Association of a low chest-to-head circumference ratio with breech or transverse lie: the Japan Environment and Children's Study.

OBJECTIVE: We examined whether the chest-to-head circumference ratio at birth was associated with breech presentation and transverse lie. We also described the obstetric management of such pregnancies in the Japan Environment and Children's Study (JECS). METHODS: We performed a cross-sectional evaluation of data collected between January 2011 and March 2014 in a nationwide prospective birth cohort study, the JECS. We analyzed 83,822 non-anomalous singletons born at 34-41 weeks' gestation to mothers with no history of previous cesareans or uterine surgery. We defined low, normal (reference group), and high chest-to-head circumference ratios as <10th percentile, 10th to 90th percentiles, and >90th percentile, respectively. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for breech presentation and transverse lie. The timing and mode of delivery of such pregnancies were examined. RESULTS: Breech presentation was recorded in 2.6% and transverse lie in 0.2%. A low chest-to-head circumference ratio was associated with increased rate of breech presentation (5.2%; adjusted OR 2.36, 95% CI: 2.10-2.65) and transverse lie (0.3%; adjusted OR 2.33, 95% CI: 1.50-3.60), whereas a high ratio was linked to reduced breech presentation (1.1%; adjusted OR 0.51, 95% CI: 0.39-0.66). Subgroup analysis of children delivered by cesarean (n = 7971) showed a similar association, albeit with slightly reduced strength for breech presentation. Eighty-three percent of breech births and 46.3% of transverse lie births occurred at 37-38 weeks' gestation. Cesarean section was performed in 96.8% of breech presentations and 63.4% of transverse-lie ones. CONCLUSIONS: These findings imply that the fetal chest-to-head circumference ratio may influence presentation at birth.

Association between eating habits during adolescence and gestational diabetes: data from the Japan environment and children's study.

Purpose: It is difficult to change pre-pregnancy eating habits, yet establishing healthy eating habits before pregnancy is important for preventing gestational diabetes mellitus (GDM). This study aimed to examine whether the weight-loss behavior of avoiding between-meal and midnight snacking in teenagers is associated with a reduction in the risk of subsequent GDM. Methods: We used a dataset (jecs-an-20,180,131) from a nationwide, prospective birth cohort study, the Japan Environment and Children's Study (JECS). We included 89,227 (85.7% of the total) mother-infant pairs with live births. Participants in their second or third trimester were asked to report their weight-loss behavior during their teenage years. The prevalence of GDM was investigated. Differences in maternal characteristics were examined using chi-square tests. Crude and adjusted logistic regression models were constructed to assess the associations of various maternal characteristics with the weight-loss behavior of avoiding between-meal and midnight snacking during teenage years. Results: A total of 2,066 (2.3%) participants had GDM. Weight-loss behavior in teenagers was associated with a decreased risk of GDM. Among participants with normal weight or overweight prior to pregnancy, the adjusted odds ratios were 0.79 (95% confidence interval, 0.70-0.89) and 0.82 (95% confidence interval, 0.69-0.98), respectively. Conclusions: The results suggest that teenage weight-loss behaviors, such as avoiding between-meal and midnight snacking, are associated with a decreased risk of developing GDM. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01294-2.

Association between maternal cholesterol level during pregnancy and placental weight and birthweight ratio: data from the Japan Environment and Children's Study.

