapartum sphincter tears are associated with levator ani avulsion. Knowledge of complex pelvic floor damage may allow for prompt referral to secondary preventive measures for pelvic floor disorders.

Third- or Fourth-Degree Intrapartum Anal Sphincter Tears Are Associated With Levator Ani Avulsion in Primiparas.

OBJECTIVES: We evaluated primiparous women with clinically diagnosed third- and fourth-degree and anal sphincter tears, to evaluate the rate of levator ani muscle injury compared to primiparous women without sphincter tears. METHODS: Primiparous women delivering in our maternity ward with intrapartum diagnoses of third- or fourth-degree anal sphincter tears, repaired by the overlapping technique, were recruited to undergo 3-dimensional transperineal sonography of the pelvic floor anatomy, including the anterior and posterior compartments. Primiparas with uncomplicated vaginal deliveries were recruited as a comparison group. Patient files were examined, and maternal backgrounds and delivery and neonatal details were extracted for all patients. RESULTS: Ninety-four women with tears were recruited to the study group, and 464 women with normal vaginal deliveries constituted the comparison group. The groups differed significantly in the rates of levator ani defects: 38 of 94 women (40.4%) in the study group versus 75 of 464 (16.2%) in the comparison group (P < .001; odds ratio, 3.53; 95% confidence interval, 2.18­5.7). Neonatal head circumference differed significantly between the study and comparison groups: (mean ・} SD, 34.5 ・} 1.3 cm in the study group versus 33.9 ・} 1.3 cm in the comparison group; P= .005), as did birth weight (3322 ・} 430 g in the study group versus 3169 ・} 458 g in the comparison group; P= .007). The groups did not differ in maternal age, gestational age at delivery, length of second stage of labor, and rates of epidural anesthesia, episiotomy, and vacuum extraction. CONCLUSIONS: Third- and fourth-degree intrapartum sphincter tears are associated with levator ani avulsion. Knowledge of complex pelvic floor damage may allow for prompt referral to secondary preventive measures for pelvic floor disorders.

Re-laparotomy following cesarean delivery - risk factors and outcomes.

INTRODUCTION: Re-laparotomy following caesarean delivery (CD) is a rare yet serious complication. The aim of this study was to identify risk factors, diagnostic features and outcomes following re-laparotomy. MATERIALS AND METHODS: This retrospective cohort study reviewed cases of re-laparotomy following CD performed at Hadassah-Hebrew University Medical Center. Occurrences were identified via the electronic medical record database. RESULTS: During the study period, 17,213 women underwent CD, of which 55 (0.3%) underwent re-laparotomy during the same hospitalization. Main indications for re-laparotomy were intra-peritoneal bleeding (62%) and wound infection/dehiscence (22%). During re-laparotomy, the bleeding source was found and ligated in 85% of the cases. Age, parity, previous CD, induction of labor, anesthesia type and operative duration were significant risk factors for re-laparotomy. In a selected group of patients, trial of conservative treatment was made. However, in 76% of these women a re-laparotomy was required. DISCUSSION: Risk factors for re-laparotomy following CD should be identified, thus enabling more intensified monitoring of patients considered at risk for this complication. When intra-peritoneal bleeding following CD is suspected, conservative management has a high failure rate and should be reserved for a selected group of stable patients.

A large head circumference is more strongly associated with unplanned cesarean or instrumental delivery and neonatal complications than high birthweight.

