Effects of Levothyroxine Treatment on Fertility and Pregnancy Outcomes in Subclinical Hypothyroidism: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Subclinical hypothyroidism, defined by elevated thyrotropin (TSH) and normal free thyroxine levels, is associated with adverse pregnancy outcomes, including preterm birth, pre-eclampsia, and small for gestational age. Despite the uncertainty regarding the effectiveness of levothyroxine (LT4) treatment on pregnancy outcomes in subclinical hypothyroidism, LT4 is widely administered with a pre-treatment threshold TSH level of 2.5 mU/L. The aim of this study is to investigate the efficacy of periconceptional LT4 treatment for subclinical hypothyroidism, including TSH levels >2.5 mU/L, and identify the characteristics of subclinical hypothyroidism that can benefit from LT4 treatment. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials from inception to February 2023. We analyzed the pooled effects of LT4 on subclinical hypothyroidism before and during pregnancy. The main outcomes before pregnancy were live birth, pregnancy, and miscarriage. The main outcomes during pregnancy were live birth, miscarriage, and preterm birth. We conducted subgroup analyses to compare the effects of LT4 on subclinical hypothyroidism with TSH levels of 2.5-4.0 and >4.0 mU/L. Results: Of the 888 studies identified, 27 full-text articles were screened for eligibility. Five studies on pre-conception treatment with 768 participants and eight studies on treatment during early pregnancy with 2622 participants were analyzed. One of the two studies on pre-conception treatment in subclinical hypothyroidism with TSH >4.0 mU/L had high risk of bias and the other was composed of 64 participants. Pre-conception LT4 treatment had no significant effect in improving rates of live births and pregnancies, or reducing miscarriages (risk ratio [RR], 95% confidence interval): 1.41 (0.84-2.36), 1.73 (0.88-3.39), and 0.46 (0.11-2.00), respectively. LT4 treatment during pregnancy was not significantly associated with higher rates of live births (RR 1.03, 0.98-1.09) nor decreased miscarriage rates (RR 1.01, 0.66-1.53). The effect of LT4 treatment on preterm birth during pregnancy was significantly different depending on the TSH values (p = 0.04); a positive effect was shown in the subclinical hypothyroidism subgroup with TSH >4.0 mU/L (RR 0.47, 0.20-1.10), while no significant effect was observed in the subgroup with TSH 2.5-4.0 mU/L (RR 1.35, 0.79-2.31). Conclusions: Pre-conceptional LT4 treatment for subclinical hypothyroidism does not improve fertility or decrease the incidence of miscarriages. However, further well-designed studies are needed for pre-conceptional treatment, especially in TSH >4.0 mU/L. LT4 treatment during pregnancy had a positive effect on preterm birth; nevertheless, this was only applicable to subclinical hypothyroidism with TSH >4.0 mU/L.

Association between gestational weight gain and chronic disease risks in later life.

To assess the association between gestational weight gain (GWG) and the risk of developing chronic diseases in later life, this historical cohort study of 318 non-overweight women was conducted between April 2017 and November 2020 at a hospital in Tokyo. Data about GWG in the last pregnancy and the development of any chronic diseases of the subjects were retrieved from the women's Maternal and Child Health Handbooks and through a questionnaire survey, respectively. The outcomes were chronic diseases, such as diabetes mellitus (DM), hypertension, hyperlipidemia, and being overweight (body mass index [BMI] ≥ 25 kg/m2). Association between GWG and outcomes were assessed using a logistic regression analysis.There were significant positive linear associations between GWG and the risks of developing DM, hypertension, and being overweight (P = 0.013, 0.050, and 0.017, respectively). After adjusting for later-life BMI, a significant association between GWG and DM (P = 0.025) remained, but the association between GWG and hypertension disappeared. GWG was significantly associated with DM, hypertension, and being overweight later in life. Although the association between GWG and DM was partially independent of BMI later in life, the association between GWG and hypertension was influenced by being overweight later in life.

Clinical features of women with thrombotic microangiopathy in pregnancy: A case series from a single Japanese tertiary perinatal care center.

