Guideline for gynecological practice in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2023 edition.

Twelve years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the 5th Revised Edition was published in 2023. The 2023 Guidelines includes 5 additional clinical questions (CQs), which brings the total to 103 CQ (12 on infectious disease, 30 on oncology and benign tumors, 29 on endocrinology and infertility and 32 on healthcare for women). Currently, a consensus has been reached on the Guidelines, and therefore, the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated.

Impaired decidualization and relative increase of PROK1 expression in the decidua of patients with unexplained recurrent pregnancy loss showing insulin resistance.

A recent meta-analysis revealed that patients with unexplained recurrent pregnancy loss (RPL) show higher insulin resistance compared to healthy controls. However, the etiology of RPL remains unknown. Prokineticin (PROK1), a pleiotropic uterine endometrial protein, is important for implantation and decidualization and is regulated by hypoxia and insulin. In this study, we investigated the decidualization status and the role of PROK1 in the decidua of patients with unexplained RPL showing insulin resistance. Thirty-two patients with unexplained RPL were included in this study. Following the diagnosis of a miscarriage, the decidua and villi of the patient were surgically collected. Fasting blood glucose and insulin levels were measured, and HOMA-ß was calculated. Using IHC and ELISA, the expression of IGFBP-1, PRL and PROK1 in the decidua and IGF-2 in the villi were analyzed in patients with euploid miscarriage with a high HOMA-ß index (n = 8) and compared to controls (euploid miscarriage with normal HOMA-ß: n = 12, aneuploid miscarriage with normal HOMA-ß: n = 12). The co-localization of PROK1 and IGFBP-1 was observed in the decidua by IHC. In the decidua of RPL patients with high HOMA-ß, the expression levels of IGFBP-1 and PRL were significantly lower, whereas the PROK1/IGFBP-1 ratio was significantly higher compared to that of the controls. IGF-2 expression in villi was significantly lower in RPL patients with high HOMA-ß. Impaired decidualization and excessive PROK1 production may have pathological implications in patients with unexplained RPL with insulin resistance, especially under the state of hyper insulin production.

Intravenous immunoglobulin treatment for obstetric antiphospholipid syndrome refractory to conventional therapy: a single-arm and open-labelled multicentre clinical trial.

OBJECTIVES: To compare the efficacy of intravenous immunoglobulin (IVIG) therapy for obstetric antiphospholipid syndrome (APS) refractory to conventional treatment. METHODS: We conducted a single-arm and open-label multicentre clinical intervention trial. The enrolled criteria were patients with refractory APS who had a history of still or premature birth before 30 weeks of gestational age, even though they had been treated with conventional treatment, i.e., heparin and low-dose aspirin. After confirming the foetal heartbeats, a single course of IVIG (0.4 g/kg body weight daily for five days) was added to conventional treatment. The primary outcome was a live birth ratio of more than 30 weeks gestational period, and the secondary included improving pregnancy outcomes comparing to previous pregnancy. RESULTS: Twenty-five percent of the patients (2 of 8 cases) achieved a live birth after the 30th week of pregnancy by IVIG-only add-on treatment, which is the same prevalence as the historical control. However, by adding other second-line therapy to IVIG and conventional treatment, further three patients (37.5%) achieved improvements in pregnancy outcome compared to previous treatments. In total, five patients (62.5%) were able to achieve preferable pregnancy outcomes through combination treatment including IVIG. CONCLUSIONS: Our clinical trial could not demonstrate the efficacy of IVIG-only add-on therapy at improving the pregnancy outcomes of patients with obstetric APS refractory to conventional treatment. However, the combination of IVIG with rituximab or statins adding to conventional treatment improved pregnancy outcomes and resulted in more live births. Further studies are needed to investigate the efficacy of multi-targeted therapy to treat obstetric refractory APS.

Cervicovaginal microbiome in patients with recurrent pregnancy loss.