OBJECTIVE: Fetal size impacts on perinatal outcomes. We queried whether the fetal head, as the fetal part interfacing with the birth canal, might impact on obstetric outcomes more than birthweight (BW). We examined associations between neonatal head circumference (HC) and delivery mode and risk of perinatal complications as compared to high BW. STUDY DESIGN: This was an electronic medical records-based study of term singleton births (37-42 weeks' gestation) from January 2010 through December 2012 (N = 24,780, 6343 primiparae). We assessed risks of unplanned cesarean or instrumental delivery and maternal and fetal complications in cases with HC or BW ≥95th centile (large HC, high BW) vs those with parameters <95th centile (normal). Newborns were stratified into 4 subgroups: normal HC/normal BW (reference, n = 22,548, primiparae 5862); normal HC/high BW (n = 817, P = 213); large HC/normal BW (n = 878, P = 265); and large HC/high BW (n = 537, P = 103). Multinomial multivariable regression provided adjusted odds ratio (aOR) while controlling for potential confounders. RESULTS: Infants with HC ≥95th centile (n = 1415) were delivered vaginally in 62% of cases, unplanned cesarean delivery 16%, and instrumental delivery 11.2%; 78.4% of infants with HC <95th centile were delivered vaginally, 7.8% unplanned cesarean, and 6.7% instrumental delivery. Odds ratio (OR) for unplanned cesarean was 2.58 (95% confidence interval [CI], 2.22-3.01) and for instrumental delivery OR was 2.13 (95% CI, 1.78-2.54). In contrast, in those with BW ≥95th centile (n = 1354) 80.3% delivered vaginally, 10.2% by unplanned cesarean (OR, 1.2; 95% CI, 1.01-1.44), and 3.4% instrumental delivery (OR, 0.46; 95% CI, 0.34-0.62) compared to infants with BW <95th centile: spontaneous vaginal delivery, 77.3%, unplanned cesarean 8.2%, instrumental 7.1%. Multinomial regression with normal HC/normal BW as reference group showed large HC/normal BW infants were more likely to be delivered by unplanned cesarean (aOR, 3.08; 95% CI, 2.52-3.75) and instrumental delivery (aOR, 3.03; 95% CI, 2.46-3.75). Associations were strengthened in primiparae. Normal HC/high BW was not associated with unplanned cesarean (aOR, 1.18; 95% CI, 0.91-1.54), while large HC/high BW was (aOR, 1.93; 95% CI, 1.47-2.52). Analysis of unplanned cesarean indications showed large HC infants had more failure to progress (27.7% vs 14.1%, P < .001), while smaller HC infants had more fetal distress (23.4% vs 16.9%, P < .05). CONCLUSION: A large HC is more strongly associated with unplanned cesarean and instrumental delivery than high BW. Prospective studies are needed to test fetal HC as a predictive parameter for prelabor counseling of women with "big babies."

Degree of bother from pelvic floor dysfunction in women one year after first delivery.

OBJECTIVE: To investigate rates and range of pelvic floor dysfunction complaints, including anterior and posterior compartments and sexual function, in an unselected population of primiparous women one year from delivery, and examine the degree of bother they cause. STUDY DESIGN: Cross sectional study. Primiparous women who delivered their first child in our delivery wards 10-14 months previously, were approached by phone and asked to complete the Pelvic Floor Symptom Bother Questionnaire (PFBQ) and provide general demographic information. Details regarding participants' labor and delivery were extracted from electronic medical records. PFBQ score was correlated to demographic and labor and delivery parameters. RESULTS: 198 women completed the questionnaire. Response rate was 94%. Scores ranged from 0 to 44.4 (out of a possible 100). At least one symptom of PFD was reported by 64% of respondents. Various degrees of urinary incontinence were reported by 9.1-12.1% of women. Some degree of fecal or flatus incontinence was reported by 10.1% of women; 11.1% reported some degree of obstructed defecation. Severe degree of bother from one or more PFD symptoms was reported by 40.1-90.9%. Some level of dyspareunia was reported by 37.3%. A "dose response" trend between mode of delivery and rate of dyspareunia was observed. CONCLUSIONS: Two-thirds of primiparous women one year after delivery suffer PFD symptoms that cause some degree of bother. When asked, women are willing to discuss pelvic floor function; caregivers should initiate discussion and refer women promptly to interventions where necessary.

Reduction in maternal circulating ouabain impairs offspring growth and kidney development.

Ouabain, a steroid present in the circulation and in various tissues, was shown to affect the growth and viability of various cells in culture. To test for the possible influence of this steroid on growth and viability in vivo, we investigated the involvement of maternal circulating ouabain in the regulation of fetal growth and organ development. We show that intraperitoneal administration of anti-ouabain antibodies to pregnant mice resulted in a >80% decline in the circulating ouabain level. This reduction caused a significant decrease in offspring body weight, accompanied by enlargement of the offspring heart and inhibition of kidney and liver growth. Kidney growth inhibition was manifested by a decrease in the size and number of nephrons. After the reduction in maternal circulating ouabain, kidney expression of cyclin D1 was reduced and the expression of the α1 isoform of the Na(+), K(+)-ATPase was increased. In addition, the elevation of proliferation signals including ERK1/2, p-90RSK, Akt, PCNA, and Ki-67, and a reduction in apoptotic factors such as Bax, caspase-3, and TUNEL were detected. During human pregnancy, the circulating maternal ouabain level increased and the highest concentration of the steroid was found in the placenta. Furthermore, circulating ouabain levels in women with small-for-gestational age neonates were significantly lower than the levels in women with normal-for-gestational age newborns. These results support the notion that ouabain is a growth factor and suggest that a reduction in the concentration of this hormone during pregnancy may increase the risk of impaired growth and kidney development.

Relationship between nulliparity and preeclampsia may be explained by altered circulating soluble fms-like tyrosine kinase 1.