BACKGROUND: Placental weight to birthweight ratio (PW/BW ratio), or its inverse, is used as an indicator of placental efficiency. Past studies have shown an association between an abnormal PW/BW ratio and adverse intrauterine environment, however, no previous studies have examined the effect of abnormal lipid levels during pregnancy on PW/BW ratio. We aimed to evaluate the association between maternal cholesterol levels during pregnancy and placental weight to birthweight ratio (PW/BW ratio). METHODS: This study was a secondary analysis using the data from the Japan Environment and Children's Study (JECS). 81 781 singletons and their mothers were included in the analysis. Maternal serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels during pregnancy were obtained from participants. Associations between maternal lipid levels and placental weight and PW/BW ratio were assessed by regression analysis using restricted cubic splines. RESULTS: Dose-response relationships were observed between maternal lipid level during pregnancy and placental weight and PW/BW ratio. High TC and LDL-C levels were associated with heavy placental weight and high PW/BW ratio, i.e., inappropriately heavy placenta for birthweight. Low HDL-C level was also associated with inappropriately heavy placenta. Low TC and LDL-C levels were associated with low placental weight and low PW/BW ratio, i.e., inappropriately light placenta for birthweight. High HDL-C was not associated with PW/BW ratio. These findings were independent of pre-pregnancy body mass index and gestational weight gain. CONCLUSIONS: Abnormal lipid levels such as elevated TC and LDL-C, and low HDL-C level, during pregnancy were associated with inappropriately heavy placental weight.

Influence of chest/head circumference ratio at birth on obstetric and neonatal outcomes: The Japan environment and children's study.

OBJECTIVES: Some newborns that are not small-for-gestational-age (non-SGA, birthweight ≥10th percentile for a given gestational age) may have pathologic growth restrictions. This study examined the association of adverse obstetric and neonatal outcomes with chest/head circumference ratio at birth in non-SGA and SGA newborns. METHODS: This study was a cross-sectional evaluation of data from a nationwide prospective birth cohort study, the Japan Environment and Children's Study. We analyzed 93 690 non-anomalous singletons born at 34-41 gestational weeks. We defined low, normal, and high chest/head circumference ratio as <10th percentile, 10th-90th percentile, and >90th percentile, respectively, according to the internally constructed chest/head circumference percentile chart. Modified Poisson regression was used to estimate adjusted prevalence ratios (aPR) for the outcomes studied. RESULTS: Compared with non-SGA newborns with a normal ratio, those with a low ratio had an increased occurrence of low birthweight (1.75, 1.58-1.94 [aPR, 95% confidence interval]), cesarean delivery (1.34, 1.29-1.38), Apgar score <7 at 5 min (1.57, 1.14-2.17), respiratory complications (1.20, 1.04-1.39), and prolonged hospitalization (1.36, 1.30-1.42). In contrast, the high-ratio group had a lower rate of low birthweight (0.71, 0.59-0.86), cesarean delivery (0.82, 0.77-0.87), and prolonged hospitalization (0.83, 0.78-0.89). In SGA newborns, a low ratio was associated with increased aPRs for low birthweight, cesarean delivery, hypoglycemia, and prolonged hospitalization, whereas a high ratio showed no such association. CONCLUSIONS: Findings indicate that the chest/head circumference ratio at birth influence obstetric and neonatal outcomes regardless of the birthweight status.

Safety and feasibility of autologous cord blood infusion for improving motor function in young children with cerebral palsy in Japan: A single-center study.

INTRODUCTION: Cerebral palsy (CP) is the most prevalent motor disorder of childhood. It typically results from in utero or perinatal brain injury. Recently, it has been reported that autologous cord blood (ACB) infusion for children with CP improved gross motor function and brain connectivity, but unfortunately, it has never been tried in Japan. We conducted a pilot study of the infusing of ACB, which was delivered from private bank, in the children with CP to assess the safety and feasibility to the procedure as well as any effect in improving neurological function. METHODS: After demonstrating the induction of tissue regeneration in animal model studies conducted a single-arm pilot study of intravenous ACB infusion in 6 young Japanese children with CP (ages 1-6 years). Primary outcomes were safety assessed by vital signs, clinical symptoms, and blood and urinary examinations at baseline and 1 weeks, 1, 2 and 3 years after treatment. In addition, motor function evaluations, neurodevelopmental examinations, magnetic resonance imaging, and electroencephalography (EEG) were performed at the same time. RESULTS: Infusion was generally well-tolerated, although one patient experienced microhematuria 1 year after treatment and another one patient experienced febrile convulsion once 9 months after treatment. These events were transient, no relapse was seen during observation study. All patients improved a median of 6.8 points on the 1-year Gross Motor Functional Measure-66 (GMFM-66) scores, greater than predicted by age and severity. Furthermore, the 2-year and 3-year GMFM-66 scores were also greater than expected (median 6.2 points and 5.5 points, respectively). Overall scales and language-social scales of the developmental quotient (DQ) improved in 3 of 6 patients, who had greater changes in their GMFM-66 scores than the other cases after treatment. There were no significant correlations among the GMFM-66 scores, DQ, and infusion cell counts. CONCLUSION: ACB infusion was safe and feasible for clinical use in patients with CP. However, much more clinical study with larger numbers of patients and in-depth studies of treatment mechanism of CP are needed.

