TRAIL and IP-10 dynamics in pregnant women post COVID-19 vaccination: associations with neutralizing antibody potency.

Introduction: The aim of this study is to investigate changes in TNF-related apoptosis-inducing ligand (TRAIL) and gamma interferon-induced protein 10 (IP-10) after COVID-19 vaccination in pregnant women and to explore their association with neutralizing antibody (Nab) inhibition. Methods: The study evaluated 93 pregnant women who had previously received two (n=21), three (n=55) or four (n=17) doses of COVID-19 vaccine. Also we evaluated maternal blood samples that were collected during childbirth. The levels of TRAIL, IP-10 and Nab inhibition were measured using enzyme-linked immunosorbent assays (ELISA). Results and discussion: Our study revealed four-dose group resulted in lower TRAIL levels when compared to the two-dose and three-dose groups (4.78 vs. 16.07 vs. 21.61 pg/ml, p = 0.014). The two-dose group had reduced IP-10 levels than the three-dose cohort (111.49 vs. 147.89 pg/ml, p=0.013), with no significant variation compared to the four-dose group. In addition, the four-dose group showed stronger Nab inhibition against specific strains (BA.2 and BA.5) than the three-dose group. A positive correlation was observed between TRAIL and IP-10 in the two-dose group, while this relationship was not found in other dose groups or between TRAIL/IP-10 and Nab inhibition. As the doses of the COVID-19 vaccine increase, the levels of TRAIL and IP-10 generally increase, only by the fourth dose, the group previously vaccinated with AZD1222 showed lower TRAIL but higher IP-10. Despite these changes, more doses of the vaccine consistently reinforced Nab inhibition, apparently without any relation to TRAIL and IP-10 levels. The variation may indicate the induction of immunological memory in vaccinated mothers, which justifies further research in the future.

Pilot Study on Evaluating the Impact of Tetanus, Diphtheria, and Pertussis (Tdap), Influenza, and COVID-19 Vaccinations on Antibody Responses in Pregnant Women.

This study assessed IgG levels to influenza/pertussis and neutralizing antibody (Nab) responses of COVID-19 vaccines in blood of pregnant women following immunization with pertussis (Tdap), influenza, and COVID-19 vaccines. We prospectively collected 71 participants categorized by the following vaccine combinations: 3TI, 4TI, 3T, and 4T groups (three and four doses of COVID-19 vaccines plus Tdap/influenza or Tdap vaccines alone). Our findings have indicated that the 3TI group exhibited elevated IgG levels for influenza B compared to the 3T group (12.90 vs. 7.75 U, p = 0.001); this pattern was not observed for influenza A. Pertussis IgG levels remained uniform across all groups. The 4TI group demonstrated a greater Nab inhibition rate from COVID-19 vaccines compared to both the 3TI and 3T groups (61.34% vs. 22.5% and 15.16%, respectively, p = 0.001). We observed no correlation between Nab inhibition rate and IgG levels for Tdap/influenza, with the exception of a moderate correlation with influenza B in the 3TI group. The efficacy of Tdap vaccine in pregnant women remained consistent, regardless of the administration of COVID-19 or influenza vaccines. Interestingly, without the influenza vaccine, both three and four doses of the COVID-19 vaccine still offered protection against influenza A, but not B. Hence, co-administering COVID-19, influenza, and Tdap vaccines during prenatal care maintains immunogenicity and is highly advised to safeguard pregnant women fully.

Assessing sugar-sweetened beverage consumption in early pregnancy using a substance abuse framework.

Sugar-sweetened beverages (SSB) are previously reported to jeopardize maternal fetal health, most well-known for gestational diabetes, childhood obesity, and cognitive impairment. Although warnings and diet recommendations urge pregnant women to consume less SSB, there is no noticeable difference in their behavior. How and why reproductive women change their SSB consumption patterns were not investigated previously. Our study aims to investigate beverage consumption patterns and how these patterns change in pregnancy in the context of substance use disorder (SUD). We invited all pregnant women visiting the clinic to answer a structured 20-min questionnaire every trimester during the regular antennal visit. At the end of the study, 337 pregnant women aged over 20 participated. A total of 301 responses entered for final analysis, with a response rate of 89.3%. Our finding showed those with high DSM-5-TR scores reduced SSB intake after becoming pregnant, while those with mild or low DSM-5-TR scores increased SSB intake after becoming pregnant. The top 3 factors related to their SSB consumption were "use despite of known health hazard (n = 133)", "increased desire to drink (n = 88)", and "excessive time spent on seeking SSB (n = 85)". The least reported factors were in the domains of social impairment (ranging from n = 3 to n = 26), pharmacologic effects (i.e., tolerance (n = 24) and withdrawal (n = 70). When participants reduced SSB consumption after becoming pregnant, their choice of beverages largely shifted to sugarless beverage but not much plain water. The result provided new insights in deciphering pregnant women's psychomotor factors for SSB intake, which served as useful references for making clinical or even public health recommendations.