OBJECTIVE: To test the hypothesis that the risk of preeclampsia in nulliparous women may be due to an anti-angiogenic state. METHODS: Maternal serum samples obtained in the third trimester from nulliparous (n = 86) and multiparous (n = 165) singleton uncomplicated pregnancies were analyzed for levels of angiogenic factors - soluble fms like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF) by enzyme-linked immunosorbent assay (ELISA). RESULTS: For nulliparous and multiparous pregnancies, serum sFlt1 levels were 12 732 ± 832 and 10 162 ± 666 (p = 0.020), serum PlGF levels were 215 ± 15 and 249 ± 14 (p = 0.093) (all reported as mean SD in pg/ml) and mean ratios of sFlt1/PlGF were 93 ± 12 and 62 ± 5 (p = 0.023), respectively. Adjustment for maternal age and fetal birth weight did not alter the results. CONCLUSIONS: Nulliparous pregnancies had higher circulating sFlt1 levels and sFlt1/PlGF ratios than multiparous pregnancies, suggesting an association with an angiogenic imbalance. Taken together with the pathogenic role of anti-angiogenic factors in preeclampsia, our data may be one explanation for the epidemiological observation that nulliparity is a risk factor for the development of preeclampsia.

Regular exercise is the most significant lifestyle parameter associated with the severity of climacteric symptoms: a cross sectional study.

OBJECTIVE: To assess the association between demographic and lifestyle parameters and perceived severity of the climacteric syndrome in perimenopausal women. STUDY DESIGN: A cross-sectional study of 151 healthy women aged 45-55 years who attended the University Medical Center affiliated menopause clinics. The analysis was based on self completion of the Greene climacteric score, consisting of psychological, somatic/physical, sexual and vasomotor subscores. The Greene total score and subscores were the main outcomes of the study. RESULTS: Of all demographic, anthropometric and lifestyle parameters recorded, the correlates with reduced total Greene score were high-order maternity and regular physical exercise. Mothers of 3 or more children reported significantly lower total Greene score (18±12.8 vs. 22.1±8.1) (p=0.01) as well as lower psychological subscore (8.7±6.8 vs. 11.5±5.4) (p=0.01). Regular physical activity was also associated with significantly lower total Greene score (17.0±11.0 vs. 22.6±11.3) (p=0.01) and specifically lower psychological subscore (9.5±6.6 vs. 12.8±7.7) (p=0.03) and sexual subscore (1.1±0.99 vs. 1.61±1.05) (p=0.03). Linear regression models showed that regular exercise was the lifestyle parameter most significantly correlated with a lower total Greene score (p=0.006) independent of menopausal status. Of particular note, regular exercise was significantly correlated with lower psychological (p=0.006) and physical subscores (p=0.06). Moreover, the higher the frequency of exercise (both aerobic and non aerobic), the lower the severity of the climacteric symptoms reported, yet the vasomotor and sexual subscores remained unchanged. CONCLUSIONS: Regular exercise of at least 3 times a week was the most significant lifestyle parameter to be associated with the severity of climacteric symptoms.

Sexual function and quality of life of women with stress urinary incontinence: a randomized controlled trial comparing the Paula method (circular muscle exercises) to pelvic floor muscle training (PFMT) exercises.

AIM: To compare the effectiveness of the Paula method (circular muscle exercises) vs. pelvic floor muscle training (PFMT) exercises on sexual function (SF) and quality of life (QoL) of women with stress urinary incontinence (SUI). METHODS: A randomized controlled trial (RCT) was conducted in outpatient urban community clinics serving diverse socioeconomic populations between September 2004 and July 2005. The intervention included two exercise regimens: Paula method--12 weeks of private 45 minutes sessions; PFMT--12 weeks of group (up to 10 participants) sessions of 30 minutes in length once a week, for 4 weeks plus two additional sessions, 3 weeks apart. MAIN OUTCOME MEASURES: The Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire; the Incontinence Quality of Life Questionnaire; 1-hour clinic pad test; gynecological examination; demographic/health history. RESULTS: Sixty-six women in the Paula group and 60 women in the PFMT group. The mean SF scores post interventions were 38.72 (5.35) in the Paula group and 38.07 (5.80) in the PFMT group. SF score improvement was found to be significant in both groups (Paula, P = 0.01; PFMT, P = 0.05), as was in the QoL scores (Paula, P < 0.001; PFMT, P ≤ 0.001), with no significant difference between groups. There was a significant correlation between the mean SF score and the mean QoL score after the intervention (Paula: r = 0.4, P = 0.002; PFMT: r = 0.4, P = 0.009). A mild to moderate significant correlation was also found between the SF score and pad test results in both groups post intervention (r = -0.3, P = 0.02; r = -0.3, P = 0.04, respectively). CONCLUSION: This RCT study demonstrated the effectiveness of two exercise methods on SF and QoL in women suffering from SUI. The Paula method of exercise was presented for the first time in the literature as a conservative noninvasive treatment for SUI and SF.