Real-world outcomes of the levonorgestrel-releasing intrauterine system for heavy menstrual bleeding or dysmenorrhea in Japanese patients: A prospective observational study (J-MIRAI).

OBJECTIVES: We collected real-world data on the safety and clinical outcomes of the levonorgestrel-releasing intrauterine system (LNG-IUS) for heavy menstrual bleeding and dysmenorrhea. STUDY DESIGN: This was a prospective, multicenter, single-cohort, open-label, post-authorization 12-month follow-up study of Japanese patients initiating the LNG-IUS for heavy menstrual bleeding and/or dysmenorrhea. The primary endpoint was the safety profile based on adverse events and adverse drug reactions (ADRs), including expulsions and abnormal bleeding, within 12 months of LNG-IUS insertion. Secondary endpoints included changes from baseline in menstrual blood loss based on bleeding days and dysmenorrhea graded on a visual analog scale (VAS). RESULTS: Of the 595 patients included, many had underlying conditions such as adenomyosis (39.5%), uterine leiomyoma (30.8%), or endometriosis (12.9%). The incidences of ADRs and serious ADRs were 59.7% and 0.3%, respectively. Frequently reported ADRs were metrorrhagia (48.9%), procedural pain (14.1%), and ovarian cyst (6.2%). The cumulative incidence of expulsions at 12 months was 8.7%. Risk factors for expulsion were obesity (body mass index ≥25 kg/m2), adenomyosis, and uterine cavity length ≥8 cm. The median [interquartile range] VAS score for dysmenorrhea improved from 46.5 [13.0-68.0] at insertion to 1.0 [0.0-13.0] at 12 months, and improvements were also observed in chronic pelvic pain and painful defecation. CONCLUSIONS: The LNG-IUS safely and effectively reduced dysmenorrhea, chronic pelvic pain, and painful defecation. Risk factors for expulsion suggest that patients with underlying organic disease should be monitored carefully when using the LNG-IUS. IMPLICATIONS: The LNG-IUS is an effective treatment for secondary dysmenorrhea with organic disease, and for the reduction of chronic pelvic pain; however, physicians should be aware of the increased risk of expulsion in patients with organic conditions.

Gestational weight gain mediates the effects of energy intake on birth weight among singleton pregnancies in the Japan Environment and Children's Study.

BACKGROUND: Extra energy intake is commonly recommended for pregnant women to support fetal growth. However, relevant data regarding variations in energy intake and expenditure, body mass index and gestational weight gain (GWG) are frequently not considered. This study aimed to investigate how energy intake during pregnancy and gestational weight gain (GWG) are associated with birth weight. METHODS: Early pregnant women were recruited into a Japanese nationwide prospective birth cohort study between 2011 and 2014. We analysed data of 89,817 mother-child pairs of live-born non-anomalous singletons after excluding births before 28 weeks or after 42 weeks. Energy intake during pregnancy was estimated from self-administered food frequency questionnaires (FFQ) and was stratified into low, medium, and high. Participants completed the FFQ in mid-pregnancy (mean 27.9 weeks) by recalling food consumption at the beginning of pregnancy. Effects of energy intake on birth weight and mediation by GWG were estimated using the Karlson-Holm-Breen method; the method separates the impact of confounding in the comparison of conditional and unconditional parameter estimates in nonlinear probability models. Relative risks and risk differences for abnormal birth size were calculated. RESULTS: Mean daily energy intake, GWG, and birth weight were 1682.1 (533.6) kcal, 10.3 (4.0) kg, and 3032.3 (401.4) g, respectively. 6767 and 9010 women had small-for-gestational-age and large-for-gestational-age infants, respectively. Relative to low energy intake, moderate and high intakes increased adjusted birth weights by 13 g and 24 g, respectively: 58 and 69% of these effects, respectively, were mediated by GWG. Compared with the moderate energy intake group, the low energy intake group had seven more women per 1000 women with a small-for-gestational-age birth, whereas the high energy intake group had eight more women per 1000 women with a large-for-gestational-age birth. CONCLUSION: GWG mediates the effect of energy intake on birth weight. All pregnant women should be given adequate nutritional guidance for optimal GWG and fetal growth.

