Maternal magnesium intake and childhood wheezing in offspring at 3 years of age: the Japan Environment and Children's Study.

This study evaluated the association between maternal magnesium intake (MMI) and childhood wheezing incidence in 3-year-old offspring. We hypothesised that higher MMI imparts anti-inflammatory and antioxidant effects that decrease childhood wheezing incidence in offspring. Data of 79 907 women (singleton pregnancy, ≥ 22 weeks) from the Japan Environment and Children's Study (enrolled between 2011 and 2014) were analysed. Participants were categorised into quintiles of MMI (< 148·00, 148·00-187·99, 188·00-228·99, 229·00-289·99 and ≥ 290·00 mg/d), quintiles of adjusted MMI for daily energy intake (aMMI) (< 0·107, 0·107-0·119, 0·120-0·132, 0·133-0·149 and ≥ 0·150 mg/kcal) and MMI levels either below or above the ideal value (< 310·00 or ≥ 310·00 mg/d). Multivariable logistic regression analysis was performed to calculate OR for the incidence of childhood wheezing in offspring among participants in each MMI category, with the lowest MMI group considered the reference group. Maternal demographic, socio-economic, medical and other nutrient intake backgrounds were considered potential confounding factors. The adjusted OR (aOR) for childhood wheezing in the offspring of women with the highest MMI was 1·09 (95 % CI, 1·00, 1·20), whereas that calculated based on aMMI categories and offspring of women with above-ideal MMI levels remained unchanged. The highest MMI was associated with slightly increased childhood wheezing incidence in the offspring. MMI during pregnancy had an insignificant clinical impact on this incidence; moreover, modifying MMI would not significantly improve childhood wheezing incidence in offspring. Therefore, further studies should clarify the association between other prenatal factors and childhood wheezing incidence in offspring.

Association of Maternal Asthma and Total Serum Immunoglobulin E levels with Obstetric Complications: The Japan Environment and Children's Study.

OBJECTIVE: To evaluate the association between maternal asthma (MA) and obstetric complications, while considering subdivided total serum immunoglobulin E (IgE) levels. METHODS: Data of the participants enrolled in the Japan Environment and Children's Study between 2011 and 2014 were analyzed. In total, 77,131 women with singleton live births at and after 22 weeks of gestation were included. MA was defined based on a self-administered questionnaire. Women with MA were stratified based on the quartile of total serum IgE levels during pregnancy as follows: low IgE levels (< 52.40 IU/mL), moderate IgE levels (52.40-331.00 IU/mL), and high IgE levels (> 331.00 IU/mL). The adjusted odds ratios (aORs) for preterm births (PTB), small for gestational age (SGA) infants, gestational diabetes mellitus, and hypertensive disorders of pregnancy (HDP) were calculated using multivariable logistic regression, while considering women without MA as reference and maternal socioeconomic factors as confounders. RESULTS: The aORs for SGA infants and HDP in women with MA and high total serum IgE levels were 1.26 (95% confidence interval [CI], 1.05-1.50) and 1.33 (95% CI, 1.06-1.66), respectively. The aOR for SGA infants among women with MA and moderate total serum IgE levels was 0.85 (95% CI, 0.73-0.99). The aOR for PTB among women with MA and low total serum IgE levels was 1.26 (95% CI, 1.04-1.52). CONCLUSIONS FOR PRACTICE: MA with subdivided total serum IgE levels was associated with obstetric complications. Total serum IgE level may be a potential prognostic marker to predict obstetric complications in pregnancies with MA.

What is Already Known on this Subject? Maternal asthma (MA) is associated with several obstetric complications, including preterm births (PTB), small for gestational age (SGA) infants, and hypertensive disorders of pregnancy (HDP). Few studies with data from nationwide cohorts have elucidated the association between MA and obstetric complications comprehensively while accounting for the subdivided objective biomarkers of MA.What this Study Adds? MA with subdivided total serum IgE levels was associated with various obstetric complications. Total serum IgE level may be a potential prognostic marker for pregnant women with MA to predict the potential risk of PTB, SGA infants, and HDP.

Landscape of somatic mutated genes and inherited susceptibility genes in gynecological cancer.

