The timing of adenomyosis diagnosis and its impact on pregnancy outcomes: a national population-based study.

OBJECTIVE: Adenomyosis impacts pregnancy outcomes, although there is a lack of consensus regarding the actual effects. It is likely, however, that the severity of adenomyosis or ultrasound findings or timing of diagnosis can have different effects on adverse pregnancy outcomes (APOs). METHODS: In this study, we aimed to investigate the impact of the timing of adenomyosis diagnosis on pregnancy outcomes. Singleton pregnant women who delivered between 2017 and 2022 were analyzed based on the timing of adenomyosis diagnosis, using a national database. The final cohort was classified into three groups: 1) group 1, without adenomyosis; 2) group 2, those diagnosed with adenomyosis before pregnancy; and 3) group 3, those diagnosed with adenomyosis during pregnancy. RESULTS: A total of 1,226,475 cases were ultimately included in this study. Women with a diagnosis of adenomyosis had a significantly higher risk of APOs including hypertensive disorder during pregnancy (HDP), gestational diabetes mellitus (GDM), postpartum hemorrhage, placental abruption, preterm birth, and delivery of a small-for-gestational-age infant even after adjusting for covariates. In particular, concerning HDP, the risk was highest in group 3 (group 2: adjusted odds ratio [aOR], 1.15 vs. group 3: aOR, 1.36). However, the highest GDM risk was in group 2 (GDM; group 2: aOR, 1.24 vs. group 3: aOR, 1.04). CONCLUSION: The increased risk of APO differed depending on the timing of adenomyosis diagnosis. Therefore, efforts for more careful monitoring and prevention of APOs may be necessary when such women become pregnant.

The Risk of Hypertension and Diabetes Mellitus According to Offspring's Birthweight in Women With Normal Body Mass Index: A Nationwide Population-Based Study.

BACKGROUND: Maladaptation to vascular, metabolic, and physiological changes during pregnancy can lead to fetal growth disorders. Moreover, adverse outcomes during pregnancy can further increase the risk of cardiovascular and metabolic diseases in mothers. Delivering a large-for-gestational-age (LGA) baby may indicate a pre-existing metabolic dysfunction, whereas delivering a small-for-gestational-age (SGA) baby may indicate a pre-existing vascular dysfunction. This study aims to assess the risk of hypertension (HTN) and diabetes mellitus (DM) in women with normal body mass index (BMI) scores who did not experience gestational DM or hypertensive disorders during pregnancy based on the offspring's birthweight. METHODS: This retrospective nationwide study included women with normal BMI scores who delivered a singleton baby after 37 weeks. Women with a history of DM or HTN before pregnancy and those with gestational DM or hypertensive disorders, were excluded from the study. We compared the risk of future maternal outcomes (HTN and DM) according to the offspring's birthweight. Multivariate analyses were performed to estimate the hazard ratio (HR) for the future risk of HTN or DM. RESULTS: A total of 64,037 women were included in the analysis. Of these, women who delivered very LGA babies (birthweight > 97th percentile) were at a higher risk of developing DM than those who delivered appropriate-for-gestational-age (AGA) babies (adjusted HR = 1.358 [1.068-1.727]), and women who delivered very SGA babies (birthweight < 3rd percentile) were at a higher risk of developing HTN than those who delivered AGA babies (adjusted HR = 1.431 [1.181-1.734]), even after adjusting for age, parity, gestational age at delivery, fetal sex, maternal BMI score, and a history of smoking. CONCLUSION: These findings provide a novel support for the use of the offspring's birthweight as a predictor of future maternal diseases such as HTN and DM.

The Role of the Aryl Hydrocarbon Receptor in Vascular Factors Related to Preeclampsia in a Smoking Mouse Model.

