Management of a pregnant woman with a large cervical polyp and moderate genital bleeding in the first trimester.

Polypectomy during pregnancy is known to be a risk for spontaneous late miscarriage or preterm delivery. We managed a pregnant woman in her 30s with a large cervical polyp without polypectomy, and we administered probiotics including Clostridium butyricum and 17-alpha-hydroxyprogesterone caproate. As a result, she delivered a healthy baby at 38 weeks.

Immunological regulation and the role of autophagy in preeclampsia.

Autophagy is a bulk degradation system that maintains cellular homeostasis by producing energy and/or recycling excess proteins. During early placentation, extravillous trophoblasts invade the decidua and uterine myometrium, facing maternal immune cells, which participate in the immune suppression of paternal and fetal antigens. Regulatory T cells will likely increase in response to a specific antigen before and during early pregnancy. Insufficient expansion of antigen-specific Treg cells, which possess the same T cell receptor, is associated with the pathophysiology of preeclampsia, suggesting sterile systemic inflammation. Autophagy is involved in reducing inflammation through the degradation of inflammasomes and in the differentiation and function of regulatory T cells. Autophagy dysregulation induces protein aggregation in trophoblasts, resulting in placental dysfunction. In this review, we discuss the role of regulatory T cells in normal pregnancies. In addition, we discuss the association between autophagy and regulatory T cells in the development of preeclampsia based on reports on the role of autophagy in autoimmune diseases.

Nationwide status of progestogen treatment to prevent spontaneous preterm birth: A questionnaire survey for childbirth healthcare facilities in Japan.

AIM: This study aimed to investigate the current status of progestogen treatment for pregnant women at a high risk for preterm birth (PTB) in childbirth healthcare facilities in Japan. METHODS: A web-based nationwide questionnaire survey regarding progestogen use for prevention of PTB was conducted among childbirth healthcare facilities from 2019 to 2021. RESULTS: Valid responses were obtained from 528 facilities (25.2% of those surveyed), including 155 tertiary perinatal facilities (making up 92.3% of all tertiary perinatal care facilities). In the survey period, progestogen treatment was implemented in 207 facilities (39.2%) for PTB prevention. Regarding types of progestogens, 17α-hydroxyprogesterone caproate was used in 170 facilities (82.1%), with a low dose (125 mg/week) administered in 62.9% of the facilities to comply with the regulations of the national health insurance system, although 250 mg/week is considered the best dose. Vaginal progesterone was used in 36 facilities (17.4%), although the cost of vaginal progesterone was not covered by health insurance. Of the facilities not administering progestogen treatment, approximately 40% expressed that vaginal progesterone would be their first choice for PTB prevention in daily practice if it would be covered by health insurance in the future. CONCLUSIONS: Due to the current regulations of the Japanese health insurance system, 17α-hydroxyprogesterone caproate, rather than vaginal progesterone, was mainly used for PTB prevention. Despite global evidence supporting vaginal progesterone as the approach with the highest efficacy, only a limited number of facilities have utilized it due to the current drug use regulations in Japan.

High doses of intravenous immunoglobulin stimulate regulatory T cell and suppress natural killer cell in women with recurrent pregnancy loss.

The aim was to evaluate whether natural killer (NK) cells and regulatory T (Treg) cells were involved in mechanisms underlying beneficial effects of a high dose of intravenous immunoglobulin (IVIG) on recurrent pregnancy losses (RPL) of unexplained etiology. In a double-blind, randomized, placebo-controlled trial of IVIG (400 mg/kg, for 5 days in 4-6 weeks of gestation) in women with RPL, blood samples were collected pre-infusion, one week after infusion (1 w), and eight weeks of gestation/when miscarried (8 w). Levels of NK and Treg cells in peripheral blood were compared between women with IVIG (n = 50) and placebo (n = 49), and between women with IVIG who gave live birth (n = 29) and those who had miscarriage with normal chromosome (n = 12). Effector Treg cell percentages in IVIG group at 1 w (mean 1.43 % vs. 1.03 %) and at 8 w (1.91 % vs. 1.18 %) were higher than those in placebo group (p < 0.01). Total Treg cell percentages in IVIG group at 1 w (4.75 % vs. 4.08 %) and at 8 w (5.55 % vs. 4.47 %) were higher than those in placebo group (p < 0.05). In women with live birth, total Treg cell percentages increased at 8 w (5.52 %, p < 0.001) compared with pre-infusion (4.54 %) and 1 w (4.47 %), while NK cell activity decreased at 1 w (20.18 %, p < 0.001) compared with pre-infusion (26.59 %). IVIG increased Treg cell percentages and suppressed NK cell activity very early in pregnancy, and these were associated with subsequent live birth. Stimulation of Treg cells and suppression of NK cell activity very early in pregnancy may be a mechanism of pharmacological effects of high dose IVIG.