Traditionally, gynecological cancers have been classified based on histology. Since remarkable advancements in next-generation sequencing technology have enabled the exploration of somatic mutations in various cancer types, comprehensive sequencing efforts have revealed the genomic landscapes of some common forms of human cancer. The genomic features of various gynecological malignancies have been reported by several studies of large-scale genomic cohorts, including The Cancer Genome Atlas. Although recent comprehensive genomic profiling tests, which can detect hundreds of genetic mutations at a time from cancer tissues or blood samples, have been increasingly used as diagnostic clinical biomarkers and in therapeutic management decisions, germline pathogenic variants associated with hereditary cancers can also be detected using this test. Gynecological cancers are closely related to genetic factors, with approximately 5% of endometrial cancer cases and 20% of ovarian cancer cases being caused by germline pathogenic variants. Hereditary breast and ovarian cancer syndrome and Lynch syndrome are the two major cancer susceptibility syndromes among gynecological cancers. In addition, several other hereditary syndromes have been reported to be associated with gynecological cancers. In this review, we highlight the genes for somatic mutation and germline pathogenic variants commonly seen in gynecological cancers. We first describe the relationship between clinicopathological attributes and somatic mutated genes. Subsequently, we discuss the characteristics and clinical management of inherited cancer syndromes resulting from pathogenic germline variants in gynecological malignancies.

Influence of preconception carbohydrate intake on hypertensive disorders of pregnancy: The Japan Environment and Children's Study.

AIM: Hypertensive disorders of pregnancy (HDP) are a crucial cause of morbidity and mortality. We aimed to examine whether preconception carbohydrate intake is associated with new-onset HDP and small for gestational age (SGA) births. METHODS: We identified 93 265 normotensive (primiparous, 37 387; multiparous, 55 878) participants from the Japan Environmental Children's Study database who delivered between 2011 and 2014. After excluding participants with multiple gestations, preconception hypertension, and insufficient data, primiparous and multiparous participants were categorized into five groups according to their preconception carbohydrate-intake quintiles (Q1 and Q5 were the lowest and highest groups, respectively). Multiple logistic regression analysis was performed to identify the effect of preconception carbohydrate intake on early (<34 weeks) and late-onset (≥34 weeks) HDP and the incidence of SGA births. RESULTS: With the middle carbohydrate intake group (Q3) as a reference, the risk for late-onset HDP among multiparous women was higher in the Q5 group (adjusted odds ratio [aOR] 1.31, 95% confidence interval [CI] 1.02-1.69). The incidence of SGA births was higher in the Q1 group among both primiparous (aOR 1.16, 95% CI 1.01-1.33) and multiparous women (aOR 1.16, 95% CI 1.02-1.32). CONCLUSIONS: Excessive carbohydrate intake increases the incidence of HDP in multiparous women, while low-carbohydrate intake increases the incidence of SGA births. New recommendations for preconception carbohydrate intake are required to prevent major HDP-related complications.

Tocolytic treatment and maternal characteristics, obstetric outcomes, and offspring childhood outcomes among births at and after 37 weeks of gestation: the Japan environment and children's study.

PURPOSE: To evaluate differences in maternal characteristics and obstetric and offspring childhood outcomes between births at and after 37 weeks of gestation (referred to as term and post-term births) according to the use of tocolytic treatment. METHODS: Data for 63,409 women with singleton births at and after 37 weeks of gestation were analyzed using data from the Japan Environment and Children's Study (JECS). We compared maternal characteristics, obstetric outcomes, and offspring childhood outcomes between term and post-term births exposed and not exposed to tocolytic treatment. Additionally, multivariable logistic regression models were used to calculate adjusted odds ratios for offspring childhood outcomes with significant between-group differences in the univariable analysis, with term and post-term births without tocolytic agents as the reference group. RESULTS: We observed differences in maternal characteristics and obstetric outcomes between term and post-term births exposed and not exposed to tocolytic treatment. The incidence of offspring childhood developmental disorders showed no significant between-group differences. However, participants exposed to tocolytic agents had higher incidence of offspring childhood allergic disorders. The adjusted odds ratio for any of the offspring childhood allergic disorders in term and post-term births with tocolytic agents was 1.08 (95% confidence interval, 1.03-1.13). CONCLUSION: This study found no significant difference in the incidence of offspring developmental disorders between term and post-term births exposed and not exposed to tocolytic treatment. However, tocolytic treatment was associated with differences in maternal characteristics and obstetric outcomes, along with a marginal increase in the incidence of childhood allergic disorders in offspring.

Meconium-stained amniotic fluid during labor may be a protective factor for the offspring's childhood wheezing up to 3 years of age: the Japan Environment and Children's Study.

