Objective: During pregnancy, vulvovaginal infections (VVIs), including abnormal vaginal flora (AVF), bacterial vaginosis (BV), and vulvovaginal candidiasis (VVC), are associated with serious complications and discomfort. We aimed to elucidate the effectiveness of oral probiotics in secondary prevention of VVIs in pregnant women. Study design: A multicenter prospective randomized, double-blind, placebo-controlled trial was conducted at three medical centers between 2016 and 2021. Women who complained of vaginal symptoms with positive smear for AVF/BV and/or candida were treated with antibiotics or an antimycotic agent, respectively. After confirmation of VVI eradiation by repeated vaginal smear, the women were divided into a research group, receiving two capsules/day of oral probiotic formula containing Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus (L.) acidophilus, L. paracasei, L. rhamnosus and Streptococcus thermophilus (>6 × 109 CFU/capsule), and a control group, receiving a placebo (two capsules/day) until delivery. At least once a month or following complaints, a vaginal smear was taken to assess vaginal microbiota. If VVIs were found, they were treated with antibiotics/antimycotics, and eradication was assessed by a repeated vaginal smear. Lactobacilli vaginal colonization, including the specific strains from the probiotic capsules, were detected using the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF-MS). The primary outcome was the rate of women who developed VVI during the study period until delivery. Results: Twenty-three and twenty-four women were analyzed in the probiotic and placebo cohorts, respectively. There was no difference in the rate of any VVI between the probiotic and placebo cohorts (16 (67%) versus 11 (48%), respectively; p = 0.19), time until first infection or pregnancy outcomes. The lactobacilli strains that colonized the vagina were similar at baseline and following probiotic or placebo administration. No woman was detected with vaginal colonization of the strains from the capsule, although the probiotics were taken for about 4 months. Conclusions: The oral probiotic product tested in this study did not reduce the recurrence rate of VVIs in pregnant women following eradication.

BACKGROUND/OBJECTIVE:This study aimed to investigate the efficacy of oral probiotic supplementation in preventing vulvovaginal infections (VVIs) in pregnant women, specifically focusing on abnormal vaginal flora (AVF), bacterial vaginosis (BV), and vulvovaginal candidiasis (VVC). METHODS:A multicenter-prospective-randomized, double-blind, placebo-controlled trial was conducted during 2016-2019. Women with normal vaginal flora (Nugent score < 4 and no candida) were divided into a research group, receiving 2 capsules/day of oral probiotic formula containing Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus acidophilus, Lacticaseibacillus paracasei, Lacticaseibacillus rhamnosus, and Streptococcus thermophilus, or a control group, receiving a placebo until delivery. Once a month and following complaints, a vaginal smear was taken to assess vaginal flora. Vaginal colonization with the specific lactobacilli from the probiotic capsules was detected using the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The primary outcome was the rate of women who developed VVI. RESULTS:Forty-nine and fifty-one women were analyzed in the probiotic and placebo cohorts, respectively. There was no difference in the rate of VVI between probiotic and placebo groups (14 (29%) versus 14 (27%), respectively; p = 0.80). No woman had vaginal colonization with lactobacilli from the probiotic capsule. CONCLUSIONS:The tested oral probiotic product did not reduce the rate of VVI in pregnant women with normal vaginal flora.

During pregnancy, abnormal vaginal flora (AVF), bacterial vaginosis (BV), and vulvovaginal candidiasis (VVC) are associated with serious complications and discomfort. We aimed to elucidate the effectiveness of oral probiotics in secondary prevention of BV/AVF and VVC in pregnant women. A multicenter prospective randomized, double blind, placebo controlled trial was conducted at three medical centers between 2016 and 2021. Women who complained on vaginal symptoms with positive smear for AVF/BV or candida were treated with antibiotics or antimycotic agent, respectively. Following normal vaginal flora in repeated vaginal smear, women were divided into a research group, receiving 2 capsules/day of oral probiotic formula containing Bifidobacteriumbifidum, Bifidobacteriumlactis, Lactobacillus (L) acidophilus, L. paracasei, L. rhamnosus and Streptococcus thermophilus ( >6X109/capsule), and a control group, receiving a placebo (2 capsules/day) until delivery. At least once a month or following complaints a vaginal smear was taken to assess vaginal flora. If positive, BV/AVF or VVC were treated with antibiotics or antimycotic agent, respectively. Eradication was assessed by a repeated vaginal smear. Vaginal colonization with the specific lactobacilli from the probiotic capsules was detected using the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF-MS).The primary outcome was the rate of women who developed any vaginal infection (BV/AVF/VVC) during the study period until delivery. Twenty-three and 24 women were analyzed in the probiotic and placebo cohorts, respectively. Baseline characteristics are presented in table 1. There was no difference in the rate of any vulvovaginal infection between the probiotic and placebo cohorts (11 (48%) versus 16 (67%), respectively; P=0.19; table 2). No woman was detected with vaginal colonization of the lactobacilli from the capsule. Oral probiotic product tested in this study did not colonized in the vagina and did not reduce the rate of repeated vulvovaginal infection in pregnant women.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Aim: Elevated human chorionic gonadotropin (HCG) and alpha fetoprotein (AFP) have been linked to placental dysfunction and associated morbidities. We aimed to compare the induction of labor with expectant management at term in those pregnancies for the prevention of neonatal and maternal morbidities. Methods: Women with second trimester HCG >= 2 and/or AFP >= 2 multiples of the median, without additional maternal or fetal complications, from their 38th gestational week were offered the choice of labor induction or expectant management. The primary outcomes were maternal composite outcome (composed of cesarean deliveries, pre-eclampsia or placental abruption) and neonatal composite outcome (composed of antenatal or neonatal death, Apgar score at 5 min < 7, admission to the neonatal intensive care unit, need for phototherapy, respiratory abnormalities, birth trauma or neonatal infection). Results: Of 305 women, 124 women chose to undergo labor induction, and 181 women chose expectant management. The composite maternal outcome in the expectant management group was twice the rate of the labor induction group, although it did not reach statistical significance (18 [10%] vs 6 [5%]; P = 0.1; relative risk [expectant/induced] 2.04; 95% confidence interval 0.8-5.0). Increased rate of phototherapy led to increased neonatal composite outcomes in the labor induction group compared with the expectant management group (34 [27%] vs 27 [15%], respectively = 0.007). Conclusion: In pregnancies with elevated AFP and/or HCG, early term labor induction initiated a trend towards improvement in maternal outcome but increased the rate of mild neonatal morbidity. The statistical insignificance of the large effect on the maternal outcome might reflect the lack of statistical power. Further research is needed to address this limitation.

