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Aims: To investigate whether the Institute of Medicine (IOM) guidelines for optimal gestational weight gain (GWG) in twin pregnancies are applicable to Japanese women. Methods: This was a retrospective study involving women who delivered full‐term twins at our tertiary center diagnosed with a normal prepregnancy body mass index. The women were divided into two groups, according to the optimal GWG recommended by the IOM (16.8–24.5 kg): the adequate GWG (AGWG) group with GWG meeting the guidelines and the low GWG (LGWG) group with GWG below the guidelines. Next, the women were divided into two groups according to birthweight: a group with both twins born appropriate for gestational age (AGA group) and a group with one or both twins born small for gestational age (SGA group). Their GWG as well as their pregnancy outcomes were compared. Results: A total of 265 women were included. The AGWG group had a significantly higher proportion of hypertensive disorders of pregnancy than the LGWG group. There was no significant difference in the proportion of women with both twins born AGA or the rate of admission to the neonatal intensive care unit. Meanwhile, the median GWG in the AGA group was 13.6 kg, which was significantly higher than 12.0 kg in the SGA group. And even the median GWG in the AGA group was below the lower limit of the IOM guidelines. Conclusion: The optimal GWG for Japanese women with twin pregnancies may be below the IOM guidelines. [ABSTRACT FROM AUTHOR]

Background: Istradefylline (IST), an adenosine A2A receptor antagonist, has been used since 2013 in Japan as an adjunctive therapy to levodopa (L‐DOPA) for patients with Parkinson's disease (PD). The long‐term use of IST as an adjunct to L‐DOPA (IST‐LD) was herein investigated to clarify the cooperative potential to keep motor functions, and an epigenetic modification for disease‐specific up‐regulated A2AR signals. Methods: The cohort comprising 62 PD patients with diurnal variations in motor function were treated with IST‐LD for 36 months, and clinical and biomarker parameters were evaluated. One monozygotic twin pair with juvenile PD and eight healthy control (HC) subjects were recruited for analyses of epigenetic biomarkers with peripheral blood lymphocyte (PBL): the A2AR protein (A2AR‐p), A2AR mRNA (A2AR‐m), and DNA methylation of the ADORA2A (Chr22q11.23) and DRD1 (Chr5q35.1) genes. Results: IST‐LD partially reversed locomotive dysfunction and motor off time and did not promote the severe dyskinesia (LID) develop. A2AR expression levels of the PBL were higher in IST‐naïve PD patients than in HC, which were associated with the effectiveness of IST‐LD and clinical global impression improvements. Intrinsic DNA demethylation of the ADORA2A gene were observed in juvenile monozygotic twin pair of the PD and IST‐naïve PD patients, which were reversed by IST‐LD at 12 months. Conclusions: IST‐LD was cooperative for long term to preserve motor execution controls and global daily activities improvement, through the canonical pharmacodynamics of inhibiting A2AR signaling, and also via the epigenetic modification on the ADORA2A gene. [ABSTRACT FROM AUTHOR]