We aimed to evaluate the association between meconium-stained amniotic fluid during labor and offspring's childhood wheezing. This study analyzed the data of participants enrolled in the Japan Environment and Children's Study, a nationwide prospective birth cohort study, between 2011 and 2014. Data of women with singleton live births between 22 and 40 weeks' gestation were analyzed. Participants were categorized into two groups according to the presence or absence of meconium-stained amniotic fluid. The primary outcome measure was the offspring's childhood wheezing up to 3 years of age. A logistic regression model was used to calculate the adjusted odds ratio for childhood wheezing in children of women with meconium-stained amniotic fluid, considering those without meconium-stained amniotic fluid as a reference, taking into account the potential confounding factors affecting the incidence of wheezing. We analyzed data from 61,991 participants: 1796 (2.9%) participants had meconium-stained amniotic fluid during labor and 18,919 (30.5%) of the offspring had childhood wheezing. The adjusted odds ratios for the offspring's childhood wheezing were 0.89 (95% confidence interval, 0.79-0.99) in total participants, 0.87 (95% confidence interval, 0.78-0.97) in term births, and 2.00 (95% confidence interval, 0.98-4.09) in preterm births. CONCLUSIONS: This study revealed a decreased incidence of childhood wheezing among the children of women with meconium-stained amniotic fluid in term births. By yet unknown mechanisms, meconium-stained amniotic fluid was associated with a decreased incidence of childhood wheezing in the offspring. Further studies are required to clarify the mechanism of one's own meconium in affecting their health condition. WHAT IS KNOWN: • Meconium-stained amniotic fluid during labor is associated with several adverse perinatal outcomes, and meconium aspiration syndrome is associated with offspring's childhood asthma and wheezing. • Meconium-stained amniotic fluid during labor could be an independent protective factor for the offspring's dermatitis and skin rash. WHAT IS NEW: • Whole cases with meconium-stained amniotic fluid during labor were associated with a decreased incidence of offspring's childhood wheezing up to 3 years of age. • This study may shed light on the effects of simple meconium-stained amniotic fluid on offspring's childhood health.

Gestational weight gain as a risk factor for dystocia during first delivery: a multicenter retrospective cohort study in Japan.

BACKGROUND: Dystocia is a common obstetric complication among nulliparous women, which requires medical intervention and carries the risk of negative maternal and neonatal outcomes. Our aim was to examine the association between body mass index (BMI) and the occurrence of dystocia. We also identified cutoffs of gestational weight gain, based on pre-pregnancy BMI, associated with the risk of dystocia. METHODS: This was a multicenter, retrospective, cohort study conducted in two tertiary Maternal-Fetal medicine units in Fukushima, Japan. The study population included nullipara women who delivered at either of the two units between January 1, 2013, and December 31, 2020. Women (n = 2597) were categorized into six groups (G) based on their pre-pregnancy BMI: G1 (< 18.5 kg/m2), G2 (18.5 to < 20.0 kg/m2), G3 (20.0 to < 23.0 kg/m2), G4 (23.0 to < 25.0 kg/m2), G5 (25.0 to < 30.0 kg/m2), and G6 (≥ 30.0 kg/m2). Using G3 as a reference, multiple logistic regression analyses were performed to estimate the risk of dystocia for each BMI category. Receiver operating characteristic curve analyses were performed to determine the cutoff value of gestational weight gain for the risk of dystocia. RESULTS: The highest BMI category (G6) was an independent risk factor for dystocia (adjusted odds ratio, 3.0; 95% confidence interval, 1.5-5.8). The receiver operating characteristic curve analysis revealed no association between gestational weight gain and the occurrence of dystocia in G5 and G6 (P = 0.446 and P = 0.291, respectively). For G1 to G4, AUC and predictive cutoffs of gestational weight gain for dystocia were as follows: G1, AUC 0.64 and cutoff 11.5 kg (P < 0.05); G2, AUC 0.63 and cutoff 12.3 kg (P < 0.05); G3, AUC 0.67 and cutoff 14.3 kg (P < 0.01); and G4, AUC 0.63 and cutoff 11.5 kg (P < 0.05). CONCLUSION: A pre-pregnancy BMI > 30.0 kg/m2 was an independent risk factor for dystocia. For women with a pre-pregnancy BMI < 25.0 kg/m2, the risk of dystocia increases as a function of gestational weight gain. These findings could inform personalized preconception care for women to optimize maternal and neonatal health.

Preconception vitamin D intake and obstetric outcomes in women using assisted reproductive technology: the Japan Environment and Children's Study.