COVID-19 Bivalent Booster in Pregnancy: Maternal and Neonatal Antibody Response to Omicron BA.5, BQ.1, BF.7 and XBB.1.5 SARS-CoV-2.

Our study was to investigate the effects of bivalent COVID-19 booster vaccination during pregnancy on neutralizing antibody (Nab) levels in maternal blood (MB), transplacental transmission in umbilical cord blood (CB), and efficacy against Omicron SARS-CoV-2 subvariants including BA.5, BF.7, BQ.1, and XBB.1.5. We collected MB and CB from 11 pregnant participants during baby delivery and detected Nab inhibition by enzyme-linked immunosorbent assays (ELISA). Nab inhibition was 89-94% in MB and 82-89% in CB for Omicron subvariants. Those receiving AZD1222 vaccines in previous monovalent vaccination demonstrated poorer maternal Nab inhibition of BA.5, BQ.1, and XBB.1.5 than others. Poorer maternal Nab inhibition of BA.5, BF.7, and BQ.1 was found in those receiving two-dose AZD1222 vaccinations than with either one or no AZD1222 vaccination. MB from those with infants weighing < 3100 g demonstrated better Nab inhibition of BF.7 than those > 3100 g (97.99 vs. 95.20%, p = 0.048), and there were also similar trends for Nab inhibition of BA.5 and BQ.1. No significant differences were seen in CB samples. Although diminished maternal Nab inhibition was seen in those with previous monovalent AZD1222 vaccination and heavier newborns, neonatal Nab inhibition was still strong after bivalent COVID-19 booster vaccination.

Pilot Study for Immunogenicity of SARS-CoV-2 Vaccine with Seasonal Influenza and Pertussis Vaccines in Pregnant Women.

Background: It is well known that the implementation of routine immunizations to prevent vaccine-preventable diseases has a significant impact on the health and well-being of infants, children, and pregnant women. We aimed to evaluate the influence of influenza, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine on the immunogenicity of SARS-CoV-2 vaccine among pregnant women, the priority population recommended for vaccination. Methods: We conducted a prospective study among pregnant women without previous SARS-CoV-2 infection in Taiwan. Maternal and umbilical cord blood samples at delivery were analyzed for the percentage of inhibition of neutralizing antibodies (NAbs) against the original strain, Delta, and Omicron variants of SARS-CoV-2 as well as the total antibody to the SARS-CoV-2 spike protein. We examined the association between different doses of SARS-CoV-2 vaccine in combination with influenza and Tdap vaccination, and two-dose SARS-CoV-2 vaccination with or without influenza and Tdap vaccines via a two-sample t-test. Results of p < 0.05 were considered to be statistically significant. Results: 98 pregnant women were enrolled in our study, with 32 receiving two doses of SARS-CoV-2 mRNA-1273 vaccine, 60 receiving three-dose of mRNA-1273, and 6 receiving one-dose of ChAdOx1 and two-dose of mRNA-1273. Twenty-one participants were immunized with SARS-CoV-2, influenza, and Tdap vaccines. Of these 21 individuals, there were no significant NAbs levels in maternal and cord blood samples against the Omicron variant, regardless of doses or type of SARS-CoV-2 vaccine. However, antibody responses against the wild-type and Delta variant were significantly lower in all maternal sera in the two-dose SARS-CoV-2 vaccine group. Among 32 women receiving two-dose mRNA-1273, significantly lower levels of NAbs in maternal sera were observed against the Delta variant and total antibody both in maternal sera and cord blood were observed in individuals receiving SARS-CoV-2 and influenza vaccine. Conclusion: This is the pilot study to demonstrate the effects of influenza and the Tdap vaccine on the immunogenicity of the SARS-CoV-2 vaccine among pregnant women. These results suggest that combination vaccination during pregnancy may result in immunogenic interactions.

