Association of placental weight at birth with maternal whole blood concentration of heavy metals (cadmium, lead, mercury, selenium, and manganese): The Japan Environment and Children's Study (JECS).

BACKGROUND: Lifelong health is dependent on prenatal growth and development, influenced by the placental intrauterine environment. Charged with dual functions--exchange of oxygen and nutrients as well as a barrier against toxins--the placenta itself is susceptible to environmental exposure to heavy metals. OBJECTIVE: To examine the use of placenta weight as a biomarker for heavy metal exposure using a large Japanese cohort of pregnant women. METHODS: The placenta weight, as a biomarker of exposure to heavy metals (cadmium, lead, and mercury), was investigated using data from the Japan Environment and Children's Study (2011-2014). Selenium and manganese were included as factors directly affecting fetal growth or heavy metal toxicity. Maternal blood samples collected in the second or third trimester were used to measure heavy metal concentrations. The association between maternal blood metal concentrations and placenta weight was explored by applying Z scores and multivariable logistic regression analysis and classifying participants into quartiles (Q1, Q2, Q3, and Q4) according to metal concentrations. RESULTS: This study included a total of 73,005 singleton pregnant women who delivered via live births and met the inclusion criteria. The median heavy metal concentrations in the maternal whole blood were 0.662 ng/g cadmium, 5.85 ng/g lead, 3.61 ng/g mercury, 168 ng/g selenium, and 15.3 ng/g manganese. Regression analysis revealed a significant correlation between placenta weight Z scores and maternal blood metal concentrations: cadmium, 0.0660 (standard error = 0.0074, p < 0.001); selenium, -0.3137 (standard error = 0.0276, p < 0.001); and manganese, 0.1483 (standard error = 0.0110, p < 0.001). CONCLUSION: This study provides a robust examination of the association between heavy metal exposure and placenta weight. Cadmium and manganese showed a positive correlation with significant differences, whereas selenium showed a negative correlation. Essential elements notably affect placenta weight differently. No significant association was noted between lead or mercury and placenta weight.

Asbestos in organochlorine insecticide powder sprinkled between pages of antiquarian books in a library in Japan.

Librarians at a university had planned to check the collection prior to the library renovations that began in 2015. They had previous knowledge of the presence of a light greyish-white powder with an unpleasant odour (hereinafter referred to as 'powder') sprinkled between the pages of antiquarian books in the library archive. The purpose of this study was to identify this powder with the help of experts from both inside and outside the university. The powder was qualitatively analysed using gas chromatography with mass spectrometry after hexane extraction. The powder was examined under a polarised light microscope and a field-emission scanning electron microscope equipped with an energy-dispersive X-ray spectrometer. Benzene hexachloride (BHC) was detected in the powder. Talc was the most abundant particle in the powder. The powder also contained 0.52 wt% asbestos, which belonged to the tremolite-actinolite series. No other types of asbestos were detected. The powder was presumed to be a bulking agent for BHC, and its major constituent was talc. This is the first report on asbestos-containing insecticides.

The COVID-19 pandemic affects pregnancy complications and delivery outcomes in Japan: a large-scale nationwide population-based longitudinal study.

The impact of the coronavirus disease 2019 (COVID-19) pandemic on pregnancy outcomes in Japan at the national level is unclear. This study aimed to assess the impact of the pandemic on pregnancy complications and delivery outcomes in Japan using nationwide population-based longitudinal data. Secondary data from the Japan Society of Obstetrics and Gynecology from 2016 to 2020 were analyzed. Obstetric information, pregnancy complications, and delivery information of pregnant women over 22 weeks of gestation were compared before and during the pandemic. The trends of hypertensive disorder of pregnancy, fetal growth restriction, and APGAR < 7 increased, whereas those of preterm birth and low birth weight decreased during the COVID-19 pandemic. Pregnancy complications and delivery outcomes have worsened during the COVID-19 pandemic in Japan. Social changes caused by unprecedented situations may have massively influenced pregnancy in several ways. Our findings suggest that even in mild lockdowns like those in Japan, the introduction of social fear during the pandemic might negatively impact pregnancy outcomes.