Objective: To establish the predictive probability for placenta-associated morbidities using second-trimester α-fetoprotein (AFP), human chorionic gonadotropin (HCG), and maternal features. Patients and Methods: A retrospective database of all singleton deliveries with available second-trimester HCG and AFP results from 2005 to 2012 was built and divided into 0, 1, or 2 elevated markers (defined as ≥2 multiples of the median [MoM]). For each group, we analyzed the risk for adverse obstetric outcome - comprising preeclampsia, placental abruption, and birth weight below the 10th percentile - and the time of delivery in those pregnancies. Additionally, prediction models for adverse obstetric outcome, using logistic regression incorporating AFP, HCG, and other maternal characteristics, were calculated. Results: Among 22,124 women who delivered, 16,197 (73%) had AFP and HCG results. Compared with the group with normal markers, the adverse obstetric outcome rate was mildly increased with elevated HCG or AFP, but it was markedly increased when both markers were elevated (13 vs. 31%, OR 2.9, 95% CI 2.0-4.3). Delivery of newborns with adverse obstetric outcome was earlier with each additional elevated marker. The accuracy of predicting adverse obstetric outcome was improved by using prediction models for women with HCG or AFP ≥1.2 MoM that incorporated maternal age, BMI, parity, and chronic hypertension (C-statistic 61-75%). Conclusion: HCG and AFP combined with other maternal characteristics are useful tools for predicting the risk for adverse obstetric outcome.

Elevated human chorionic gonadotropin (HCG) and alpha fetoprotein (AFP) were linked to increased risk for pre-eclampsia, placental abruption, growth restriction, and fetal/neonatal death. We aimed to compare induction of labor with expectant management at term in those pregnancies for prevention of neonatal and maternal morbidities. Retrospective, non-randomized interventional cohort study of women with HCG≥2 and/or AFP≥2 multiples of the median in the second trimester triple test, without additional maternal or fetal complications, from their 38th gestational week who were offered the choice of labor induction or expectant management. Women with maternal vascular disease, fetal malformations, previous cesarean delivery (CD), and contraindications for vaginal delivery or expectant management at 38th gestational weeks were excluded. The primary outcomes were maternal composite outcome (composed of CDs, pre-eclampsia, or placental abruption) and neonatal composite outcome (composed of antenatal or neonatal death, Apgar score at 5 minutes<7, admission to the neonatal intensive care unit, need for phototherapy, respiratory abnormalities, birth trauma, or neonatal infection). A sample size of 120 women for each group was calculated to detect a rate of the neonatal composite outcome of 30% in the labor induction group and 15% in the expectant management group (5% 2-sided alpha, 80% power) and a rate of maternal composite outcome of 10% and 25%, respectively (5% 2-sided alpha, 90% power). One hundred and twenty four women chose to undergo labor induction and 181 women chose expected management. Groups' demographic characteristics and outcomes are presented in table 1 and table 2, respectively. The composite maternal outcome was comparable between the groups (6 (5%) and 18 (10%) in the labor induction and expectant management groups, respectively; P=0.1). However, the neonatal composite outcome was higher in the labor induction group compared with the expectant management group (34 (27%) versus 27 (15%), respectively; P=0.007). In pregnancies with elevated AFP or HCG labor induction from the 38th gestational week increased neonatal morbidity without improving the maternal outcome. Thus, early term labor induction should be avoided in those pregnancies.View Large Image Figure ViewerDownload Hi-res image Download (PPT)