AIM: Although perinatal thrombotic microangiopathy has become increasingly understood, the racial characteristics of patients with this condition remain unclear. Herein, we report the characteristics of patients with perinatal thrombotic microangiopathy at a single institution in Japan. METHODS: We conducted a retrospective study over a 5-year period from January 1, 2017, to December 31, 2021, using the electronic medical records of pregnant women who delivered at the perinatal center of our hospital. We extracted the data of those who developed perinatal thrombotic microangiopathy and evaluated their characteristics at the time of disease onset, final diagnosis, and maternal and fetal outcomes. RESULTS: Of the 10 224 deliveries that occurred during the 5-year period, only seven patients (0.06%) had perinatal thrombotic microangiopathy. The median pre-pregnant body mass index was 18.65 kg/m2 (minimum 17.3 kg/m2 , maximum 20.7 kg/m2 ). More than half of the patients were conceived by in-vitro fertilization, and 42% these had twin deliveries. Four patients had a history of rheumatic disease. The other three patients without underlying diseases developed thrombotic microangiopathy with HELLP syndrome, and one patient transitioned to atypical hemolytic uremic syndrome. CONCLUSIONS: Based on low body mass index and in-vitro fertilization, which are characteristic of Japanese women, medical complications and twin pregnancies may be a risk for thrombotic microangiopathy. Additionally, depending on the cause of thrombotic microangiopathy, its timing and onset differed.

Association of Isolated Hypothyroxinemia and Subclinical Hypothyroidism With Birthweight: A Cohort Study in Japan.

Context: Isolated hypothyroxinemia (low maternal free thyroxine [FT4] in the absence of thyroid-stimulating hormone [TSH] elevation) and subclinical hypothyroidism (high TSH in the absence of FT4 elevation) during early pregnancy are common. However, there are limited data regarding pregnancy outcomes, particularly their association with birthweight. Objective: We assessed the association between isolated hypothyroxinemia and subclinical hypothyroidism during the first trimester and birthweight. Methods: Analyses were conducted using a database of pregnant women (n = 1105; median age, 35 years) who delivered at the National Center for Child Health and Development, a tertiary hospital in Tokyo. The primary outcomes included the rates of small for gestational age (SGA), large for gestational age (LGA), and low birth weight. Results: Of the 1105 pregnant women, 981 were classified into the euthyroidism group, 25 into the isolated hypothyroxinemia group, and 26 into the subclinical hypothyroidism group during the first trimester. The prevalence of SGA was significantly higher in isolated hypothyroxinemia and subclinical hypothyroidism groups than the euthyroidism group (28.0% and 19.2%, respectively, vs 5.7%; P < .01). The odds ratio with 95% CI for SGA was 12.51 (4.41-35.53) for isolated hypothyroxinemia and 4.44 (1.57-12.56) for subclinical hypothyroidism in a multivariable adjustment model. Isolated hypothyroxinemia and subclinical hypothyroidism were not significantly associated with LGA and low birth weight. Conclusion: Pregnant women with isolated hypothyroxinemia and subclinical hypothyroidism in the first trimester have an increased likelihood of SGA. Screening and careful perinatal checkups for isolated hypothyroxinemia and subclinical hypothyroidism may help identify pregnant women at high risk for SGA.

Risk of fetal undergrowth in the management of gestational diabetes mellitus in Japan.

AIMS/INTRODUCTION: In Japan, the increasing frequency of underweight among women of reproductive age and the accompanying increase in the rate of low birth weight (LBW) are social issues. The study aimed to establish a prospective registry system for gestational diabetes mellitus (GDM) in Japan and to clarify the actual status of GDM according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. MATERIALS AND METHODS: Pregnant women with gestational diabetes mellitus and those in the normal glucose tolerance (NGT) group were enrolled in the Diabetes and Pregnancy Outcome for Mother and Baby study from October 2015. Pregnant women with positive glucose screening in early and mid-to-late pregnancy underwent a 75 g oral glucose tolerance test by gestational week 32. Gestational diabetes mellitus was diagnosed according to IADPSG criteria. Women with a positive glucose screening test at mid-to-late pregnancy but NGT were enrolled as references (NGT group). Treatment for gestational diabetes mellitus and maternal and neonatal pregnancy data were prospectively collected on outcomes. RESULTS: In total 1,795 singleton pregnancies (878 women with GDM and 824 NGT women) were analyzed. The risk of LBW and small-for-gestational age in the GDM group was significantly higher than in the NGT group. A similar relationship was found for LBW risk in the non-overweight/obese group but not in the overweight/obese group. CONCLUSIONS: We established a prospective GDM registry system in Japan. In the management of GDM in Japan, suppression of maternal weight gain may be associated with reduced fetal growth, especially in non-overweight/obese women with GDM; however, further investigation is required.