BACKGROUND: In reproductive medicine, vitamin D (VitD) is of particular interest because its deficiency has been linked to various infertility issues. Thus, preconception care, including appropriate VitD supplementation, is essential, especially in women using assisted reproductive technology (ART). Despite the therapeutic benefits of VitD, adverse events due to a high daily intake may influence obstetric outcomes. However, the effects of either low or high preconception VitD intake on obstetric outcomes, including the outcomes in women who used ART, remain unclear. Therefore, the aim of this study was to examine the association between pre-pregnancy daily VitD intake and obstetric outcomes in Japanese women, including those who conceived through ART. METHODS: Data were obtained from the Japan Environment and Children's study database comprising 92,571 women recruited between January 2011 and March 2014 in Japan. Participants were categorized into five quintiles according to pre-pregnancy VitD intake (Q1 and Q5 had the lowest and highest VitD intake, respectively) and stratified according to the use of ART. Multiple logistic regression was performed to identify the effects of pre-pregnancy VitD intake on preterm birth (PTB), low-birth weight infant (LBW), and small for gestational age (SGA). RESULTS: Using Q3 (middle VitD intake) as a reference, our analysis revealed that Q5 (highest VitD intake) showed an increased risk of LBW < 1500 g (adjusted odds ratio [aOR]: 1.09, 95% confidence interval [CI]: 1.00-1.18) and SGA (aOR: 1.26, 95% CI: 1.14-1.39) among women who conceived without ART. Among women who conceived with ART, we found that Q5 (highest VitD intake) showed an increased risk of PTB at < 37 weeks (aOR: 2.05, 95% CI: 1.27-3.31). CONCLUSION: The present study revealed that higher VitD intake before pregnancy may affect perinatal outcomes, particularly in women using ART. Our findings may facilitate personalized preconceptional counseling regarding VitD intake based on the method of conception, especially among women using ART.

Association of preconception dysmenorrhea with obstetric complications: the Japan Environment and Children's Study.

BACKGROUND: The association of maternal preconception dysmenorrhea, especially primary dysmenorrhea, with obstetric complications has not been clearly described. Therefore, we evaluated the association of preconception dysmenorrhea with obstetric complications while accounting for the presence of pelvic pathologies. METHODS: We analyzed the data of women with singleton live births at and after 22 weeks of gestation enrolled in the Japan Environment and Children's Study, a nationwide birth cohort study, between 2011 and 2014. Participants with psychological disorders were excluded. Preconception dysmenorrhea, identified in the medical record transcripts, was categorized into mild dysmenorrhea (MD) and severe dysmenorrhea (SD). Furthermore, excluding those who had pelvic pathologies via self-reported questionnaires (endometriosis, adenomyosis, and uterine myomas) with MD and SD, preconception dysmenorrhea was categorized into mild primary dysmenorrhea (MPD) and severe primary dysmenorrhea (SPD), respectively. Using multiple logistic regression, adjusted odds ratios (aORs) for obstetric complications, including preterm birth (PTB) before 37 weeks and 34 weeks, small-for-gestational-age infants, preterm premature rupture of membrane, and hypertensive disorders of pregnancy, were calculated (considering confounders) in women with (1) MD or SD and (2) MPD or SPD. Women without preconception dysmenorrhea were used as a reference. RESULTS: A total of 80,242 participants were analyzed. In women with SD, the aOR for PTB before 37 weeks was 1.38 (95% confidence interval [CI] 1.10, 1.72). In women with SPD, the aOR for PTB before 37 weeks was 1.32 (95% CI 1.02, 1.71). There was no association between women with MD or MPD and obstetric complications. CONCLUSIONS: SD and SPD are significantly associated with an increased incidence of PTB before 37 weeks. Care providers should provide proper counseling regarding the association between preconception dysmenorrhea and obstetric complications. Optimal management of pregnant women with preconception dysmenorrhea to reduce the incidence of PTB should be elucidated in further studies, with detailed clinical data of pelvic pathologies.

Effect of gestational weight gain on preeclampsia among underweight women: A single tertiary referral center study in Japanese women.

AIM: To examine the effect of weight gain during pregnancy on preeclampsia among women with a prepregnancy body mass index < 18.5 kg/m2 . METHODS: This retrospective cohort study included 479 Japanese women with singleton pregnancies and a prepregnancy body mass index < 18.5 kg/m2 , who gave birth between 2013 and 2019 at Ohta Nishinouchi Hospital. The study included 22 (18 with preeclampsia and four with gestational hypertension) and 457 patients with and without hypertensive disorders of pregnancy, respectively. RESULTS: The prevalence of hypertensive disorders of pregnancy and preeclampsia was 4.6% and 3.8%, respectively. With weight gain during pregnancy (continuous variable) set as a reference, multiple logistic regression revealed that excessive weight gain during pregnancy increased the risk of preeclampsia (adjusted odds ratio: 1.13, 95% confidence interval: 1.00-1.28, p < 0.05) and hypertensive disorders of pregnancy (adjusted odds ratio: 1.15, 95% confidence interval: 1.03-1.29, p < 0.05). Based on receiver operating characteristic curve analyses (area under the curve 0.65, 95% confidence interval: 0.50-0.80; p < 0.05), we determined the cutoff value of weight gain during pregnancy for the occurrence of preeclampsia among women with body mass index < 18.5 kg/m2 to be 13.0 kg, with sensitivity and specificity of 0.50 and 0.78, respectively. CONCLUSION: This study indicates that excessive weight gain during pregnancy increases preeclampsia risk among underweight women and provides new recommendations for weight gain during pregnancy for such women. Further research regarding the pathogenesis of preeclampsia for underweight women is warranted.