The Role of Autophagy in the Female Reproduction System: For Beginners to Experts in This Field.

Autophagy is a fundamental process involved in regulating cellular homeostasis. Autophagy has been classically discovered as a cellular process that degrades cytoplasmic components non-selectively to produce energy. Over the past few decades, this process has been shown to work in energy production, as well as in the reduction of excessive proteins, damaged organelles, and membrane trafficking. It contributes to many human diseases, such as neurodegenerative diseases, carcinogenesis, diabetes mellitus, development, longevity, and reproduction. In this review, we provide important information for interpreting results related to autophagic experiments and present the role of autophagy in this field.

An up to 43-year longitudinal study of fixed prosthetic restorations retained with 4-META/MMA-TBB resin cement or zinc phosphate cement.

STATEMENT OF PROBLEM: Adhesive resin cement has been the preferred choice for the placement of prosthetic restorations, but evidence-based studies supporting this selection are sparse. PURPOSE: The purpose of this study was to test the hypothesis that restoration placement with the adhesive 4-methacryloxyethyl trimellitate anhydride/methyl methacrylate-tributylborane (4-META/MMA-TBB) resin cement is associated with better longevity of teeth than zinc phosphate cement up to 43 years. MATERIALS AND METHODS: Study participants were individuals who had been visiting the clinic regularly for more than 20 years from their first visit between November 1970 and April 1985. The vital teeth with prosthetic restorations (N=454), including cast inlays, onlays, crowns, and fixed partial dentures, of 53 patients were assessed from dental charts and radiographs. Most of the bonding surfaces were precious metal alloy, excluding 4 restorations cemented with zinc phosphate and 6 ceramic crowns cemented with 4-META/MMA-TBB resin cement. The Kaplan-Meier method and log-rank test (α=.05) were used to compare longevity between the 2 materials. Chi-squared tests (α=.001) were also used to examine the occurrence rates of events such as secondary caries, endodontic treatment, and the dislodgement of restorations affecting the longevity of the 2 cements. RESULTS: Clinical review examination demonstrated that 55.4% of teeth retained with 4-META/MMA-TBB resin cement had been in service for 30 years compared with 43.5% of those retained with zinc phosphate cement, with a significant difference (P=.006). 4-META/MMA-TBB resin cement also demonstrated lower event occurrence rates than zinc phosphate cement for 3 assessed types of events (P<.001). CONCLUSIONS: Within the limitations of this study, 4-META/MMA-TBB resin adhesive cement demonstrated a higher survival rate than conventional zinc phosphate cement in service for 30 years with a lower occurrence of critical events.

Chloroquine is a safe autophagy inhibitor for sustaining the expression of antioxidant enzymes in trophoblasts.

Inhibition of autophagy contributes to the pathophysiology of preeclampsia. Although chloroquine (CHQ) is an autophagy inhibitor, it can reduce the occurrence of preeclampsia in women with systemic lupus erythematosus. To clarify this important clinical question, this study aimed to address the safety of CHQ in trophoblast cells from the viewpoint of homeostasis, in which the anti-oxidative stress (OS) response and autophagy are involved. We used Western blotting to evaluate the protein levels in the trophoblast cells. The expression levels of heme oxygenase-1 (HO-1), an anti-OS enzyme, mediate resistance to OS induced by hydrogen peroxide (H2O2) in trophoblast cell lines. Among the autophagy modulators, bafilomycin A1 (BAF), an autophagy inhibitor, but not autophagy activators, suppressed HO-1 expression in BeWo cells; CHQ did not suppress HO-1 expression in BeWo cells. To clarify the role of autophagy in HO-1 induction, we observed no difference in HO-1 induction by H2O2 between autophagy-normal and autophagy-deficient cells. As for the mechanism of HO-1 induction by OS, BAF suppressed HO-1 induction by downregulating the expression of neighbor of BRCA1 gene 1 (NBR1) in the selective p62-NBR1-nuclear factor erythroid 2-related factor 2 (Nrf2) autophagy pathway. CHQ did not inhibit HO-1 expression by sustaining NBR1 expression in human villous tissues compared to BAF treatment. In conclusion, CHQ is a safer medicine than BAF for sustaining NBR1, which resist against OS in trophoblasts by connecting selective autophagy and the anti-OS response.

