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Objective: To examine the association between adverse childhood experiences (ACEs) and pregnancy morbidities, including preterm birth (PTB), gestational diabetes (GDM), preeclampsia, and small‐for‐gestational‐age (SGA) among the general population in Japan. Methods: The data were from the JACSIS study, an online‐based nationwide survey conducted from July to August 2021 in Japan (N = 5444). ACEs included physical, sexual, and psychological abuse, neglect, childhood poverty, bully victimization, domestic violence, parental death, and parental divorce. Pregnancy morbidities, including PTB, GDM, preeclampsia, and SGA were identified through questionnaires. A multivariable logistic regression model was applied. Results: Of 5444 women, 2778 (51.0%) had no ACEs, and 374 (6.9%) had four or more ACEs. A dose–response association was found between total ACE score and PTB and preeclampsia (p‐value: 0.016 and 0.001). Women with four or more ACE scores showed higher risks of preeclampsia (adjusted odds ratio [aOR] [95% confidence interval, CI]: 3.06 [1.57–5.94], p‐value: 0.001). Besides, those with two or three ACEs had higher risks of PTB (aOR [95%CI]: 1.42 [1.01–2.02], p‐value: 0.046, and aOR [95%CI]: 1.61 [1.04–2.50], p‐value: 0.041), and women with one ACE showed a higher risk of GDM (aOR [95%CI]: 1.34 [1.02–1.77], p‐value: 0.035). SGA was not associated with ACEs. Conclusion: ACEs were associated with an increased risk of PTB, preeclampsia, and GDM, but not SGA among the general population in Japan. [ABSTRACT FROM AUTHOR]

Aim: To examine associations between children being born small for gestational age and childhood hospitalisation following term and preterm births. Methods: This study included 34 564 children from a nationwide population‐based longitudinal survey starting in 2010, comprising 32 603 term births and 1961 preterm births. Children's hospitalisation history was examined during two observational periods, 6–18 and 6–66 months of age. Logistic regression analysis was conducted, adjusting for child and parental confounders, with children born appropriate for gestational age as reference. Results: Children born small for gestational age were more likely to be hospitalised during early childhood than those born appropriate for gestational age. The odds ratio (95% confidence interval) for hospitalisation from 6 to 66 months of age was 1.19 (1.05–1.34) in term children born small for gestational age and 1.47 (1.05–2.06) for preterm children born small for gestational age, compared with those born appropriate for gestational age. The risk of hospitalisation from 6 to 66 months of age in children born small for gestational age was observed for bronchitis/pneumonia. Conclusion: We observed the adverse effects of small for gestational age on hospitalisation during early childhood in both term and preterm births, particularly for bronchitis and pneumonia. [ABSTRACT FROM AUTHOR]

Background: Catch-up growth issues among children born small for gestational age (SGA) present a substantial public health challenge. Prenatal exposure to heavy metals can cause adverse effects on birth weight. However, comprehensive studies on the accurate assessment of individual blood concentrations of heavy metals and their effect on the failure to achieve catch-up growth remain unavailable. This study aimed to evaluate the effects of uterine exposure to toxic metals cadmium, lead, and mercury and essential trace metals manganese and selenium at low concentrations on the postnatal growth of children born SGA. Methods: Data on newborn birth size and other factors were obtained from the medical record transcripts and self-administered questionnaires of participants in the Japan Environment and Children's Study. The blood concentrations of lead, cadmium, mercury, selenium, and manganese in pregnant women in their second or third trimester were determined by inductively coupled plasma mass spectrometry. These heavy metal concentrations were also assessed in pregnant women's cord blood. Furthermore, the relationship between each heavy metal and height measure/catch-up growth in SGA children aged 4 years was analyzed using linear and logistic regression methods. These models were adjusted for confounders. Results: We studied 4683 mother–child pairings from 103,060 pregnancies included in the Japan Environment and Children's Study. Of these, 278 pairs were also analyzed using cord blood. At 3 and 4 years old, 10.7% and 9.0% of children who were born below the 10th percentile of body weight had height standard deviation scores (SDSs) below 2, respectively. Cord blood cadmium concentrations were associated with the inability to catch up in growth by 3 or 4 years old and the height SDS at 3 years old. In maternal blood, only manganese was positively associated with the height SDS of SGA children aged 2 years; however, it was not significantly associated with catch-up growth in these children. Conclusion: Cadmium exposure is associated with failed catch-up development in SGA children. These new findings could help identify children highly at risk of failing to catch up in growth, and could motivate the elimination of heavy metal (especially cadmium) pollution to improve SGA children's growth. [ABSTRACT FROM AUTHOR]

This study aimed to examine the factors associated with physical growth status among children aged 12-59 months in Japan. Data from the 2010 National Growth Survey on Preschool Children, a nationwide cross-sectional survey, were used for this analysis (n = 4196). After adjustment for confounding factors, multiple logistic regression analyses showed that boys who were born small-for-gestational-age were more likely to be underweight (adjusted odds ratio [aOR]: 12.55, 95% confidence interval [CI]: [6.76-23.3], p < 0.001), stunted (aOR: 5.78, 95% CI: [3.48-9.60], p < 0.001) and wasted (aOR: 7.02, 95% CI: [3.30-15.0], p < 0.001), while boys who were large-for-gestational-age were less likely to be stunted (aOR: 0.26, 95% CI: [0.11-0.60], p < 0.01). Girls who were born small-for-gestational-age were more likely to be underweight (aOR: 5.42, 95% CI: [2.73-10.7], p < 0.001), stunted (aOR: 4.04, 95% CI: [2.43-6.73], p < 0.001) and wasted (aOR: 6.27, 95% CI: [2.55-15.4], p < 0.001), while girls who were large-for-gestational age were more likely to be overweight (aOR: 5.90, 95% CI: [1.64-21.3], p < 0.001). Moreover, the following factors were associated with the physical growth status in children: maternal prepregnancy body mass index, complications during pregnancy, continuous breastfeeding, initiation age of complementary feeding, smoking status of the father or those living with the mother during pregnancy and birth order. Further research is needed to expand support for high-risk families and to verify their effectiveness. [ABSTRACT FROM AUTHOR]

Aim: While associations between vitamin D deficiency and neurodevelopmental disorders have been found, large studies on child vitamin D, neurodevelopment, and sex differences among the general population are lacking. This study aimed to investigate the association between child serum 25‐hydroxyvitamin D (25(OH)D)) levels and neurodevelopmental problems (NDPs). Methods: Serum 25(OH)D and NDPs were measured at age two among the subcohort study of the Japan Environment and Children's Study. NDPs were assessed with the Kyoto Scale of Psychological Development 2001 (Kyoto scale). Adjusted odds ratios (aORs) for the Kyoto‐scale developmental quotient scores <70 were calculated, for postural–motor, cognitive–adaptive, and language–social domains and overall scores, adjusted for test month, latitude, small for gestational age, maternal age, and daycare attendance. Results: Among 2363 boys and 2290 girls, boys had higher 25(OH)D levels, but scored lower in the Kyoto scale. For boys in the vitamin D deficiency (<20 ng/mL) group, aORs of scoring the Kyoto‐scale DQs <70 were 2.33 (p = 0.006) for overall DQs, 1.91 (p = 0.037) for cognitive–adaptive, and 1.69 (p = 0.024) for language–social domains. For girls, results were inconclusive. Conclusion: Only boys showed a clear and cross‐modal association between vitamin D deficiency and NDPs. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the association between parental and infant birth weights in Japan. In total, 37,504 pregnant Japanese women and their partners were included in this birth cohort study. A multinomial logistic regression model was used to evaluate the associations of parental birth weights with small-for-gestational-age (SGA) or large-for-gestational-age (LGA) infants. Associations between parental birth weight and low birth weight (LBW) infants or macrosomia were also examined, and linear associations between parental birth weight and SGA or LGA were found. The adjusted odds ratios (aORs) for SGA infants per 500 g decrease in maternal and paternal birth weights were 1.50 (95% confidence interval [CI],1.43–1.58) and 1.31 (95% CI, 1.25–1.38), respectively. The aORs for LGA infants per 500 g increase in maternal and paternal birth weights were 1.53 (95% CI, 1.47–1.60) and 1.41 (95% CI, 1.35–1.47), respectively. The association between parental birth weight and LBW infants or macrosomia was also linear. The aORs for LBW infants per 500 g decrease in maternal and paternal birth weights were 1.47 (95% CI, 1.40–1.55) and 1.25 (95% CI, 1.19–1.31), respectively. The aORs for macrosomia per 500 g increase in maternal and paternal birth weights were 1.59 (95% CI, 1.41–1.79) and 1.40 (95% CI, 1.23–1.60), respectively. Parental birth weight was found to be associated with infant birth weight even after adjusting for various parental factors. Furthermore, maternal birth weight was more strongly associated with infant birth weight than with paternal birth weight. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of antenatal corticosteroid (ACS) treatment on neonatal outcomes in small for gestational age (SGA) infants born at 24–31 gestational weeks compared with non-SGA infants. Methods: A population-based retrospective study was conducted that analyzed clinical data from the Neonatal Research Network of Japan database, which enrolls neonates born at < 32 gestational weeks and weighing 1500 g or less (n = 22,414). Propensity score matching (with the ratio of ACS to no-ACS groups of 1:1) was performed in SGA (n = 7028) and non-SGA (n = 15,386) infants, respectively. Univariate logistic and interaction analyses were performed to compare the short-term neonatal outcomes of infants with and without ACS treatment in utero. Results: In the SGA and non-SGA infants, ACS treatment significantly reduced in-hospital mortality (odds ratio 0.67 95% confidence interval [0.50–0.88] and 0.62 [0.50–0.78], respectively), respiratory distress syndrome (0.77 [0.69–0.87] and 0.63 [0.58–0.68], respectively), and composite adverse outcomes (0.73 [0.58–0.91] and 0.57 [0.50–0.65], respectively). ACS treatment also significantly reduced intraventricular hemorrhage (grade III/IV), periventricular leukomalacia, and sepsis in the non-SGA infants, but not in the SGA infants. However, interaction analyses revealed no significant differences between the SGA and non-SGA infants in the efficacy of ACS treatment on short-term outcomes except for respiratory distress syndrome. Conclusions: ACS treatment was associated with beneficial effects on mortality, respiratory distress syndrome, and adverse composite outcomes in extremely and very preterm SGA infants, with similar efficacy on all neonatal outcomes except for respiratory distress syndrome observed in the non-SGA infants. [ABSTRACT FROM AUTHOR]