Increased sugar-sweetened beverage use tendency in pregnancy positively associates with peripartum Edinburgh postpartum depression scores.

The association among sugar sweetened beverages (SSB) consumption, addiction and depression in adults, children and adolescents is widely reported. Dieting patterns during pregnancy is complicated by maternal fetal concerns. Specifically, restrained use of SSB might be potentially a source of perinatal distress. The current study modified diagnostic criteria for Substance Use Disorder (SUD) in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), into SSB-specific questions to assess SSB use tendency. Edinburgh Postpartum Depression Scores (EPDS) is used to assess maternal distress during pregnancy. One hundred and ninety-six consecutive pregnant women receiving antenatal care at Kaohsiung Medical University Hospital were invited to participate in this study. In the first trimester, 46.6% of women had none or 1 DSM-5 symptom, 27.0% had 2-3 symptoms, while 26.4% had ≥ 4 symptoms. The mean numbers of DSM-5 symptoms in each trimester were found to be 2.5 ± 2.25, 2.6 ± 2.45, 2.4 ± 2.43 for the first, second and third trimester, respectively, p = 0.750. While EPDS score showed no difference among DSM-5 symptoms 0-1, 2-3 and ≥ 4 groups in the first trimester (8.1 ± 4.59, 8.4 ± 5.00, 8.8 ± 4.82, p = 0.343), women with ≥ 4 DSM-symptoms was found significantly higher EPDS scores than those with < 4 DSM-symptoms in the second (7.2 ± 4.81, 7.7 ± 4.98, 8.8 ± 4.33, p = 0.030) and third trimester (6.8 ± 5.00, 7.2 ± 4.63, 8.7 ± 5.24, p = 0.019). The relationship remained significant after adjusting for covariates including actual SSB amount consumed (adjusted ß = 0.25 with 95% confident interval (CI) 0.04-0.45 and 0.21 with 95% CI 0.04-0.38 for the second and third trimesters, respectively). Overall, the study is the first to characterize the positive relationship between SSB use tendency and antenatal distress in pregnancy, independent of actual SSB amount consumed. The observational nature of the study design precludes inferences of its underlying socio-psychomotor mechanisms, although restrained SSB use in pregnancy is suspected to contribute. The novel employment of modified SSB-specific DSM-5 scores and EPDS in this setting is feasible and further validation is promising. With better understanding and awareness, pregnant women with increased SSB use tendency should be properly counseled with special attention to their mental state.

The effects of simulated childbirth trauma on the gene expression of neurotransmitter receptors in the bladder of female rats.

BACKGROUND/PURPOSE: To investigate the effects of simulated childbirth on the gene expression of parasympathetic muscarinic, purinergic (P2X), and neurokinin receptors of lower urinary tract in rats. METHODS: In all, twenty-four primiparous pregnant Sprague-Dawley female rats were equally divided into three groups: (1). Control group; 8 rats, (2) intra-vaginal balloon dilation for 2 h group; 8 rats, (3) and for 4 h group; 8 rats. After balloon dilatation for 4 months, all rats were sacrificed. We analyzed the gene expression of parasympathetic muscarinic, purinergic (P2X), and neurokinin receptors by real-time quantitative PCR (q-PCR). We quantified pro-inflammatory cytokines of TNF-α and IL-6 by Enzyme-linked immunosorbent assays (ELISA). The urodynamic parameters and micturition frequency by cystometry (CMG) were recorded. RESULTS: Our results showed that the balloon dilation significantly increased micturition frequency and modified peak micturition pressure compare to those in the control groups. Balloon dilation significantly decreased voiding interval and bladder volume compared to those in the control groups. Gene expressions of M3 muscarinic, P2X3 purinergic receptors, and significantly increased following balloon dilation for 2 hours and 4 hours than those in the control group. In addition, we found that NK1R and NK3R receptors were significantly decreased after balloon dilation compare to control group. The marked increase of TNF-α and IL-6 were also seen in the 2 balloon groups. CONCLUSION: The results of our study suggested that birth trauma may impair the function of urinary tract, this being partly related to the changes in the gene expression of the neurotransmitter receptors of the lower urinary tract.