Quality of Life of Japanese Dysmenorrhea/Heavy Menstrual Bleeding Patients Treated with Levonorgestrel Intrauterine Delivery System in a Real-World Setting.

INTRODUCTION: The present study collected 1-year follow-up patient-reported outcome data from Japanese women with dysmenorrhea and/or heavy menstrual bleeding (HMB) who underwent insertion of the levonorgestrel-releasing intrauterine system (LNG-IUS) 52 mg. We aimed to evaluate the quality of life (QOL) of Japanese women over the course of the investigational period. METHODS: This was a multicenter, non-interventional, prospective, single-cohort, post-marketing surveillance study (J-MIRAI). The primary outcome was the median change in the Menstrual Distress Questionnaire (MDQ) and Menorrhagia Multi-Attribute Scale (MMAS) scores from baseline to 3 and 12 months after LNG-IUS insertion, with decreasing and increasing scores, respectively, indicating improvement. The secondary outcomes were the statistical relationships between the MDQ and menstrual pain (measured by a visual analog scale, VAS), and between the MMAS and pictorial blood loss assessment chart (PBAC) scores by regression analysis. RESULTS: In total, 593 patients were evaluated; 376, 467, and 250 patients were diagnosed with dysmenorrhea, HMB, or both, respectively. The median MDQ score decreased significantly at 3 and 12 months after LNG-IUS insertion in both the premenstrual and menstrual periods (both p < 0.001 vs baseline), and the median MMAS score showed a similar improvement during the menstrual period. Changes in median MDQ and MMAS scores were observed regardless of patient background. Correlations between MDQ and menstrual pain (VAS) and between MMAS and PBAC scores were found (estimated regression coefficients 0.29 and - 0.15, respectively). CONCLUSION: The LNG-IUS contributed to improvements in the QOL of patients with dysmenorrhea, HMB, and both, regardless of patient background characteristics. TRIAL REGISTRATION: Registered at ClinicalTrials.gov (NCT02475356) on 18 June 2015.

Bleeding patterns of women with heavy menstrual bleeding or dysmenorrhoea using the levonorgestrel-releasing intrauterine system: results from a real-world observational study in Japan (J-MIRAI).

PURPOSE: To collect real-world safety and clinical outcome data on the levonorgestrel-releasing intrauterine system (LNG-IUS) for functional/organic heavy menstrual bleeding (HMB) and dysmenorrhoea in Japanese women (J-MIRAI). MATERIALS AND METHODS: In this prospective, multicentre, single-cohort, open-label, post-authorisation study, we assessed menstrual blood loss after LNG-IUS insertion by changes from baseline in pictorial blood loss assessment chart (PBAC) scores. Scores for the menorrhagia multi-attribute scale (MMAS) were collected for 12 months to assess quality of life. RESULTS: We included 47 patients with complete PBAC score and patient diary data. The median PBAC score before LNG-IUS insertion was 159.0, which decreased significantly to 6.0 at 12 months post-insertion; for patients with adenomyosis (n = 20), PBAC score decreased from 174.5 pre-insertion to 19.5 at 12 months. The number of patient-reported bleeding days was correlated with PBAC score ≥5. The proportion of women with prolonged bleeding decreased from 85.7% to 34.6% by the study's end. Some women reported no bleeding after the first 90-day reference period. The mean MMAS overall score significantly increased from 50.50 before insertion to 88.67 at 12 months. CONCLUSIONS: Japanese women with functional/organic HMB experienced substantial reductions in bleeding symptoms and improvements in quality of life after 12-month use of the LNG-IUS.