Objectives: In this study, an association between the mother's occupations with preterm and small-for-gestational-age (SGA) births was investigated using national data in Japan, and individual-level birth data from the Report of Vital Statistics: Occupational and Industrial Aspects in the 2015 fiscal year were used. Preterm and SGA birth rates were calculated for each of infant characteristics, and relative risk of each type of maternal occupations (categorized into 12 types) for the outcomes was estimated using a log binomial regression model. Results: Data of 997,600 singleton births were analyzed. Among maternal occupations, preterm birth rate was highest among carrying, cleaning, packaging, and related workers (5.65%) and lowest among security workers (4.24%). SGA birth rate was highest among manufacturing process workers (5.91%) and lowest among security workers (4.00%). We found significantly elevated risks for preterm birth among manufacturing process workers compared with unemployed mothers, and significantly elevated risks for SGA birth compared with unemployed mothers were observed among sales workers, service workers, and manufacturing process workers. In contrast, security workers had a significantly decreased risk for SGA birth compared with unemployed mothers. [ABSTRACT FROM AUTHOR]

Late preterm (LP, born between 34 0/7 and 36 6/7 weeks of gestation) infants may experience several adverse outcomes, similar to those experienced by low birthweight (LBW, birthweight <2500 g) infants. However, while LP infants are often born with LBW, the association between LP and LBW remains unknown. This study aimed to investigate LBW rate and independent risk factors for LBW in LP singleton neonates. We retrospectively analyzed data of LP singleton neonates, born between 2013 and 2017, from the Japan Society of Obstetrics and Gynecology Successive Pregnancy Birth Registry System. The exclusion criteria included stillbirths and infants with missing data. Logistic regression analyses were performed to investigate maternal and perinatal factors associated with LBW in LP singletons. LBW was observed in 62.5% (n = 35,113) of 56,160 LP singleton births. In the multiple logistic regression analysis, LBW in LP neonates was independently associated with modifiable maternal factors, including pre-pregnancy underweight, inadequate gestational weight gain, and smoking during pregnancy, as well as non-modifiable factors, including younger maternal age, nulliparity, hypertensive disorder of pregnancy, preeclampsia, cesarean section delivery, and female offspring. According to the Japanese pregnancy birth registry data, more than half of LP neonates were LBW. We previously discussed the issue of LBW regarding infants with different backgrounds, as there are many different causes of LBW. Several risk factors should be subdivided and considered for the risk of LP and LBW. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between maternal asthma (MA) and obstetric complications, while considering subdivided total serum immunoglobulin E (IgE) levels. Methods: Data of the participants enrolled in the Japan Environment and Children's Study between 2011 and 2014 were analyzed. In total, 77,131 women with singleton live births at and after 22 weeks of gestation were included. MA was defined based on a self-administered questionnaire. Women with MA were stratified based on the quartile of total serum IgE levels during pregnancy as follows: low IgE levels (< 52.40 IU/mL), moderate IgE levels (52.40–331.00 IU/mL), and high IgE levels (> 331.00 IU/mL). The adjusted odds ratios (aORs) for preterm births (PTB), small for gestational age (SGA) infants, gestational diabetes mellitus, and hypertensive disorders of pregnancy (HDP) were calculated using multivariable logistic regression, while considering women without MA as reference and maternal socioeconomic factors as confounders. Results: The aORs for SGA infants and HDP in women with MA and high total serum IgE levels were 1.26 (95% confidence interval [CI], 1.05–1.50) and 1.33 (95% CI, 1.06–1.66), respectively. The aOR for SGA infants among women with MA and moderate total serum IgE levels was 0.85 (95% CI, 0.73–0.99). The aOR for PTB among women with MA and low total serum IgE levels was 1.26 (95% CI, 1.04–1.52). Conclusions for Practice: MA with subdivided total serum IgE levels was associated with obstetric complications. Total serum IgE level may be a potential prognostic marker to predict obstetric complications in pregnancies with MA. Significance: What is Already Known on this Subject? Maternal asthma (MA) is associated with several obstetric complications, including preterm births (PTB), small for gestational age (SGA) infants, and hypertensive disorders of pregnancy (HDP). Few studies with data from nationwide cohorts have elucidated the association between MA and obstetric complications comprehensively while accounting for the subdivided objective biomarkers of MA. What this Study Adds? MA with subdivided total serum IgE levels was associated with various obstetric complications. Total serum IgE level may be a potential prognostic marker for pregnant women with MA to predict the potential risk of PTB, SGA infants, and HDP. [ABSTRACT FROM AUTHOR]

• Maternal triglyceride is important for fetal growth. • Higher maternal triglyceride levels in the second or third trimesters were associated with risks of LGA. • Lower maternal triglyceride levels in the second or third trimesters were associated with risks of SGA. Although maternal triglyceride (TG) is important for fetal growth, there are few large cohort studies investigating the relationships between maternal TG during pregnancy and neonatal outcomes. The objective of this study was to investigate the associations between maternal TG during the second and third trimesters and neonatal outcomes including preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA) and large for gestational age (LGA). This was a prospective birth cohort study using data of the Japan Environment and Children's Study included data of births from 2011–2014 in Japan including 79,519 pairs. Participants were divided into tertiles according to maternal TG in the second or third trimesters. Multiple logistic regression modeling was used to examine the risks of LBW, SGA, LGA and PTB in association with maternal TG levels in the second or third trimesters In the second trimester, compared with reference TG group (T2), women in higher TG group (T3) and lower TG group (T1) were also at increased risk of LGA (aOR 1.20, 95% CI 1.11–1.29) and SGA (aOR 1.25, 95% CI 1.10–1.41), respectively. In the third trimester, women in T3 and T1 were at increased risk of LGA (aOR 1.27, 95% CI 1.17–1.38) and SGA (aOR 1.17, 95% CI 1.02–1.34), respectively. In this study, higher maternal TG levels in the second or third trimesters were associated with risks of LGA, however, lower maternal TG levels in the second or third trimesters were conversely associated with risks of SGA. [ABSTRACT FROM AUTHOR]