Aim: The aim of the survey is to investigate current practice and complications of percutaneous umbilical cord blood sampling (PUBS) in Japan. Methods: In this retrospective survey, data including perioperative information, indications, details of the procedure and procedure‐related complications were collected for patients who underwent PUBS between 2012 and 2016 in Japanese perinatal care centers. Results: One hundred and fifty‐three patients underwent PUBS and a total of 223 procedures were analyzed in this study. Fetal anemia was the most common indication for PUBS, representing greater than 70% of all cases. Anemia specific to monochorionic twins, such as acute feto‐fetal hemorrhage subsequent to single intrauterine fetal death (IUFD) and twin anemia‐polycythemia sequence, were the leading causes of suspected fetal anemia. Maternal anesthetics were given during the procedure in 70% of cases. The PTC needle (Hakko, Japan) was most commonly used in the procedure. The most frequent complication was bleeding from the umbilical cord puncture site; however, it did not require immediate delivery during or after the procedure in any case. IUFD occurred in 11 (4.9%) procedures, 7 of which appeared to be related to the underlying fetal disease. The overall completion rate of the procedure was 97%. Conclusion: Percutaneous umbilical cord blood sampling was most commonly performed for the evaluation of fetal anemia, usually due to complications of monochorionic twins, followed by the measurement of fetal thyroid function. The safety and the completion rate of the procedure in Japan appear satisfactory. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The purpose of this study was to describe the characteristics of women with twin pregnancies who undergo noninvasive prenatal testing (NIPT) as well as the post‐partum and neonatal outcomes of such cases in Japan. Methods: The study population consisted of women who were pregnant with twins and who underwent NIPT using massively parallel sequencing (MPS) at Nagoya City University Hospital between April 2013 and June 2016. Questionnaires were completed pre‐NIPT and post‐partum. Results: Among 4009 women who underwent NIPT during the study period, 75 women (1.9%) were pregnant with twins. Fifteen women (20%) experienced vanishing twin/intrauterine fetal deaths at <22 weeks, and 60 women (80%) had normal twin pregnancies at the time of genetic counseling for NIPT. The use of NIPT was correlated with increased proportions of women using assisted reproductive technology (ART). The test had a high performance, with a false‐positive rate of 1.7% and no false negatives. Conclusion: In this study, NIPT had a high performance, with a false positive rate of 1.7% and no false negatives. When treating women with twin pregnancies, the efficacy of NIPT should be explained during genetic counseling. Further larger studies are required to assess the reliability and validity of NIPT in twin pregnancies. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Orofacial clefts (OFCs) are common and etiologically complex birth defects. This study explored potential genetic differences in a pair of Japanese monozygotic (MZ) twins with different forms of OFC using whole‐genome sequencing. Subjects and Methods: One co‐twin (MZ‐1) presented with nonsyndromic bilateral cleft lip and palate; the other co‐twin (MZ‐2) had nonsyndromic bilateral cleft lip and unilateral left‐sided cleft alveolus. Neither parent had an OFC. Craniofacial morphologic features and potential genetic differences were compared using standard cephalometry and whole‐genome sequencing, respectively. Results: Morphologically, MZ‐1 had a smaller vertical mandibular height, compared to MZ‐2. However, no discordant genetic differences were detected. Moreover, both twins and their parents harbored rare candidate gene variants (GRHL3; TPM1) considered to be associated with OFCs. Conclusion: The observed differences between MZ‐1 and MZ‐2 in craniofacial morphology assessed by cephalograms might be directly attributable to the effects of the OFC on growth and/or differences in surgical history, given the lack of any differences in genetic background. However, comparisons of discordant MZ twins should continue to identify novel candidates that might control OFC or that might partly explain the missing heritability for this common birth defect, in addition to understanding craniofacial growth and development. [ABSTRACT FROM AUTHOR]

Abstract: Background: Admission to the neonatal intensive care unit (NICU) due to respiratory distress is determined according to subjective clinician judgement. We investigated prenatal factors predictive of NICU admission in neonates with respiratory distress. Methods: This case–control study was conducted at Nara Prefecture General Medical Center, Nara, Japan, from February 2013 to April 2017 and included neonates with birthweight ≥2,000 g, ≥36 weeks of gestational age, who required oxygen due to respiratory distress at birth. The cases consisted of neonates admitted to the NICU, and the control group consisted of neonates who did not require NICU admission. Perinatal factors between the groups were compared, and multivariate logistic regression analysis carried out to evaluate predictive factors. Results: The NICU group consisted of 94 neonates, and the control group, 417 neonates during the period reviewed. On multivariate analysis, maternal anemia (OR, 2.97; 95%CI: 1.42–6.21), infertility treatment (OR, 2.79; 95%CI: 1.36–5.71), threatened preterm labor (OR, 2.16; 95%CI: 1.10–4.23), premature rupture of membranes (OR, 5.30, 95%CI: 2.52–11.17), fibroids (OR, 6.06; 95%CI: 1.57–23.41), history of uterine surgery (OR, 3.53, 95%CI: 1.13–11.06), abruptio placentae (OR, 10.21; 95%CI: 1.83–57.17), intrauterine growth restriction (OR, 6.69; 95%CI: 1.96–22.85), and having twins (OR, 0.23; 95%CI: 0.09–0.58) were significant prenatal predictors of NICU admission. Conclusion: Factors that potentially predict NICU admission were identified. Clinicians may wish to consider these factors when treating neonates with respiratory distress. [ABSTRACT FROM AUTHOR]