There have been few studies concerning an association between unexplained recurrent pregnancy loss (RPL) and the microbiome. A recent study including 67 patients demonstrated that an increase in Ureaplasma species in the endometrium raised the risk of miscarriage with an euploid karyotype. While endometrial sampling is invasive, cervicovaginal sampling is not. We compared vaginal and cervical microbiomes with a 16 S ribosomal RNA sequence between 88 patients with unexplained RPL and 17 healthy women with no history of miscarriage. We prospectively assessed risk factors for maternal colonization at a subsequent miscarriage without an aneuploid karyotype in patients. Cervicovaginal bacteria were dominated by Lactobacillus iners, Gardnerella vaginalis, Atopobium vaginae and Bifidobacterium breve in Japanese population. The proportions of Delftia and unknown bacteria in the cervix were significantly higher in patients with RPL than in controls. Streptococcus, Microbacterium, Delftia, Anaerobacillus and Chloroplast in the cervix were significantly higher in patients with a history of chorioamnionitis compared to the controls. The abundance of Cutibacterium and Anaerobacillus in the cervix was significantly higher in patients who had subsequently miscarried compared to those who gave birth. The miscarriage rate in patients with higher proportions of both Cutibacterium and Anaerobacillus (66.7%, 2/3) was significantly greater than that of patients who lacked these bacteria (9.2%, 6/65, adjusted odds ratio 16.90, 95% confidence interval 1.27-225.47, p = 0.032). The presence of certain bacteria could be a predictor of subsequent miscarriage without an aneuploid karyotype. The cervicovaginal microbiome might be useful for investigating a possible cause of RPL.

Relationship between Birth Order and Postnatal Growth until 4 Years of Age: The Japan Environment and Children's Study.

Later-borns tend to be shorter than first-borns in childhood and adulthood. However, large-scale prospective studies examining growth during infancy according to birth order are limited. We aimed to investigate the relationship between birth order and growth during the first 4 years of life in a Japanese prospective birth cohort study. A total of 26,249 full-term singleton births were targeted. General linear and multivariable logistic regression models were performed and adjusted for birth weight, parents' heights, maternal age at delivery, gestational weight gain, maternal smoking and alcohol drinking status during pregnancy, household income, breastfeeding status, and Study Areas. The multivariate adjusted mean length Z-scores in "first-borns having no sibling", "first-borns having siblings", "second-borns", and "third-borns or more" were -0.026, -0.013, 0.136, and 0.120 at birth and -0.324, -0.330, -0.466, and -0.569 at 10 months, respectively. Results similar to those at 10 months were observed at 1.5, 3, and 4 years. The adjusted odds ratios (95% confidence intervals) of short stature at 4 years in "first-borns having siblings", "second-borns", and "third-borns or more" were 1.08 (0.84-1.39), 1.36 (1.13-1.62), and 1.50 (1.20-1.88), respectively, versus "first-borns having no sibling". Birth order was significantly associated with postnatal growth and may be a factor predisposing to short stature in early childhood.

Hematocolpos due to lower vaginal agenesis in an adolescent girl.

Background: Hematocolpos due to imperforate hymen is an important differential diagnosis of abdominal pain in early adolescent stage. However, hematocolpos due to lower vaginal agenesis must be considered because the management differs. Case Presentation: A healthy 11-year-old girl presented with a 2-day left lower abdominal pain history. Her breast development had begun, but she had not reached menarche. Computed tomography showed high absorptive value liquid filling the upper vaginal to uterine cavity, a pale highly absorptive fluid component suggestive of hemorrhagic ascites in the abdominal cavity on both sides of the uterus, and normal bilateral ovaries. Magnetic resonance imaging diagnosed hematocolpos due to lower vaginal agenesis. The blood clot was aspirated with a transabdominal ultrasound-guided transvaginal puncture. Conclusion: History-taking, imaging tests, and appropriate collaboration with obstetrician/gynecologist with awareness of secondary sexual characteristics were crucial in this case.

Adverse pregnancy outcomes of cancer survivors and infectious disease in their infants: The Japan Environment and Children's Study.