Gestational glycosuria, proteinuria, and borderline hypertension in pregnancy are predictors for the later onset of maternal chronic disease.

AIM: Although hypertensive disorders of pregnancy and gestational diabetes mellitus (DM) are risk factors for hypertension, DM, and kidney disease in later life, the association of gestational glycosuria, proteinuria, and borderline hypertension with these chronic diseases has been unclear. METHODS: This cross-sectional study was conducted between April 2017 and November 2020 at a Japanese tertiary hospital. Three variables listed in the Maternal and Child Health Handbook were analyzed: glycosuria, proteinuria, and systolic blood pressure (<130, 130-139, and ≥ 140 mmHg) during pregnancy. The incidences of DM, kidney disease, and hypertension self-reported by mothers of pregnant women on a questionnaire were assessed with logistic regression analysis. RESULTS: The 312 women completed the questionnaires an average of 35.8 ± 4.2 years after delivering their daughters. Risk for DM was significantly increased among women with glycosuria (adjusted odds ratio [aOR], 3.62; 95% confidence interval [CI], 1.21-10.9), and risk for kidney disease was significantly increased among women with proteinuria (aOR, 4.07; 95% CI, 1.29-12.9). Risk for hypertension was significant in women whose blood pressures were ≥ 140 mmHg (aOR, 4.26; 95% CI, 1.96-9.24), but the association between blood pressures of 130-139 mmHg and hypertension was not significant (aOR, 1.72; 95% CI, 0.95-3.11); however, a significant positive trend (p < 0.001) between increasing blood pressure and hypertension was observed. CONCLUSIONS: Gestational glycosuria, proteinuria, and increased blood pressure were associated with the development of maternal chronic diseases. These standard and inexpensive assessments may improve lifelong health management in women.

Development of a health literacy scale for preconception care: a study of the reproductive age population in Japan.

BACKGROUND: Preconception care aims to improve both maternal and child health in the short as well as long term, along with providing health benefits to adolescents, women, and men, whether or not they plan to become parents. However, there is limited evidence regarding the effectiveness of interventions for improving preconception health in population-based settings. To accumulate evidence in this field, this study focused on the concept of health literacy, and aimed to develop a self-report health literacy scale in Japanese, focusing on preconception care. METHODS: We conducted a cross-sectional online survey. Participants were recruited from December 2019 to February 2020 from the registered members of a web-based research company. Participants were Japanese men and women aged 16-49 (n = 2000). A factor analysis was conducted to select both factors and items for health-related behavior and skills (33 initial items were generated), along with an item response theory analysis to examine how the 16 items were related to people's knowledge of preconception care. RESULTS: We developed a 6-factor (including "appropriate medical examinations," "appropriate diet," "stress coping," "healthy weight," "safe living environment," and "vaccinations"), 25-item behavior and skills scale, as well as a 13-item knowledge scale, to evaluate participants' health literacy around preconception care. A shortened version, consisting of 17 items, was also prepared from the 25 items. The reliability coefficients of total scores and each factor of the behavior and skills scale were comparatively high, with weak-to-moderate correlation between behavior and skills and knowledge. CONCLUSIONS: The new scale will, ideally, provide information on the current state of preconception care health literacy of the general population. In addition, this scale, which consists of both behavioral/skills and knowledge dimensions, should help support the effective implementation of risk assessment programs and interventions aimed at promoting behavioral changes using a population-based approach. Future studies using different question/administration formats for diverse populations, and considering respondents' opinions on health literacy scales should be effective in improving this scale.

Protocol for an interventional study to reduce postpartum weight retention in obese mothers using the internet of things and a mobile application: a randomized controlled trial (SpringMom).