Intravenous immunoglobulin treatment in women with four or more recurrent pregnancy losses: A double-blind, randomised, placebo-controlled trial.

Background: There is no effective treatment for women with unexplained recurrent pregnancy loss (RPL). We aimed to investigate whether treatment with a high dose of intravenous immunoglobulin (IVIG) in early pregnancy can improve pregnancy outcomes in women with unexplained RPL. Methods: In a double-blind, randomised, placebo-controlled trial, women with primary RPL of unexplained aetiology received 400 mg/kg of IVIG daily or placebo for five consecutive days starting at 4-6 weeks of gestation. They had experienced four or more miscarriages except biochemical pregnancy loss and at least one miscarriage of normal chromosome karyotype. The primary outcome was ongoing pregnancy rate at 22 weeks of gestation, and the live birth rate was the secondary outcome. We analysed all women receiving the study drug (intention-to-treat, ITT) and women except those who miscarried due to fetal chromosome abnormality (modified-ITT). This study is registered with ClinicalTrials.gov number, NCT02184741. Findings: From June 3, 2014 to Jan 29, 2020, 102 women were randomly assigned to receive IVIG (n = 53) or placebo (n = 49). Three women were excluded; therefore 50 women received IVIG and 49 women received placebo in the ITT population. The ongoing pregnancy rate at 22 weeks of gestation (31/50 [62·0%] vs. 17/49 [34·7%]; odds ratio [OR] 3·07, 95% CI 1·35-6·97; p = 0·009) and the live birth rate (29/50 [58·0%] vs. 17/49 [34·7%]; OR 2·60, 95% CI 1·15-5·86; p = 0·03) in the IVIG group were higher than those in the placebo group in the ITT population. The ongoing pregnancy rate at 22 weeks of gestation (OR 6·27, 95% CI 2·21-17·78; p < 0·001) and the live birth rate (OR 4·85, 95% CI 1·74-13·49; p = 0·003) significantly increased in women who received IVIG at 4-5 weeks of gestation as compared with placebo, but these increases were not evident in women who received IVIG at 6 weeks of gestation. Four newborns in the IVIG group and none in the placebo group had congenital anomalies (p = 0·28). Interpretation: A high dose of IVIG in very early pregnancy improved pregnancy outcome in women with four or more RPLs of unexplained aetiology. Funding: The Japan Blood Products Organization.

Probiotics including Clostridium butyricum, Enterococcus faecium, and Bacillus subtilis may prevent recurrent spontaneous preterm delivery.

AIM: A large cohort study of Japanese women reported that the rate of recurrent spontaneous preterm delivery (sPTD) in the next pregnancy was 22.3%; therefore, it is important to prevent recurrent sPTD. The present study investigated the rate of recurrent sPTD in pregnant women treated with probiotics. METHODS: This was a retrospective study. Fifty-one pregnant women with a history of sPTD and who had been taking probiotics before 14 weeks of gestation were selected. The rate of sPTD in the next pregnancy among 255 pregnant women with a history of sPTD who had not taken probiotics was compared with that in the probiotics group. RESULTS: The rate of recurrent sPTD was 9.8% (5/51), which was lower than previously reported values. Furthermore, the rate of recurrent sPTD was significantly lower in the probiotics group (9.8%) than in the nonprobiotics group (31.0% [79/255]; p = 0.002). CONCLUSIONS: Probiotics may reduce the rate of recurrent sPTD.

Pre-eclampsia Complicated With Maternal Renal Dysfunction Is Associated With Poor Neurological Development at 3 Years Old in Children Born Before 34 Weeks of Gestation.