Association of placenta previa with placental size in Japanese women: A study from a single tertiary referral center.

AIM: The effect of placenta previa on age-specific placental size has not yet been elucidated. This study aimed to examine the effect of placenta previa on the Japanese standardized z-scores of placental size. METHODS: This retrospective cohort study included Japanese participants from Ohta Nishinouchi Hospital with single pregnancies who gave birth during 2013-2019. The participants were categorized into two groups based on the presence or absence of placenta previa. Multiple linear regression analyses were used to identify the association of placenta previa with the z-score of placental size, after adjusting for factors, such as maternal smoking status, maternal age, assisted reproductive technology, myoma uteri, uterine anomaly, maternal hypertension at the time of pregnancy, and body mass index before pregnancy. RESULTS: A total of 4071 Japanese women (76 with placenta previa and 3995 without placenta previa) were identified. Placenta previa significantly increased the placental weight z-score (partial regression coefficient: 0.44, 95% confidence interval 0.10-0.70, p < 0.001). CONCLUSION: Placenta previa increased the age-specific placental size. Further studies are required to examine whether placenta previa is associated with the risk of obstetrics complications related to the placental size.

Age at menarche and risk of adverse obstetric outcomes during the first childbirth in Japan: The Japan Environment and Children's Study.

AIM: Age at menarche is used as a risk indicator of gestational diabetes mellitus, preterm birth, and fetal growth. However, little is known regarding the age impact on obstetric outcomes among nulliparous women. This study investigated whether menarche age was correlated with obstetric outcomes among nulliparous women. METHODS: We analyzed the data obtained for 37 645 singleton pregnancies between 2011 and 2014 in the Japan Environment and Children's Study. Age at menarche was categorized into the ≤9-, 10-, 11-, 12-, 13-, 14-, and ≥15-year-old groups (n = 363, 3155, 8390, 11 164, 6713, 5446, and 2414, respectively). We calculated the relative risk for cases of preterm birth <37 weeks, low birthweight <2500 g, small for gestational age, early and late-onset hypertension disorders of pregnancy, and early- and late-diagnosed (diagnosed < or ≧ 24 weeks) gestational diabetes mellitus using a reference of 12 years at menarche. RESULTS: Women with an age at menarche ≤9 years showed an increased incidence of developing early-diagnosed gestational diabetes mellitus (relative risk: 2.42; 95% confidence interval: 1.05-5.60). A high body mass index before pregnancy increased the risk of developing gestational diabetes mellitus. CONCLUSIONS: Age at menarche helped in assessing the risk of early-diagnosed gestational diabetes mellitus among nulliparous women. Future studies are needed to clarify the underlying mechanisms. This study is the first to use data from the largest prospective birth cohort study of Japan and to investigate the relationship between menarche age and obstetric outcomes among nulliparous women.

Maternal disease activity and serological activity as predictors of adverse pregnancy outcomes in women with systemic lupus erythematosus: a retrospective chart review.

PURPOSE: To evaluate the association between disease activity, serological activity, and adverse pregnancy outcomes (APOs) in women with systemic lupus erythematosus (SLE) and determine the cut-off values of complements to predict APOs in live birth cases. METHODS: This retrospective chart review included pregnant women with SLE who had singleton live births after 22 weeks between 2006 and 2020. First trimester maternal disease activity was assessed for SLE onset during pregnancy, antiphospholipid syndrome, SLE pregnancy disease activity index (SLEPDAI), disease flare-ups, lupus nephritis, pancytopenia, and daily prednisolone dosage. Serological activity was assessed for autoantibodies and complements. APOs included preterm birth (PTB), low birth weight infants, small-for-gestational age infants, preterm premature rupture of membranes, and preeclampsia (PE). Chi-square and Fisher's exact tests were used to compare categorical variables; a receiver-operating characteristic analysis was performed to calculate the cut-off values of complements to predict APOs. RESULTS: Fifty-two participants met the inclusion criteria. The incidence of PTB and PE was associated with a high SLEPDAI (p < 0.001, p = 0.001), disease flare-ups (p = 0.007, p < 0.001), lupus nephritis (p = 0.020, p = 0.012), anti-dsDNA antibodies (p = 0.047, p = 0.016), anti-SSA antibodies (p = 0.003, p = 0.004), low CH 50 (p < 0.001, p < 0.001), low C3 (p < 0.001, p < 0.001), and low C4 (p < 0.001, p = 0.001), respectively. The cut-off values of C4 to predict PTB and PE were 13.0 mg/dL (higher than the normal lowest limit). CONCLUSION: High maternal disease activity and high serological activity in the first trimester in women with SLE are significantly associated with APOs. Proper disease control and close management for hypocomplementemia are required for better perinatal outcomes.

