Longitudinal hematological change in uncomplicated twin pregnancies: The white blood cell count decreases through pregnancy after the first trimester.

OBJECTIVE: Longitudinal hematological changes throughout twin pregnancies have not been reported. This study aimed to reveal longitudinal changes in hematological indices in twin pregnancies. MATERIALS AND METHODS: We conducted a retrospective chart review of hematological changes in uncomplicated twin pregnancies delivered at ≥37 weeks of gestation between 2010 and 2013 and randomly selected uncomplicated singletons during the same period. A complete blood count and hemogram were performed as blood examinations in the first trimester (9-13 weeks), late second trimester (22-27 weeks), mid-third trimester (33-35 weeks, only in twin pregnancies), and late third trimester (36-38 weeks). We evaluated inter-trimester differences in hematological indices and compared the values between twin and singleton pregnancies in each trimester. RESULTS: The final analysis group included 60 twin pregnancies and 63 singleton pregnancies. The white blood cell (WBC) count in twin pregnancies decreased throughout the pregnancy after the first trimester and became significantly lower than that in singletons in the late third trimester. The WBC count showed only a slight decrease in the third trimester in singleton pregnancies, whereas it showed a marked decrease throughout the pregnancy in twin pregnancies. The marked decrease in the total WBC count in twin pregnancies is mainly due to a decrease in neutrophils. The red blood cell count and hemoglobin and hematocrit values in twin pregnancies showed more marked decreases in the second trimester than in singletons. No decrease was observed after the second trimester of pregnancy. The platelet count decreased in the third trimester of twin pregnancies. CONCLUSION: We clarified the longitudinal hematological changes in twin pregnancies that showed augmentation of or differed from those of singleton pregnancies. It should be specifically mentioned that the WBC count markedly decreased through pregnancy after the first trimester, which is a characteristic change in twin pregnancies.

No role of the third-trimester inflammatory factors in the association of gestational diabetes mellitus with postpartum cardiometabolic indicators.

BACKGROUND: The influence of gestational diabetes mellitus (GDM) on postpartum cardiometabolic indicators is primarily restricted to glucose and lipid metabolism, however the indicators for liver and kidney function have been rarely explored, and the role of the third-trimester inflammatory factors in these associations has never been investigated. METHODS: Based on the Ma'anshan birth cohort (MABC), women with or without GDM history were selected and invited to participate in a 6-year postpartum follow-up. The fasting blood samples were collected to measure 16 comprehensive metabolic indicators during a 6-year postpartum follow-up: fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), triglycerides (TG), total cholesterol (TC), uric acid (UA), blood urea nitrogen (BUN), serum creatinine (SCR), etc. Seven inflammatory factors, including TNF-α, IFN-γ, IL-1ß, IL-6, IL-10, IL-12p70, and IL-17 A, were measured with serum samples collected during the third trimester of pregnancy. Linear regression models were used to analyze the associations between GDM and 6-year postpartum metabolic indicators, GDM and third-trimester inflammatory factors, and the third-trimester inflammatory factors and 6-year postpartum metabolic indicators. Mediating and moderating effect analyses were further performed to explore if the third-trimester inflammatory factors mediate or modify the association between GDM and postpartum cardiometabolic indicators. RESULTS: From July 2021 to August 2022, 307 participants have been followed up, with 99 women with a prior GDM history. Compared with those without GDM, individuals with a prior history of GDM had significantly elevated levels of FPG (ß = 0.40, 95% CI: 0.18 to 0.62, PFDR < 0.001), HbA1c (ß = 0.22, 95% CI: 0.09 to 0.34, PFDR = 0.009), TyG (ß = 0.22, 95% CI: 0.07 to 0.37, PFDR = 0.024) at 6 years postpartum, and the association between GDM and SCR (ß = 2.43, 95% CI: 0.02 to 4.85, PFDR = 0.144) reached nominal significance level. GDM history was associated with a decreased level of third-trimester IL-17 A (ß = -0.58, 95% CI: -0.99 to -0.18, PFDR = 0.035). No significant association between third-trimester inflammatory factors and 6-year postpartum metabolic indicators was observed. And no mediating or moderating effect of third-trimester inflammatory factors was observed in those associations. CONCLUSION: A prior history of GDM was significantly associated with elevated FPG, HbA1c, and TyG in women at 6 years postpartum, whereas third-trimester inflammatory factors had no role in mediating or moderating these associations.