Smoking cigarettes is known to lower the risk of preeclampsia. The objective of this study is to evaluate the effect of smoking on the expression of soluble FMS-like tyrosine kinase-1 (sFlt-1), vascular endothelial growth factor (VEGF), and endoglin (sEng)-1 and the role of the aryl hydrocarbon receptor (AhR) in pregnant mice. We developed a smoking mouse model using a gas-filling system. One or two cigarettes per day were exposed to each of the five pregnant mice for five days a week throughout pregnancy. AhR agonist and antagonist were injected. Serum levels and expression in the placenta of sFlt-1, VEGF, and sEng-1 were analyzed and compared among the cigarette smoke and no-exposure groups after delivery. Compared to the no-smoke exposure group, the serum level of sFlt-1 was significantly decreased in the two-cigarette-exposed group (p < 0.001). When the AhR antagonist was added to the two-cigarette-exposed group, sFlt-1 levels were significantly increased compared to the two-cigarette group (p = 0.002). The levels of sFlt-1 in the AhR antagonist group did not change regardless of two-cigarette exposure (p = 0.064). With the AhR agonist, sFlt-1 decreased significantly compared to the control (p = 0.001) and AhR antagonist group (p = 0.002). The sFlt-1 level was significantly decreased after the injection of the AhR agonist compared to the control group (p = 0.001). Serum levels of VEGF were significantly decreased in the one-cigarette-exposed group compared to the control group; however, there was no difference between the control and the two-cigarette-exposed groups. The placental expression of sFlt-1, VEGF, and sEng were inconsistent. This study offers insights into the potential role of AhR on antiangiogenic sFlt-1 associated with preeclampsia. It may support the invention of a new treatment strategy for preeclampsia using AhR activation.

Investigating the regenerative effects of folic acid on human amniotic epithelial stem cells and amniotic pore culture technique (APCT) model in vitro using an integrated pharmacological-bioinformatic approach.

INTRODUCTION: Disruption of fetal membranes before the onset of labor is referred to as premature rupture of membranes (PROM). Lack of maternal folic acid (FA) supplementation reportedly leads to PROM. However, there is a lack of information on the location of FA receptors in the amniotic tissue. Additionally, the regulatory role and potential molecular targets of FA in PROM in vitro have rarely been investigated. METHODS: The three FA receptors (folate receptor α isoform [FRα], transporter of reduced folate [RFC], and proton-coupled folate transporter [PCFT]) in human amniotic epithelial stem cells (hAESCs) and amniotic tissue were localized using immunohistochemistry and immunocytochemistry staining. Effect and mechanism analyses of FA were performed in hAESCs and amniotic pore culture technique (APCT) models. An integrated pharmacological-bioinformatics approach was utilized to explore the potential targets of FA for the treatment of PROM. RESULTS: The three FA receptors were widely expressed in human amniotic tissue, especially in the hAESC cytoplasm. FA stimulated the amnion regeneration in the in vitro APCT model. This mimics the PROM status, in which cystathionine-ß-synthase, an FA metabolite enzyme, may play an important role. The top ten hub targets (STAT1, mTOR, PIK3R1, PTPN11, PDGFRB, ABL1, CXCR4, NFKB1, HDAC1, and HDAC2) of FA for preventing PROM were identified using an integrated pharmacological-bioinformatic approach. DISCUSSION: FRα, RFC, and PCFT are widely expressed in human amniotic tissue and hAESCs. FA aids the healing of ruptured membrane.

Pre-pregnancy blood pressure and pregnancy outcomes: a nationwide population-based study.

BACKGROUND: Hypertension has been known to increase the risk of obstetric complications. Recently, the American College of Cardiology endorsed lower thresholds for hypertension as systolic blood pressure of 130-139 mmHg or diastolic blood pressure 80-89 mmHg. However, there is a paucity of information regarding the impact of pre-pregnancy blood pressure on pregnancy outcomes. We aimed to evaluate the effect of pre-pregnancy blood pressure on maternal and neonatal complications. METHODS: In this nationwide, population based study, pregnant women without history of hypertension and pre-pregnancy blood pressure < 140/90 mmHg were enrolled. The primary outcome of composite morbidity was defined as any of the followings: preeclampsia, placental abruption, stillbirth, preterm birth, or low birth weight. RESULTS: A total of 375,305 pregnant women were included. After adjusting for covariates, the risk of composite morbidity was greater in those with stage I hypertension in comparison with the normotensive group (systolic blood pressure, odds ratio = 1.68, 95% CI: 1.59 - 1.78; diastolic blood pressure, odds ratio = 1.56, 95% CI: 1.42 - 1.72). There was a linear association between pre-pregnancy blood pressure and the primary outcome, with risk maximizing at newly defined stage I hypertension and with risk decreasing at lower blood pressure ranges. CONCLUSIONS: 'The lower, the better' phenomenon was still valid for both maternal and neonatal outcomes. Our results suggest that the recent changes in diagnostic thresholds for hypertension may also apply to pregnant women. Therefore, women with stage I hypertension prior to pregnancy should be carefully observed for adverse outcomes.