Effects of acute tocolysis using ritodrine hydrochloride on foetal heart rate patterns in intrauterine foetal resuscitation: a retrospective, single-centre observational study.

No consistent recommendations concerning the preferred tocolytic agents for intrauterine foetal resuscitation are available. We evaluated the effects of acute tocolysis (AT) using ritodrine hydrochloride on foetal heart rate (FHR) patterns and neonatal outcomes. We retrospectively analysed the data of patients undergoing emergency caesarean section because of non-reassuring foetal status indicated by foetal scalp electrodes. Patients were classified into AT (ritodrine hydrochloride approximately 500 µg/min) and control groups with 15 and 12 participants, respectively. FHR patterns, Apgar scores, umbilical arterial analysis, and neonatal admission were compared. All participants had FHR category II; decelerations disappeared in all foetuses in the AT group, with no significant difference in neonatal outcomes. The AT group had a higher baseline FHR and lower short-term FHR variability than the control group, indicating foetal autonomic responses. Further studies are needed to clarify the effects of AT on FHR patterns, neonatal outcomes, and foetal and neonatal autonomic responses.Impact statementWhat is already known on this subject? The usefulness of acute tocolysis using ritodrine hydrochloride has been well-documented in several studies; however, such an application often induces side effects, such as maternal tachycardia, palpitations, and tremors.What the results of this study add? The short-term administration of ritodrine hydrochloride eliminated decelerations, with no significant difference in neonatal outcomes in pregnant women with foetal heart rate category II. Meanwhile, there were higher foetal heart rate and lower short-term foetal heart rate variability in pregnant women administered with ritodrine hydrochloride, indicating foetal autonomic responses.What the implications are of these findings for clinical practice and/or further research? Ritodrine hydrochloride administration, even for short-term, appears to be associated with foetal autonomic responses. Further studies with stratification of patient groups based on the severity and aetiology of non-reassuring foetal status, including pregnant women with foetal category III, would elucidate the risk and benefit of acute tocolysis using ritodrine hydrochloride, based on foetal heart rate patterns, neonatal outcomes, and foetal and neonatal autonomic responses.

Association between maternal ritodrine hydrochloride administration during pregnancy and childhood wheezing up to three years of age: The Japan environment and children's study.

BACKGROUND: The effects of maternal ritodrine hydrochloride administration (MRA) during pregnancy on fetuses and offspring are not entirely clear. The present study aimed to evaluate the association between MRA and childhood wheezing using data from a nationwide Japanese birth cohort study. METHODS: This study analyzed the data of the participants enrolled in the Japan Environment and Children's Study, a nationwide prospective birth cohort study, between 2011 and 2014. Data of women with singleton live births after 22 weeks of gestation were analyzed. The participants were divided according to MRA status. Considering childhood factors affecting the incidence of wheezing, including smoking environment and childhood viral infections, a logistic regression model was used to calculate odds ratios for "wheezing ever," diagnosis of asthma in the last 12 months, and "asthma ever" in women with MRA, with women who did not receive MRA as the reference. Additionally, participants were stratified by term births, and odds ratios for outcomes were calculated using a logistic regression model. RESULTS: A total of 68,123 participants were analyzed. The adjusted odds ratio for wheezing was 1.17 (95% confidence interval, 1.12-1.22). The adjusted odds ratios for the other outcomes did not significantly increase after adjusting for childhood factors. The same tendency was confirmed after excluding women with preterm births. CONCLUSION: MRA was associated with a slightly increased incidence of childhood wheezing up to three years, irrespective of term or preterm birth status. It is important that perinatal physicians consider the potential effects of MRA on the offspring's childhood health.

Labor dystocia and risk of histological chorioamnionitis and funisitis: a study from a single tertiary referral center.