Dynamics of serum levels and reference ranges of copeptin in the 3rd trimester of pregnancy in healthy pregnant women with uncomplicated pregnancy and delivery.

OBJECTIVE: Copeptin is a stable fragment of vasopressin. Copeptin levels have been found to reflect the degree of endothelial stress in various conditions, including acute coronary syndrome. Copeptin may be a bio marker for endothelial stress during pregnancy. However, there is still a lack of understanding of its dynamics and levels throughout pregnancy. This study aims to describe intra-individual and longitudinal changes in copeptin levels at 30th and 36th gestational weeks in healthy pregnant women with uncomplicated pregnancy and delivery and to establish specific reference ranges. METHODS: A total of 125 pregnant women with uncomplicated pregnancy and delivery were included. These women were monitored throughout their pregnancy and gave birth at the Department of Obstetrics and Gynecology Olomouc University Hospital. The blood was taken at ~30 and ~36 gestational weeks. Serum copeptin levels were measured using a Kryptor Compact PLUS analyzer. For statistics, we used R software and the "referenceRanges" package. RESULTS: It was found that serum levels of copeptin were significantly higher in the 36th week group than in the 30th week group (P < 0.05). Cook's distance was used to eliminate outliers. The 30th week median was 3.377 pmol/l, reference range = 1.343-7.829 pmol/l, and the 36 week was median 4.735 pmol/l and reference range = 2.06-13.2 pmol/l. In the 36th week reference range, the median was higher than in healthy, non-pregnant women (P < 0.05). Copeptin values can exceed 10 pmol/l, particularly after the 36th week. In the 3rd trimester, this value may indicate cardiovascular and endothelial overload. CONCLUSION: Copeptin levels were found to vary significantly depending on gestational week. The proposed reference ranges take into account the increased secretion of vasopressin in pregnancy. The existence of specific upper reference limits represents a potential advantage in detecting pregnant women prone to hypertensive disease in the 3rd trimester.

First trimester plasma PER- AND Polyfluoroalkyl Substances (PFAS) and blood pressure trajectories across the second and third trimesters of pregnancy

BACKGROUND: Evidence suggests that exposure to per- and polyfluoroalkyl substances (PFAS) increases risk of high blood pressure (BP) during pregnancy. Prior studies did not examine associations with BP trajectory parameters (i.e., overall magnitude and velocity) during pregnancy, which is linked to adverse pregnancy outcomes. OBJECTIVES: To estimate associations of multiple plasma PFAS in early pregnancy with BP trajectory parameters across the second and third trimesters. To assess potential effect modification by maternal age and parity. METHODS: In 1297 individuals, we quantified six PFAS in plasma collected during early pregnancy (median gestational age: 9.4 weeks). We abstracted from medical records systolic BP (SBP) and diastolic BP (DBP) measurements, recorded from 12 weeks gestation until delivery. BP trajectory parameters were estimated via Super Imposition by Translation and Rotation modeling. Subsequently, Bayesian Kernel Machine Regression (BKMR) was employed to estimate individual and joint associations of PFAS concentrations with trajectory parameters - adjusting for maternal age, race/ethnicity, pre-pregnancy body mass index, income, parity, smoking status, and seafood intake. We evaluated effect modification by age at enrollment and parity. RESULTS: We collected a median of 13 BP measurements per participant. In BKMR, higher concentration of perfluorooctane sulfonate (PFOS) was independently associated with higher magnitude of overall SBP and DBP trajectories (i.e., upward shift of trajectories) and faster SBP trajectory velocity, holding all other PFAS at their medians. In stratified BKMR analyses, participants with ≥ 1 live birth had more pronounced positive associations between PFOS and SBP velocity, DBP magnitude, and DBP velocity - compared to nulliparous participants. We did not observe significant associations between concentrations of the overall PFAS mixture and either magnitude or velocity of the BP trajectories. CONCLUSION: Early pregnancy plasma PFOS concentrations were associated with altered BP trajectory in pregnancy, which may impact future cardiovascular health of the mother.