Objective: Tacrolimus is one of the drugs that can be used in pregnancies complicated with systemic lupus erythematosus (SLE), but there are still few reports on its pregnancy outcomes. Although tacrolimus has been reported to cause adverse events, such as increased blood pressure, abnormal glucose metabolism, and susceptibility to infection, there have been no studies on the impact of tacrolimus in SLE pregnancies at these points. We performed a retrospective observational study of pregnancies complicated by SLE at St Luke's International Hospital in Tokyo from April 2003 to August 2021. Methods: Basic clinical information on SLE, pregnancy outcomes, disease activity before and after pregnancy, laboratory results, blood pressure, blood glucose levels, treatment regimens, and presence of infection was extracted from electronic medical records. We defined overall adverse pregnancy outcomes (APOs) as follows: (1) fetal death after 10 gestational weeks, (2) preterm delivery, (3) delivery due to hypertensive disorders of pregnancy, preeclampsia, or placental insufficiency, or (4) the diagnosis of small for gestational age infants. We also examined whether there was a statistical difference in APO incidence between patients treated with and without tacrolimus. Results: Pregnancy outcomes were obtained for 48 patients with a total of 60 pregnancies complicated by SLE. In 20 (33.3%) of these pregnancies, the patients took tacrolimus, and 28 (46.7%) of the pregnancies had APOs. APO incidence did not statistically differ between the tacrolimus and non-tacrolimus groups in the multivariate analysis (p = 1.00, adjusted OR 1, 95% CI: 0.23–4.39). Multiple regression analyses indicated that tacrolimus use did not significantly affect systolic blood pressure in the third trimester (B = −2.23, p =.74) or blood glucose levels in the first trimester (B = 10.2, p =.056). Incidence of infections did not significantly differ between patients treated with and without tacrolimus in the univariate analysis (10.8% vs. 21.1%, p =.42). Conclusion: Tacrolimus did not significantly affect pregnancy outcomes, blood pressure, or glucose levels. Further research is required to confirm its effects in a larger population. [ABSTRACT FROM AUTHOR]

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

Aims: To evaluate the perinatal outcomes by gestational weight gain (GWG) range at 30 weeks of gestation among underweight pregnant women (pre‐pregnancy body mass index ≤ 18.5 kg/m2) in Japan. Methods: This retrospective study was conducted at a hospital in Japan from 2003 to 2020. The underweight pregnant women (UPW; n = 3643) were divided into quartile groups based on the weight gain at 30 weeks of gestation: group Q1 ≤ 5.7 kg, 5.7 kg < Q2 ≤ 7.2 kg, 7.2 kg < Q3 ≤ 8.8 kg, and 8.8 kg < Q4. Clinical characteristics and outcomes were compared using the t‐test, chi‐square test, and multivariable logistic regression analysis. Results: The cumulative incidences of preterm births were 7.5% (n = 70), 5.0% (n = 45), 5.4% (n = 50), and 4.9% (n = 44), and the birth rates of small for gestational age (SGA) infants were 15.7% (n = 147), 9.6% (n = 87), 6.9% (n = 64), and 5.9% (n = 53) in Q1, Q2, Q3, and Q4, respectively. Multivariable analysis revealed that Q1 was significantly associated with preterm births (adjusted odds ratio [aOR] = 1.6; 95% confidence interval [CI] = 1.0–2.3), and Q1 and Q2 were significantly associated with SGA (adj. OR = 3.0; 95% CI = 2.2–4.3; adj. OR = 1.7; 95% CI = 1.2–2.5, respectively). None of the quartile groups were significantly associated with the incidence of primary cesarean sections, gestational diabetes mellitus, and macrosomia. Conclusions: In UPW, GWG at 30 weeks of ≤5.7 kg and ≤7.2 kg are associated with preterm birth and SGA rates, respectively. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the coronavirus disease 2019 pandemic's impact on pregnancy outcomes in a Japanese rural area. Methods: This retrospective study focused on the periods between March 1, 2020, and February 28, 2021 (during the coronavirus disease 2019 pandemic), and January 1, 2017, and December 31, 2019. Singleton pregnancies delivered at or after 22 gestational weeks were included. Preterm delivery, low‐birth‐weight, and small‐for‐gestational‐age infant rates during the pandemic were compared to those in the preceding 3 years. Results: In the pandemic and control groups, 1650 and 5762 pregnant women were included, respectively. Two pregnant women with coronavirus disease 2019 were identified (0.1%). There were no significant intergroup differences in preterm delivery rates (control, 4% vs. pandemic, 3.3%; difference: −0.7% [95% confidence interval: −1.7%–0.3%], p = 0.22). The low‐birth‐weight rate tended to decrease; however, the difference was insignificant (7.9% vs. 6.5%; difference: −1.4% [95% confidence interval: −2.8–0%], p = 0.06). The small‐for‐gestational‐age infant rate was significantly lower in the pandemic than in the control group (7.3% vs. 5.2%; difference: −2.1% [95% confidence interval: −3.3–0.8%], p < 0.01). However, the interrupted time series analysis showed no significant trend. Conclusions: There were no significant changes in the rates of preterm delivery, low‐birth‐weight infants, and small‐for‐gestational‐age infants during the pandemic's first year compared to those in the preceding 3 years. Behavioral changes, such as "stay‐at‐home" measures, may not improve pregnancy outcomes in Japan. [ABSTRACT FROM AUTHOR]

Low birth weight (LBW), small for gestational age (SGA), and preterm birth (PTB) are important neonatal outcomes that may affect infant morbidity and mortality. The aim of this study is to investigate associations between maternal hemoglobin (Hb) concentrations and pregnancy outcomes of LBW, SGA, and PTB. This was a prospective birth cohort study using data of the Japan Environment and Children's Study. Participants were divided into five groups according to maternal Hb (g/dL) in the first and second trimesters: group 1, Hb < 9; group 2, 9 ≤ Hb < 11.0; group 3, 11.0 ≤ Hb < 13.0; group 4, 13.0 < Hb < 14.0; and group 5, 14.0 ≤ Hb. We examined the relationships between LBW, PTB, SGA, and maternal Hb in the first and second trimesters. Excluding 29,673, a total of 74,392 newborns (first trimester: n = 39,084, second trimester: n = 35,308) were included. We obtained adjusted odds ratios (aORs) (95% confidence intervals (CIs)) using multivariate analysis; compared with group 3 in the first trimesters, women in group 1 were at increased risk of PTB (aOR, 3.20; 95% CI, 1.69–6.09), LBW (aOR, 2.21; 95% CI, 1.19–4.09). In the second trimester, multivariate analysis revealed that, compared with group 3 in the second trimester, women in group 1 were at increased risk of PTB (aOR, 2.30; 95% CI, 1.19–4.42) and women in group 5 were at increased risk of LBW (aOR, 1.87; 95% CI, 1.24–2.81) and PTB (aOR, 1.73; 95% CI, 1.06–2.83). Elevated maternal Hb in the second trimester was associated with risks of PTB and LBW. [ABSTRACT FROM AUTHOR]