BACKGROUND: Obese pregnant women are known to experience poorer pregnancy outcomes and are at higher risk of postnatal arteriosclerosis. Hence, weight control during and after pregnancy is important for reducing these risks. The objective of our planned randomized controlled trial is to evaluate whether the rate of change in body weight in obese women before pregnancy to 12 months postpartum would be lower with the use of an intervention consisting of Internet of Things (IoT) devices and mobile applications during pregnancy to 1 year postpartum compared to a non-intervention group. METHODS: Women will be recruited during outpatient maternity checkups at four perinatal care institutions in Japan. We will recruit women at less than 30 weeks of gestation with a pre-pregnancy body mass index ≥ 25 kg/m2. The women will be randomly assigned to an intervention or non-intervention group. The intervention will involve using data (weight, body composition, activity, sleep) measured with IoT devices (weight and body composition monitor, activity, and sleep tracker), meal records, and photographs acquired using a mobile application to automatically generate advice, alongside the use of a mobile application to provide articles and videos related to obesity and pregnancy. The primary outcome will be the ratio of change in body weight (%) from pre-pregnancy to 12 months postpartum compared to before pregnancy. DISCUSSION: This study will examine whether behavioral changes occurring during pregnancy, a period that provides a good opportunity to reexamine one's habits, lead to lifestyle improvements during the busy postpartum period. We aim to determine whether a lifestyle intervention that is initiated during pregnancy can suppress weight gain during pregnancy and encourage weight loss after delivery. TRIAL REGISTRATION: UMIN: UMIN (University hospital Medical Information Network) 000,041,460. Resisted on 18th August 2020. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000047278.

Association of maternal birth weight with the risk of low birth weight and small-for-gestational-age in offspring: A prospective single-center cohort study.

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.

Economic Evaluations of Gestational Diabetes Mellitus Screening: A Systematic Review.

BACKGROUND: This study aims to find evidence of the cost-effectiveness of gestational diabetes mellitus (GDM) screening and assess the quality of current economic evaluations, which have shown different conclusions with a variation in screening methods, data sources, outcome indicators, and implementation in diverse organizational contexts. METHODS: Embase, Medline, Web of Science, Health Technology Assessment, database, and National Health Service Economic Evaluation Database databases were searched through June 2019. Studies on economic evaluation reporting both cost and health outcomes of GDM screening programs in English language were selected, and the quality of the studies was assessed using Drummond's checklist. The general characteristics, main assumptions, and results of the economic evaluations were summarized. RESULTS: Our search yielded 10 eligible economic evaluations with different screening strategies compared in different settings and perspectives. The selected papers scored 81% (68-97%) on the items in Drummond's checklist on average. In general, a screening program is cost-effective or even dominant over no screening. The one-step screening, with more cases detected, is more likely to be cost-effective than the two-step screening. Universal screening is more likely to be cost-effective than screening targeting the high-risk population. Parameters affecting cost-effectiveness include: diagnosis criteria, epidemiological characteristics of the population, efficacy of screening and treatment, and costs. CONCLUSIONS: Most studies found GDM screening to be cost-effective, though uncertainties remain due to many factors. The quality assessment identified weaknesses in the economic evaluations in terms of integrating existing data, measuring costs and consequences, analyzing perspectives, and adjusting for uncertainties.

Age-Dependent and Seasonal Changes in Menstrual Cycle Length and Body Temperature Based on Big Data.

OBJECTIVE: To evaluate the effects of age and season on menstrual cycle length and basal body temperature (BBT). We also examined the effects of climate on cycle length and BBT, taking into account Japanese geographic and social characteristics. METHODS: In this retrospective cohort study, we analyzed data from 6 million menstrual cycles entered into a smartphone application from 310,000 females from 2016 to 2017. Only those who entered more than 10 cycles in 2 years were included. Generalized estimation equations were used to adjust for confounding factors and for within-person correlations of multiple records. Multiple regression analysis was conducted, with age, external average temperature, precipitation amount, and sunshine hours as confounding factors. RESULTS: The mean menstrual cycle length increased from age 15-23 years, subsequently decreased up to age 45 years, and then increased again. Average follicular phase body temperature showed no significant age-dependent changes, but luteal phase body temperature gradually increased up to 29 years and then stabilized and started to decrease after age 42 years. A significant association between external temperature and body temperature (follicular and luteal phase) was observed, though menstrual cycle length did not show such an association. CONCLUSION: These results, derived from data self-entered into a smartphone application, revealed underrecognized age-dependent and seasonal changes in menstrual cycle length and BBT, which will contribute to a better understanding of female reproductive health in the modern world.

Ultrasonographic assessment of fetal thyroid in Japan: thyroid circumference and distal femoral and proximal tibial ossification.