Objective: The purpose of this study was to investigate perinatal factors associated with a poor neurodevelopmental outcome in preterm infants. Methods: A retrospective study was conducted by searching our clinical database between January 2006 and December 2016. A total of 165 singleton children who were born between 23 and 33 weeks of gestation were included. We defined poor neurological development outcomes as follows: cerebral palsy; intellectual disability; developmental disorder including autism and attention-deficit/hyperactivity disorder; low score (<85 points) on Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III); or low score of Kyoto Scale of Psychological Development corrected at 3 years old. We diagnosed maternal renal dysfunction according to the Clinical Practice Guideline for chronic kidney disease 2018 and the Best Practice Guide 2015 for Care and Treatment of Hypertension in Pregnancy. Results: The rate of poor neurological development was 25/165 (15.2%): cerebral palsy (n = 1), intellectual disability (n = 1), developmental disorder (n = 2), low score of Bayley-III (n = 20), and low score of Kyoto Scale of Psychological Development (n = 1). Preeclampsia complicated with maternal renal dysfunction (P = 0.045) and delivery at <30 weeks of gestation (P = 0.007) were independent risk factors for poor neurological development. Conclusions: In addition to previous risk factors such as delivery at <30 weeks of gestation, preeclampsia complicated with renal dysfunction was also associated with poor neurodevelopmental outcomes corrected at 3 years old.

Aggrephagy Deficiency in the Placenta: A New Pathogenesis of Preeclampsia.

Aggrephagy is defined as the selective degradation of aggregated proteins by autophagosomes. Protein aggregation in organs and cells has been highlighted as a cause of multiple diseases, including neurodegenerative diseases, cardiac failure, and renal failure. Aggregates could pose a hazard for cell survival. Cells exhibit three main mechanisms against the accumulation of aggregates: protein refolding by upregulation of chaperones, reduction of protein overload by translational inhibition, and protein degradation by the ubiquitin-proteasome and autophagy-lysosome systems. Deletion of autophagy-related genes reportedly contributes to intracellular protein aggregation in vivo. Some proteins recognized in aggregates in preeclamptic placentas include those involved in neurodegenerative diseases. As aggregates are derived both intracellularly and extracellularly, special endocytosis for extracellular aggregates also employs the autophagy machinery. In this review, we discuss how the deficiency of aggrephagy and/or macroautophagy leads to poor placentation, resulting in preeclampsia or fetal growth restriction.

The role of decidual regulatory T cells in the induction and maintenance of fetal antigen-specific tolerance: Imbalance between regulatory and cytotoxic T cells in pregnancy complications.

Fetal antigen-specific tolerance is important for maintaining allogeneic pregnancies. Maternal conventional T cells recognize fetal antigens; however, regulatory T (Treg) cells suppress immune reactions against the fetus. Fetal antigen-specific Treg cells are induced in the decidua upon contact with antigen-presenting cells and extravillous trophoblasts (EVTs). Functional alteration of cytotoxic T cells (CTLs) in the decidua also contributes to maintaining the pregnancy. Reduced, dysfunctional, and imbalanced Treg cell distribution likely contributes to the pathogenesis of pregnancy complications, such as miscarriage and preeclampsia. Recent studies have revealed differences in Treg cell characteristics during preeclampsia and miscarriage. Treg cell reduction in the decidua is likely associated with miscarriage. Insufficient expansion of fetal antigen-specific Treg cells in the decidua probably plays a role in preeclampsia pathogenesis. In addition, the balance between Treg cell-mediated tolerance and functional alteration of CTLs is important. Further investigations of functional molecules in Treg cells will contribute to the development of immunotherapy for pregnancy complications.

Molecular and immunological developments in placentas.

Cytotrophoblasts differentiate in two directions during early placentation: syncytiotrophoblasts (STBs) and extravillous trophoblasts (EVTs). STBs face maternal immune cells in placentas, and EVTs, which invade the decidua and uterine myometrium, face the cells in the uterus. This situation, in which trophoblasts come into contact with maternal immune cells, is known as the maternal-fetal interface. Despite fetuses and fetus-derived trophoblast cells being of the semi-allogeneic conceptus, fetuses and placentas are not rejected by the maternal immune system because of maternal-fetal tolerance. The acquired tolerance develops during normal placentation, resulting in normal fetal development in humans. In this review, we introduce placental development from the viewpoint of molecular biology. In addition, we discuss how the disruption of placental development could lead to complications in pregnancy, such as hypertensive disorder of pregnancy, fetal growth restriction, or miscarriage.

CDX2 Expression and Prognostic Factors of Resectable Pulmonary Large Cell Neuroendocrine Carcinoma.