Background: Cerclage for uterine cervical incompetence can be performed by the transabdominal or transvaginal approach. Transabdominal cerclage (TAC) is indicated for women with a short cervix or a cervical laceration who are inapplicable to transvaginal cerclage (TVC). The larger the volume of tissue removed in cervical conization, the greater the rate of miscarriage or preterm delivery in the subsequent pregnancy. Aims: The aim of this study was to compare TAC and TVC in post‐cervical conization pregnancies. Methods: A retrospective, two‐group, comparative study was conducted involving subjects who underwent cervical cerclage (TAC, n = 14; TVC, n = 18) following cervical conization and who were cared for at the University of Miyazaki Hospital between 2008 and 2020. We compared study subject characteristics and outcomes between the two groups. Primary outcome was incidence of preterm labor <37 weeks of gestation between the two groups. Results: The preoperative median cervical length was significantly shorter in the TAC group (20.0 mm) than in the TVC group (31.0 mm; p < 0.01). Preoperative vaginal discharge cultures positive for Gardnerella showed a tendency to be greater in the TAC group (p = 0.073). There was no significant difference in the preterm delivery rate < 37 weeks of gestation between TAC (1/14, 7.1%) and TVC (6/18, 33.3%) groups, p = 0.10. Noninferiority test using multiple regression analysis showed that TAC is not inferior to TVC regarding gestational age at delivery, even though cervical length of TAC was significantly shorter. Conclusion: Women who were inapplicable to TVC due to a short cervix still achieved an equivalent outcome with TAC. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the association between stage 1 hypertension, defined as systolic blood pressure (BP) of 130-139 mmHg or diastolic BP of 80-89 mmHg, in the first and second trimesters and the risk of adverse pregnancy outcomes.Study Design: We analyzed 79,249 singleton pregnancies from a nationwide birth cohort study. BP in the first and second trimesters was classified into normal, elevated, stage1 hypertension, and stage 2 hypertension. We examined the risk of adverse pregnancy outcomes in each group using multivariable logistic regression analysis. We also investigated the influence of BP changes between the first and second trimesters on adverse pregnancy outcomes.Main Outcome Measures: Overall preterm birth (PTB < 37 weeks), early PTB (<34 weeks), and small for gestational age (SGA).Results: Stage 1 hypertension in the first trimester was associated with increased risks of overall PTB (aOR, 1.23; 95 %CI, 1.08-1.39), early PTB (aOR, 1.38; 95 %CI, 1.07-1.79), and SGA (aOR, 1.19; 95 %CI, 1.04-1.36) compared to normal BP. These risks were more evident in the second trimester; overall PTB (aOR, 1.87; 95 %CI, 1.64-2.14), early PTB (aOR, 2.21; 95 %CI, 1.69-2.87), and SGA (aOR, 1.38; 95 %CI, 1.18-1.62). The risk of PTB was higher among women with an upward BP trajectory between the first and second trimesters.Conclusions: Stage 1 hypertension in the first and second trimesters was associated with increased risks of overall PTB, early PTB, and SGA. Monitoring the BP trajectory for stage 1 hypertension may be useful for identifying high-risk groups. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have reported that ambient air pollutants such as PM2.5 can increase the risk of adverse birth outcomes. The objective of this study was to ascertain whether air purifier usage during pregnancy is associated with a lower risk of adverse birth outcomes in a large Japanese birth cohort., Methods: We conducted a prospective cohort analysis using data from the Japan Environment and Children's Study. Use of air purifiers during pregnancy was assessed using a self-administered questionnaire. Primary outcomes were the prevalence of preterm birth (PTB), small for gestational age (SGA), and low birth weight (LBW). Logistic regression analysis was performed to estimate odds ratios (ORs) and 95% confidence intervals (CIs)., Results: The prevalence of outcomes was 4.5% for PTB, 7.4% for SGA, and 8.1% for LBW. The crude model analysis revealed that PTB, SGA, and LBW showed lower ORs in the group that used an air purifier, although the association disappeared in the adjusted model except for SGA (OR: 0.94; 95% CI: 0.89, 1.00, p = 0.048) and LBW (OR: 0.93; 95% CI: 0.88, 0.98, p = 0.003). Subgroup analysis stratified by infant sex revealed that the lower OR for LBW was observed only in male infants., Conclusions: Our results suggest that avoiding maternal air pollution exposure during pregnancy may be useful in preventing adverse birth outcomes. These findings provide evidence supporting the development of protective measures against air pollutants in the gestational period by relevant health agencies., Competing Interests: Declarations. Ethics approval and consent to participate: All procedures involving human subjects in the JECS protocol were reviewed and approved by the Japanese Ministry of the Environment’s Institutional Review Board on Epidemiological Studies (100910001) and the ethics committees of all participating institutions. All participants in this study gave their informed consent. This specific research was further approved by the Institutional Review Board of the University of Toyama (R2023221). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective  We examined the effects of maternal hypertensive disorders of pregnancy (HDP) on the mortality and neurodevelopmental outcomes in preterm very low birth weight (VLBW) infants (BW ≤1,500 g) based on their intrauterine growth status and gestational age (GA). Study Design  We included singleton VLBW infants born at <32 weeks' gestation registered in the Neonatal Research Network Japan database. The composite outcomes including death, cerebral palsy (CP), and developmental delay (DD) at 3 years of age were retrospectively compared among three groups: appropriate for GA (AGA) infants of mothers with and without HDP (H-AGA and N-AGA) and small for GA (SGA) infants of mothers with HDP (H-SGA). The adjusted odds ratios (AOR) and 95% confidence intervals (CI) stratified by the groups of every two gestational weeks were calculated after adjusting for the center, year of birth, sex, maternal age, maternal diabetes, antenatal steroid use, clinical chorioamnionitis, premature rupture of membranes, non-life-threatening congenital anomalies, and GA. Results  Of 19,323 eligible infants, outcomes were evaluated in 10,192 infants: 683 were H-AGA, 1,719 were H-SGA, and 7,790 were N-AGA. Between H-AGA and N-AGA, no significant difference was observed in the risk for death, CP, or DD in any GA groups. H-AGA had a lower risk for death, CP, or DD than H-SGA in the 24 to 25 weeks group (AOR: 0.434, 95% CI: 0.202–0.930). The odds for death, CP, or DD of H-SGA against N-AGA were found to be higher in the 24 to 25 weeks (AOR: 2.558, 95% CI: 1.558–3.272) and 26 to 27 weeks (AOR: 1.898, 95% CI: 1.427–2.526) groups, but lower in the 30 to 31 weeks group (AOR: 0.518, 95% CI: 0.335–0.800). Conclusion  There was a lack of follow-up data; however, the outcomes of liveborn preterm VLBW infants of mothers with HDP depended on their intrauterine growth status and GA at birth. Key Points The effects of HDP on preterm low birth weight infants need to be further examined. The outcomes were not different between AGA infants with and without maternal HDP. The outcomes of SGA infants with maternal HDP were dependent on their GA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: Infants born small for gestational age (SGA) with no catch-up growth (No-CU) are at high risk of intellectual and developmental disabilities. However, factors leading to No-CU among SGA infants are unclear. This study aimed to examine the association between maternal total cholesterol (TC) in mid-pregnancy and No-CU at 3 years among full-term SGA infants. Study Design: The Japan Environment and Children's Study (JECS) is a nationwide prospective birth cohort study. We extracted a total of 2,222 mothers and full-term SGA infants (length and/or weight <-2 standard deviation [SD]) without congenital abnormalities from the original JECS cohort comprising a total of 104,062 fetal records. According to the distribution of maternal TC in the entire cohort, participants were classified into nine groups per each fifth percentile with the 20th-79th percentiles (204-260 mg/dl) as the reference group. No-CU was defined by a Z-score of height at 3 years <-2 SD according to the growth standard charts for Japanese children. Multivariable-adjusted logistic regression models were carried out using multiple imputations. Additionally, a multipleadjusted restricted cubic spline model was performed in the complete dataset. Results: A total of 362 (16.3%) children were No-CU at 3 years. After adjusting for the Zscore of birth weight, age of mother, smoking status, weight gain during pregnancy, breastfeeding and meal frequency at 2 years, and parents' heights, the odds ratio (95% confidence intervals) of No-CU was 2.95 (1.28-6.80) for children whose maternal TC levels were in the highest category (=294 mg/dl), compared to the reference group. A multiple-adjusted restricted cubic spline model showed a non-linear trend of the significant association between high maternal TC and No-CU (p for linear trend = 0.05, p for quadratic trend <0.05). Conclusion: High maternal TC at mid-pregnancy was associated with No-CU among SGA infants. Such infants should be carefully followed up to introduce appropriate growth hormonal treatment. The findings may support previous animal experimental studies which indicated that maternal high-fat diet exposure induces impairment of growth and skeletal muscle development in the offspring. Future studies are required to elucidate the detailed mechanism. [ABSTRACT FROM AUTHOR]

This study aimed to construct a prediction model for small-for-gestational-age (SGA) infants in Japan by creating a risk score during pregnancy. A total of 17,073 subjects were included in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study, a prospective cohort study. A multiple logistic regression model was used to construct risk scores during early and mid-gestational periods (11–17 and 18–21 weeks of gestation, respectively). The risk score during early gestation comprised the maternal age, height, body mass index (BMI) during early gestation, parity, assisted reproductive technology (ART) with frozen-thawed embryo transfer (FET), smoking status, blood pressure (BP) during early gestation, and maternal birth weight. The risk score during mid-gestation also consisted of the maternal age, height, BMI during mid-gestation, weight gain, parity, ART with FET, smoking status, BP level during mid-gestation, maternal birth weight, and estimated fetal weight during mid-gestation. The C-statistics of the risk scores during early- and mid-gestation were 0.658 (95% confidence interval [CI]: 0.642–0.675) and 0.725 (95% CI: 0.710–0.740), respectively. In conclusion, the predictive ability of the risk scores during mid-gestation for SGA infants was acceptable and better than that of the risk score during early gestation. [ABSTRACT FROM AUTHOR]