A pilot study: effectiveness of local injection of autologous platelet-rich plasma in treating women with stress urinary incontinence.

The study aims to evaluate the effectiveness of local injection of autologous platelet rich plasma (A-PRP) as a treatment for women suffering from stress urinary incontinence (SUI). In a prospective intervention study, twenty consecutive women suffering from SUI were treated with A-PRP injection at anterior vaginal wall where mid-urethra locates. Self-reported questionnaires were used to measure pre-treatment, 1 month and 6 months post-treatment symptom severity. Secondary outcomes of sexual function and treatment effect sorted by age were analyzed with valid statistical methods. A-PRP is effective in relieving SUI symptoms at both 1 month and 6 months post-treatment without significant adverse reactions reported. It seems to have a trend that treatment success rate with cured and improved symptoms was slightly higher in the younger group, although it did not reach statistical significance (P = 0.07). No significant changes in sexual function before and after the treatment were reported by the patients. This pilot study is the first to report A-PRP treatment effect for SUI in women. The result suggested that A-PRP is a considerable treatment option for mild to moderate SUI cases. It also opens up further research opportunities for A-PRP's clinical applications.

500 Cases of High-intensity Focused Ultrasound (HIFU) Ablated Uterine Fibroids and Adenomyosis.

OBJECTIVE: Clinical outcomes of 500 high-intensity focused ultrasound (HIFU)-treated uterine fibroids and adenomyosis are analyzed and presented. MATERIALS AND METHODS: This is a retrospective cross-sectional analysis from a single tertiary medical center. From April 2015 to October 2018, 546 cases were enrolled for the study. After excluding 46 patients with less than 3 months of follow-up period, there were 404 fibroids, 149 adenomyosis and 53 mixed conditions entered for analysis. The patients' uterine fibroids and adenomyosis were treated by HIFU according to Chongqing Haifu protocol, with 12 cm diameter transducer of focal length 10-16  cm at 0.8 or 1.6 MHz T2-weight MRI imaging was rendered prior to and 3 month post treatment to assess lesion volume change using non-perfusion volume, which was the primary outcome. Secondary outcomes including quality of life, subjective satisfaction, adverse events and pregnancy rate were determined using self-reported questionnaires. The mean follow up period ranged from 3 to 38 months with an average of 21 months. RESULTS: Three months after HIFU-treated uterine fibroids and adenomyosis, the lesion size reduced 40.2% and 46.3%, respectively. Symptoms all improved with better quality of life for the fibroid group, while those with adenomyosis or combined diseases benefit the most from pain control. Serum CA125 decreased significantly for all studied groups, and LDH only showed improvement for fibroids group. Number of adverse events is comparable to Chongqing data (approximately 10.2%), with mostly mild and self-resolving conditions. No permanent sequelae or death was documented. Twelve pregnancies are reported in this cohort. CONCLUSION: HIFU is safe and effective in treating uterine fibroids and adenomyosis. The results are reproducible if standardized treatment schedules are followed. It is a promising treatment alternative with the advantages of precision, non-invasiveness, rapid recovery and readiness for pregnancy.

Endometrial adenocarcinoma initially mistaken as urinary incontinence.

OBJECTIVE: The report aims to present a case of endometrial cancer with unusual initial presentation. A literature review is conducted to speculate symptoms presented by endometrial cancer other than vaginal bleeding. CASE REPORT: A 43-year-old, para 1, lean female suffered from copious watery vaginal discharge that was odorless and colorless for 8 months without any signs of abnormal vaginal bleeding. Preliminary surveys in private clinics with per vaginal examination and Papanicolaou smear were normal. Urinary incontinence was mistakenly impressed. When the patient turned to our center for help as symptoms aggravated, transvaginal sonography revealed hydrometra with papillary endometrium lesions. Hysteroscopy survey with endometrial biopsy revealed endometrial adenocarcinoma. CONCLUSION: This is a case of endometrial cancer with unusual presentation. Transvaginal sonography and hysteroscopy are easy and sensitive screening tools that should be readily offered to patients with suspicious symptoms.

Acute renal insufficiency and thrombocytopenia after high-intensity focused ultrasound (HIFU) ablation for uterine myomas.

