There is global concern over significant threats from a wide variety of environmental hazards to which children face. Large-scale and long-term birth cohort studies are needed for better environmental management based on sound science. The primary objective of the Japan Environment and Children’s Study (JECS), a nation-wide birth cohort study that started its recruitment in January 2011, is to elucidate environmental factors that affect children’s health and development.

Observational studies have shown that fetoscopic endoluminal tracheal occlusion (FETO) has been associated with increased survival among infants with severe pulmonary hypoplasia due to isolated congenital diaphragmatic hernia on the left side, but data from randomized trials are lacking. In this open-label trial conducted at centers with experience in FETO and other types of prenatal surgery, we randomly assigned, in a 1:1 ratio, women carrying singleton fetuses with severe isolated congenital diaphragmatic hernia on the left side to FETO at 27 to 29 weeks of gestation or expectant care. Both treatments were followed by standardized postnatal care. The primary outcome was infant survival to discharge from the neonatal intensive care unit. We used a group-sequential design with five prespecified interim analyses for superiority, with a maximum sample size of 116 women. The trial was stopped early for efficacy after the third interim analysis. In an intention-to-treat analysis that included 80 women, 40% of infants (16 of 40) in the FETO group survived to discharge, as compared with 15% (6 of 40) in the expectant care group (relative risk, 2.67; 95% confidence interval [CI], 1.22 to 6.11; two-sided P=0.009). Survival to 6 months of age was identical to the survival to discharge (relative risk, 2.67; 95% CI, 1.22 to 6.11). The incidence of preterm, prelabor rupture of membranes was higher among women in the FETO group than among those in the expectant care group (47% vs. 11%; relative risk, 4.51; 95% CI, 1.83 to 11.9), as was the incidence of preterm birth (75% vs. 29%; relative risk, 2.59; 95% CI, 1.59 to 4.52). One neonatal death occurred after emergency delivery for placental laceration from fetoscopic balloon removal, and one neonatal death occurred because of failed balloon removal. In an analysis that included 11 additional participants with data that were available after the trial was stopped, survival to discharge was 36% among infants in the FETO group and 14% among those in the expectant care group (relative risk, 2.65; 95% CI, 1.21 to 6.09). In fetuses with isolated severe congenital diaphragmatic hernia on the left side, FETO performed at 27 to 29 weeks of gestation resulted in a significant benefit over expectant care with respect to survival to discharge, and this benefit was sustained to 6 months of age. FETO increased the risks of preterm, prelabor rupture of membranes and preterm birth. (Funded by the European Commission and others; TOTAL ClinicalTrials.gov number, NCT01240057.)

While several studies have demonstrated the increased risk of pregnancy complications for women of advanced age, few studies have focused on women with very advanced age (≥ 45), despite the increasing rate of pregnancy among such women. Furthermore, how such risks of increase in age differ by maternal characteristics are also poorly understood. Thus, we aimed to clarify pregnant outcomes among women with very advanced age and how the effect of age differs by method of conception and parity. We used the national multicenter Japan Society of Obstetrics and Gynecology perinatal database, including 365,417 women aged 30 years or older who delivered a singleton between 2005 and 2011. We divided women into four groups based on age (years): 30–34, 35–39, 40–44, and ≥45, and compared risk of adverse birth outcomes between the groups using Poisson regression. Effect modification by parity and use of assisted reproductive technology (ART) was also evaluated. Results: Compared with women aged 30–34 years, women aged 45 or older had higher risk of emergency cesarean delivery [adjusted risk ratio (aRR): 1.77, 95% confidence interval (95% CI): 1.58–1.99], preeclampsia (aRR: 1.86, 95% CI: 1.43–2.42), severe preeclampsia (aRR: 2.03, 95% CI: 1.31–3.13), placenta previa (aRR: 2.17, 95% CI: 1.60–2.95), and preterm birth (aRR: 1.20, 95% CI: 1.04–1.39). The effect of older age on risk of emergency cesarean section, preeclampsia, and preterm birth were significantly greater among those who conceived naturally compared to those who conceived by ART. The effect on emergency cesarean section was stronger among primiparous women, whereas the risk of preeclampsia associated with older age was significantly greater among multiparous women. Very advanced maternal age (≥ 45) was related to greater risk for adverse birth outcomes compared to younger women, especially for maternal complications including cesarean section, preeclampsia, severe preeclampsia, and placenta previa. The magnitude of the influence of age also differed by conception method and by parity.