Aims/Introduction: We investigated the association between gestational diabetes mellitus (GDM) and perinatal outcomes stratified by pre‐pregnancy body mass index (BMI) and/or gestational weight gain (GWG). Materials and Methods: Data from the national birth cohort in the Japan Environment and Children's Study from 2011 to 2014 (n = 85,228) were used. Japan uses the GDM guidelines of the International Association of Diabetes and Pregnancy Study Groups. The odds ratios (ORs) of perinatal outcomes were compared between women with and those without GDM. Results: The OR (95% confidence interval) of having a small for gestational age infant in the GDM group with a pre‐pregnancy BMI of ≥25.0 kg/m2 and insufficient GWG (<2.75 kg) was 1.78 (1.02–3.12). The OR of having a large for gestational age infant of the same BMI group with excessive GWG (>7.25 kg) was 2.04 (1.56–2.67). The OR of hypertensive disorders of pregnancy was higher in women with a BMI ≥18.5 kg/m2 in the GDM group than in the non‐GDM group. Conclusions: Large for gestational age and hypertensive disorders of pregnancy were associated with pre‐pregnancy BMI and GWG in either normal weight or overweight/obese women, and the relationship was strengthened when GDM was present. Women with GDM and a BMI of ≥25.0 kg/m2 are at risk of having small for gestational age and large for gestational age infants depending on GWG. [ABSTRACT FROM AUTHOR]

The article presents a case study of two siblings diagnosed with cartilage-hair hypoplasia (CHH) through newborn screening for severe combined immunodeficiency (SCID) followed by next-generation sequencing (NGS). It is reported that CHH is a rare disorder characterized by skeletal dysplasia, short stature, hair hypoplasia, immunodeficiency, and an increased risk of various conditions.

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

Context: Maternal cholesterol is important for fetal development. Whether maternal serum total cholesterol (maternal TC) levels in midpregnancy are associated with small SGA) or large (LGA) for gestational age independent of prepregnancy body mass index (BMI) and weight gain during pregnancy is inconclusive. Objective: This work aimed to prospectively investigate the association between maternal TC in midpregnancy and SGA or LGA. Methods: The Japan Environment and Children's Study is a nationwide prospective birth cohort study in Japan. Participants in this study included 37 449 nondiabetic, nonhypertensive mothers with singleton birth at term without congenital abnormalities. Birth weight for gestational age less than the 10th percentile and greater than or equal to the 90th percentile were respectively defined as SGA and LGA by the Japanese neonatal anthropometric charts. Results: The mean gestational age at blood sampling was 22.7 ± 4.0 weeks. After adjustment for maternal age, sex of child, parity, weight gain during pregnancy, prepregnancy BMI, smoking, alcohol drinking, blood glucose levels, household income, and study areas, 1-SD decrement of maternal TC was linearly associated with SGA (odds ratio [OR]: 1.20; 95% CI, 1.15-1.25). In contrast, 1-SD increment of maternal TC was linearly associated with LGA (OR: 1.13; 95% CI, 1.09-1.16). Associations did not differ according to prepregnancy BMI and gestational weight gain (P for interaction > .20). Conclusion: Maternal TC levels in midpregnancy were associated with SGA or LGA in a Japanese cohort. It may help to predict SGA and LGA. Favorable maternal lipid profiles for fetal development must be explored. [ABSTRACT FROM AUTHOR]

Aim: In postpartum women, retained placenta is diagnosed in the absence of signs of placental separation and expulsion, and requires manual removal of the placenta (MROP). MROP may lead to massive hemorrhage, hemodynamic instability, and the need for emergency interventions including blood transfusion, interventional radiology, and hysterectomy. In this study, we aimed to identify the risk factors for retained placenta requiring MROP after vaginal delivery and postpartum hemorrhage (PPH) following MROP. Methods: A multicenter retrospective study was performed using data from women who delivered at term between 2010 and 2018 at 13 facilities in Japan. Of 36 454 eligible women, 112 women who required MROP were identified. Multivariate logistic regression analyses were conducted to evaluate the risk factors for retained placenta and PPH following MROP. Results: A history of abortion, assisted reproductive technology (ART), instrumental delivery, and delivery of small‐for‐gestational‐age infant were independent risk factors for MROP (adjusted odds ratios [95% confidence intervals]: 1.93 [1.28–2.92], 8.41 [5.43–13.05], 1.80 [1.14–2.82], and 4.32 [1.97–9.48], respectively). ART was identified as an independent risk factor for PPH (adjusted odds ratio [95% confidence interval]: 6.67 [2.42–18.36]) in patients who underwent MROP. Conclusion: ART pregnancies significantly increased the risk of retained placenta requiring MROP and PPH. Our results suggest that clinicians need consider patient transfer to a higher‐level facility and preparation of sufficient blood products before initiating MROP in cases of ART pregnancies. Our study may assist in identifying high‐risk women for PPH before MROP and in guiding treatment decisions, especially in facilities without a blood bank. [ABSTRACT FROM AUTHOR]

Background: Children born small for gestational age (SGA), particularly when associated with an extremely low birthweight (ELBW), have a higher risk of renal dysfunction. Growth hormone (GH) treatment is used to treat short‐statured children born SGA; however, its effects on renal function remain elusive, especially in those born SGA with ELBW. Methods: Short‐statured children born SGA (N = 42) were included. Subjects were subdivided into two groups based on their birthweight: the ELBW group (N = 15) with a birthweight of <1,000 g, and the non‐ELBW group (N = 27) with birthweights ranging between 1,000 and 2,500 g. The creatinine‐based estimated glomerular filtration rates (eGFR) before (pre‐eGFR) and 5 years after GH treatment (post‐eGFR) were compared. Correlations between eGFR, anthropometric, or birth parameters, and cumulative GH dose were evaluated using Spearman's rank correlation coefficient. Results: The ELBW group had a lower pre‐ and post‐eGFR than the non‐ELBW group. Five‐year GH treatment did not significantly reduce eGFR in either group. Post‐eGFR was positively associated with gestational week and birthweight. However, the cumulative GH dose was not correlated with pre‐eGFR, post‐eGFR, or percentage change in eGFR (%ΔeGFR). The change in bodyweight standard deviation score during GH treatment was positively correlated with %ΔeGFR in the ELBW group. Conclusions: The current results indicated that GH treatment was unlikely a risk for the reduction in eGFR in short‐statured children born SGA. However, eGFR should be carefully monitored, especially in those born SGA with ELBW because these subjects had lower eGFR than non‐ELBW subjects. [ABSTRACT FROM AUTHOR]

Low-birthweight (LBW; <2,500 g) babies are at a higher risk of poor educational achievement, disability, and metabolic diseases than normal-birthweight babies in the future. However, reliable data on factors that contribute to LBW have not been considered previously. Therefore, we aimed to examine the distribution of the causes for LBW. A retrospective review of cases involving 4,224 babies whose mothers underwent perinatal care at Keio University Hospital between 2013 and 2019 was conducted. The LBW incidence was 24% (1,028 babies). Of the 1,028 LBW babies, 231 babies were from multiple pregnancies. Of the 797 singleton LBW babies, 518 (65%) were born preterm. Obstetric complications in women with preterm LBW babies included premature rupture of membrane or labor onset (31%), hypertensive disorders of pregnancy (HDP, 64%), fetal growth restriction (24%), non-reassuring fetal status (14%), and placental previa/vasa previa (8%). Of the 279 term LBW babies, 109 (39%) were small for gestational age. Multiple logistic regression analyses revealed the following factors as LBW risk factors in term neonates: low pre-pregnancy maternal weight, inadequate gestational weight gain, birth at 37 gestational weeks, HDP, anemia during pregnancy, female sex, and neonatal congenital anomalies. HDP was an LBW risk factor not only in preterm births but also in term births. Our results suggest that both modifiable and non-modifiable factors are causes for LBW. It may be appropriate to consider a heterogeneous rather than a simple classification of LBW and to evaluate future health risks based on contributing factors. [ABSTRACT FROM AUTHOR]