Women with multiple gestations have an increased risk of development of hypertension in the future.

BACKGROUND: Multiple gestations are associated with an increased incidence of preeclampsia. However, there exists no evidence for an association between multiple gestations and development of hypertension(HTN) later in life. This study aimed to determine whether multiple gestations are associated with HTN beyond the peripartum period. METHODS: In this retrospective nationwide population-based study, women who delivered a baby between January 1, 2007, and December 31, 2008, and underwent a national health screening examination within one year prior to their pregnancy were included. Subsequently, we tracked the occurrence of HTN during follow-up until December 31, 2015, using International Classification of Diseases-10th Revision codes. RESULTS: Among 362,821 women who gave birth during the study period, 4,944 (1.36%) women had multiple gestations. The cumulative incidence of HTN was higher in multiple gestations group compared with singleton group (5.95% vs. 3.78%, p < 0.01, respectively). On the Cox proportional hazards models, the risk of HTN was increased in women with multiple gestations (HR 1.35, 95% CI 1.19, 1.54) compared with those with singleton after adjustment for age, primiparity, preeclampsia, atrial fibrillation, body mass index, blood pressure, diabetes mellitus, high total cholesterol, abnormal liver function test, regular exercise, and smoking status. CONCLUSIONS: Multiple gestations are associated with an increased risk of HTN later in life. Therefore, guidelines for the management of high-risk patients after delivery should be established.

Association of Preterm Birth with Depression and Particulate Matter: Machine Learning Analysis Using National Health Insurance Data.

This study uses machine learning and population data to analyze major determinants of preterm birth including depression and particulate matter. Retrospective cohort data came from Korea National Health Insurance Service claims data for 405,586 women who were aged 25-40 years and gave births for the first time after a singleton pregnancy during 2015-2017. The dependent variable was preterm birth during 2015-2017 and 90 independent variables were included (demographic/socioeconomic information, particulate matter, disease information, medication history, obstetric information). Random forest variable importance was used to identify major determinants of preterm birth including depression and particulate matter. Based on random forest variable importance, the top 40 determinants of preterm birth during 2015-2017 included socioeconomic status, age, proton pump inhibitor, benzodiazepine, tricyclic antidepressant, sleeping pills, progesterone, gastroesophageal reflux disease (GERD) for the years 2002-2014, particulate matter for the months January-December 2014, region, myoma uteri, diabetes for the years 2013-2014 and depression for the years 2011-2014. In conclusion, preterm birth has strong associations with depression and particulate matter. What is really needed for effective prenatal care is strong intervention for particulate matters together with active counseling and medication for common depressive symptoms (neglected by pregnant women).

Role of sex hormones in cervical changes in a cervical excision-related preterm delivery mouse model.

Progesterone and oestrogen play important roles during parturition; however, their roles in the uterine cervix during preterm labour and delivery are unknown. We evaluated the serum progesterone and oestrogen levels and changes in their receptors (PR and ER) in the cervix in a cervical excision-associated preterm delivery mouse model. Adult female C57BL/6 mice were divided into four groups: sham, cervical excision (Ex), lipopolysaccharide (LPS) and Ex + LPS. Mating was permitted at 3 weeks post-Ex. On gestation day 16, mice were administered LPS intrauterine (100 µg/100 µL/mouse) or physiological saline (100 µL) via laparotomy. Uterine cervices and blood were sampled immediately postpartum. As a result, epithelial PR and muscular ERα were down- and upregulated, respectively, in the proximal cervix in Ex + LPS group compared to in the sham group. These results indicate that unique sex hormone effects are exerted on the uterine cervix during cervical excision-associated spontaneous preterm labour and delivery.Impact statementWhat is already known on this subject? Preterm and term parturition require the withdrawal of progesterone and the activation of oestrogen in the uterine body and systemic levels. However, we have little understanding of the role of the sex hormones in the uterine cervix.What do the results of this study add? Increased ERα-to-PR expression ratio in the proximal cervix was associated with preterm labour and delivery. ERα expression in the smooth muscle layer of the proximal cervix was higher and PR expression in the proximal cervix epithelium was lower during preterm labour and delivery.What are the implications of these findings for clinical practice and/or further research? This study revealed the differences between the roles of sex hormones and their receptors in epithelial and muscle layers of proximal and distal cervices in preterm labour and delivery.