Birth cohort studies examining pregnancy and infant outcomes among adolescent and young adult (AYA) cancer survivors have been limited. The present study examined whether AYA cancer affects pregnancy outcomes of survivors and infectious diseases in their infants up to 1 year of age. Pregnant women were recruited for the Japan Environment and Children's Study, a nationwide, large-scale, prospective cohort study. The present study included 103,060 pregnant women and collected questionnaire-based data during the first and second/third trimester, and at 1 month, 6 months and 1 year after delivery. Adverse pregnancy outcomes and infectious diseases in infants up to 1 year of age were compared between AYA cancer survivors and pregnant women without a history of cancer using binominal logistic regression analyses and a multiple imputation method. Of 99,816 participants (3,244 were missing), 1,102 (1.1%) had a cancer history, including 812 participants (0.8%) with a history of cervical cancer. Among cervical cancer survivors, the adjusted (a)ORs were as follows: 3.25 (95% CI, 2.31-4.57; q=0.00) for a preterm birth <34 weeks' gestation; 2.82 (95% CI, 2.31-3.44; q=0.00) for a preterm birth <37 weeks' gestation; and 1.67 (95% CI, 1.36-2.06; q=0.00) for premature rupture of the membrane. Among the other cancer survivors, the aOR for caesarean section was 1.43 (95% CI, 1.10-1.87; q=0.0). Furthermore, lower respiratory tract inflammation in 1-year-old infants born by vaginal delivery increased significantly in cases with a history of cervical cancer (aOR, 1.77; 95% CI, 1.33-2.36; q=0.00). The present study identified the risk of lower respiratory tract inflammation in 1-year-old infants born by vaginal delivery in cervical cancer survivors for the first time. In addition, the frequency of caesarean section increased in all cancer survivors. No risk of congenital anomalies or other infections were found in the total group of cancer survivors.

The association between chronic deciduitis and recurrent pregnancy loss.

Chronic deciduitis (CD) is defined as the presence of lymphocytes or plasma cells in decidual tissue. CD suggests the presence of chronic endometritis (CE) which is associated with recurrent pregnancy loss (RPL). In this study, we examined the role CD plays in RPL patients with aneuploid and euploid miscarriage. The frequency of CD in 49 RPL patients (22 euploid and 27 aneuploid miscarriages) and 17 control women was assessed and the subsequent live birth rate (LBR) in the presence and absence of CD were compared. When only one CD138-positive endometrial stromal plasma cell (ESPC) was found per high-power field (HPF), we diagnosed small-positive CD (Grade 1). When a cluster of two or more CD138-positive ESPCs was found per HPF, we diagnosed it as CD Grade 2. The prevalence of Grade 1 was 18.2% (4/22) in patients with euploid miscarriage, 37.0% (10/27) in patients with aneuploid miscarriage and 23.5% (4/17) in control women. The prevalence of Grade 2 was 45.5% (10/22) in patients with euploid miscarriage, 55.6% (15/27) in patients with aneuploid miscarriage and 23.5% (4/17) in control women. There was a significant difference in the prevalence of CD (p = 0.015). The LBR of patients with CD was similar to that of patients without CD. CD was associated with RPL, especially in patients with aneuploid miscarriage. However, since there was no difference in the LBR of patients with or without CD in the next pregnancy, it was unclear whether CD was a contributing cause of RPL.

Quantitative Measurement of Phthalate Exposure Biomarker Levels in Diaper-Extracted Urine of Japanese Toddlers and Cumulative Risk Assessment: An Adjunct Study of JECS Birth Cohort.

Phthalate exposure monitoring and risk assessment in non-toilet-trained children are rarely reported. This adjunct study of the Japan Environment and Children's Study assessed cumulative health risks in 1.5-year-old toddlers in the Aichi regional subcohort by biomonitoring 16 urinary metabolites of eight phthalate plasticizers. Overnight urine was extracted from toddlers' diapers (n = 1077), and metabolites were quantified using ultraperformance liquid chromatography coupled with tandem mass spectrometry. The analyses' quality was assured by running quality control samples. The highest geometric mean concentration was found for mono-(2-ethyl-5-carboxypentyl) phthalate, followed by mono-isobutyl phthalate (23 and 21 µg/L, respectively). Di-2-ethylhexyl phthalate (DEHP) and di-butyl phthalate exhibited higher risks [hazard quotient (HQ) > 1] than the cutoff level in a small proportion of toddlers; 8 and 14% of toddlers were at cumulative risk of multiple phthalates beyond the cutoff level [hazard index, (HI) > 1], based on the tolerable daily intake of the European Food Safety Authority and the United States Environmental Protection Agency Reference Dose. HI > 1 for antiandrogenicity in creatinine-unadjusted and -adjusted estimations were exhibited by 36 and 23% of the children, respectively. Thus, identifying exposure sources and mitigating exposure are necessary for risk management. Additionally, continuous exposure assessment and evaluation of health outcomes, especially antiandrogenic effects, are warranted.