Peritoneal natural killer cell chemotaxis is decreased in women with pelvic endometriosis.

PROBLEM: NK cell and macrophage function are decreased in endometriosis, and the disease may involve reduced immune surveillance in the peritoneal cavity. NK cell cytotoxicity and migration ability (chemotaxis) are considered important; the former has been investigated, but the latter has not. METHOD OF STUDY: We compared chemotaxis of immunocompetent cells (NK cells, macrophages, T cells) in peritoneal fluid obtained during laparoscopy in 27 women with and 13 without endometriosis. Peripheral blood NK cells were also obtained by the peripheral blood antibody beads method. Micro-cultured cells were examined by time-lapse photography, and the mean migration speed per cell was calculated as the chemotaxis. We investigated the relationship between chemotaxis and endometriosis. RESULTS: NK cell chemotaxis was significantly lower in the endometriosis group. Macrophages and lymphocytes were not significantly different between the groups. During menstruation, NK cell chemotaxis decreased in both groups. Postmenstrual chemotaxis was increased significantly in women without endometriosis but remained low in women with endometriosis. The Revised-American Society for Reproductive Medicine score was not correlated with chemotaxis; in women with endometriosis, chemotaxis was decreased even at early stages. Peripheral blood NK cells showed no significant differences. CONCLUSIONS: In women with endometriosis, not only cytotoxicity but also chemotaxis by NK cells in peritoneal cavity is significantly decreased, and particularly chemotaxis is decreased throughout the menstrual cycle. Therefore, antigens in retrograde menstrual blood that enters the peritoneal cavity might be left unprocessed. Repetition of this immune process in the peritoneal cavity may lead to the onset and subsequent progression of endometriosis.

Perinatal Care Preparedness in Kochi Prefecture for When a Nankai Trough Earthquake Occurs: Action Plans and Disaster Liaisons for Pediatrics and Perinatal Medicine.

A Nankai Trough earthquake is highly likely to occur in near future, and perinatal medical resources and care in Kochi Prefecture may be insufficient after such an event. Therefore, we evaluated the medical and public health measures needed to prepare for caring for pregnant women in Kochi Prefecture in the aftermath of such an earthquake and the potential action plans for the prefecture. We estimated that immediately after an earthquake, approximately 30 pregnant women will require urgent medical treatment, most of whom will be in the prefectural capital, Kochi City, and perinatal medical care in Kochi City may be insufficient. Therefore, we used the projected flooding areas to divide Kochi City and its surrounding areas into 3 areas and allocated at least one Disaster Liaison for Pediatrics and Perinatal Medicine (DLPPM) to each disaster base hospital in those 3 areas. In a disaster, the DLPPMs will serve as key individuals in their respective areas and coordinate the allocation of medical care. A DLPPM will be allocated also within the Disaster Medical Response Headquarters of Kochi Prefecture and be responsible for overseeing perinatal care in the whole of Kochi Prefecture. Our study shows that estimating the number of affected pregnant women and requirement for perinatal medical care is an effective way to prepare realistic disaster measures and to enable a specific plan to be formulated for effective allocation and management of DLPPMs. We believe that our system can serve as a model in perinatal disaster medicine.

Exogenous oxytocin used to induce labor has no long-term adverse effect on maternal-infant bonding: Findings from the Japan Environment and Children's Study.