Peripartum Blood Transfusions are Associated with Increased Risk of Cancer: A National Retrospective Cohort Study.

BACKGROUND: The effect of blood transfusions on the risk of developing primary cancer remains unclear, especially when administered in the peripartum period. MATERIALS AND METHODS: We conducted a retrospective cohort study of 270,529 pregnant women who delivered between January 1, 2007 and December 31, 2009, with data obtained from three national databases in South Korea. From this cohort, we identified 4569 patients who received peripartum blood transfusions. We calculated hazard ratios (HRs) for new diagnoses of cancer and adjusted them for relevant clinical factors using a Cox proportional hazards model. RESULTS: During follow-up, patients who received peripartum transfusions had an increased risk of developing cancer, with an adjusted HR of 1.16 (95% confidence interval [CI], 1.01-1.34). In a subgroup analysis, this risk was significant only among patients who received 3 or more units of blood, with an adjusted HR of 1.40 (95% CI, 1.10-1.79). Increased risk after transfusions were seen with brain, lung, ovarian, and gallbladder cancers. The difference in cancer risk between the transfusion and no-transfusion groups remained significant during both the first (1.29% vs 1.07%, p < 0.01) and second year (0.74% vs 0.56%, p < 0.01) after delivery. CONCLUSION: Receipt of 3 or more blood transfusions in the peripartum period was associated with a significantly increased risk of developing cancer. Prospective studies should be pursued to further understand the link between blood transfusions and long-term oncologic risks.

Serum sFlt-1, cystatin C and cathepsin B are potential severity markers in preeclampsia: a pilot study.

PURPOSE: Preeclampsia is associated with abnormal invasion of the trophoblast through decidua and subsequently altered remodeling of the maternal spiral arteries and endothelial dysfunction. This phenomenon is explained by the dysregulation of various kinds of vascular factors and proteases. The purpose of this study was to compare the circulating levels of sFlt-1, cathepsin B, and cystatin C in preeclamptic and normotensive pregnancies. STUDY DESIGN: Sixty-two pregnant women were enrolled in this prospective study. Twenty women were preeclamptic and 42 were normotensive. Serum levels of sFlt-1, cathepsin B, and cystatin C were measured using an enzyme-linked immunosorbent assay kit. RESULTS: Circulating levels of sFlt-1, cathepsin B, and cystatin C were significantly higher in preeclamptic than in normotensive pregnant women (p < 0.001; p = 0.017; p = 0.003). Preeclamptic women with severe features demonstrated significantly higher levels of cathepsin B (p = 0.05). Serum sFlt-1 and cystatin C levels were positively correlated with elevated systolic and diastolic blood pressure. The levels of cathepsin B were positively correlated with alanine and aspartate aminotransferase. The amount of 24 h proteinuria was positively, but non-significantly correlated with sFlt-1 and cystatin C. CONCLUSIONS: In addition to sFlt-1 levels, the serum levels of cathepsin B and cystatin C significantly change when preeclampsia develops. These markers are associated with severity markers of elevated blood pressure and liver injury in preeclampsia.

Predicting peripartum blood transfusion: focusing on pre-pregnancy characteristics.

BACKGROUND: Obstetric hemorrhage is one of the most common causes of obstetrical morbidity and mortality, and transfusion is the most important management for hemorrhage. The aim of our study was to investigate the pre-pregnancy and pregnancy risk factors for peripartum transfusion. METHODS: Women who delivered a baby from 2010 to 2014 in Korea and participated in the Korean National Health Screening Program for Infants and Children were included. To analyze pre-pregnant risk factors for peripartum transfusion, an additional analysis was done for women who underwent a National Health Screening Examination within 1 year before pregnancy, including maternal waist circumference, body mass index, blood pressure, laboratory tests and history of smoking. Multivariable logistic regression analysis was used to estimate the risk factors for peripartum transfusion. RESULTS: Of the total 1,980,126 women who met the inclusion criteria, 36,868 (1.86%) were transfused at peripartum. In a multivariable regression model, the pregnancy risk factors for peripartum transfusion included maternal age above 35 years [odds ratio (OR): 1.41; 95% confidence interval (CI): 1.32-1.50], preterm birth (OR: 2.39; 95% CI: 2.15-2.65), and maternal hypertension (OR: 2.49; 95% CI: 2.24-2.77). Pre-pregnancy risk factors including fasting glucose level of more than 126 mg/dL (OR: 1.11; 95% CI: 1.02-1.20), current-smoker status (OR: 1.20; 95% CI: 1.06-1.37), and waist-circumference less than 80 cm (OR: 1.18; 95% CI: 1.06-1.30) were independently associated with peripartum blood transfusion. CONCLUSIONS: Several pre-pregnancy and pregnancy risk factors were associated with peripartum blood transfusion. Some identified factors are modifiable before conception, and our study validated peripartum blood transfusion as a form of triage.