Maternal DHA intake in mice increased DHA metabolites in the pup brain and ameliorated MeHg-induced behavioral disorder.

Although pregnant women's fish consumption is beneficial for the brain development of the fetus due to the DHA in fish, seafood also contains methylmercury (MeHg), which adversely affects fetal brain development. Epidemiological studies suggest that high DHA levels in pregnant women's sera may protect the fetal brain from MeHg-induced neurotoxicity, but the underlying mechanism is unknown. Our earlier study revealed that DHA and its metabolite 19,20-dihydroxydocosapentaenoic acid (19,20-DHDP) produced by cytochrome P450s (P450s) and soluble epoxide hydrolase (sEH) can suppress MeHg-induced cytotoxicity in mouse primary neuronal cells. In the present study, DHA supplementation to pregnant mice suppressed MeHg-induced impairments of pups' body weight, grip strength, motor function, and short-term memory. DHA supplementation also suppressed MeHg-induced oxidative stress and the decrease in the number of subplate neurons in the cerebral cortex of the pups. DHA supplementation to dams significantly increased the DHA metabolites 19,20-epoxydocosapentaenoic acid (19,20-EDP) and 19,20-DHDP as well as DHA itself in the fetal and infant brains, although the expression levels of P450s and sEH were low in the fetal brain and liver. DHA metabolites were detected in the mouse breast milk and in human umbilical cord blood, indicating the active transfer of DHA metabolites from dams to pups. These results demonstrate that DHA supplementation increased DHA and its metabolites in the mouse pup brain and alleviated the effects of MeHg on fetal brain development. Pregnant women's intake of fish containing high levels of DHA (or DHA supplementation) may help prevent MeHg-induced neurotoxicity in the fetus.

Sleep quality and temperament in association with autism spectrum disorder among infants in Japan.

BACKGROUND: Sleep problems and irritable temperaments are common among infants with autism spectrum disorder (ASD). The prospective association between such sleep problems and irritable temperaments and ASDs needs to be determined for elucidating the mechanism and exploring the future intervention study. Thus, in this study, we investigated whether sleep quality and temperament in 1-month-old infants are associated with the onset of ASD in 3-year-old children. We also assessed its sex-stratified associations. METHODS: We conducted a longitudinal study using data from 69,751 mothers and infants from a large-cohort study, the Japan Environment and Children's Study. We examined the prospective association between infant sleep quality and temperament at 1 month of age and ASD diagnosis by 3 years of age. RESULTS: Here we show infants with longer daytime sleep have a higher risk of later ASD than those with shorter daytime sleep (risk ratio [RR]: 1.33, 95% confidence interval [CI]: 1.01-1.75). Infants who experienced intense crying have a higher risk of ASD than those who did not (RR: 1.31, 95% CI: 1.00-1.72). There is a difference in sex in the association between a bad mood and later ASD. In particular, female infants experiencing bad moods have a higher risk of ASD than others (RR: 3.59, 95% CI: 1.91-6.75). CONCLUSIONS: The study findings provide important information for future intervention to reduce the risk of future ASD.

Sleep problems and irritable temperaments are common among infants with autism. This study looked at the sleep and temperament of nearly 70,000 1-month-old infants in Japan and whether they were subsequently diagnosed with autism spectrum disorder during the first three years of life. Children who had slept for longer during the day and were more prone to frequent, prolonged, or intense crying were more likely to have been diagnosed with Autism Spectrum Disorder by age 3. The findings of this study might be useful for those monitoring the development of autism spectrum disorder or developing support for those with autism spectrum disorders.