BACKGROUND: This study investigated the association between exogenous oxytocin use for labor induction and adverse maternal-infant bonding (MIB). METHODS: Data on 19 700 mother-infant pairs were collected, in which the infants were live-birth singletons, born in cephalic position and at >37 weeks of gestation; the drug used to induce labor was noted. Between 2011 and 2014, Japanese pregnant women were enrolled in a nationwide prospective birth cohort study, the Japan Environment and Children's Study. The Japanese version of the Mother-to-infant Bonding Scale (MIBS-J) was administered and demographic information was collected through medical record transcripts. MIBS-J scores were obtained at one month, six months, and one year after delivery. We estimated the risk of adverse MIB between use of oxytocin and other methods for labor induction using multiple linear regression analyses; interaction and mediation analyses to assess the relationship among MIBS-J scores also followed. RESULTS: Exogenous oxytocin was used during labor on 15 252 (77.4%) participants. After adjusting for confounders, there were no significant differences in adverse MIB between groups for which exogenous oxytocin was used and not used for labor induction. LIMITATION: The MIBS-J scores at one and six months were compiled using five instead of 10 questions. Moreover, detailed information was unavailable; for example, the questionnaire did not ask for the dosage and timing of the drugs used to induce labor. CONCLUSIONS: Exogenous oxytocin is a safe and vital drug to induce labor, and has been shown in this study to have no significant impact on long-term adverse MIB.

Association between nausea and vomiting of pregnancy and postpartum depression: the Japan Environment and Children's Study.

OBJECTIVE: Postpartum depression (PPD) is a global emotional distress that affects women and their offspring regardless of their culture. The association between nausea and vomiting of pregnancy (NVP) and PPD has been widely described only for the severe form of NVP. We aimed to assess the relationship between PPD and NVP with regards to its severity. METHODS: Data from the Japan Environment and Children's Study (JECS), a birth cohort study, were analyzed. PPD was assessed using the Edinburgh Postnatal Depression Scale (EPDS). Multiple logistic regression models were performed to assess the association between NVP and PPD. RESULTS: Out of the 80,396 women included in the study 14% had PPD. Among them 4,640 (42.1%) had mild NVP; 3,295 (29.9%) had moderate NVP whereas 1,481 (13.4%) had severe NVP. All forms of NVP were associated with PPD and the association gradually increased with the severity of NVP symptoms with odd ratio (OR): 1.26; 95% confidence interval (CI): 1.18-1.35 for mild, OR: 1.28; 95% CI: 1.19-1.38 for moderate and OR: 1.54; 95% CI: 1.42-1.68 for severe NVP. CONCLUSION: Japanese women with NVP were more susceptible to develop PPD and the more severe the NVP symptoms were, the greater the risk of PPD. Thus, close monitoring of NVP-affected women is recommended.

Dose-response relationships between maternal urinary cotinine and placental weight and ratio of placental weight to birth weight: The Japan Environment and Children's Study.

INTRODUCTION: Studies on the relationship between maternal self-reported smoking status and placental weight report inconsistent results. This study examined the relationships between maternal urinary cotinine concentration and placental weight and the ratio of placental weight to birth weight (PW/BW ratio). The study also examined the relationship between maternal smoking status, as determined by cotinine concentration, with placental weight and with PW/BW ratio, stratified by sex of offspring. METHODS: Our analysis used information of 91,049 mother-child pairs enrolled in the Japan Environment and Children's Study. Maternal urinary cotinine concentration was quantified (during the second or third trimester) with high-performance liquid chromatography-tandem mass spectrometry. Using restricted cubic splines, placental weight and PW/BW ratio were plotted against natural log-transformed cotinine concentration. Taking cotinine levels of <0.17 ng/mL, 0.17 to <21.5 ng/mL (natural log-transformed values, -1.77 to 3.07), and ≥21.5 ng/mL as indicative of non-smokers, passive smokers, and active smokers, respectively, the relationships between maternal smoking status and placental weight and PW/BW ratio were examined, adjusting for confounders. RESULTS: Placental weight and PW/BW ratio increased with increasing cotinine concentration. After cotinine reached a certain concentration, the placental weight decreased in male offspring whereas it plateaued in female offspring. Compared with not smoking, active smoking during pregnancy significantly increased placental weight and PW/BW ratio. CONCLUSION: Placental weight responded as an inverted U-shape whereas the PW/BW ratio followed a J-shape with increasing maternal urinary cotinine concentration measured during pregnancy, suggesting exposure to tobacco smoke induces a disproportionate reduction in fetal growth. The effect of tobacco smoke on placental growth varied by sex of offspring.