PURPOSE: The present study established a nomogram of fetal thyroid circumference (FTC) and the appearance timing of fetal distal femoral and proximal tibial ossification to assess fetal thyroid function in Japan. METHODS: Between April 2015 and July 2019, normal pregnant women at our hospital were recruited for the study. FTC was measured by the automatic ellipse outline and plotted against gestational age (GA). Fetal distal femoral and proximal tibial ossification measurements were obtained with standard electronic calipers from outer-to-outer margins (> 1 mm as the presence of ossification). RESULTS: A total of 199 pregnant women were examined. FTC increased logarithmically to GA. A nomogram of FTC was expressed by a logarithmic formula: [Formula: see text]. The respective 5-95th percentiles of FTC at each GA were 20.2-36.2 mm at 22 weeks, 25.0-44.8 mm at 26 weeks, 29.2-52.3 mm at 30 weeks, and 32.9-59.0 mm at 34 weeks. The fetal distal femoral epiphysis was not visualized before 30 weeks, but was visualized in 100% of fetuses after 35 weeks of gestation. The fetal proximal tibial epiphysis was not visualized before 33 weeks, but was visualized in 73.7% of fetuses at 37 weeks of gestation. CONCLUSION: We generated a GA-dependent FTC nomogram for Japanese fetuses. We also confirmed the appearance timing of fetal distal femoral and proximal tibial ossification to assess bone maturation. These assessments may be very useful for evaluating fetal thyroid function in Japan.

Thyroid dysfunction following pregnancy and implications for breastfeeding.

Subclinical autoimmune thyroiditis exacerbates after delivery through immune rebound mechanisms and results in 5 types of thyroid dysfunction. The prevalence of postpartum thyroid dysfunction is around 5% in mothers in the general population. Typically, an exacerbation induces destructive thyrotoxicosis followed by transient hypothyroidism, known as postpartum thyroiditis. Late development of permanent hypothyroidism is found frequently and patients should be followed up once every one to two years. Destructive thyrotoxicosis in postpartum thyroiditis should carefully be differentiated from post-partum Graves' disease. Postpartum thyroiditis typically occurs 1-4 months after parturition whereas Graves' disease develops at 4-12 months postpartum. Anti-TSH receptor antibodies (TRAb) are typically positive and thyroid blood flow is high in Graves' disease, whereas these features are absent in postpartum thyroiditis. Postpartum Graves' disease should be treated with antithyroid drugs.

A CASE OF FAMILIAL NONAUTOIMMUNE HYPERTHYROIDISM DURING PREGNANCY.

OBJECTIVE: Familial nonautoimmune hyperthyroidism (FNAH) is a rare disease. To date there are few, if any, reports of pregnancies in women with FNAH. Our objective here is to present such a case. METHODS: Free thyroxine (free T4), free triiodothyronine (free T3), thyroid-stimulating hormone (TSH), and antibodies related to the thyroid were measured. Fetal thyroid function indicators including thyroid volume and ossification were checked using ultrasound. Thyroid-stimulating hormone receptor (TSHR) gene analyses were performed. RESULTS: The patient was a 30-year-old woman with no past medical history. She was introduced to our hospital in the fifth gestational week for pregnancy care because her family history revealed that her mother had nonautoimmune hyperthyroidism with a TSHR-activating germ-line mutation (Asn406Ser). The serum free T4 was 1.88 ng/dL (normal, 0.62 to 1.19 ng/dL), free T3 was 3.27 pg/mL (normal, 2.55 to 3.88 pg/mL), TSH was 0.02 µIU/mL (normal, 0.007 to 3.619 µIU/mL), and TSHR was negative which were considered to be consistent with mild primary hyperthyroidism. Serum free T4, free T3, and TSH concentrations were monitored every 4 to 6 weeks with a peak free T4 of 2.23 ng/dL noted at gestational week 9. The patient had no signs related to hyperthyroidism throughout pregnancy. The patient delivered a 3,518 g girl at 40 weeks of gestation. Genetic analysis of her TSHR gene showed heterozygous Asn406Ser mutation. The offspring did not show any signs of prenatal hyperthyroidism, and thyroid function at day 6 after delivery revealed a free T4 of 2.41 ng/dL (normal, 1.83 to 2.91 ng/dL) and a TSH of 3.55 µIU/mL (normal, 0.51 to 4.57 µIU/mL). CONCLUSION: Women with FNAH and mild thyrotoxicosis prior to pregnancy may have continuous hyperthyroidism with additional change due to the series of human chorionic gonadotropin secretion during pregnancy.