Background: Although low birth weight in Japan has slightly increased over the past several decades, the association between maternal birth weight and pregnancy outcomes remains poorly understood. Methods: In this hospital-based, prospective cohort study conducted at the National Center for Child Health and Development, we obtained information on pregnant women's birth weight via their maternal and child health handbook. We analyzed 944 women born at term after dividing them into five categories according to their birth weight: <2500 g, 2500–2999 g, 3000–3499 g, 3500–3999 g, and ≥4000 g. Multivariate logistic regression analysis and trend analysis were used to elucidate the extent to which maternal birth weight was associated with small-for-gestational-age and low birth weight in offspring, as well as with hypertensive disorders of pregnancy. Results: Compared with women with a birth weight of 3000–3499 g, those born with a birth weight <2500 g had a significantly higher risk of low birth weight (adjusted odds ratio: 5.39, 95% confidence interval: 2.06–14.1) and small-for-gestational-age (adjusted odds ratio: 9.11, 95% confidence interval: 3.14–26.4) infants. No significant association was found between the incidence of hypertensive disorders of pregnancy and preterm birth. A linear relationship was observed between the lower birth weight categories and a higher risk of low birth weight and small-for-gestational-age (p-values for trends: 0.009 and <0.001, respectively), but no linear relationship was observed for the risk of preterm birth and hypertensive disorders of pregnancy (p-value for trends: 0.317 and 0.157, respectively). Conclusions: Our findings suggest that lower maternal birth weight is associated with small-for-gestational-age and low birth weight in offspring of women born at term. [ABSTRACT FROM AUTHOR]

Background: (Epi)genetic disorders associated with small-for-gestational-age with short stature (SGA-SS) include imprinting disorders (IDs). Silver-Russell syndrome (SRS) is a representative ID in SGA-SS and has heterogenous (epi)genetic causes.Subjects and Methods: To clarify the contribution of IDs to SGA-SS and the molecular and phenotypic spectrum of SRS, we recruited 269 patients with SGA-SS, consisting of 103 and 166 patients referred to us for genetic testing for SGA-SS and SRS, respectively. After excluding 20 patients with structural abnormalities detected by comparative genomic hybridization analysis using catalog array, 249 patients were classified into 3 subgroups based on the Netchine-Harbison clinical scoring system (NH-CSS), SRS diagnostic criteria. We screened various IDs by methylation analysis for differentially methylated regions (DMRs) related to known IDs. We also performed clinical analysis.Results: These 249 patients with SGA-SS were classified into the "SRS-compatible group" (n = 148), the "non-SRS with normocephaly or relative macrocephaly at birth group" (non-SRS group) (n = 94), or the "non-SRS with relative microcephaly at birth group" (non-SRS with microcephaly group) (n = 7). The 44.6% of patients in the "SRS-compatible group," 21.3% of patients in the "non-SRS group," and 14.3% in the "non-SRS with microcephaly group" had various IDs. Loss of methylation of the H19/IGF2:intergenic-DMR and uniparental disomy chromosome 7, being major genetic causes of SRS, was detected in 30.4% of patients in the "SRS-compatible group" and in 13.8% of patients in the "non-SRS group."Conclusion: We clarified the contribution of IDs as (epi)genetic causes of SGA-SS and the molecular and phenotypic spectrum of SRS. Various IDs constitute underlying factors for SGA-SS, including SRS. [ABSTRACT FROM AUTHOR]

This study aimed to characterize the safety and effectiveness of GH treatments, in usual clinical practice, in children with short stature born small for gestational age (SGA). This was a multicenter, open-label, non-interventional study (NCT01110928) conducted at 150 sites in Japan (2009-2018). The primary objective was to assess the type and frequency of serious adverse drug reactions (SADRs) associated with long-term GH use. Overall, 452 naïve and 46 non-naïve (previously treated) children were enrolled. GH treatment was well-tolerated, with SADRs occurring in 1.3% (6/452) and 0% (0/46) of naïve and non-naïve children, respectively. No new safety concerns or notable changes in glucose metabolism were identified during long-term treatment. Altogether, 57 children (32 naïve and 25 non-naïve) reached near adult height (NAH). In naïve and non-naïve children, mean ± standard deviation (SD) height standard deviation score (SDS) at NAH were -2.03 ± 0.77 and -1.53 ± 0.81, respectively, representing a change of +0.85 ± 0.72 and +1.24 ± 0.66 from baseline height SDS, respectively. Mean treatment duration to NAH was 4.29 (naïve) and 7.26 (non-naïve) yr. Thus, long-term GH treatment for short stature in children born SGA was confirmed to have a good safety profile and was effective for improving adult height. [ABSTRACT FROM AUTHOR]

Introduction: The average birth weight in Japan has gradually decreased and the number of low birth weight infant has increased over the last 30 years. Japanese pregnant women are characterized with lower prevalence of obesity than those in other developed countries, and maternal underweight before pregnancy is independently associated with low birth weight. However, the association between maternal inadequate gestational weight gain (GWG) and the risk of small for gestational age (SGA) in Japanese uncomplicated pregnant women has not been fully understood. This study aimed to examine the effect of maternal inadequate GWG on the risk of SGA in Japanese uncomplicated pregnancies.Methods: We retrospectively analyzed uncomplicated Japanese singleton pregnancies that delivered at term gestation in our institution from 2006 to 2016. The association between GWG and birth weight was analyzed by multiple linear regression. Potential confounding factors included maternal age, parity, prepregnancy BMI, and neonatal sex. The association between inadequate GWG and SGA was also examined by logistic regression.Results: A total of 3837 mother-neonate dyads were analyzed. Maternal GWG was 10.1 ± 3.7 kg (mean ± SD), and 2529 (66%) had inadequate GWG. After adjusting for confounding factors, GWG significantly correlated with birth weight (standardized β  =  0.199, p < .001). Inadequate GWG increased the risk of delivering SGA neonate (adjusted odds ratio (aOR) = 1.97 [1.45-2.68], p < .001). This association was particularly pronounced in underweight (aOR = 2.95 [1.38-6.29], p = .005) and normal weight mothers (aOR = 1.79 [1.27-2.52], p = .001), and not in overweight/obese mothers (p = .115).Conclusion: Maternal GWG is associated with birth weight in Japanese women with uncomplicated singleton pregnancies. Inadequate GWG is an important risk factor of SGA, particularly in non-obese women. The present finding would potentially provide further evidence that promoting adequate gestational weight gain in Japanese underweight and normal weight mothers would reduce SGA, as well as metabolic dysfunction in later life. [ABSTRACT FROM AUTHOR]

Background: The hypothesis of the Developmental Origins of Health and Disease states that environmental factors during fetal and infantile life are risk factors for some chronic diseases in adulthood. Few studies, however, have confirmed this hypothesis early in childhood. Therefore, we assessed how premature birth and low‐birthweight (LBW) affect the renal function of Japanese children. Methods: This retrospective study surveyed 168 patients who were born before 35 weeks of gestation and were cared for at the present neonatal intensive care unit. Follow‐up duration was >2 years. Serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) recorded in medical records were reviewed. Results: The eGFR at 2 years of age was significantly correlated with birthweight and gestational age (P < 0.01). Approximately 10.7% of the children had low eGFR (<90 mL/min/1.73 m2) without clinical symptoms or abnormal urine examination. These children had high sCr on day 7 after birth (P < 0.01) and delayed recovery of these levels during the first month after birth. Conclusion: Premature gestational age and LBW directly affect renal function in young children. High sCr on day 7 after birth is a risk factor for chronic kidney disease in children. Careful follow up of renal function is therefore required for premature infants and infants with LBW beginning in early childhood to prevent renal dysfunction. [ABSTRACT FROM AUTHOR]