OBJECTIVE: Ultrasound-guided high-intensity focused ultrasound (USg-HIFU) has emerged in recent years as the new treatment modality for uterine myomas and adenomyosis with the advantages of being non-invasive, safe and effective. As its utility increases, adverse reactions emerge and deserve clinicians' attention for experience accrual. We herein report a case who suffered from acute renal insufficiency and thrombocytopenia immediately after receiving HIFU for uterine myomas. CASE REPORT: A 38-year-old nulliparous healthy female received HIFU for huge uterine myoma that caused heavy vaginal bleeding and chronic anemia. The procedure went smoothly but the patient immediately suffered from oliguria and dark-colored urine. With conservative management and aggressive hydration, her condition had improved spontaneously after 1 week without leaving any long-term sequelae. Myoma size reduced by 70% 3 months post-treatment and her bleeding problems significantly improved. CONCLUSION: This is the first report of post-HIFU acute renal failure and thrombocytopenia. Thermal injuries, drug toxicity and mechanical obstruction of ureters are some plausible explanations for speculations.

Laparoscopic Long Mesh Surgery with Augmented Round Ligaments: A Novel Uterine Preservation Procedure For Apical Pelvic Organ Prolapse.

We aim to assess the surgical outcomes of our novel hysteropexy procedure, laparoscopic long mesh surgery (LLMS) with augmented round ligaments. Twenty-five consecutive women with stage II or greater main uterine prolapse defined by the POP quantification staging system were referred for LLMS. Long mesh is a synthetic T-shaped mesh, with the body fixed at the uterine cervix and the two arms fixed along the bilateral round ligaments. The clinical evaluations performed before and 6 months after surgery included pelvic examinations, urodynamic studies, and questionnaires for urinary and sexual symptoms. After a follow-up time of 12 to 24 months, the anatomical reduction rate was 92% (23/25) for the apical compartment. The average operative time was 65.4 ± 28.8 minutes. No major complications were recognized during LLMS. The lower urinary tract symptoms and scores on the questionnaires improved significantly after the surgery, except urgency urinary incontinence and nocturia. Neither voiding nor storage dysfunction was observed after the operations. All of the domains and total Female Sexual Function Index (FSFI) scores of the 15 sexually active women did not differ significantly after LLMS. The results of our study suggest that LLMS is an effective, safe, and time-saving hysteropexy surgery for the treatment of apical prolapse.

Therapeutic effects of Low intensity extracorporeal low energy shock wave therapy (LiESWT) on stress urinary incontinence.

This study aimed to evaluate the therapeutic effects of Low intensity extracorporeal low energy shock wave therapy (LiESWT) on stress urinary incontinence (SUI). The investigation was a single-arm, open-label, multicentre study conducted in Taiwan. 50 female patients with SUI received LiESWT-treated with 0.25 mJ/mm2 intensity, 3000 pulses, and 3 pulses/second, once weekly for 4-weeks (W4) and 8-weeks (W8). The pad test, uroflowmetry, life quality questionnaires, and 3-day urinary diary measurement were performed before and after LiESWT intervention. The results revealed that 8-week of LiESWT treatment meaningfully improved urine leakage (pad test), maximum flow rate, post-voided residual urine, average urine volume, functional bladder capacity, urinary frequency, urgency symptom, and nocturia, which also persisted to show significant improvements at 1-month follow up (F1). Moreover, bothersome questionnaires scores were significantly improved at W4, W8, and F1 as compared to the baseline (W0). These results indicated that 8 weeks of LiESWT attenuated SUI symptoms on physical activity, reduced bladder leaks and overactive bladder (OAB), implying that LiESWT brought significant improvement in the quality of life. (ClinicalTrials.gov number, NCT04059133).

Urine retention caused by urethral prolapse mimicking uterine prolapse.

OBJECTIVE: Urethral prolapse is a rare clinical condition, which has been reported mostly in prepubertal girls; few menopaused and only 5 cases of premenopausal women. Strangulated urethral prolapse is even rarer. CASE REPORT: A 64-year-old woman presented with urinary retention, painful vaginal bleeding and a protruding mass. Pelvic examination revealed a reddish doughnut-shaped mass located at introitus. The patient felt uncomfortable with attempts to reduce the presumed prolapse. Urethral prolapse was impressed and topical estrogen cream was prescribed. However, urethral mucosa became congested and without shrinkage three days later. As a result, simple excision was performed. No recurrence was noted at the time of manuscript submission. CONCLUSION: Most common symptoms of urethral prolapse are vaginal bleeding and visible vaginal mass. Urethral prolapse can be diagnosed primarily by physical examinations. Surgical excision is a good way to treat recurrence or strangulated urethral prolapse with almost no complications and high success rate.