Sphingosine 1-Phosphate (S1P) in the Peritoneal Fluid Skews M2 Macrophage and Contributes to the Development of Endometriosis.

Sphingosine 1-phosphate (S1P), an inflammatory mediator, is abundantly contained in red blood cells and platelets. We hypothesized that the S1P concentration in the peritoneal cavity would increase especially during the menstrual phase due to the reflux of menstrual blood, and investigated the S1P concentration in the human peritoneal fluid (PF) from 14 non-endometriosis and 19 endometriosis patients. Although the relatively small number of samples requires caution in interpreting the results, S1P concentration in the PF during the menstrual phase was predominantly increased compared to the non-menstrual phase, regardless of the presence or absence of endometriosis. During the non-menstrual phase, patients with endometriosis showed a significant increase in S1P concentration compared to controls. In vitro experiments using human intra-peritoneal macrophages (MΦ) showed that S1P stimulation biased them toward an M2MΦ-dominant condition and increased the expression of IL-6 and COX-2. An in vivo study showed that administration of S1P increased the size of the endometriotic-like lesion in a mouse model of endometriosis.

Lack of concern about body image and health during pregnancy linked to excessive gestational weight gain and small-for-gestational-age deliveries: the Japan Environment and Children's Study.

BACKGROUND: Pregnant women in Japan express various reasons for limiting gestational weight gain (GWG). We aimed to identify and characterise groups where the women share common reasons to limit GWG and to examine how these groups are associated with inappropriate GWG and abnormal foetal size. METHODS: We prospectively studied information from the Japan Environment and Children's Study (JECS) on 92,539 women who gave birth to live singletons from 2011 through 2014. Pregnant women were recruited during early pregnancy. Their reasons for limiting GWG and other information were collected through self-reported questionnaires and medical records. We applied latent class analysis to group the women based on their reported reasons. We used multinomial logistic regression to compare the risks of inappropriate (inadequate and excessive) GWG and abnormal foetal size (determined by new-born weight for gestational age) between the identified groups. RESULTS: We identified three groups: Group 1 (76.7%), concerned about delivery and new-born health (health-conscious women); Group 2 (14.5%), concerned about body shape, delivery, and new-born health (body-shape- and health-conscious women); and Group 3 (8.8%), women without strong reasons to limit GWG (women lacking body-shape and health consciousness). Compared with Group 1 members, Group 2 members tended to be younger, have lower pre-pregnancy weight, be unmarried, be nulliparous, have practiced weight loss before pregnancy, and not have chronic medical conditions. Group 3 members tended to be less educated, unmarried, multiparous, smokers, and have a higher prevalence of pre-pregnancy underweight and previous caesarean delivery. Relative to Group 1, Group 2 had a lower unadjusted risk for inadequate GWG (relative risk ratio [RRR] = 0.86, 95% CI: 0.81-0.90) and large-for-gestational-age birth (RRR = 0.91, 95% CI 0.86-0.97), whereas Group 3 had a higher unadjusted risk for excessive GWG (RRR = 1.36, 95% CI: 1.29-1.43) and small-for-gestational-age (SGA) births (RRR = 1.15, 95% CI: 1.05-1.25). CONCLUSIONS: In this Japanese nationwide birth cohort study, pregnant women who were less conscious about body shape and health had complex risks for excessive GWG and SGA birth. Health care providers should consider a woman's perception of GWG when addressing factors affecting GWG and foetal growth.

Association between maternal hemoglobin concentration and placental weight to birthweight ratio: The Japan Environment and Children's Study (JECS).