Changes in the sleeping habits of Japanese university students during the COVID-19 pandemic: a 3-year follow-up study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has greatly changed our daily life. Owing to the imposed restrictions, many educational facilities have introduced remote teaching. This study aims to clarify the association between remote teaching and Japanese university students' sleeping habits. METHODS: The participants were medical students at Aichi Medical University. We used data from an ongoing longitudinal sleeping habits survey. For the participants who enrolled in the university during 2018-2020, multilevel analyses of sleep duration during weekdays and weekends across 3 years were conducted, adjusting for sex, grade, place of stay, sleep problems and lifestyle habits. RESULTS: Among the students enrolled in the university, the data of 677 in 2018, 657 in 2019, and 398 in 2020 was available for analysis. The mean sleep duration during weekdays (in minutes) was 407.6 ± 60.3 in 2018, 406.9 ± 63.0 in 2019, and 417.3 ± 80.9 in 2020. The mean sleep duration during weekends (in minutes) was 494.5 ± 82.5 in 2018, 488.3 ± 87.9 in 2019, and 462.3 ± 96.4 in 2020. Multilevel analysis conducted for the 684 participants who enrolled during 2018-2020 showed that sleep duration during weekdays was associated with the place of stay and survey year. Moreover, students reported significantly longer sleep duration during weekdays in 2020 than in 2019, but no significant difference in sleep duration was found between 2018 and 2019. The other multilevel analysis found sleep duration during weekends to be associated with the survey year, sex and always doing something before going to bed. Sleep duration during weekends was shorter in 2020 than in 2019 and longer for male students and students who always do something before going to bed. Ten students were reported to have a delayed sleep phase in 2020. CONCLUSIONS: Students' sleep duration increased during weekdays and decreased during weekends in 2020. This difference could be explained by the COVID-19 pandemic and the introduction of remote teaching.

The incidence of Jarisch-Herxheimer reactions and associated risk factors in pregnant women and nonpregnant women: A retrospective chart review at a university hospital in Japan.

AIMS: Jarisch-Herxheimer reactions (JHR) is a transient adverse event that occurs during initial antimicrobial treatment for syphilis patients, and is known to develop uterine contractions and fetal distress in pregnant women complicated with syphilis. The aim of this study is to identify risk factors for JHR in patients with syphilis, and to clarify whether pregnancy status is a risk factor for JHR, and to describe the characteristics of pregnant women who develop JHR. METHODS: This was a retrospective chart review in a singleton university hospital in Japan. We collected data of syphilis patients who were diagnosed and treated at department of obstetrics and gynecology, dermatology between January 2010 and May 2022. There were no validated diagnostic criteria for JHR, we defined JHR as one or more of the following in addition to raised body temperature (≧38.0°C) within 24 h of initial antibiotic treatment: headache, chills, myalgias, tachycardia (≧110 bpm), new rash. RESULTS: There were 30 syphilis patients. Of whom nine (30%) were pregnant women and all their neonates were not diagnosed with congenital syphilis. Five patients (17%) developed JHR at the time of initial treatment (JHR group, n = 5). There was no difference between JHR group and non-JHR group (n = 25) in pregnancy status. Secondary syphilis was an only significant risk factor for JHR. Two pregnant women with JHR were both treated for secondary syphilis in the third trimester of pregnancy. CONCLUSION: Pregnancy status was not a risk factor for JHR in syphilis patients. Further research is needed.

Relationship between placental hemodynamics and placental histological analysis in third trimester.

AIM: To investigate whether vascularization index (VI), flow index (FI), and vascularization flow index (VFI) correlate with the pathological structure of the placenta and whether there were any differences in VI, FI, VFI, and placental pathological structure between the normal and preeclampsia (PE) groups. METHODS: Fifty-five pregnant women (normal group, n = 27; PE group, n = 28) underwent VI, FI, and VFI at four locations in the placenta during the second and third trimesters. Two hematoxylin and eosin (HE)-stained specimens of the postpartum placenta were prepared. We randomly selected two of these locations and used ImageJ, an open-source image package, to quantify intervillous blood vessels (IBV), intervillous spaces (IS), and intervillous blood vessels + intervillous spaces (IBV + IS) per unit placenta and analyzed their correlation with VI, FI, and VFI. RESULTS: There was no positive correlation between VI, FI, VFI, IBV, IS, and IBV + IS. There were no significant differences in VI, FI, and VFI between the normal and PE groups; however, there were significant differences in IBV, IS, and IBV + IS in the PE group compared to those in the normal group. CONCLUSIONS: Placental hemodynamics measured by VI, FI, and VFI were not positively correlated with placental morphology in the third trimester. There were no differences in the VI, FI, and VFI in the third trimester between the normal and PE groups, suggesting that these may reflect placental circulatory insufficiency.