Changes in Sexual Function Following Uphold Transvaginal mesh Surgery for the Treatment of Urogenital Prolapse.

Uphold transvaginal mesh implantation is an option for treating pelvic organ prolapse (POP). This prospective cohort study aims to evaluate the effect of Uphold transvaginal mesh implantation on female sexual function. 205 women with symptomatic POP were recruited and evaluated pre-operatively and re- evaluated six months post-operatively in terms of anatomical restoration, quality of life influenced by urinary incontinence and female sexual function. 30 women eventually completed the assessments and been statistically evaluated. The main outcome focused on sexual function. In our study, we found that Uphold transvaginal mesh surgery could achieve effective anatomical restoration of POP and better sexual function regardless of concomitant sling surgery.

A survey of current use, dilemma and outlook of antenatal ultrasonography in Taiwan.

OBJECTIVE: According to World Health Organization's Jungner and Wilson criteria for competent screening programs, routine antenatal ultrasound screening is legit and effective to improve both maternal and perinatal outcomes. Health Promotion Administration, Ministry of Health and Welfare in Taiwan followed expert recommendations and started reimbursing one antenatal ultrasonography around mid-second trimester since 1995. However, medical disputes pertaining to examination results grew, while confusions challenged doctors and patients alike. The aim of this study is to assess current use of antenatal ultrasonography for low-risk pregnancies in Taiwan. Specifically, the indications, test frequencies, test items, methods of payment, obstetricians' opinions on important scan timing and areas to be improved are surveyed and analyzed. An overview of international antenatal ultrasound practice guidelines are examined and compared to enhance the quality of antenatal ultrasound screening in Taiwan. MATERIALS AND METHODS: From December 2015 to December 2016, 925 questionnaires were distributed to all licensed obstetricians registered to Taiwan Association of Obstetrics and Gynecology as well as Taiwan Society of Perinatology. A 10-min self-reporting questionnaire was sent by mail, with stamped return envelopes included. Respondents remained entirely anonymous and disclosed no personal information. Data was collected and analyzed for statistical analysis. RESULTS: Most hospitals are well equipped with ultrasound machines of 3 or more functions. Eighty-eight percent of the obstetricians in Taiwan perform prenatal ultrasonography in every office visit for their patients, mostly free of charge. Scans at gestational age 15-22 weeks, <10 weeks, 11-14 weeks and 28-32 weeks are polled as the most importance in the order of significance. In general, they perceive the one-time antenatal scan offered by the Health Promotion Administration as for general obstetrics scan but not higher-leveled studies. Patient education and doctor-patient communications are opined as the 2 most important aspects to enhance antenatal ultrasound quality. CONCLUSION: This report is the first of its kind in Taiwan. It could potentially serve as guidance for national health policy innovations in maternal and fetal care, such as increasing frequency of scans, specifications of scan timing, indications and consequences as well as patient education about this screening modality.

Cervical varices unrelated to placenta previa as an unusual cause of antepartum hemorrhage: A case report and literature review.

OBJECTIVE: Ruptured cervical varicose veins can cause significant vaginal bleeding during the third trimester of pregnancy. The etiology is not uncommon, yet receives little discussion in current literature. We here report such a case with complete evaluations, managements and follow ups; while analyzing similar cases published. CASE REPORT: A 34-year-old pregnant woman, gravida 1, presented with sudden onset of painless antepartum hemorrhage at 31+5 weeks of gestation. Speculum examination revealed ruptured cervical varicose veins; further evaluations with transvaginal sonography and magnetic resonance imaging were done to study the extensiveness and characteristics of the lesion. The cervical varices spontaneously regressed by postpartum day 4 and no recurrence was observed in the immediate postpartum follow-up period or in the subsequent pregnancy. CONCLUSION: The case is unique for the lack of association with placenta previa. Cervical varicose veins rupture should be considered for painless vaginal bleeding during the third trimester pregnancy.