The Institute of Medicine (IOM) guidelines are the most widely used guidelines on gestational weight gain; however, accumulation of evidence that body composition in Asians differs from other races has brought concern regarding whether their direct application is appropriate. We aimed to study to what extent optimal gestational weight gain among women in Japan differs by pre-pregnancy body mass index (BMI) and to compare estimated optimal gestational weight gain to current Japanese and Institute of Medicine (IOM) recommendations. We retrospectively studied 104,070 singleton pregnancies among nulliparous women in 2005-2011 using the Japanese national perinatal network database. In five pre-pregnancy BMI sub-groups (17.0-18.4, 18.5-19.9, 20-22.9, 23-24.9, and 25-27.4 kg/m2), we estimated the association of the rate of gestational weight gain with pregnancy outcomes (fetal growth, preterm delivery, and delivery complications) using multivariate regression. Weight gain rate associated with the lowest risk of adverse outcomes decreased with increasing BMI (12.2 kg, 10.9 kg, 9.9 kg, 7.7 kg, and 4.3 kg/40 weeks) for the five BMI categories as described above, respectively. Current Japanese guidelines were lower than optimal gains, with the lowest risk of adverse outcomes for women with BMI below 18.5 kg/m2, and current IOM recommendations were higher than optimal gains for women with BMI over 23 kg/m2. Optimal weight gain during pregnancy varies largely by pre-pregnancy BMI, and defining those with BMI over 23 kg/m2 as overweight, as proposed by the World Health Organization, may be useful when applying current IOM recommendations to Japanese guidelines.

The relationship between maternal hemoglobin (Hb) levels during pregnancy and birth outcomes has been controversial. Changes in Hb level during pregnancy may have an impact on birth outcomes. This study aimed to investigate whether changes in Hb levels from early to mid- or late pregnancy is associated with birth outcomes. Participants were singleton mothers who delivered at the National Center for Child Health and Development between 34 and 41 weeks of gestation in 2010 and 2011 (n = 1,986). Hb levels were measured at three time points: early (<16 weeks), mid- (16–27 weeks), and late (28–36 weeks) pregnancy. Associations between changes in Hb levels from early to mid- or late pregnancy and birth outcomes (birth weight, Z-score of birth weight, placental weight, and placental ratio) were assessed by multiple regression, adjusting for maternal and fetal covariates. A smaller reduction in Hb levels from early to mid- or late pregnancy was significantly associated with lower birth weight, Z-score of birth weight, placental weight, and placental ratio. Compared to women with an intermediate reduction from early to late pregnancy, women with the least reduction had a significantly increased risk of delivering low birth weight (LBW) (adjusted odds ratio [aOR], 2.0; 95% confidence interval [CI], 1.3-3.1) and small-for-gestational-age (SGA) (aOR, 1.6; 95% CI, 1.04-2.3) infants, while women with the greatest reduction had a significantly decreased risk of delivering SGA (aOR, 0.38; 95% CI, 0.23-0.65) infants, but an increased risk of high placental ratio (aOR, 1.7; 95% CI, 1.2-2.5). Hb changes from early to mid- or late pregnancy were inversely associated with birth weight, placental weight, and placental ratio.

Although pregnancies conceived by assisted reproductive technology (ART) have a higher risk of maternal/perinatal complications, the overall risk of adverse outcomes necessitating advanced obstetric care has not been closely examined. The present study aimed to assess and compare the risk of maternal/perinatal complications and adverse outcomes in pregnancy and childbirth conceived by ART with those conceived naturally. This study was conducted as a part of the Japan environment and children’s study (JECS), an ongoing nationwide birth cohort study in Japan. The risk of maternal/perinatal complications and adverse outcomes was assessed by mode of conception (natural conception, ovulation induction [OI] without ART, conventional in vitro fertilization and embryo transfer [IVF-ET], or intracytoplasmic sperm injection [ICSI]) using logistic regression and generalized estimating equations controlling for potential confounders. The final dataset included women who conceived naturally (N = 90,506), by OI without ART (N = 3939), by conventional IVF-ET (N = 1476), and by ICSI (N = 1671). Compared with women who conceived naturally, those who conceived by conventional IVF-ET were at higher risk of placenta previa (adjusted OR 2.90 [95% CI 1.94, 4.34]), morbidly adherent placenta (6.85 [3.88, 12.13]), and pregnancy-induced hypertension (1.40 [1.10, 1.78]) whereas those who conceived by ICSI had a higher risk of placental abruption (2.16 [1.20, 3.88]) as well as placenta previa (2.01 [1.29, 3.13]) and morbidly adherent placenta (7.81 [4.56, 13.38]). Women who conceived by ART had a higher risk of blood transfusion (conventional IVF-ET: 3.85 [2.52, 5.88]; ICSI: 3.76 [2.49, 5.66]) and ICU admission (conventional IVF-ET: 2.58 [1.11, 6.01]; ICSI: 3.45 [1.68, 7.06]) even after controlling for potential confounders. Neonates conceived by ART had a higher risk of preterm birth (conventional IVF-ET: 1.42 [1.13, 1.78]; ICSI: 1.31 [1.05, 1.64]). Women who conceived by ART had a higher risk of maternal/perinatal complications necessitating advanced obstetric care. Obstetricians should be aware of the increased risk of adverse outcomes among this population.