Subacute exposure to bisphenol F diglycidyl-ether induces chronic dermatitis characterized by psoriasis-like skin inflammation in mice.

Bisphenol F diglycidyl ether (BFDGE) is widely used in the synthesis process of plastic products. While exposure to bisphenol A diglycidyl ether (BADGE), which has a similar structure to BFDGE and which is used for the same purpose, has been reported to cause health risks, there is still little information on BFDGE. Because it is estimated that the industrial workers are exposed to large amounts of BFDGE, the health risks associated with BFDGE exposure need to be clarified. We investigated the toxicity of cutaneous exposure to BFDGE using an in vitro evaluation system and a mouse exposure model. The tumorigenic potential of BFDGE was confirmed by the Bhas 42 cell transformation assay, which showed that BFDGE has both promoter and initiator activity, in vitro. A single dermal application of BFDGE was associated with minor contact hypersensitivity symptoms. In contrast, repeated dermal exposure to BFDGE for 2 weeks induced persistent acute inflammation with features similar to inflammation in human psoriasis. This is the first report evaluating the toxicity of BFDGE in animals, and we showed that BFDGE carries a health risk of inducing skin dermatitis similar to that in human psoriasis in an exposure period-dependent manner.

Gestational Weight Gain Growth Charts Adapted to Japanese Pregnancies Using a Bayesian Approach in a Longitudinal Study: The Japan Environment and Children's Study.

BACKGROUND: Tracking gestational weight gain (GWG) during pregnancy makes it possible to optimize pregnancy outcomes, and GWG growth curves are well suitable for this purpose. The GWG guidelines for Japanese were revised in 2021. However, currently, there are no GWG growth curves to guide women on how to gain weight to meet these guidelines. METHODS: Using data on 96,631 live births from the Japan Environment and Children's Study (JECS), we created descriptive GWG percentile curves estimating the trajectory of GWG required to meet the GWG guidelines stratified by pre-pregnancy body mass index (BMI). For both analyses, Bayesian mixed models with restricted cubic splines adjusted for maternal characteristics were used. RESULTS: GWG curves substantially differed by pre-pregnancy BMI and were higher among multiparas and those with lower maternal age and with no previous disease. We estimated that underweight, normal weight, overweight, and obese women who gain 8.4 to 11.1 kg, 6.4 to 9.1 kg, 3.8 to 6.5 kg, and <1.9 kg at 30 weeks of gestation are on the trajectory to reach the new guidelines at 40 weeks of gestation. CONCLUSION: We provide GWG percentiles curves for Japanese women, as well as GWG trajectory curves to meet the new GWG recommendations. These results may help pregnant women monitor weight during pregnancy.

[Allergy and immunotoxicology in preventive and clinical medicine from theory to practice: Occupational allergy and isocyanate-induced asthma].

Genetic and environmental factors and their interactions cause diseases and deteriorate health (Genetic and Environmental Interaction). Exposure to environmental factors plays a major role in the deterioration of health in the workplace.Occupational asthma (OA) is a common disorder in the workplace. Approaches to OA are well described and discussed in "Japanese Guideline for Diagnosis and Management of Occupational Allergic Diseases" by the Japanese Society of Occupational and Environmental Allergy. According to the guideline, OA and work-aggravated asthma comprise work-related asthma, and OA can be further divided into two disease entities: sensitizer-induced OA and irritant-induced OA. The guidelines also describe diagnostic and therapeutic strategies for OA. Since a definitive diagnosis of OA requires a comprehensive decision based on a detailed interview on clinical symptoms related to employment status and clinical tests, including inhalation tests of suspected substances as needed, the possibility of OA should be considered as the first step toward diagnosis of the patient. Otherwise, OA may not be diagnosed. Therapeutic strategies include exposure avoidance, environmental arrangements in the workplace, utilization of social resources for workers, and conventional pharmacotherapy for asthma.Artificially synthesized small compounds are used in various industries and can cause allergies. For example, isocyanates are small compounds in the -NCO group, which have been toxicologically studied. It was later shown that isocyanate could cause various nontoxic adverse health effects, including allergic reactions. Since small agents with low molecular weights bind to proteins, detecting their specific immunoglobulin E (IgE) antibodies targeting small compounds is generally difficult. In contrast, isocyanate-specific IgE antibodies are detectable in individuals with isocyanate allergies.Suspecting OA is essential in cases exposed to newly synthesized compounds, or to those that are already known but applied to new uses, which can be better understood and predicted by studying the health effects of isocyanates.Academic interest in various issues related to allergies, immunology, and toxicology in the workplace includes clinical medicine, epidemiology, and epigenetics related to environmental exposure. Further advanced research in these areas is necessary and promising.