BACKGROUND: Intrauterine inflammation affects short- and long-term neonatal outcomes. Histological chorioamnionitis and funisitis are acute inflammatory responses in the fetal membranes and umbilical cord, respectively. Although labor dystocia includes a potential risk of intrauterine inflammation, the risk of histological chorioamnionitis and funisitis of labor dystocia has not been evaluated yet. This study aimed to examine the association between labor dystocia and risk of histological chorioamnionitis and funisitis. METHODS: In this retrospective cohort study, the cases who underwent histopathological examinations of the placenta and umbilical cord at Fukushima Medical University Hospital, Japan, between 2015 and 2020, were included. From the dataset, the pathological findings of the patients with labor dystocia and spontaneous preterm birth were reviewed. Based on the location of leukocytes, the inflammation in the placenta (histological chorioamnionitis) and umbilical cord (funisitis) was staged as 0-3. Multiple logistic regression analysis was performed to evaluate the risk of histological chorioamnionitis, histological chorioamnionitis stage ≥2, funisitis, and funisitis stage ≥2. RESULT: Of 317 women who met the study criteria, 83 and 144 women had labor dystocia and spontaneous preterm birth, respectively, and 90 women were included as controls. Labor dystocia was a risk factor for histological chorioamnionitis (adjusted odds ratio, 6.3; 95% confidential interval, 1.9-20.5), histological chorioamnionitis stage ≥2 (adjusted odds ratio, 6.0; 95% confidence interval, 1.7-21.8), funisitis (adjusted odds ratio, 15.4; 95% confidence interval, 2.3-101.3), and funisitis stage ≥2 (adjusted odds ratio, 18.5; 95% confidence interval, 2.5-134.0). Spontaneous preterm birth was also a risk factor for histological chorioamnionitis (adjusted odds ratio, 3.7; 95% confidence interval, 1.7-7.8), histological chorioamnionitis stage ≥2 (adjusted odds ratio, 3.0; 95% confidence interval, 1.2-7.9), and funisitis (adjusted odds ratio, 6.6; 95% confidence interval, 1.4-30.6). However, the adjusted odds ratio was smaller in spontaneous preterm births than in labor dystocia. CONCLUSION: Labor dystocia is a risk factor for severe histological chorioamnionitis and funisitis. Further studies are required to evaluate the effects of histological chorioamnionitis and funisitis on long-term neonatal outcomes.

Maternal sleep duration and neonatal birth weight: the Japan Environment and Children's Study.

BACKGROUND: The adequate maternal sleep duration required for favorable obstetric outcomes is unknown. We evaluated the association between maternal sleep duration and low birth weight infants, small for gestational age infants, and macrosomia. METHODS: Participants enrolled in the Japan Environment and Children's Study, a nationwide birth cohort study, with singleton pregnancies after 22 weeks, who gave birth between 2011 and 2014 were enrolled and categorized into five groups according to maternal sleep duration during pregnancy: < 6.0 h, 6.0-7.9 h, 8.0-8.9 h, 9.0-9.9 h, and 10.0-12.0 h. We evaluated the association between maternal sleep duration and the incidence of low birth weight infants (< 2500 g), very low birth weight infants (< 1500 g), small for gestational age infants, and macrosomia (> 4000 g), with women with maternal sleep duration of 6.0-7.9 h as the reference, using a multiple logistic regression model. RESULTS: In total, 82,171 participants were analyzed. The adjusted odds ratios (95% confidence intervals) for low birth weight infants in women with maternal sleep duration of 9.0-9.9 h and 10.0-12.0 h and for small for gestational age infants in women with maternal sleep duration of 9.0-9.9 h were 0.90 (0.83-0.99), 0.86 (0.76-0.99), and 0.91 (0.82-0.99), respectively, before adjusting for excessive gestational weight gain. No significant association was observed between maternal sleep duration and these outcomes after adjusting for excessive gestational weight gain. Among women with appropriate gestational weight gain, the adjusted odds ratios (95% confidence intervals) for low birth weight infants and for small for gestational age infants with sleep duration of 9.0-9.9 h were 0.88 (0.80-0.97) and 0.87 (0.78-0.97), respectively. CONCLUSIONS: Maternal sleep duration of 9.0-9.9 h was significantly associated with the decreased incidence of low birth weight infants and small for gestational age infants in pregnant women with appropriate gestational weight gain, compared with that of 6.0-7.9 h. Care providers should provide proper counseling regarding the association between maternal sleep duration and neonatal birth weight and suggest comprehensive maternal lifestyle modifications to prevent low birth weight and small for gestational age infants.

Preventing recurrent preterm birth with 125 mg of 17-alpha-hydroxyprogesterone caproate.