Risk of Adverse Obstetric Outcomes and the Abnormal Growth of Offspring in Women with a History of Thyroid Cancer.

Background: It is unclear whether a history of thyroid cancer is associated with an increased risk of adverse pregnancy outcomes in subsequent pregnancies. This study aimed to evaluate the risk of adverse obstetric outcomes and the abnormal growth of offspring in women with a history of thyroid cancer. Methods: This retrospective observational study used nationwide data from between 2006 and 2014 to compare pregnancy outcomes of women with a history of thyroid cancer and those with no such history. Cases of thyroid cancer were identified using ICD-10 codes. Results: During the study period, 7232 women with a history of thyroid cancer and 2,269,051 women without a history of thyroid cancer gave birth. The risks of cesarean section, preterm birth, low birth weight, large for gestational age, preeclampsia, placental abruption, placenta previa, and stillbirth were not different between the groups. Women with a history of thyroid cancer had a statistically higher risk of postpartum hemorrhage (odds ratio [OR] = 1.23 [confidence interval (CI) 1.15-1.32], p < 0.05, corrected with the false discovery rate). Additionally, generalized estimating equations analysis showed that there was no difference in the risk of underweight (OR = 1.05 [CI 0.93-1.19]) and obese (OR = 0.94 [CI 0.84-1.05]) offspring assessed over a period of 80 months after adjusting for confounding factors. Conclusions: Women with a history of thyroid cancer have similar pregnancy outcomes and offspring growth to those with no such history.

Prepregnancy liver enzyme levels and risk of preeclampsia in a subsequent pregnancy: A population-based cohort study.

BACKGROUND & AIMS: Preeclampsia is a serious multisystemic disorder leading to maternal and neonatal adverse outcomes. However, little is known about the early markers of this disease. The aim of this study was to investigate the association between prepregnancy liver function and the development of preeclampsia. METHODS: We enrolled 192 571 Korean women who had their first delivery between January 1, 2008, and December 31, 2014, and had undergone a national health screening examination through the National Health Insurance Corporation during 1-2 years before delivery. RESULTS: Preeclampsia developed in 3973 (2.0%) women. The rate of development of preeclampsia was higher in women with abnormal prepregnancy liver enzyme levels than in those with normal liver enzyme levels before pregnancy. On multivariate analysis, women with abnormal alanine aminotransferase level before pregnancy had a 1.21-fold increased risk of developing preeclampsia than those with normal alanine aminotransferase level before pregnancy, after adjusting for age, family history of hypertension, hepatitis B virus carrier status, smoking, alcohol status, prepregnancy body mass index and blood pressure. Prepregnancy γ-glutamyltransferase and aspartate aminotransferase levels were not associated with the risk of preeclampsia development. CONCLUSION: Abnormal prepregnancy alanine aminotransferase level was associated with the development of preeclampsia in a subsequent pregnancy. Further studies are needed to evaluate whether early intervention for liver function before pregnancy can decrease the risk of preeclampsia.

Previous uterine artery embolization increases the rate of repeat embolization in a subsequent pregnancy.

This study aimed to determine the rate of repeat uterine artery embolization (UAE) in women with a previous UAE. Study data were collected from the Korea National Health Insurance Claims Database of the Health Insurance Review and Assessment Service for 2009-2013. We enrolled women who had a first delivery in 2009 and a second delivery between 2010 and 2013. Among 226,408 women who had a first delivery in 2009, 296 underwent UAE. A total of 127,506 women had a second delivery between 2010 and 2013. Of 296 women who underwent UAE after the first delivery, 94 had a second delivery between 2010 and 2013. Women with a previous UAE had a higher rate of UAE at the second delivery than women without a previous UAE. Multivariate adjusted analysis showed that a UAE at the first delivery increased the rate of UAE at the second delivery (odds ratio 25.56, 95% confidence interval 9.86-66.23). Women with a previous UAE should be appropriately counseled and monitored for the need for a repeat UAE.