Association of sleep quality with temperament among one-month-old infants in The Japan Environment and Children's Study.

This study aimed to examine the association between infant sleep quality and temperament in one-month-old infants using a large cohort study data. We used data from the Japan Environment and Children's Study, a cohort study which follows around 100,000 women from pregnancy until their children's development. The mothers were asked about their infants' sleep and temperament using a structured questionnaire. Frequent crying (adjusted odds ratio [AOR]: 1.05, 95% confidence interval [CI]: 1.00-1.10) and intense crying (AOR: 1.19, 95% CI: 1.13-1.25) were positively associated with longer sleep periods during the day than at night. Female infants with longer daytime sleep periods than that at nighttime were more likely to cry frequently (AOR: 1.11, 95% CI: 1.04-1.20). Parous women with infants who had frequent night awakening believed their infants cried more intensely (AOR: 1.17, 95% CI: 1.03-1.31). The study demonstrated a specific association between sleep quality and temperament in one-month-old infants. Based on the results of this study, further sleep intervention studies are required to improve infant temperament.

Pre-Cerclage cervical length predicts long-term pregnancy sustenance: A case-control study.

Background: This study aimed to assess a predictor of long-term pregnancy sustenance post cervical cerclage in women with or without a medical history of cervical insufficiency. Materials and methods: We included pregnant women who underwent cerclage at 12-25 weeks gestation in four perinatal medical centers between January 2009 and December 2010. We classified the cerclage modality as ultrasound-indicated cervical cerclage if the pre-cerclage CL was <25 mm because the prophylactic and therapeutic cerclage definitions varied among institutions. The procedure was deemed successful if the pregnancy continued for more than 13 weeks post cerclage. We compared the outcomes of women who underwent successful and unsuccessful cerclage and investigated whether the pre-cerclage CL could predict pregnancy outcomes in women who underwent successful cerclage using receiver-operating characteristic curves. Results: We screened 114 pregnant women; 91 met the inclusion criteria. Pre-cerclage CL was a moderately accurate predictor of long-term pregnancy sustenance in the successful group (optimal cut-off value: 17 mm; area under the curve: 0.76; P = 0.0016). Approximately 87% of patients with a pre-cerclage CL ≥ 17 mm sustained their pregnancies for more than 13 weeks post cerclage; however, 64% of patients with a pre-cerclage CL < 17 mm did not. Conclusion: We speculate that the use of other treatment options in addition to cerclage in women with a pre-cerclage CL < 17 mm may result in a successful pregnancy.

The impact of the National Health Program on diabetes incidence among working-age men with prediabetes: A regression discontinuity analysis of a nation-wide database in Japan.

AIM: This study aimed to investigate the impact of the National Health Program in Japan ("Specific Health Check-ups and Specific Health Guidance") on diabetes prevention among working-age men with prediabetes. METHODS: This study used a regression discontinuity design, based on the program's criterion that the program starts at age 40 or older and that the intervention is provided only to prediabetic individuals with abdominal obesity, to assess the impact of the program on the diabetes incidence in a total of 49,848 men with prediabetes, aged 37-42 years. RESULTS: The National Health Program in which interventions were provided for individuals aged 40 years or over with both prediabetes and abdominal obesity was associated with a decrease in diabetes incidence rate equivalent to 10.1 reduction/1000 person-years. The relative risk was 0.75. However, among those without abdominal obesity and not subjected to the intervention, there was no significant change in the diabetes incidence at age 40. CONCLUSIONS: The National Health Program in Japan was associated with a decrease in the incidence of diabetes among working-age men with prediabetes and abdominal obesity and may have a meaningful impact among working-age men.