BACKGROUND AND AIM: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare neoplasm, and its clinical features and management are still limited. We evaluated the clinicopathological factors, including CDX2 immunohistochemical expression, to predict survival in patients with LCNEC. PATIENTS AND METHODS: In all, 50 patients with LCNEC who underwent surgery at 4 institutes between 2001 and 2017 were included. Clinicopathological characteristics were evaluated for prognostic factors and statistically analyzed by Kaplan-Meier curve with a log-rank test or Cox regression models. We used immunohistochemical (IHC) analysis to determine the expressions of CDX2 and compared them with clinicopathological factors and survival. RESULTS: Sixteen of the 50 cases (32%) were CDX2 positive. No correlation was found between the CDX2 expression by IHC and clinicopathological factors. Multivariate analysis identified adjuvant chemotherapy (hazard ratio [HR] =2.86, 95% confidence interval [CI] = 1.04-8.16, P = .04) and vascular invasion (HR = 4.35, 95% CI = 1.21-15.63, P = .03) as being associated with a significantly worse rate of recurrence-free survival. CONCLUSION: CDX2 was expressed in 1/3 of LCNEC but not associated with prognostic factor. Adjuvant chemotherapy and vascular invasion were associated with a negative prognostic factor of LCNEC.

Placental autophagy failure: A risk factor for preeclampsia.

Hypertensive disorders of pregnancy, including preeclampsia, directly affect maternal and perinatal morbidity and mortality. As the pathophysiology of preeclampsia is multi-factorial and has been studied using different approaches, we have demonstrated that impaired autophagy is an intertwined risk factor for preeclampsia. This concept has been verified in both in vitro and in vivo experiments. Autophagy is primarily involved in maintaining cellular homeostasis, and in immune regulation, longevity, cytokines secretion and a variety of other biological functions. Here, we review the role of autophagy in normal embryogenesis and placentation. Once placental autophagy is impaired by metabolic stress such as hypoxia, endoplasmic reticulum stress or starvation, placental development could be disrupted, resulting in functional maladaptations at the maternal-fetal interface. These malfunctions may result in fetal growth restriction or preeclampsia.

Method to evaluate intravenous maintenance tocolysis for preterm labor.

AIM: Despite the lack of evidence-based medicine, continuous intravenous maintenance tocolysis is the main treatment for preterm labor (PTL) in Japan because it is considered to prolong the gestational period. This treatment needs to be evaluated in more detail, and we herein propose one method to assess maintenance tocolysis using the timing of delivery by PTL patients. METHODS: PTL patients (n = 307) were divided into three groups according to delivery weeks of gestation. Group A (severe PTL) delivered at <34 weeks, group B (mild PTL) at 34-37 weeks and group C (cases suspected overtreatment) at ≥38 weeks. The percentages of patients in each group was calculated and clinical characteristics were compared between groups. RESULTS: The percentages of patients (%) in groups A, B and C were 33.9, 43.6 and 22.5, respectively. Gestational weeks on admission, maternal white blood cell count and C-reactive protein, PTL index, fetal fibronectin levels in vaginal secretions, amniotic fluid interleukin-8 levels, staying at neonatal intensive care unit were significantly different between these three groups by analysis of variance. Furthermore, amniotic fluid interleukin-8 levels were significantly higher in group B (3.5 [0.1-46.5] ng/mL) than in group C (1.7 [0.1-16.1], P < 0.05). CONCLUSIONS: PTL patients were classified according to the prognosis. The ratio of patients in each group represented the severity of PTL and the risk of overtreatment. When this ratio is investigated on a nationwide scale, the use of intravenous maintenance tocolysis or definition of PTL may need to be reconsidered.

Disruption of Placental Homeostasis Leads to Preeclampsia.

Placental homeostasis is directly linked to fetal well-being and normal fetal growth. Placentas are sensitive to various environmental stressors, including hypoxia, endoplasmic reticulum stress, and oxidative stress. Once placental homeostasis is disrupted, the placenta may rebel against the mother and fetus. Autophagy is an evolutionally conservative mechanism for the maintenance of cellular and organic homeostasis. Evidence suggests that autophagy plays a crucial role throughout pregnancy, including fertilization, placentation, and delivery in human and mouse models. This study reviews the available literature discussing the role of autophagy in preeclampsia.

Risk factors for spontaneous miscarriage above 12 weeks or premature delivery in patients undergoing cervical polypectomy during pregnancy.