High Maternal Total Cholesterol Is Associated With No-Catch-up Growth in Full-Term SGA Infants: The Japan Environment and Children's Study.

Objectives: Infants born small for gestational age (SGA) with no catch-up growth (No-CU) are at high risk of intellectual and developmental disabilities. However, factors leading to No-CU among SGA infants are unclear. This study aimed to examine the association between maternal total cholesterol (TC) in mid-pregnancy and No-CU at 3 years among full-term SGA infants. Study Design: The Japan Environment and Children's Study (JECS) is a nationwide prospective birth cohort study. We extracted a total of 2,222 mothers and full-term SGA infants (length and/or weight <-2 standard deviation [SD]) without congenital abnormalities from the original JECS cohort comprising a total of 104,062 fetal records. According to the distribution of maternal TC in the entire cohort, participants were classified into nine groups per each fifth percentile with the 20th-79th percentiles (204-260 mg/dl) as the reference group. No-CU was defined by a Z-score of height at 3 years <-2 SD according to the growth standard charts for Japanese children. Multivariable-adjusted logistic regression models were carried out using multiple imputations. Additionally, a multiple-adjusted restricted cubic spline model was performed in the complete dataset. Results: A total of 362 (16.3%) children were No-CU at 3 years. After adjusting for the Z-score of birth weight, age of mother, smoking status, weight gain during pregnancy, breastfeeding and meal frequency at 2 years, and parents' heights, the odds ratio (95% confidence intervals) of No-CU was 2.95 (1.28-6.80) for children whose maternal TC levels were in the highest category (≥294 mg/dl), compared to the reference group. A multiple-adjusted restricted cubic spline model showed a non-linear trend of the significant association between high maternal TC and No-CU (p for linear trend = 0.05, p for quadratic trend <0.05). Conclusion: High maternal TC at mid-pregnancy was associated with No-CU among SGA infants. Such infants should be carefully followed up to introduce appropriate growth hormonal treatment. The findings may support previous animal experimental studies which indicated that maternal high-fat diet exposure induces impairment of growth and skeletal muscle development in the offspring. Future studies are required to elucidate the detailed mechanism.

Epidemiological Studies of Children's Gut Microbiota: Validation of Sample Collection and Storage Methods and Microbiota Analysis of Toddlers' Feces Collected from Diapers.

The composition of human gut microbiota influences human health and disease over the long term. Since the flora in specimens can easily change at ambient temperature outside the body, epidemiological studies need feasible methods of stool specimen collection and storage to be established. We aimed to validate two methods: feces frozen-stored in tubes containing guanidine thiocyanate solution for two months after collection (Method B), and feces excreted in diapers and frozen-stored (Method C). Validation was by comparison with a gold standard Method A. Bacterial flora of five adults were sampled and stored by all three methods. Bacterial composition was examined by amplicon sequencing analysis. Bland-Altman analyses showed that Methods B and C might change relative abundances of certain bacterial flora. Thereafter, we analyzed the bacterial flora of 76 toddlers (two age groups) in stools sampled and processed by Method C. The diversity indices of toddlers' flora were less than those of adults. The relative abundance of some bacteria differed significantly between children aged 1.5 and 3 years. The specimen collection and storage methods validated in this study are worth adopting in large-scale epidemiological studies, especially for small children, provided the limited accuracy for some specific bacteria is understood.

Characteristic DNA methylation profiles of chorionic villi in recurrent miscarriage.