Association of physical activity and sleep habits during pregnancy with autistic spectrum disorder in 3-year-old infants.

Background: We hypothesized that maternal lifestyle factors, such as physical activity and sleep habits, may be associated with autism spectrum disorder (ASD) in infants. This study aimed to investigate the association between maternal physical activity and sleep before and during pregnancy with infant ASD diagnosed by the age of 3 years. Methods: We used the data from the Japan Environment and Children's Study between 2011 and 2014. The study included 103,060 pregnant women, among which, 69,969 women were analyzed. Participants were asked about their physical activity and sleep before and during pregnancy using questionnaires during pregnancy. Maternal physical activity was estimated using the international physical activity questionnaire. Based on the levels of physical activity before or during pregnancy, the participants were divided into five groups. Maternal sleep was analyzed based on sleep duration and bedtime. The outcome was diagnosis of ASD in 3-year-old infants. Results: In mothers with higher physical activity levels during pregnancy, the risk ratios (RR) for ASD in their 3-year-old infants were lower (RR = 0.61, 95% confidence interval (CI) = 0.42-0.90). In contrast, too short (<6 h) and too long (>10 h) sleep durations during pregnancy were associated with higher risk ratios for ASD than 7-8 h sleep duration (too short: RR = 1.87, 95% CI = 1.21-2.90; too long: RR = 1.56, 95% CI = 1.00-2.48). These associations were not observed before pregnancy. Conclusion: Maternal physical activity and sleep duration during pregnancy may be associated with ASD in infants.

A case of preeclampsia developing massive ascites after delivery.

We experienced a case of preeclampsia in which massive ascites became apparent in the postpartum period. The patient had isolated proteinuria without hypertension before delivery. The infant had fatal growth restriction and neonatal distress. Massive ascites and isolated proteinuria are important symptoms for predicting the aggravation of PE.

Association of maternal hemoglobin levels during pregnancy with sleep and developmental problems in 1-year-old infants: A cohort study.

Background and Aims: Maternal hemoglobin concentration during pregnancy is reported to be associated with various perinatal outcomes and may also be associated with infant development. This study aims to investigate the association between maternal hemoglobin levels during early or mid-pregnancy and sleep and developmental problems in 1-year-old infants. Methods: We used the data of 66,935 pregnant women who were participants of the Japan Environment and Children's Study, a nationwide cohort study in Japan, between 2011 and 2014. Maternal hemoglobin level was examined at recruitment (mean gestational age, 15.3 weeks; SD, 2.85 weeks; range, 6-22 weeks). Information on infant sleep and development at the age of 1 year was acquired using a questionnaire. Infant development was evaluated using the Ages and Stages Questionnaire (ASQ). Results: The mean (SD) maternal hemoglobin level was 12.0 (1.0) g/dl. Maternal hemoglobin levels were not associated with the majority of infant sleep and developmental outcomes. In the group with maternal hemoglobin <10.0 g/dl, the risk ratio (RR) for sleep at 22:00 or later was higher than that in the reference group with 11.0 g/dl ≤ hemoglobin < 14.0 g/dl (RR 1.12, 95% confidence interval = 1.00-1.25). In the analysis with maternal hemoglobin level as a continuous variable, both high and low hemoglobin levels were associated with a higher RR of a late bedtime. In addition, a low maternal hemoglobin level was associated with a higher RR for abnormal fine motor skills in the ASQ. Conclusion: Our results suggest that a low level of maternal hemoglobin during pregnancy is associated with late bedtime and abnormal fine motor skills in 1-year-old infants. Conversely, a high level of maternal hemoglobin may also be associated with the infant's late bedtime.