The safety of progestogen in the prevention of preterm birth: meta-analysis of neonatal mortality.

BACKGROUND: The safety of preventive progestogen therapy for preterm birth remains to be established. This meta-analysis aimed to evaluate the effects of preventive progestogen therapy on neonatal mortality. METHODS: Randomized controlled trials (RCTs) on the preventive use of progestogen therapy, published between October 1971 and November 2015, were identified by searching MEDLINE/PubMed, EMBASE, Scopus, ClinicalTrials.gov, Cochrane Library databases, CINAHL, POPLINE, and LILACS using "progesterone" and "preterm birth" as key terms. We conducted separate analyses according to the type of progestogen administered and plurality of the pregnancy. RESULTS: Twenty-two RCTs provided data on 11,188 neonates. Preventive progestogen treatment in women with a history of preterm birth or short cervical length was not associated with increased risk of neonatal death compared to placebo in all analyzed progestogen types and pregnancy conditions. The pooled relative risks (95% confidence interval) of neonatal mortality were 0.69 (0.31-1.54) for vaginal progestogen in singleton pregnancies, 0.6 (0.33-1.09) for intramuscular progestogen in singleton pregnancies, 0.96 (0.51-1.8) for vaginal progestogen in multiple pregnancies, and 0.96 (0.49-1.9) for intramuscular progestogen in multiple pregnancies. CONCLUSIONS: The results of this meta-analysis suggest that administration of preventive progestogen treatment to women at risk for preterm birth does not appear to negatively affect neonatal mortality in single or multiple pregnancies regardless of the route of administration.

Pregnancy-Associated Risk Factors of Postpartum Breast Cancer in Korea: A Nationwide Health Insurance Database Study.

Patients with postpartum breast cancer have been reported to have a poor prognosis. The present study aimed to evaluate the pregnancy-related risk factors of postpartum breast cancer in Korea. We collected patient data from the Korea National Health Insurance (KNHI) Claims Database of the Health Insurance Review and Assessment Service (HIRA) for the 2009-2013 period. We evaluated the pregnancy-related risk factors for postpartum breast cancer in two population groups. For Group 1 (women who had given birth during the 2010-2012 period), data on those who were diagnosed with breast cancer from childbirth to 1-year postpartum were extracted. For Group 2, we extracted the data of women who gave birth in 2010 and traced them until December 31, 2013. In Group 1, 1,384,551 deliveries and 317 postpartum breast cancer patients were recorded in Korea between January 1, 2010, and December 31, 2012. Women aged ≥35 years (Odds Ratio [OR], 2.003; 95% Confidence Interval [CI], 1.567-2.560) and those who gave birth via cesarean delivery (OR, 1.237; 95% CI, 0.986-1.553) were considered to be at a higher risk for breast cancer. Lower risk was noted in primiparous women (OR, 0.737; 95% CI, 0.585-0.928). In Group 2, the data of 457,924 women who gave birth in 2010 were traced until December 31, 2013. Among them, 655 patients were diagnosed with breast cancer, and age ≥35 years and cesarean delivery were associated with an higher risk of breast cancer, whereas primiparous status was associated with a lower risk of breast cancer. In conclusion, older age (≥35 years) and cesarean delivery are significant risk factors for postpartum breast cancer, and primiparous women have a lower risk of developing postpartum breast cancer.

Influences of body size phenotype on the incidence of gestational diabetes needing prescription; analysis by Korea National Health Insurance (KNHI) claims and the National Health Screening Examination (NHSE) database.