Dysregulation of transcriptional programs that are tightly regulated by DNA methylation during placental and fetal development at different gestational stages, may cause recurrent miscarriage. Here, we examined genome-wide DNA methylation in chorionic villi and decidual tissues from patients suffering RM and from healthy women who had undergone artificial abortion (n = 5 each). We found that 13,426 and 5816 CpG sites were differentially methylated in chorionic villi and decidua, respectively. DNA methylation profiles of chorionic villi, but not decidua, in RM patients was clearly distinct from AA controls. Among the differentially methylated genes, the enhancer region of SPATS2L was significantly more highly methylated in RM patients (n = 19) than AA controls (n = 19; mean methylation level, 52.0%-vs.-28.9%, P < 0.001), resulting in reduced expression of SPATS2L protein in the former. Functionally, depletion of SPATS2L in extravillous trophoblast cells decreased their invasion and migration abilities. Our data indicate that particularly the chorionic villi in RM patients exhibit distinct DNA methylation profiles compared with normal pregnancies and that this changed DNA methylation status may impede the progression of embryo development via the altered expression of genes such as SPATS2L in the villi.

Depression symptoms during pregnancy and postpartum in patients with recurrent pregnancy loss and infertility: The Japan environment and children's study.

There are a limited number of studies in which the depression status was followed up throughout pregnancy and postpartum to 1 year after delivery though 8.6-33% of women with recurrent pregnancy loss (RPL) and 10-25% of women who undergo in vitro fertilization and embryo transfer (IVF-ET) suffer from depression. We examined whether RPL and IVF-ET affect depressive symptoms during pregnancy and postpartum. A nationwide large-scale birth cohort study known as the "Japan Environment and Children's Study (JECS)" was conducted. The subjects consisted of 99,202 pregnant women recruited between January 2011 and March 2014. The Kessler Psychological Distress Scale was used for the 1st trimester, 2nd/3rd trimester and 1 year postpartum. The Edinburgh Postnatal Depression Scale was used for the first and the sixth month postpartum. The screening instruments were used to quantify depressive symptoms. Women with no live births had a significantly higher prevalence of elevated depressive symptoms throughout pregnancy and postpartum. The prevalence of elevated depressive symptoms was significantly higher in the second/third trimester among women with three or more pregnancy losses with no live births. IVF-ET was associated with reduced risk of developing depressive symptoms during all pregnancies and at 1 and 6 months after delivery in women with no live births. RPL and IVF-ET did not affect postpartum depressive symptoms, and IVF-ET rather reduced the risk of depression throughout pregnancy and postpartum. Psychological support for RPL women would be necessary.

Simultaneous quantification of pyrethroid metabolites in urine of non-toilet-trained children in Japan.

BACKGROUND: Pyrethroid (PYR) insecticides are widely used for controlling various pests. There are two types that differ in terms of usage: agricultural-purpose PYR (agriculture-PYR) and hygiene purpose PYR (hygiene-PYRs). Few studies exist on the exposure to these chemicals in small children. In this study, we conducted biomonitoring of urinary pyrethroid metabolites in 1.5-year-old children throughout the year. METHODS: Study subjects were 1075 children participating in an Aichi regional sub-cohort of the Japan Environment and Children's Study as of 18-month health check-up. The concentrations of four specific hygiene-PYR metabolites including 2,3,5,6-tetrafluoro-1,4-benzenedimethanol (HOCH2-FB-Al), and five common metabolites of hygiene- and agriculture-PYRs including 3-phenoxybenzoic acid (3PBA) and cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (DCCA), were measured in urine samples extracted from soiled diapers using a triple quadrupole gas chromatograph-mass spectrometer. RESULTS: The highest detection frequencies were for 3PBA, followed by DCCA, 1R-trans-chrysanthemum dicarboxylic acid, and HOCH2-FB-Al. Among the six metabolites, urinary concentrations were seasonally varied. However, this variation was not observed in the most studied PYR metabolite, 3PBA. Spearman's correlation analysis demonstrated a significant positive correlation between FB-Al and DCCA (r = 0.56) and HOCH2-FB-Al and 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol (r = 0.60). CONCLUSIONS: This biomonitoring survey found widespread and seasonally specific exposure to multiple hygiene- and agriculture-PYRs in 1.5-year-old Japanese children.