INTRODUCTION: Past studies have shown that maternal anemia is associated with a heavy placenta or a higher placental weight/birthweight (PW/BW) ratio. Although these findings suggest a non-linear relationship between maternal hemoglobin concentration and PW/BW ratio, this relationship has not been closely examined. METHODS: We evaluated 83,354 singletons and their mothers in a nation-wide birth cohort study, the Japan Environment and Children's Study (JECS). The associations between maternal hemoglobin concentration and placental weight, birthweight, and PW/BW ratio were assessed. RESULTS: Mean placental weight was significantly higher in women with moderate or severe anemia (576 [183] g), but not in women with elevated hemoglobin levels (564 [117] g), compared with in women with normal hemoglobin levels (560 [115] g). In contrast, mean PW/BW ratio was significantly higher in women with moderate or severe anemia (0.190 [0.049]) or elevated hemoglobin levels (0.189 [0.033]) than in women with normal hemoglobin levels (0.185 [0.033]). In a regression analysis with cubic spline, a U-shaped relationship was found between maternal hemoglobin concentration and PW/BW ratio. DISCUSSION: We demonstrated non-linear and concentration-dependent relationships between maternal hemoglobin concentration and placental weight, birthweight, and PW/BW ratio. Although the mechanisms underlying these associations are not fully understood, we suggest that low or elevated hemoglobin concentration may lead to placental compensatory hypertrophy and fetal growth restriction. Prevention and proper management of anemia before and during pregnancy are important for a well-functioning placenta and favorable fetal growth.

Induction of regional chemokine expression in response to human umbilical cord blood cell infusion in the neonatal mouse ischemia-reperfusion brain injury model.

Regenerative medicine using umbilical cord blood (UCB) cells shows promise for the treatment of cerebral palsy. Although the efficacy of this therapy has been seen in the clinic, the mechanisms by which UCB cells interact and aid in the improvement of symptoms are not clear. We explored the chemokine expression profile in damaged brain tissue in the neonatal mouse ischemia-reperfusion (IR) brain injury model that was infused with human UCB (hUCB) cells. IR brain injury was induced in 9-day-old NOD/SCID mice. hUCB cells were administered 3 weeks post brain injury. Chemokine expression profiles in the brain extract were determined at various time points. Inflammatory chemokines such as CCL1, CCL17, and CXCL12 were transiently upregulated by 24 hours post brain injury. Upregulation of other chemokines, including CCL5, CCL9, and CXCL1 were prolonged up to 3 weeks post brain injury, but most chemokines dissipated over time. There were marked increases in levels of CCL2, CCL12, CCL20, and CX3CL1 in response to hUCB cell treatment, which might be related to the new recruitment and differentiation of neural stem cells, leading to the induction of tissue regeneration. We propose that the chemokine expression profile in the brain shifted from responding to tissue damage to inducing tissue regeneration. hUCB cell administration further enhanced the production of chemokines, and chemokine networks may play an active role in tissue regeneration in neonatal hypoxic-ischemic brain injury.

Severity of Nausea and Vomiting in Singleton and Twin Pregnancies in Relation to Fetal Sex: The Japan Environment and Children's Study (JECS).

BACKGROUND: Some studies have indicated that female birth and multiple births were risk factors for nausea and vomiting during pregnancy (NVP). The results, however, were conflicting. Our study was conducted to evaluate the association of maternal NVP with fetal sex in singleton and twin pregnancies. METHODS: We used the data set from a birth cohort study, the Japan Environment and Children's Study (JECS). In the self-administered questionnaire, participants were asked whether they experienced NVP prior to 12 gestational weeks. Main outcome measures were the presence of NVP and severity of NVP. We estimated the association of fetal sex and birth plurality with NVP using logistic regression analysis, followed by interaction analysis. RESULTS: Of 91,666 women, 75,828 (82.7%) experienced at least some symptoms of NVP and 10,159 (11.1%) experienced severe NVP. Women with female pregnancies and twin pregnancies had higher odds for the presence of NVP and severe NVP compared to women with male pregnancies and singleton pregnancies, respectively. Moreover, of mothers with twin pregnancies, higher odds for the presence of NVP and severe NVP were reported when one or both infants were female, compared to those in which both infants were male. There was no significant interaction between fetal sex and birth plurality. CONCLUSIONS: Female sex birth and multiple births are risk factors for the presence of NVP, and especially for severe NVP without interaction. These findings suggest that a factor abundant in the female fetus associates with the severity of NVP.