Long-Term Tocolysis With Magnesium Sulfate as a Risk Factor for Low Bone Mass: A Case Series.

Pregnancy and lactation-associated osteoporosis (PLO) is a disease caused by vertebral compression fracture, and it is characterized by low back pain during pregnancy or the postpartum period. However, it is difficult to predict and prevent PLO prepartum in high-risk groups. Recently, long-term tocolysis with magnesium sulfate (MgSO4) has been reported to be associated with PLO. The purpose of this case series was to assess postpartum bone mass after long-term tocolysis with MgSO4 and accumulated doses of MgSO4. We report the case of a pregnant woman with vertebral compression fractures during pregnancy following long-term tocolysis with MgSO4. We investigated whether long-term tocolysis with MgSO4 was a high risk factor for PLO. Therefore, we retrospectively evaluated bone mineral density after delivery in nine women who had long-term tocolysis with MgSO4 (more than 8 days) for treatment of threatened preterm birth at our hospital from January 2020 to December 2020. The age of the women was between 20 and 41 years (mean age, 30 years). The body mass index of the women was between 18.1 and 25.4 kg/m2 (mean 20.0 kg/m2). Three women had a positive smoking history, and none had a family history of osteoporosis. The average duration of tocolysis with MgSO4 was 11 - 97 days. The accumulated doses of MgSO4 were between 168 and 3,756 g. Four of nine cases were diagnosed with low bone mass of young adult mean (YAM) value ≤ 80%. Of them, one case (accumulated doses of MgSO4: 1,260 g) was diagnosed with PLO of YAM value ≤ 70%, and one case (accumulated doses of MgSO4: 3,756 g) was diagnosed with bone fracture with a YAM value of ≤ 70%. Long-term tocolysis with MgSO4 may be suggested as one of the risk factors of PLO. Nutritional guidance and rehabilitation are important interventions for target patients.

Lack of catch-up in weight gain may intermediate between pregnancies with hyperemesis gravidarum and reduced fetal growth: the Japan Environment and Children's Study.

BACKGROUND: Women with nausea and vomiting of pregnancy (NVP) have higher birth weight infants, while those with hyperemesis gravidarum, a severe manifestation of NVP, have lower birth weight infants. We aimed to investigate the associations between maternal weight loss (a consequence of hyperemesis gravidarum), NVP, and infant birth weight. METHODS: This study was a secondary analysis of a nationwide birth cohort in Japan. Singleton pregnancies delivered at 28-41 weeks of gestation were included in the analysis. Women were categorized based on their weight change in the 1st trimester (as a proportion to their pre-pregnancy weight: > + 3%, > 0 to + 3%, > -3 to 0%, > -5 to -3%, ≤ -5%) and severity of NVP (no nausea, only nausea, vomiting but able to eat, vomiting and unable to eat). The effects of weight change and severity of NVP on infant birth weight and small for gestational age (SGA) were assessed using regression models. We further examined how these effects could be modified by maternal weight gain up to the 2nd trimester. RESULTS: Among 91,313 women, 5,196 (5.7%) lost ≥ 5% of their pre-pregnancy weight and 9,983 (10.9%) experienced vomiting and were unable to eat in the 1st trimester. Women with weight loss ≥ 5% in the 1st trimester had infants 66 (95% CI: 53, 78) g lighter and higher odds of SGA (aOR: 1.29; 95% CI: 1.14, 1.47) than women who gained > 3% during the same period. However, when adjusting for weight gain up to the 2nd trimester, women with weight loss ≥ 5% in the 1st trimester had infants 150 (95% CI: 135, 165) g heavier and lower odds of SGA (aOR: 0.39; 95% CI: 0.33, 0.46) than those who gained > 3% during the same period. In contrast, women with more severe NVP tended to have infants with larger birth weight and lower odds of SGA compared to women without NVP. These trends were strengthened when adjusting for weight gain up to the 2nd trimester. CONCLUSIONS: Our study suggests the possibility that reduced fetal growth in pregnancies with hyperemesis gravidarum may be caused by the lack of catch-up in gestational weight gain up to the 2nd trimester.