Establishment of pregnancy-specific lipid reference intervals in pregnant women in a single-centre and assessment of the predictive value of early lipids for gestational diabetes mellitus: a prospective cohort study.

INTRODUCTION: This study was aimed at establishing a pregnancy-specific lipid reference interval (RI) in pregnant women in a single-centre in the Beijing area of China, simultaneously exploring the predictive value of lipid levels in early pregnancy for gestational diabetes mellitus (GDM). MATERIAL AND METHODS: From October 2017 to August 2019, Peking University International Hospital established records for 1588 pregnant women, whose lipid profiles were determined during the first and third trimesters. The Hoffmann technique was used to calculate gestation-specific lipid RI. The 95% reference range for gestational lipids was also estimated for 509 healthy pregnant women screened according to the Clinical and Laboratory Standards Institute guideline. Multivariate logistic regression analysis was used to calculate odds ratios (OR) and their 95% confidence interval (CI), and the receiver operating characteristic (ROC) curve was applied to assess the predictive value of lipids in the first trimester for the diagnosis of GDM. RESULTS: Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher in the third trimester (p < 0.05). Hoffmann technique RI of the lipid profiles and the 95% reference range of the lipid profiles in healthy pregnant women did not differ statistically (p > 0.05). TC, TG, and LDL-C levels were higher in the GDM group in the first trimester (p < 0.05), and the risk of GDM was 2.1 times higher in women with higher TG (95% CI: 1.13-3.77, p < 0.05). The optimal ROC cut-off for TG to predict GDM was 2.375 mmol / L, and the area under the ROC curve was 0.622 (95% CI: 0.592-0.751), with a sensitivity of 73.7% and a specificity of 59.3%. CONCLUSIONS: This study established pregnancy-specific lipid RI for pregnant women in a single centre in the Beijing area of China. Pregnant women with TG ≥ 2.375 mmol/L in the first trimester were at significantly increased risk for GDM.

The association between aspartate aminotransferase (AST) to platelets (PLT) ratio (APRI) and the development of intrahepatic cholestasis in pregnancy and other related complications.

OBJECTIVE: To assess the association between aspartate aminotransferase (AST) to platelet count ratio index (APRI score), during the first and third trimesters of pregnancy and the development of intrahepatic cholestasis in pregnancy (ICP). METHODS: Case-control study was conducted. The study included patients diagnosed with ICP by elevated bile acids (n = 118) and a control group of women with symptoms such as elevated liver enzymes or pruritus with normal level of bile acids (n = 127) who attended a large tertiary teaching medical center between the years 2014 and 2021. The groups were compared in terms of obstetrical characteristics, perinatal outcomes, first- and third-trimester laboratory tests, and APRI scores during the first and third trimester. A receiver operating characteristic (ROC) analysis was performed to determine the APRI score cutoff value that could predict ICP. RESULTS: The third-trimester APRI scores of patients with ICP were significantly higher than those of the control group (P < 0.001). The ROC analysis revealed that the cutoff value for the APRI score was 0.42 with 65.3% sensitivity and 73.2% specificity. CONCLUSION: Our results suggest that the third-trimester APRI score is positively associated with ICP.

Iodine Intake Based on a Survey from a Cohort of Women at Their Third Trimester of Pregnancy from the Bosque County Chile.