Executive functions (EF) are an important predictor of later adaptive development. A number of environmental influences, such as parenting, have been suggested as important promoters of EF development. However, behavioural genetic research has demonstrated that many environmental influences could be affected by genetic influences. Therefore, it is important to consider genetic variations when investigating environmental influences on EF development in children. To date, few studies have used genetically informative designs to assess the etiology of EF development during the preschool years, a period of rapid development. As a result, it remains unclear how and to what extent the environmental influences that are not confounded by genetic influences affect EF development during this developmental period. The present study explored EF development during the preschool years using a longitudinal and genetically informative design and a non-Western population. Japanese twins were visited at their homes and individually tested on EF measures at 24, 36, and 48 months of age. Phenotypic correlations and confirmatory factor analyses suggested that EF are less cohesive at 24 months of age and emerge as a common single factor at 36 and 48 months. Additionally, longitudinal and multivariate behavioural genetic analyses indicated that the EF developmental change during this period is promoted by both shared and nonshared environmental influences as well as genetic influences, while EF stability is brought about by shared environments. The present findings elucidated the etiology of EF development during the preschool years and confirmed that this period is an important transitional stage for EF development. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The objective of this article is to measure the causal effect of education on earnings using a large dataset of twins compiled in Japan with wide-ranging socioeconomic information. Recent research conducted in China showed that, contrary to the case in Western countries, ability bias is large in estimating the return to education. It is argued that the low rate of return in China is in part due to the competitive and exam-oriented education system, which is similar to the system in Japan. The empirical results in our study show that the estimated rate of return to education using the sample of identical twins in Japan is 9.3 percent even after omitted ability bias and measurement errors in self-reported schooling were corrected. Our findings suggest that the conventional OLS estimate is not significantly contaminated by potential biases in Japan. [ABSTRACT FROM AUTHOR]

Background: Genetic factors associated with Tojikomori (being housebound without any limitations in physical functioning or mental problems) are unclear. We performed a twin study to help clarify the causes of Tojikomori and investigate the association between Tojikomori and depressive symptoms. Methods: Participants were members of the Osaka University Aged Twin Registry. A total of 157 twin pairs (314 individuals) who provided data in 2008 and 2012 were included. Depressive symptoms were measured by the Geriatric Depression Scale short version (GDS). Social Activities Scores (SAS) were measured with questions assessing the frequency of going out and contact with others. Activities of daily living were assessed with the Barthel index. Structural equation modelling analysis was used to evaluate the relative importance of genes and environments for the phenotypes measured. Results: In the first analysis, for SAS (2012), 25% of the variance was explained by additive genetic effects, and 75% was explained by unique environmental (including error) effects. For the GDS (2012), 28% of the variance was explained by additive genetic effects, and 72% was explained by unique environmental (including error) effects. In the second analysis, 25% of the total variance in SAS (2012) was explained by additive genetic factors, which influenced GDS scores (2008 and 2012). However, only 10% of the total variance in GDS scores (2012) was explained by additive genetic factors that influenced SAS (2008 and 2012). Conclusions: Tojikomori was influenced by genetic factors in the elderly Japanese subjects. The association between Tojikomori and depressive symptoms was explained by genetic and environmental factors that are common to both phenotypes. Depressive symptoms were a cause of future Tojikomori and were affected by additive genetic factors. Genetic factors of Tojikomori were not a major cause of future depressive symptoms. [ABSTRACT FROM AUTHOR]

Using information on 1045 pairs of Japanese monozygotic twins, we examined differences in education by considering both the years of schooling (quantity) and the reputation of the last attended school (quality). We found that a difference in learning performance at 15 years of age is one of the key factors determining the differences. We also found that a female eldest child in the family from the 1950s and 1960s birth cohorts averaged 0.54 years less schooling than did her 'younger' twin. However, for the same birth cohorts, a male eldest child in the family generally had access to higher-quality education than his 'younger' twin. Nonetheless, as the Japanese economy matured in the 1970s and thereafter, educational differences between twins disappeared, regardless of gender and sibling order. [ABSTRACT FROM AUTHOR]