Time course of metabolic status in pregnant women: The Japan Environment and Children's Study.

AIMS/INTRODUCTION: We aimed to evaluate the metabolic status of pregnant women by assessing metabolic biomarkers of participants in the Japan Environment and Children's Study, a nationwide, multicenter, pregnancy and birth cohort. MATERIALS AND METHODS: Pregnant women aged 14-50 years were studied in 15 centers across Japan. Clinical information was obtained using self-administered questionnaires. Blood samples were taken during the first two trimesters to measure metabolic biomarkers. Samples were divided into seven groups according to the weeks of pregnancy. RESULTS: Among 82,972 pregnant women, 43 had only type 1 diabetes, 78 had only type 2 diabetes, 2,315 had only gestational diabetes and 354 had only dyslipidemia. Glycated hemoglobin, total cholesterol, low-density lipoprotein cholesterol and triglyceride across all the percentiles increased as prepregnancy body mass index increased, whereas high-density lipoprotein cholesterol levels across all the percentiles decreased as body mass index increased. Glycated hemoglobin was high in participants with type 1 diabetes or type 2 diabetes only, but not in those with gestational diabetes or hyperlipidemia only. Participants with type 2 diabetes or dyslipidemia only had high triglyceride in the first trimester, which then decreased in the second trimester. Participants with type 2 diabetes only also showed low high-density lipoprotein cholesterol, whereas participants with dyslipidemia only showed high total cholesterol and low-density lipoprotein cholesterol throughout. CONCLUSIONS: Metabolic biomarkers were affected by blood sample timing and underlying metabolic disease. The Japan Environment and Children's Study will clarify the influences of metabolic status during pregnancy on the health and development of the offspring in future studies.

Risk factors during the early postpartum period for type 2 diabetes mellitus in women with gestational diabetes.

For women with gestational diabetes mellitus (GDM), the evaluation of glucose tolerance (GT) in the early postpartum period is universally recommended. Nevertheless, few studies have evaluated the risk factors for T2DM on the basis of GT data obtained during the early postpartum period. We aimed to identify the risk factors for type 2 diabetes mellitus (T2DM) by evaluating GT in the first 12 weeks postpartum (12wPP) in women with GDM and to categorize the risk using a combination of the principal risk factors. This retrospective multicenter observational study included 399 East Asian women with GDM who underwent a 75-g oral glucose tolerance test (OGTT) within 12wPP, which was repeated annually or biennially and used to identify the postpartum development of T2DM. Forty-three women (10.8%) developed T2DM during a median follow-up period of 789 ± 477 days. The independent risk factors for T2DM were pre-pregnancy obesity (BMI ≥25 kg/m2), early postpartum impairment in glucose tolerance (IGT), and an early postpartum glycated hemoglobin (HbA1c) ≥5.7%. The odds ratios (95% confidence intervals) for T2DM were 3.2 (1.3-7.8) in women with either early postpartum IGT or pre-pregnancy obesity, 9.2 (3.0-28.3) in those with early postpartum IGT, pre-pregnancy obesity, and HbA1c <5.7%, and 51.4 (16.1-163.9) in those with early postpartum IGT, pre-pregnancy obesity, and HbA1c ≥5.7%, compared with those without obesity or IGT. T2DM risk in East Asian women with GDM should be stratified according to pre-pregnancy obesity and early postpartum IGT, and these patients should be followed up and receive appropriate care for their risk category.

Safety of Amlodipine in Early Pregnancy.

Background Amlodipine is used for the treatment of hypertension, but reports on its use in early pregnancy are limited. Methods and Results In the present study, we recruited 231 women with chronic hypertension, including those who received amlodipine or other antihypertensives during early pregnancy, and investigated frequencies of morphologic abnormalities in their 231 offspring. Specifically, we evaluated 48 neonates exposed to amlodipine in the first trimester (amlodipine group, Group A), 54 neonates exposed to antihypertensives other than amlodipine (other antihypertensive group, Group O), and 129 neonates not exposed to antihypertensives (no-antihypertensive group, Group N). The number of morphologic abnormalities of offspring in each group were 2 in Group A (4.2%; 95% CI, 0.51-14.25); 3 in Group O (5.6%; 95% CI, 1.16-15.39) and 6 in Group N (4.7%; 95% CI, 1.73-9.85). The odds ratio of the primary outcome comparing Group A and Group O was 0.74 (95% CI: 0.118-4.621) and Group A and Group N was 0.89 (95% CI: 0.174-4.575). Conclusions The odds of birth defects in Group A in the first trimester were not significantly different from those with or without other antihypertensives.