Abnormal accumulation of OFD1 in endometrial cancer with poor prognosis inhibits ciliogenesis.

The aim of the present study was to examine primary cilia in endometrial tissue during the menstrual cycle and to clarify their morphological changes with different grades of endometrial cancer. Images of fluorescence immunostaining taken by confocal microscopy were used to count the number of primary cilia in normal endometrium and endometrioid carcinoma Grade 1 and Grade 3 specimens. To examine the association between autophagy and ciliogenesis in endometrioid carcinoma, the expression of p62/Sequestosome-1, a selective substrate for autophagy, and oral-facial-digital syndrome 1 protein (OFD1), a protein associated with ciliogenesis, were examined using images of fluorescence immunostaining taken by confocal microscopy. The level of p62 expression was confirmed by western blotting. In proliferative and secretory endometrial stromal cells, the percentage of cells that were ciliated was 7.2 and 32.7% (95% confidence interval=21.61-39.79; P<0.01), and the length of the primary cilia was 1.24 µm and 2.34 µm (0.92-1.26; P<0.01), respectively. In stromal cells of endometrioid carcinoma Grade 1 and Grade 3, the percentage of ciliated cells was 13.5 and 2.9% (7.89-15.05; P<0.001), and the length of the primary cilia was 2.02 and 1.14 µm (0.76-0.99; P<0.001), respectively. In both normal menstrual cycle tissue and endometrial carcinomas, the percentage of primary cilia was lower and their length was shorter in tissues with higher proliferative potential. The expression of OFD1 was significantly higher in Grade 3 compared with Grade 1 as indicated by quantifying the intensity of the fluorescence images (133-12248; P=0.046). To the best of our knowledge, this is the first study concerning the distribution of primary cilia in normal endometrium and endometrial cancer tissues. Overall, fewer ciliated cells in the highly malignant endometrial cancer tissues may be associated not only to the proliferation of cancer cells, but also to the excessive accumulation of OFD1 due to dysfunctional autophagy.

Does a cervical pessary reduce the rate of preterm birth in women with a short cervix?

OBJECTIVES: To evaluate neonatal outcomes after the use of a cervical pessary in Japanese women with short cervical length (CL) less than 25 mm. METHODS: This multicenter study involved women with singleton pregnancies between 20 and 29+6 gestational weeks and a CL of less than 25 mm. The primary outcome was preterm birth (PTB) before 34 weeks of gestation. This study was registered in the Japan Registry of Clinical Trials (JRCT: jRCTs042180102). RESULTS: Two hundred pregnant women were enrolled; 114 in the pessary group and 86 in the expectant management group as controls. In the pessary group, all 114 neonates were investigated for perinatal outcomes, and 112 pregnant women were investigated for primary, and secondary outcomes. In the control group, 86 pregnant women were investigated for primary and secondary outcomes and 86 neonates were investigated for neonatal outcomes. There were no significant differences in PTB in ≤34, ≤37, and ≤28 weeks of gestation or in preterm rupture of membranes (PROM) ≤34 weeks between the groups. The gestational weeks at birth and birth weight were significantly higher in the pessary group. Regression analysis demonstrated that the CL decreased without a pessary, whereas the shortening rate was suppressed during the intervention. No significant differences were observed in adverse neonatal outcomes, chorioamnionitis, or preterm PROM. CONCLUSIONS: The cervical pessary effectively reduced CL shortening during pregnancy resulting in an average increased gestational age, however, did not reduced the rates of preterm birth.

Repeated maternal non-responsiveness to baby's crying during postpartum and infant neuropsychological development: The Japan Environment and Children's Study.