Aim Our aim was to determine factors that affect maternal serum magnesium (Mg) levels, to help ensure the safety and efficacy of long-term magnesium sulfate (MgSO4) therapy for threatened preterm labor in singleton and twin pregnancies. Material and Methods We retrospectively and arbitrarily studied 100 patients (singleton pregnancy, n = 65; twin pregnancy, n = 35) who received i.v. MgSO4 for >48 h for tocolysis of threatened preterm labor. We used multiple regression analysis to investigate the functional relations between the candidate factors and maternal serum Mg levels. Results MgSO4 was administered as a loading dose of 3 g for 1 h followed by a maintenance dose of 1.0-2.0 g/h. There were no maternal severe adverse events related to the elevated Mg levels in any of the subjects. The results of multiple regression analysis revealed that total dose of MgSO4 for 24 h before blood collection (g/day), total serum protein level (g/dL), serum total calcium level (mg/dL), serum creatinine level (mg/dL) and maternal bodyweight (kg) significantly affected maternal serum Mg levels in both singleton and twin pregnancies (all P-values were < 0.001). Gestational age (weeks) and period of MgSO4 administration (days) at blood collection had no significant effect in singleton or twin pregnancies. Conclusion Our study statistically shows that dose of MgSO4, total serum protein level, serum total calcium level, serum creatinine level and maternal bodyweight are key factors to achieving safe and effective long-term tocolysis with MgSO4 in not only singleton but also twin pregnancies. [ABSTRACT FROM AUTHOR]

Aim To assess the outcome of monochorionic diamniotic ( MD) twins with the aid of the MD-twin score. Methods We enrolled 112 MD-twin women in a tertiary perinatal center from 1997 to 2009. The MD-twin score was prospectively applied once per week to women who did not have twin-to-twin transfusion syndrome ( TTTS) after 26 weeks of gestation. The MD-twin score consists of five variables: (i) fetal weight discordance; (ii) amniotic fluid discordance; (iii) hydrops fetalis; (iv) umbilical cord insertion; and (v) fetal heart rate monitoring. Normal was assigned a value of 0, abnormal was assigned 1, and total score was used for evaluation. Women with scores of 2 at 26 weeks gestation were managed expectantly until the score reached 3. Outcome measures were fetal death, neonatal death and neurological sequelae. The incidence of poor outcome according to score was investigated. The characteristics of MD twins with poor outcome were investigated. Results MD-twin scores were applied to 90 women. Among them, 79 had scores of 2 or less and all had good outcomes. There were 11 women with a score of 3, four of whom had adverse outcome for at least one twin. Neonates born to women with scores of 0-2 had good outcomes without respect to birthweight percentile, while neonates with scores of 3 had poor outcomes when their birthweight percentile was less than the third percentile. Conclusion The MD-twin score is applicable to 90% of MD twins without TTTS. An MD-twin score of 2 is reassuring, while a score of 3 indicates increased risks for adverse outcome. [ABSTRACT FROM AUTHOR]

Clinical guidelines for obstetrical practice were first published by the Japan Society of Obstetrics and Gynecology (JSOG) and the Japan Association of Obstetricians and Gynecologists (JAOG) in 2008, and a revised version was published in 2011. The aims of this publication include the determination of current standard care practices for pregnant women in Japan, the widespread use of standard care practices, the enhancement of safety in obstetrical practice, the reduction in burdens associated with medico-legal and medico-economical problems, and a better understanding between pregnant women and maternity-service providers. These guidelines include a total of 87 Clinical Questions followed by several Answers (CQ&A), a Discussion, a List of References, and some Tables and Figures covering common problems and questions encountered in obstetrical practice. Each answer with a recommendation level of A, B or C has been prepared based principally on 'evidence' or a consensus among Japanese obstetricians in situations where 'evidence' is weak or lacking. Answers with a recommendation level of A or B represent current standard care practices in Japan. All 87 CQ&A are presented herein to promote a better understanding of the current standard care practices for pregnant women in Japan. [ABSTRACT FROM AUTHOR]

