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 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.

Association between the ratio of placental weight to birthweight and the risk of neurodevelopmental delay in 3-year-Olds: The Japan environment and Children's study.

INTRODUCTION: The ratio of placental weight to birthweight (PW/BW ratio) is well known as a simple indicator of the prenatal intrauterine environment and placental functioning. We assessed the impact of PW/BW ratio on the risk of neurodevelopmental delay in 3-year-olds. METHODS: We used data of 71 205 mother-child pairs enrolled in the Japan Environment and Children's Study. Low PW/BW ratio was defined as a PW/BW ratio below the 10th percentile of the study population, high PW/BW ratio was defined as above the 90th percentile, and normal PW/BW ratio was defined as between the low and high PW/BW ratio. Neurodevelopment was assessed using the Japanese translation of the Ages and Stages Questionnaires, third edition. Associations between PW/BW ratio and risk of developmental delay were examined using multivariable models. RESULTS: Compared with boys in the normal PW/BW group, boys in the high PW/BW group had higher risk for developmental delays in all domains except fine motor skills (communication: adjusted risk ratio [aRR], 1.17; 95% confidence interval [CI], 1.04-1.33; gross motor skills: aRR, 1.28; 95% CI, 1.13-1.46; problem solving: aRR, 1.20; 95% CI, 1.09-1.31; personal-social: aRR, 1.26; 95% CI, 1.10-1.43), and boys in the low PW/BW group also had higher risk for developmental delays in some domains. For girls, there was almost no association between PW/BW ratio and developmental delay. DISCUSSION: An unbalanced PW/BW ratio, especially high PW/BW ratio, might indicate intrauterine suboptimality, which affects child neurodevelopment in a sex-specific manner.

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.

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.

Breastfeeding and risk of febrile seizures in the first 3 years of life: The Japan Environment and Children's Study.

OBJECTIVE: Our study was conducted to examine the association between breastfeeding and febrile seizures (FS) in the first 3 years of life. METHODS: We analyzed the dataset of the Japan Environment and Children's Study (JECS), which is a birth cohort study undertaken to elucidate the influence of environmental factors on children's health during the fetal period and early childhood. Information on feeding duration and feeding pattern, as well as information on febrile seizures, were obtained from questionnaires sent to mothers/caregivers. We categorized a child as having experienced FS if the child was reported as having been diagnosed with FS in the first 3 years. Modified Poisson regression with a robust error variance was used to estimate the effect of duration of breastfeeding and the risk of FS. RESULTS: Of the 84,321 children included in the analysis, 6264 (7.4%) were reported to have experienced FS at least once in the first 3 years of life. Multivariate analyses showed that the risk of FS during the first 3 years of life tended to decrease as the duration of breastfeeding increased. Male sex and frequent fever episodes were also associated with an increased risk of FS. CONCLUSIONS: Continued breastfeeding until 2 years of age, the most susceptible age for FS, had a small but protective effect on FS.

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.

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.

Breastfeeding and risk of febrile seizures in infants: The Japan Environment and Children's Study.

OBJECTIVE: Our study was conducted to examine the association between breastfeeding and febrile seizures (FS) in the first year of life. METHODS: We used data from a birth cohort study, the Japan Environment and Children's Study (JECS). In a self-administered questionnaire, we asked participants the duration of breastfeeding and whether their children were diagnosed as having FS during their first 12 months. We estimated the association of duration and exclusiveness of breastfeeding with the FS by using multiple logistic regression analysis. RESULTS: Of 84,082 children, 995 (1.2%) were diagnosed as having FS by the age of 12 months. The prevalence of FS was higher in children who were breastfed for shorter duration. Multiple logistic regression analysis showed that, compared with children breastfed for less than 1 month, those breastfed for 4-6 months and 7-12 months had lower risks of FS (adjusted odds ratio [aOR], 0.65 [95% confidence interval {CI}, 0.42-0.99]; aOR, 0.66 [95% CI: 0.45-0.96], respectively). Moreover, compared with infants who received both breast milk and formula milk for 6 months, infants who were breastfed exclusively for 6 months had lower risk of FS (aOR: 0.78 [95% CI: 0.64-0.95]). CONCLUSIONS: Our results suggest that breastfeeding has a protective effect against FS in the first year of life.

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.

Nausea and vomiting during pregnancy associated with lower incidence of preterm births: the Japan Environment and Children's Study (JECS).

BACKGROUND: Nausea and vomiting during pregnancy (NVP) is considered to be associated with favorable fetal outcomes, such as a decreased risk for spontaneous abortion. However, the relationship between NVP and preterm births remains unknown. This study was conducted to evaluate the association between NVP and the risk of preterm births. METHODS: The dataset of a birth cohort study, the Japan Environment and Children's Study (JECS), was retrospectively reviewed. Participants' experience of NVP prior to 12 gestational weeks were evaluated by a questionnaire administered from 22 weeks of pregnancy to 1 month before delivery. NVP responses were elicited against four choices based on which the study population was divided into four subcohorts. Preterm birth was the main study outcome. Logistic regression analysis was used to quantify an association between NVP and risk of preterm birth. RESULTS: Of 96,056 women, 79,460 (82.7%) experienced some symptoms of NVP and 10,518 (10.9%) experienced severe NVP. Compared to those who did not experience NVP, women with severe NVP had lower odds for preterm birth [adjusted odds ratio (aOR) 0.84, 95% confidence interval (95% CI) 0.74-0.95]. An even lower OR was found among very preterm birth and extremely preterm birth (aOR 0.44, 95% CI 0.29-0.65). CONCLUSION: An inverse association exists between NVP and preterm births, especially, very preterm births and extremely preterm births.

[A case of persistent cerebellar ataxia complicated by conversion disorder--confirmed by positive cerebrospinal fluid glutamate receptor delta2 and epsilon2 antibodies].

We recently encountered a 13-year-old girl who developed persistent cerebellar symptoms one month after mixed measles/rubella vaccination, making it difficult to distinguish this condition from conversion disorders. Severe truncal ataxia was the initial manifestation in this case. The patient had no abnormalities in objective tests but began to show extraordinary circadian variations in certain parameters. Her cerebellar symptoms were thus considered to possibly be associated with conversion disorders. Later, she tested positive for cerebrospinal fluid anti-glutamic acid receptor (GluR) delta2 antibody. The lymphocyte stimulation test yielded a positive reaction to GluRdelta2 antigen. In addition, in the chronic stage SPECT revealed reduced cerebellar blood flow. She was thus diagnosed as having persistent cerebellar ataxia due to autoimmune mechanisms and modification of cerebellar symptoms due to secondary conversion disorders. Our experience with this case suggests that checking cerebrospinal fluid for anti-GluRdelta2 antibody is possibly useful for distinguishing between conversion disorders and cerebellar ataxia due to autoimmune mechanisms.

[The head MRI by fluid attenuated inversion recovery (FLAIR) was useful for diagnosis in the patient with post influenza vaccinal acute disseminated encephalomyelitis (ADEM)].

A 6-year-old, previously healthy boy developed ataxia and muscle weakness, 16 days after influenza vaccination. The CSF showed an elevated level of myelin basic protein, pleocytosis and negative influenza virus isolation. The head MRI revealed an extensive high intensity area in the deep white matter, which was more clearly defined on FLAIR images. The diagnosis of post influenza vaccinal ADEM was made, and he was successfully treated by steroid pulse therapy with a monophasic course and favorable outcome.