Background: Women with congenital heart disease (CHD) commonly experience complications related to CHD during pregnancy. The clinical features of neonates born to mothers with CHD, however, have not been fully investigated. The frequency of small for gestational age (SGA) is high in infants born to mothers with CHD, but the risk factors have not been examined sufficiently. Therefore, we analyzed the maternal features associated with SGA infants. Methods and Results: We enrolled pregnant women with repaired CHD and infants born to them at Tokyo Women's Medical University Hospital between April 2007 and March 2015. Eleven SGA (11%) and 91 non‐SGA infants (89%) were included. On multivariate logistic regression, SGA infants were significantly more likely to be associated with a high maternal brain‐type natriuretic peptide (BNP) level (OR, 6.7; 95%CI: 1.3–34.5; P = 0.02) and maternal single ventricle disease (OR, 8.4; 95%CI:1.4–51.8; P = 0.02) than were non‐SGA infants. Conclusions: The incidence of SGA infants born to mothers with CHD was not high in this study. High BNP and maternal single ventricle disease, however, are independent predictors of SGA in infants. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate whether there was a high incidence of young Japanese mothers being underweight (pregravid body mass index [BMI] < 18.5 kg/m2) and if they delivered infants who were small for gestational age (SGA).Materials and methods: Our study was carried out from 2013 to 2017 and included adolescent women (maternal age at delivery: <20 years old; n = 94), women in their early twenties (maternal age at delivery: 20-24 years; n = 479), and controls (maternal age at delivery: 25-34 years; n = 2061).Results: In both the adolescent and early twenties groups, the incidence of being underweight, based on prepregnancy BMI, was significantly higher than controls (p < .0001 and p < .05, respectively). In both groups, gestational weight gain (GWG) was significantly higher than controls (p < .0001). There were no notable group differences in the incidences of SGA.Conclusion: The incidence of being underweight was higher in younger mothers than in controls. However, the risk of SGA did not increase in younger mothers, possibly because their GWG overcame the influence of their pre-pregnancy body composition. [ABSTRACT FROM AUTHOR]

Aim: The effect that intrauterine or extrauterine growth restriction (EUGR) had on the build of very low birthweight (VLBW) infants was investigated before Japanese children started school.Method: Between 2005 and 2017, the National Hospital Organization, Saga, Japan, carried out preschool checks on 322 children born with a VLBW at approximately six years of age. Growth restriction was defined as being born small for gestational age (SGA) or EUGR if they were born at term. The prevalence of short stature, thinness and obesity was determined, and associations between SGA or EUGR and subsequent body build were investigated.Results: In this study, 77 of 322 (23.9%) infants were SGA and 153 of 322 (47.5%) were EUGR: 14 of 77 (18.2%) SGA infants caught up in growth to the 169 non-EUGR infants, while 90 of 245 (36.7%) appropriate for gestational age infants subsequently demonstrated EUGR. There were 38 (11.8%) short stature, 38 (11.8%) thin and six (1.9%) obese subjects in the total cohort and growth hormone deficiencies in nine (2.8%) cases. We found significant associations between EUGR and both short stature and thinness.Conclusion: Extrauterine growth restriction was significantly associated with short stature and thinness in VLBW infants at around six years, irrespective of the degree of SGA. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Previous studies have shown adverse obstetric outcomes of the laparoscopic resection of a rudimentary horn. Our study aimed to investigate the obstetric outcome in our institution and to review previous studies. Methods: Using a retrospective analysis, data were reviewed from singleton pregnancies with maternal uterine anomalies at a medical center in Osaka, Japan, between January 2011 and March 2016. The uterine anomaly cases were divided into a ‘postlaparoscopic resection of the rudimentary horn’ group (study group) and an ‘other uterine anomalies’ (bicornuate uterus, uterine didelphys and unicornuate uterus) group (control group). Primary outcomes of interest were differences in obstetric outcomes, such as spontaneous preterm birth rate, small for gestational age (SGA) infant rate and hypertensive disorders of pregnancy (HDP) rate between the study and the control group, and the secondary outcome of interest was mode of delivery in the study group. Results: Data from 40 deliveries were included in the study (7 deliveries: study group, 33 deliveries: control group). No significant difference was observed between the two groups in terms of either mean gestational weeks at delivery (36.4 weeks vs 37.1 weeks; P = .38), cesarean delivery rate (57.1% vs 57.5%; P = 1.0), SGA infant rate (<10th percentile) (0% vs 24.2%; P = .31) and HDP rate (0.0% vs 3.0%; P = 1.0). Three of seven cases with postlaparoscopic resection of the rudimentary horn were able to deliver vaginally without complications. Conclusion: Our study shows that the obstetric outcome observed in the study group was similar to that observed in the control group. [ABSTRACT FROM AUTHOR]

Evidence supporting an inverse association between maternal exposure to air pollutants and foetal growth has been accumulating. However, the findings from Asian populations are limited, and the question of critical windows of exposure remains unanswered. We examined whether maternal exposure to air pollutants, in particular exposure during the first trimester (an important period of placental development), was associated with foetal growth in Japanese term infants. From the Japan Perinatal Registry Network database, we received birth data for 29,177 term singleton births in western Japan (Kyushu-Okinawa Districts) between 2005 and 2010. Exposure was expressed in terms of average concentrations of air pollutants (ozone, suspended particulate matter, nitrogen dioxide, and sulphur dioxide), as measured at the nearest monitoring stations to the respective delivery hospitals of the pregnant women, during the entire pregnancy and each trimester. As proxy markers of foetal growth restriction, we used small for gestational age (SGA), and adverse birth weight (low birth weight in addition to SGA). For pollutant exposure during the entire pregnancy, we did not observe the association with SGA and adverse birth weight. In the single-trimester model for the first trimester, however, we found a positive association between ozone exposure, and SGA (odds ratio [OR] per 10 ppb increase = 1.07, 95% confidence interval [CI] = 1.01–1.12) and adverse birth weight (OR = 1.07; 95% CI = 1.01–1.14). This association persisted in the multi-trimester model, and no association for exposure during the second or third trimester was observed. Exposure to other pollutants during each trimester was not associated with these outcomes. In conclusion, maternal exposure to ozone during the first trimester was independently associated with an elevated risk of poor foetal growth. [ABSTRACT FROM AUTHOR]

Objectives: Small for gestational age infants have an increased risk of immediate complications, short-term morbidity and mortality, and long-term neurologic and metabolic disorders in adulthood. Previous research has shown that reduced sleep duration is a risk factor for SGA birth. However, only a few studies have evaluated maternal sleep as a risk factor for SGA birth. In the present study, we investigated the relationship between the amount and quality of mothers' sleep and infants' birth weight. Results: This cohort study (n = 8631) used data from the Japan Environment and Children's Study, an ongoing cohort study that began in January 2011. Data on sleep status (sleep duration and one indicator of sleep quality) and potential confounding factors were recorded. A log-binomial regression model was used to estimate the risk of small for gestational age birth, and the results were expressed as risk ratios and their respective 95% confidence interval. No significant results were observed for sleep duration or tiredness upon waking. Neither the amount nor the quality of mothers' sleep was associated with the risk of small for gestational age birth. [ABSTRACT FROM AUTHOR]

Background: Although adult height is inversely related with the risk of chronic disease, the association between maternal height and ischaemic placental disease remains unclear.Methods: We used the national, multicentre Japan Society of Obstetrics and Gynecology perinatal database to assess the risk of preeclampsia, placental abruption, and small for gestational age (SGA) births (birthweight < 10th percentile), which together constitute the syndrome 'ischaemic placental disease', in relation to self-reported height in 218 412 women with no underlying diseases before pregnancy, who delivered singletons in 2005-11. Height was categorised into quartiles as well as considered in linear terms, and its effect on each outcome was estimated using multivariable log binomial regression adjusted for the maternal characteristics.Results: The risk of preeclampsia, placental abruption, and SGA birth was inversely related to maternal height. In the adjusted model, mothers in the lowest quartile for height (<155 cm) were at higher risk of preeclampsia (relative risk (RR) 1.35, 95% confidence interval (CI) 1.25, 1.45), placental abruption (RR 1.20, 95% CI 1.07, 1.34), and SGA (RR 1.96, 95% CI 1.90, 2.03) compared with mothers in the highest quartile (>162 cm). When the association between height and outcomes was considered in linear terms, each 5 cm decrement in height was associated with an increased risk of preeclampsia (RR 1.11, 95% CI 1.09, 1.14), placental abruption (RR 1.04, 95% CI 1.01, 1.09), and SGA birth (RR 1.30, 95% CI 1.28, 1.31).Conclusion: Shorter height was associated with an increased risk of preeclampsia, placental abruption, and SGA birth. [ABSTRACT FROM AUTHOR]