BACKGROUND: Longitudinal adverse effects of neglect-related behaviors during postpartum, especially repeated maternal non-responsiveness to the crying baby on their neuropsychological developmental trajectory, have not been fully clarified. OBJECTIVE: This study aimed to examine the association between postpartum maternal neglect-related behaviors and infant neuropsychological outcomes using the Japan Environment and Children's Study (JECS). PARTICIPANTS AND SETTING: JECS data on 100,286 mother-child pairs were analyzed. Explanatory variables were "frequency of leaving the baby alone at home" (i.e., leaving the baby alone at home) and "frequency of ignoring the baby when he or she cries" (i.e., ignoring the crying baby) at one month postpartum. The outcomes were measured using the Japanese version of the Ages & Stages Questionnaires-Third Edition (J-ASQ-3). METHODS: After multiple imputations, logistic regression analysis was performed to evaluate the association between neglect-related behaviors and the J-ASQ-3 domains at each age. RESULTS: The "sometimes or more" group of "ignoring the crying baby" from six months to three years reported relatively consistent significant associations with developmental delay in communication (maximum adjusted odds ratio [aOR]: 1.456, 95% confidence interval [CI]: 1.261-1.682), gross motor (maximum aOR: 1.279, 95% CI: 1.159-1.411), fine motor (maximum aOR: 1.274, 95% CI: 1.113-1.457), problem-solving (maximum aOR: 1.178, 95% CI: 1.104-1.256), and personal-social domains (maximum aOR: 1.326, 95% CI: 1.255-1.402). The adverse effects of "leaving the baby alone at home" disappeared in many domains by the age of one. CONCLUSIONS: Repeated maternal non-responsiveness to baby's crying during postpartum may suppress multiple neuropsychological development during early childhood.

Impact of Ready-Meal Consumption during Pregnancy on Birth Outcomes: The Japan Environment and Children's Study.

Ready-meal consumption is increasing worldwide; however, its impact on human health remains unclear. We aimed to examine the association between processed food and beverage consumption during pregnancy and pregnancy outcomes. Pregnant women were recruited for the Japan Environment and Children's Study (JECS), a nationwide, large-scale, prospective cohort study. This study included 104,102 registered children (including fetuses or embryos) and collected questionnaire-based data during the first and second/third trimester of pregnancy. Participants' medical records were transcribed at pregnancy registration, immediately after delivery, and 1 month after delivery. Logistic regression analysis was used to estimate the association between processed food consumption and pregnancy outcomes. The incidence of stillbirth was higher in the group that consumed moderate (1-2 times per week) and high (≥3-7 times per week) amounts of ready-meals (adjusted odds ratio (aOR) = 2.054, 95% confidence interval (CI): 1.442-2.926, q = 0.002; aOR = 2.632, 95% CI: 1.507-4.597, q = 0.007, respectively) or frozen meals (aOR = 2.225, 95% CI: 1.679-2.949, q < 0.001; aOR = 2.170, 95% CI: 1.418-3.322, q = 0.005, respectively) than in the group that rarely consumed such foods. Processed food consumption during pregnancy should be carefully considered.

Abnormal ciliogenesis in decidual stromal cells in recurrent miscarriage.

Primary cilia regulate cellular signaling and are involved in both sensing and transducing extracellular stimuli. A recent study of patients with recurrent miscarriage (RM) identified mutations affecting DYNC2H1, which were involved in ciliary biogenesis. However, there has been no study concerning primary cilia in the decidua. We compared the number and the length of primary cilia in the decidua of 15 patients with unexplained RM with those of 7 pregnant controls who underwent an artificial termination of pregnancy. Immunohistochemistry was performed using antibodies against primary cilia, extravillous trophoblasts (EVTs), macrophages, uterine Natural Killer (uNK) cells, decidual stromal cells, and the activation of TGF-ß and CREB signaling in the decidua of early pregnancy was studied. The density of decidual stromal cells, but not EVTs, macrophages or uNK cells, was found to be significantly higher in the decidua of patients compared to controls. The percentage of ciliated decidual stromal cells was significantly decreased in patients. There was no difference in the primary ciliary length. Regarding TGF-ß signaling, p-Smad2 in these cells was diminished significantly in patients, and most of the TGF-ß-activated decidual stromal cells of both patients and controls had primary cilia. No difference in the activation of CREB was found. Abnormal primary cilia on decidual stromal cells may be one of the explanatory factors for unknown RM. The inactivation of TGF-ß signaling may lead to abnormal ciliogenesis in the decidua.