Aim: In singletons, neonatal small-for-gestational age (SGA) status is an unfavorable postpartum outcome leading to cesarean section (CS) and increasing the possibility of maternal operative complications. Perinatal characteristics of SGA newborns in dichorionic (DC) twins were investigated for the prognostic impact on their mothers. Methods: A retrospective study was performed from 2004 to 2009 on 329 DC twins with two live births. Neonates were classified as SGA if they weighed less than the 10th percentile at birth according to Japanese singleton norms. Statistical differences between DC twins delivering appropriate-for-gestational age (AGA)/ AGA pairs (control group) and AGA/SGA, SGA/AGA or SGA/SGA pairs (the first/second twins) were analyzed. Results: The median (range) of the gestational ages at delivery for AGA/AGA, AGA/SGA, SGA/AGA and SGA/SGA pairs were 37.1 (27.1–40.3), 37.2 (29.0–40.9), 37.1 (28.1–40.7) and 37.3 (33.3–40.4) weeks, and the complete vaginal delivery rates of both fetuses were 66.2% (43/65), 84.8% (28/33), 82.4% (14/17) and 70.0% (7/10), respectively. Compared with AGA/AGA pairs, AGA/SGA pairs showed a higher incidence of spontaneous vaginal births of both fetuses (31.3% [26/83] vs 19.9% [37/186], OR 1.84, 95% CI 1.4 –4.73) and a lower incidence of emergent CS (25.3% [21/83] vs 38.7% [72/186], OR 0.53, 95% CI 0.30–0.95). Conclusion: The relatively small size of SGA fetuses allows both fetuses to remain inside the uterus for a longer time and to easily pass through the maternal parturient canal for complete vaginal delivery. Neonatal SGA status is a favorable factor for avoiding operative complications of CS and optimizing maternal perinatal outcomes. [ABSTRACT FROM AUTHOR]

Tobe RG, Mori R, Shinozuka N, Kubo T, Itabashi K. A nationwide investigation on gestational age specific birthweight and mortality among Japanese twins. Paediatric and Perinatal Epidemiology 2011; : 228-235. Gestational age specific birthweight has been used as an important indicator to identify the health status of neonates and to provide appropriate neonatal care services to those at high risk. To identify the gestational age specific birthweight of twins born in secondary and tertiary hospitals in Japan and to explore factors affecting mortality, we used a nationwide obstetric database in Japan. Liveborn twins from 2001 to 2005 in the database, which was established with the national Perinatal Health Care Project, were enrolled ( n = 22 240). Obstetric data from the medical records were collected and analysed. Approximately 60% of liveborn twins were delivered between weeks 33 and 38, most frequently at 36 and 37 weeks. The mean birthweight of liveborn twins was 2084 g and the mean gestational age was 34.9 weeks. Intrauterine growth differed by parity, mode of delivery, birth order, chorionicity and sex. Using logistic regression, lower gestational age, small for gestational age, monochorionic twins and vaginal delivery tended to have higher risks of mortality. [ABSTRACT FROM AUTHOR]

To investigate the maternal risk factors for small-for-gestational age (SGA) newborns in Japanese dichorionic (DC) twins. A retrospective study was conducted from 2003 to 2008 on 340 DC twin pregnancies resulting in two live births. Newborns were classified as SGA if their birth weight was below the 10th percentile according to Japanese singleton norms. Statistical differences were evaluated between pregnancies resulting in appropriate-for-gestational age (AGA) pairs and those resulting in at least one SGA neonate. The study population consisted of AGA/AGA (50.8%), AGA/SGA (37.0%) and SGA/SGA pairs (12.0%). Logistic regression analysis identified significant interrelations for SGA with maternal nulliparity (odds ratio [OR] 0.52, 95% confidence interval [CI] 0.30-0.91), smoking (OR 3.25, 95% CI 1.09-9.66), assisted reproductive technology (OR 0.52, 95% CI 0.30-0.89), pregnancy-induced hypertension (OR 2.00, 95% CI 1.01-4.31), pregravid weight (kg) (unitary OR 0.94, 95% CI 0.91-0.97) and monthly weight gain (kg/month) (unitary OR 0.25, 95% CI 0.14-0.44). Bivariable receiver operating characteristic curves were generated for monthly weight gain (area under the curve [AUC] 0.626, cutoff 1.41 kg/month, P < 0.001) and total weight gain (AUC 0.615, cutoff 14.0 kg, P < 0.001). Cigarette smoking and weight gain control are relatively modifiable factors for which interventional management is necessary to avoid perinatal problems arising from SGA pregnancy. Further studies are needed to investigate optimal nutrition, health guidance and subsequent weight gain control that lead to concrete improvement in maternal and infant prognoses. [ABSTRACT FROM AUTHOR]