Some children born small for gestational age (SGA) have short stature and are at an increased risk of developing psychosocial or behavioral problems. Here we evaluated the efficacy of GH and its effects on the timing of pubertal onset in a 3-yr extension of our previous 2-yr (total 5 yr) multicenter, randomized, double-blind, parallel-group clinical trial of 65 short Japanese children born SGA. Patients received low or high doses of GH (0.033 or 0.067 mg/kg/day, respectively). Age at onset of puberty was not statistically different for male and female patients receiving high- or low-dose GH. After the onset of puberty, no difference in height gain was observed between the two GH dose groups. At the onset of puberty, height standard deviation scores for chronological age of boys and girls improved significantly in both dose groups with evidence of a dose-response effect. Mean bone age/chronological age ratios in the low- and high-dose groups were significantly increased compared with baseline, being significantly greater in the high-dose group at 5 yr after treatment initiation. Delayed bone age at baseline was close to chronological age following GH treatment. GH treatment, especially high-dose GH, induced advanced bone age in short children born SGA. [ABSTRACT FROM AUTHOR]

Background: Progress in reducing the global low birthweight (LBW) has been insufficient. Although the focus has been on preventing preterm birth, evidence regarding LBW in term births is limited. Despite its low preterm birth prevalence, Japan has a higher LBW proportion than other developed countries. This study aimed to examine the prevalence of LBW in term singleton births and its associated factors using a national database., Methods: We retrospectively analyzed the data of neonates registered in the Japan Society of Obstetrics and Gynecology Successive Pregnancy Birth Registry System who were born 2013-2017. Exclusion criteria included stillbirths, delivery after 42 gestational weeks, and missing data. Logistic regression analyses were performed to investigate the maternal and perinatal factors associated with LBW in term singletons using the data of 715,414 singleton neonates., Results: The overall prevalence of LBW was 18.3%, and 35.7% of LBWs originated from singleton term pregnancies. Multiple logistic regression analyses indicated that both modifiable and non-modifiable factors were independently associated with LBW in term neonates. The modifiable maternal factors included pre-pregnancy underweight, inadequate gestational weight gain, and smoking during pregnancy, while the non-modifiable factors included younger maternal age, nulliparity, hypertensive disorders of pregnancy, cesarean section delivery, female offspring, and congenital anomalies., Conclusion: Using the Japanese pregnancy birth registry data, more than one-third of LBWs were found to originate from singleton term pregnancies. Both modifiable and non-modifiable factors were independently associated with LBW in term neonates. Prevention strategies on modifiable risk factor control will be effective in reducing LBW worldwide.

Background: Controversy exists as to whether birthweight-for-gestational age references used to classify infants as small for gestational age (SGA) should be country specific or based on an international (common) standard. We examined whether different birthweight-for-gestational age references affected the association of SGA with adverse outcomes among very preterm neonates.Methods: Singleton infants (n = 23 788) of 24(0) -28(6) weeks' gestational age in nine high-resource countries were classified as SGA (<10th centile) using common and country-specific references based on birthweight and estimated fetal weight (EFW). For each reference, the adjusted relative risk (aRR) for the association of SGA with composite outcome of mortality or major morbidity was estimated.Results: The percentage of infants classified as SGA differed slightly for common compared with country specific for birthweight references [9.9% (95% CI 9.5, 10.2) vs. 11.1% (95% CI 10.7, 11.5)] and for EFW references [28.6% (95% CI 28.0, 29.2) vs. 24.6% (95% CI 24.1, 25.2)]. The association of SGA with the composite outcome was similar when using common or country-specific references for the total sample for birthweight [aRRs 1.47 (95% CI 1.43, 1.51) and 1.48 (95% CI 1.44, 1.53) respectively] and for EFW references [aRRs 1.35 (95% CI 1.31, 1.38) and 1.39 (95% CI 1.35, 1.43) respectively].Conclusion: Small for gestational age is associated with higher mortality and morbidity in infants born <29 weeks' gestational age. Although common and country-specific birthweight/EFW references identified slightly different proportions of SGA infants, the risk of the composite outcome was comparable. [ABSTRACT FROM AUTHOR]

Risk of subsequent short stature remains unclear among mild small-for-gestational-age (SGA) infants with birthweight <10th percentile and ≥−2 standard deviations. In this multicenter cohort study in Japan, height was found to be <−2 standard deviations at 3 years old even in 18 % of mild-SGA infants. • Mild small-for-gestational-age (SGA) infants are commonly not indicated for growth hormone therapy. • The incidence of short stature or non-catch-up growth has not been well studied in this population. • Even among mild-SGA infants, short stature at 3 years of age was observed in 18 %. • Our findings provide basic data on the development of mild-SGA infants and risk factors for subsequent short stature. [ABSTRACT FROM AUTHOR]

Objective: To assess whether the mortality and morbidity risks vary with birth weight standard deviation score (BWSDS) in growth restricted extremely preterm infants.Study Design: This was a multicenter retrospective cohort study using the database of the Neonatal Research Network of Japan and including 9149 infants born between 2003 and 2010 at <28 weeks gestation. According to the BWSDSs, the infants were classified as: <-2.0, -2.0 to -1.5, -1.5 to -1.0, -1.0 to -0.5, and ≥-0.5. Infants with BWSDS≥-0.5 were defined as non-growth restricted group.Results: After adjusting for covariates, the risks of mortality and some morbidities were different among the BWSDS groups. Compared with non-growth restricted group, the adjusted odds ratio (aOR) for mortality [aOR, 1.69; 95% confidence interval (CI), 1.35-2.12] and chronic lung disease (CLD) (aOR, 1.28; 95% CI, 1.07-1.54) were higher among the infants with BWSDS -1.5 to <-1.0. The aOR for severe retinopathy of prematurity (ROP) (aOR, 1.36; 95% CI, 1.09-1.71) and sepsis (aOR, 1.72; 95% CI, 1.32-2.24) were higher among the infants with BWSDS -2.0 to <-1.5. The aOR for necrotizing enterocolitis (NEC) (aOR, 2.41; 95% CI, 1.64-3.55) was increased at a BWSDS<-2.0.Conclusion: Being growth restricted extremely preterm infants confer additional risks for mortality and morbidities such as CLD, ROP, sepsis and NEC, and these risks may vary with BWSDS. [ABSTRACT FROM AUTHOR]

Aim There is no consensus opinion regarding a possible relation between low 50-g glucose challenge test (GCT) results and small-for-gestational-age infants (SGA). This study aimed to clarify the relation between low 50-g GCT results and SGA, after adjusting for potential confounding factors, using a large clinical dataset. Material and Methods Our retrospective cohort study evaluated the obstetric records of women who delivered at Kofu Municipal Hospital (Japan) between January 2011 and December 2013. The exclusion criteria were gestational diabetes mellitus, diabetes in pregnancy, and GCT results of ≥140 mg/dL. Based on these criteria, we included 1603 women who had undergone a GCT between 24 and 28 weeks of gestation, and divided the subjects into a low-GCT group (≤90 mg/dL) and a non-low-GCT group (91-139 mg/dL). The χ2-test and multivariate logistic regression analysis were used to investigate the association between low GCT results and SGA. Results The mean subject age was 30.4 ± 5.4 years, with 45.1% nulliparity ( n = 723) and 1538 (96.0%) term deliveries. The incidence of SGA was 10.7% (172/1603), and 17.9% (287/1603) of the women had low GCT results. Low GCT results were significantly associated with an increased risk of SGA (odds ratio, 1.66; 95% confidence interval, 1.14-2.42), after controlling for maternal age, pre-pregnancy maternal weight, maternal weight gain during pregnancy, and pregnancy-induced hypertension. Conclusion It appears that there is a significant association between low GCT results and SGA. However, further studies are needed to explore the detailed mechanisms of this association. [ABSTRACT FROM AUTHOR]

Background Poor nutritional status during the fetal period could cause perinatal and lifelong health disadvantages in neonates. The aim of this study was to investigate the background of pregnant women receiving childbirth expense support (CES), pregnancy outcome, and neonatal anthropometric data. Methods A retrospective cohort study was conducted using 823 antenatal and delivery records in a perinatal center located in one of the poorest areas in Japan. Neonates who were small for gestational age (SGA) were compared between the CES and the non-CES groups. Results The incidences of low birthweight (LBW) and SGA were significantly higher in the group receiving CES (14.6% and 14.6%, respectively). The adjusted OR of CES was 2.78 (95%CI: 1.32-5.87) and the adjusted OR of maternal smoking was 5.03 (95%CI: 2.74-9.21), indicating that CES and maternal smoking were directly associated with SGA. Conclusions CES recipients had a higher prevalence of SGA infants. CES was independently associated with SGA. Previous studies have shown that smoking is a major risk factor for SGA. Further studies are needed to identify risk factors of SGA specific to CES recipients. [ABSTRACT FROM AUTHOR]