OBJECTIVES: Although growing evidence has emphasized the pivotal role of metabolic status irrespective of body mass index (BMI), there has been no study to examine the association of body size phenotype with development of gestational diabetes that requires treatment with oral hypoglycemic agent or insulin (GDM+T) in primiparas. METHODS: Data from a total of 216,961 women who participated in the National Health Screening Examination (NHSE) between January 2007 and December 2011 and delivered their first babies within two years of the NHSE were analyzed. Body size phenotypes were classified according to body mass index (BMI) and the presence/absence of metabolic syndrome according to the results of the NHSE. GDM+T was identified using the International Classification of Diseases-10th Revision (ICD-10) and prescription codes using Korea National Health Insurance (KNHI) claims. RESULTS: Approximately 0.39% of primiparas developed GDM+T. Compared to metabolically healthy normal weight (MHNW) women, both metabolically unhealthy normal weight (MUNW) and metabolically healthy obese (MHO) women had a significantly increased risk for developing GDM+T (odds ratio, OR: 9.53, 95% confidence interval, CI: 5.64-16.09 and OR: 3.30, 95% CI: 2.56-4.25, respectively). Specifically, MUNW individuals had a significantly higher risk of GDM+T when directly compared to MHO women even after adjusting for other GDM risk factors (OR: 2.92, 95% CI: 1.67-5.10). Furthermore, underweight women with metabolic syndrome showed a significantly increased frequency of GDM+T compared to MHNW subjects (OR: 8.87, 95% CI: 1.19-66.32). CONCLUSIONS: Pre-pregnant metabolic status is critical for development of GDM+T, regardless of their BMI. Therefore, intensive intervention for the components of metabolic syndrome may be helpful for the prevention of GDM+T even in low or normal weight women.

Metabolic syndrome in the non-pregnant state is associated with the development of preeclampsia.

BACKGROUND: The aim of this study was to investigate the association between metabolic syndrome in the non-pregnant state and the development of preeclampsia. METHODS: We enrolled 212,463 Korean women who had their first delivery between January, 2011 and December, 2012 and had undergone a national health screening examination through the National Health Insurance during the 1-2 years before their first delivery. Women who had hypertension in the non-pregnant state were excluded. The presence of metabolic syndrome was defined using the modified criteria published in National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS: The prevalence of metabolic syndrome in non-pregnant state was 1.2%. Preeclampsia developed in 3.1% and its prevalence among women with and without metabolic syndrome was 7.3% and 3.0%, respectively. The pre-pregnancy prevalence of metabolic syndrome was higher in women who developed preeclampsia compared to that in those who had a normal pregnancy (1.1% vs. 2.8%; p<0.001). On multivariate regression analysis, women with metabolic syndrome had an increased risk of developing preeclampsia (odds ratio: 1.48; 95% CI: 1.26 to 1.74) compared to that in those without metabolic syndrome, after adjusting for age, family history of hypertension, smoking status, and pre-pregnancy body mass index. The risk of preeclampsia increased with a rise in the number of components of metabolic syndrome. CONCLUSION: Metabolic syndrome in the non-pregnant state was associated with the development of preeclampsia. Further studies are needed to evaluate whether early intervention for metabolic syndrome before pregnancy can decrease the risk of developing preeclampsia.

A case report of a fetus with mosaic autosomal variegated aneuploidies and literature review.

Mosaic variegated aneuploidy (MVA) is a recessive condition characterized by mosaic aneuploidies, predominantly trisomies and monosomies, involving multiple chromosomes and tissues. The phenotype of MVA syndrome includes severe microcephaly and growth deficiency, central nervous system anomalies, mental retardation, mild physical anomalies, and predisposition to cancer. We report a case of true fetal mosaicism for variegated aneuploidies detected in amniotic fluid cells. A 33-year-old primigravida woman at 5 weeks 1 day of gestation was referred to our tertiary hospital because of a high-risk pregnancy associated with IgA nephropathy. In a quadruple screening test performed at the 15(th) week of gestation, alpha fetoprotein was 73.4 IU/mL (2.792 MoM), suggesting that she was at high risk of neural tube defect. Following amniocentesis performed at the 17 weeks' gestation, chromosome examination of amniocyte culture showed premature chromatic separation in 63% of the metaphases (58/92) and a high frequency of gain and loss of chromosomes. Repeat amniocentesis at 21 weeks' gestation consistently showed the presence of multiple mosaic autosomal variegated aneuploidies. Ultrasonography at 21 weeks' gestation revealed relatively small head circumference for gestational age (<3%) and vermis defect, suggesting that the fetus would have microcephaly and Dandy-Walker malformation. Cytogenetic analysis with peripheral blood of the parents showed normal karyotype. In summary, we hereby report the cytogenetic analysis and prenatal findings of MVA.