To clarify the birth length of twins according to gestational age.We studied a total of 51 910 live-birth–live-birth pairs of twins, 4561 triplet live births and 256 quadruplet live births, using data obtained from corresponding birth certificates. The birth length of twins was analyzed according to gestational age.Compared to singleton neonates, the median birth length of twins was approximately 0.5 cm smaller after the gestational age of 34 weeks, increasing to approximately 2.0 cm at 42 weeks of gestation. The median birth length according to gestational age was found to be the greatest in twins, lower in triplets and the lowest in quadruplets, in which the difference was<2.0 cm.The birth length of twins was smaller than that of singletons, but the difference was smaller than the difference in birthweight between twins and singletons. [ABSTRACT FROM AUTHOR]

The effect of assisted reproductive technology is more pronounced in unlike-sexed twins than in like-sexed. Trends in perinatal mortality of twins were compared between the two types of sex combination. Certificates for births (478 276 cases), stillbirths (50 542 cases), and early neonatal deaths (8747 cases) were the subjects of this analysis. Since 1984, the decline in the perinatal mortality of unlike-sexed twins has been slower than that of like-sexed twins. In both light-for-dates (LFD) and non-LFD, the decline in the gestational age standardised mortality ratio has been slower in unlike-sexed twins. We suggest this is due to the introduction of assisted reproductive technologies. [ABSTRACT FROM AUTHOR]

The perinatal mortality rate (PMR) in twins was analysed using Japanese vital statistics during the period 1980-98. There was a total of 1992 twin perinatal deaths. The PMR in twins significantly decreased from 91 per 1000 births in 1980 to 31 per 1000 in 1998. The PMR was higher in males than females, but the differences between the sexes decreased over time. It was significantly higher in the second-born than the first-born of the twins. The fetal death rate was 2.8 times higher in monozygotic than dizygotic twins. The PMR decreased to one-sixth for the maternal age group > or =40 years, one-fifth for <20 years, and between one-third and a half for 20--39 years during the period 1980--98. It was lowest for birthweights (BW) between 2500 g and 2999 g during the entire period; the PMR decreased with gestational age (GA) up to 38--39 weeks and increased thereafter. The effect of BW on the PMR was greater than that of GA except in the shorter GA group. The proportion of twin perinatal deaths with extremely low BW (<1000 g) increased from 50% in 1980 to 68% in 1998. Thus, the declining PMR was unlikely to be due to the improvement in BW in twins. It is likely that it is related to the improved medical management of twins during the perinatal period and the first week of life. [ABSTRACT FROM AUTHOR]

Background: Although the frequency of twin births has increased in Japan, little information is available about breastfeeding twins. An intervention of breastfeeding support was implemented to promote breastfeeding for mothers of twins and to compare the factors related to breastfed and formula-fed twins. Methods: Eleven Japanese twins-mother pairs received breastfeeding support according to a breastfeeding protocol for twins, and a control group of seven pairs received routine care. Perinatal data were obtained from clinical records for analysis. Results: No significant differences were evident between the two groups in terms of maternal age, gestational age, birthweight, the age at which breastfeeding was initiated, amount of supplementary feeding in hospital, infants' age at discharge, or duration of mothers' hospital stay. At age 3 months, 13 infants in the intervention group were being exclusively breastfed and 9 were almost exclusively breastfed. In the control group 4 infants were almost exclusively and 10 were exclusively formula-fed. The mothers in the intervention group breastfed and expressed milk significantly more frequently than the mothers in the control group during their hospital stay. Conclusions: Mothers of twins face many obstacles in breastfeeding, and health care professionals should offer individualized care and support. [ABSTRACT FROM AUTHOR]

A case study is presented of Japanese monochorionic twin boys. Topics discussed include diagnosis of twin A with oligohydramnios; abdominal magnetic resonance imaging showed iron deposition in the liver; diagnosis of neonatal hemochromatosis in monochorionic twins with disparate clinical findings was performed.