BACKGROUND: It currently remains unknown whether the resection of cervical polyps during pregnancy leads to miscarriage and/or preterm birth. This study evaluated the risk of spontaneous PTB below 34 or 37 weeks and miscarriage above 12 weeks in patients undergoing cervical polypectomy during pregnancy. METHODS: This was a retrospective monocentric cohort study of patients undergoing cervical polypectomy for clinical indication. Seventy-three pregnant women who underwent polypectomy were selected, and risk factors associated with miscarriage above 12 weeks or premature delivery below 34 or 37 weeks were investigated. A multivariable regression looking for predictors of spontaneous miscarriage > 12 weeks and PTB < 34 or 37 weeks were performed. RESULTS: Sixteen patients (21.9%, 16/73) had spontaneous delivery at < 34 weeks or miscarriage above 12 weeks. A univariate analysis showed that bleeding before polypectomy [odds ratio (OR) 7.7, 95% confidence interval (CI) 1.6-37.3, p = 0.004], polyp width ≥ 12 mm (OR 4.0, 95% CI 1.2-13.1, p = 0.005), the proportion of decidual polyps (OR 8.1, 95% CI 1.00-65.9, p = 0.024), and polypectomy at ≤10 weeks (OR 5.2, 95% CI 1.3-20.3, p = 0.01) were significantly higher in delivery at < 34 weeks than at ≥34 weeks. A logistic regression analysis identified polyp width ≥ 12 mm (OR 11.8, 95% CI 2.8-77.5, p = 0.001), genital bleeding before polypectomy (OR 6.5, 95% CI 1.2-55.7, p = 0.025), and polypectomy at ≤10 weeks (OR 5.9, 95% CI 1.2-45.0, p = 0.028) as independent risk factors for predicting delivery at < 34 weeks. Polyp width ≥ 12 mm and bleeding before polypectomy are risk factors for PTB < 37 wks. CONCLUSIONS: Our cohort of patients undergoing polypectomy in pregnancy have high risks of miscarriage or spontaneous premature delivery. It is unclear whether these risks are given by the underlying disease, by surgical treatment or both. This study establishes clinically relevant predictors of PTB are polyp size> 12 mm, bleeding and first trimester polypectomy. PTB risks should be exposed to patients and extensively discussed with balancing against the benefits of intervention in pregnancy.

Multiple management strategies to prolong gestational period after radical trachelectomy.

Preterm premature rupture of membranes and massive genital bleeding in the second trimester are serious obstetrical problems in pregnancy after trachelectomy. We had managed a twin post-trachelectomy pregnancy by multiple strategies, and two healthy infants were delivered at 32+5 weeks, although the optimum management for such patients is unknown.

Fermented foods and preterm birth risk from a prospective large cohort study: the Japan Environment and Children's study.

BACKGROUND: The dietary pattern of pregnant women is known to be associated with preterm birth (PTB). We investigated whether PTB was associated with intake of fermented food by using data from the Japan Environment and Children's Study. METHODS: From a data set of 103,099 pregnancies, 77,667 cases at low risk for PTB were analyzed. The primary outcome measurements were based on PTB. Fermented food (miso soup, yogurt, cheese, and fermented soybeans) consumption was assessed by using a semi-quantitative food frequency questionnaire. RESULTS: Intake of miso soup, yogurt, and fermented soybeans before pregnancy significantly reduced the risk of early PTB (< 34 weeks). The adjusted odds ratio (OR) for early PTB in women who had miso soup 1-2 days/week, 3-4 days/week, or ≥ 5 days/week were 0.58, 0.69, and 0.62, respectively, compared with those who had miso soup < 1 day/week (95% confidence interval (CI) 0.40-0.85, 0.49-0.98, and 0.44-0.87). The adjusted OR for early PTB in women who ate yogurt ≥ 3 times/week was 0.62 (95% CI, 0.44-0.87) compared to those who ate yogurt < 1 time/week. The adjusted OR for early PTB in women who ate fermented soybeans ≥ 3 times/week was 0.60 (95% CI, 0.43-0.84) compared to those who ate < 1 time/week. However, the incidence of overall PTB and late PTB (34-36 weeks) was not associated with fermented food intake. CONCLUSION: PTB low-risk women with a high consumption of miso soup, yogurt, and fermented soybeans before pregnancy have a reduced risk of early PTB.