Clinical and genetic characteristics of abnormal glucose tolerance in Japanese women in the first year after gestational diabetes mellitus.

AIMS/INTRODUCTION: Risk factors of type 2 diabetes mellitus in Japanese women with recent gestational diabetes mellitus are unknown. The objective of the present study was to investigate the clinical and genetic characteristics associated with postpartum abnormal glucose tolerance in Japanese women with gestational diabetes mellitus. MATERIALS AND METHODS: A total of 213 Japanese women with recent gestational diabetes mellitus who underwent a postpartum 2-h oral glucose tolerance test were investigated. The association between antepartum clinical characteristics and postpartum abnormal glucose tolerance (diabetes or prediabetes based on the Japan Diabetes Society criteria) was examined. Frequencies of 45 known type 2 diabetes mellitus-associated genetic variants were also compared between women with and without postpartum abnormal glucose tolerance. RESULTS: A total of 59 women showed postpartum abnormal glucose tolerance (prediabetes, n = 51; diabetes, n = 8). Plasma glucose levels at 1 or 2 h, the insulinogenic index and the insulin secretion-sensitivity index-2 of the antepartum oral glucose tolerance test were independent of postpartum abnormal glucose tolerance risk factors (P = 0.006, P = 0.00002, P = 0.01 and P = 0.006, respectively). Four genetic variants (rs266729 [ADIPOQ], rs6017317 [HNF4A], rs5215 [KCNJ11] and rs7177055 [HMG20A]) showed a nominally significant association with postpartum abnormal glucose tolerance (P < 0.05, respectively). Among these, three were related to insulin secretion. Postpartum abnormal glucose tolerance risk significantly increased with increasing risk-allele number (P = 0.0005; odds ratio 1.91). CONCLUSIONS: Clinical features and genetic variants related to impaired insulin secretion are risk factors of postpartum abnormal glucose tolerance in Japanese women with recent gestational diabetes mellitus.

Obesity and abnormal glucose tolerance in the offspring of mothers with diabetes.

PURPOSE OF REVIEW: Type 2 diabetes and obesity during childhood, puberty, and adulthood have become more common. This trend presents a global problem in terms of public health and health economics. Associations between intrauterine exposure to hyperglycemia, obesity, and abnormal glucose tolerance (AGT) in offspring have been reported in populations at high risk of diabetes such as Pima Indians, but these associations have not been established in other groups. In this review, we summarize the evidence on obesity and AGT in the offspring of mothers with diabetes. RECENT FINDINGS: Although there are many reports indicating that the incidence of obesity or overweight is higher in the offspring of mothers with gestational diabetes, there is no consensus on whether maternal prepregnancy obesity has a larger impact than intrauterine exposure to hyperglycemia. While the risk of AGT or type 2 diabetes in the offspring of mothers with gestational diabetes is thought to increase after puberty, the incidence of AGT is elevated by the age of 7 years in the offspring of mothers with untreated gestational diabetes. Maternal gestational diabetes is a risk factor for AGT or type 2 diabetes independent of maternal prepregnancy BMI. When the offspring of women who had gestational diabetes and received therapeutic intervention in two randomized controlled studies were followed, the prevalence of obesity and impaired fasting glucose was lower in some 7-year-old girls, but the effect of maternal intervention was limited. The risk of obesity or overweight is higher in the offspring of mothers with type 1 diabetes, even after adjustment for maternal prepregnancy BMI. The risk of type 2 diabetes in such offspring is also higher. Although the offspring of mothers with type 2 diabetes are likely to be at high risk for type 2 diabetes, there are only limited reports supporting this hypothesis. SUMMARY: Intrauterine exposure to hyperglycemia is associated with obesity and AGT among offspring. The present review suggests that these associations might depend on the type of maternal diabetes, that is, the timing and degree of exposure to hyperglycemia. There are only a small number of studies on the effect of therapeutic interventions for maternal diabetes on metabolism in the offspring.