AIM: There is strong evidence that weekly intramuscular (IM) injections of 250 mg of 17-alpha-hydroxyprogesterone caproate (17-OHPC) reduce the risk of recurrent preterm birth (PTB); however, whether a lower dose of 17-OHPC could reduce the risk of recurrent PTB remains unclear. This study aimed to assess whether 125 mg of 17-OHPC reduces recurrent PTB among women with a prior singleton spontaneous PTB and cervical length >25 mm. METHODS: This retrospective cohort study at a tertiary-care medical center in Japan included women with a prior singleton spontaneous PTB between 20 and 36 weeks' gestation and cervical length >25 mm, between 2008 and 2018. Primary outcomes were PTB <37 and <34 weeks' gestation. We calculated the adjusted odds ratio (aOR) and 95% confidence interval (CI) using a multiple logistic regression model. Gestational age at delivery was compared using the Kaplan-Meier survival curve and log-rank test. RESULTS: Overall, 173 women met the inclusion criteria. Eighty-four women received weekly injections of 125 mg of 17-OHPC, and 89 did not. Treatment with 125 mg of 17-OHPC significantly reduced the risk of recurrent spontaneous PTB <37 (aOR: 0.156 [95% CI: 0.049-0.497]) and <34 weeks' gestation (aOR: 0.156 [95% CI: 0.049-0.497]). The mean delivery gestational age was also significantly longer in the 17-OHPC group (log-rank p = 0.005). CONCLUSIONS: In this study population, weekly IM injections of 125 mg of 17-OHPC reduced the risk of recurrent PTB <37 and <34 weeks' gestation.

Effect of gestational weight gain on placental weight: A single tertiary referral center study of Japanese women.

AIM: The effect of gestational weight gain on placental weight has not been elucidated. We aimed to examine the effect of body weight gain during pregnancy on the Japanese standardized z-score of placental weight, based on the pre-pregnancy body mass index. METHODS: This retrospective cohort study included Japanese women with singleton pregnancies who gave birth during 2013-2019 at Ohta Nishinouchi Hospital. Participants (n = 3610) were categorized by their pre-pregnancy body mass index: G1 (<18.5 kg/m2 ), G2 (18.5 to <20.0 kg/m2 ), G3 (20.0 to <23.0 kg/m2 ), G4 (23.0 to <25.0 kg/m2 ), and G5 (≥25.0 kg/m2 ). Multiple linear regression analysis was used to identify associations between insufficient or excessive gestational weight gain in each body mass index category and z-score of placental weight, with adjustments for maternal age, assisted reproductive technology, and maternal pre-pregnancy conditions, such as hypertension, diabetes mellitus, myoma uteri, and uterine anomalies. RESULTS: Among the 3610 women assessed, 479, 692, 1292, 435, and 711 were in G1-G5, respectively. In G1, G3, and G4, excessive weight gain increased the placental weight z-score ([B: 0.50, 95% confidence interval [CI]: 0.23-0.76], [B: 0.19, 95% CI: 0.19-0.33], and [B: 0.18, 95% CI: 0.10-0.26]). Insufficient weight gain decreased the placental weight z-score in G3 (B: -0.19, 95% CI: -0.33 to -0.06) and G4 (B: -0.21, 95% CI: -0.29 to -0.13) women. CONCLUSION: The effect of weight gain during pregnancy on placental size varies by pre-pregnancy body mass index. This result may guide personalized pre-conception counseling to improve the outcomes of offspring.

Association between pre-pregnancy calcium intake and hypertensive disorders during the first pregnancy: the Japan environment and children's study.

BACKGROUND: Determining the appropriate preconception care to reduce the occurrence of hypertensive disorder of pregnancy (HDP) remains a challenge in modern obstetrics. This study aimed to examine the association between pre-pregnancy calcium (Ca) intake and HDP in normotensive primiparas. METHODS: We used data from the Japan Environment Children's study (JECS), which is the largest birth cohort study. A total of 33,894 normotensive Japanese primiparas were recruited for JECS between January 2011 and March 2014. Participants were categorized into five groups according to pre-pregnancy Ca intake quintiles (Q1 and Q5 were the lowest and highest Ca intake groups, respectively) to compare their basic background and obstetrics outcome. Multiple logistic regressions were performed to identify the effect of pre-pregnancy Ca intake on HDP, early onset HDP, and late-onset HDP, using Ca intake thresholds of 500, 550, 650, 700, 1000, 1500, and 1500 mg. RESULTS: We found significant differences in maternal background among the Ca intake groups; in particular, there were more participants with low socioeconomic status, indicated by low education level and low household income, and smokers in the lowest Ca intake group. Multiple logistic regression did not show any significant difference with regard to HDP, early onset HDP, and late-onset HDP in each Ca intake threshold. CONCLUSIONS: Despite considerable recommendations concerning Ca intake for women of reproductive age, the present study indicates that pre-pregnancy Ca intake was not associated with an increased risk of new-onset hypertension among primiparas during pregnancy. Further studies examining the effect of other pre-pregnancy dietary factors on obstetric outcomes should be considered in the formulation of earlier preventive strategies for primiparas.