Adequate iodine nutrition is fundamental for all humans and is critical during pregnancy and lactation due to iodine forms part of the structure of thyroid hormones (THs) and it is required for THs function. Iodine is a scarce micronutrient that must be obtained from the diet. Sufficient iodine can be found in the nature from seafood and given it is not frequently consumed by Chileans, public health policies state that table salt in Chile must be iodized. Health plans must be monitored to determine if the intake of iodine is being appropriated and the population has not fallen in deficiency or excess. The aim of this work was to evaluate iodine intake in 26 women at the third trimester of pregnancy. Pregnant women are resident from El Bosque a low-income County located in Santiago de Chile. These Chilean pregnant women were recruited by nutritionist at the Centros de Salud familiar (CESFAM). A 24 h dietary recall (24 h-DR) was applied to them to evaluate iodine intake. Samples of urine and blood were taken by health professionals to analyze parameters of thyroid function and to measure urine iodine concentration (UIC). The survey analysis showed that the iodine consumption in these pregnant women derived mainly from salt, bread and milk and not from seafood. The survey analysis indicated that iodine intake was above the requirements for pregnant women. However, the average UIC indicated that iodine intake was adequate, suggesting the need to find a better parameter to determine iodine intake in pregnant women.

Maternal HPV-antibodies and seroconversion to HPV in children during the first 3 years of life.

To assess the dynamics of human papillomavirus (HPV) serology, we analyzed HPV6-,11-,16-,18-, and 45 antibodies in infants during the first 36 months of their life. Serial serum samples of 276/327 mother-child pairs were collected at baseline (mothers) and at months 1, 2, 6, 12, 24 and 36 (offspring), and tested for HPVL1-antibodies using the GST-L1 assay. Concordance between maternal and infant HPV-antibody levels remained high until month-6 (p < = 0.001), indicating maternal antibody transfer. At 1 month, 40-62% of the infants tested seropositive to any of the 5 HPV-types. Between 1-3 years of age, 53% (58/109) of the children born to HPV-seronegative mothers tested HPV-seropositive. Times to positive seroconversion varied between13.4 and 18.7 months, and times to negative seroconversion (decay) between 8.5 and 9.9 months. Significant independent predictors of infants' seroconversion to LR-HPV were hand warts and mother's history of oral warts and seroconversion to LR-HPV. No predictors of seroconversion to HR-HPV were identified. Maternal HPV-IgG-antibodies are transferred to her offspring and remain detectable for 6 months, corroborating the IgG molecule's half-life. Seroconversion to HPV-genotypes 6, 11, 16 and 18 was confirmed among children born to HPV-seronegative mothers, implicating an immune response to these HPV-genotypes during early infancy.

The sFlt-1 to PlGF ratio in pregnant women with rheumatoid arthritis: impact of disease activity and sulfasalazine use.

OBJECTIVES: An elevated sFlt-1/PlGF ratio has been validated as a significant predictor of preeclampsia, but has not been established in women with RA. We explored whether the sFlt-1/PlGFratio could be altered due to disease activity in RA, and could be applied in this population to predict preeclampsia. Since SSZ has been suggested to improve the angiogenic imbalance in preeclampsia, we also aimed to examine whether SSZ could affect sFlt-1 or PlGF levels. METHODS: Making use of a nationwide, observational, prospective cohort study on pregnant women with RA, sFlt-1 and PlGF were measured in the third trimester. A total of 221 women, aged 21-42 years, were included, with a median gestational age of 30 + 3 weeks. RESULTS: No differences in sFlt-1 or PlGF were observed between women with high, intermediate or low disease activity (P = 0.07 and P = 0.41), whereas sFlt-1 and PlGF did not correlate with DAS28-CRP score (r = -0.01 and r = -0.05, respectively). Four (2%) women with a sFlt-1/PlGF ratio ≤38 developed preeclampsia in comparison to three (43%) women with a ratio > 38, corresponding to a negative predictive value of 98.1%. SSZ users (n = 57) did not show altered levels of sFlt-1 or PlGF in comparison to non-SSZ users (n = 164, P = 0.91 and P = 0.11). CONCLUSION: Our study shows that in pregnant women with RA, the sFlt-1/PlGF ratio is not altered due to disease activity and a cut-off ≤38 can be used to exclude preeclampsia. Additionally, SSZ use did not affect sFlt-1 or PlGF levels in this population.

Third trimester cortisol is positively associated with gestational weight gain in pregnant women with class one obesity.

BACKGROUND/OBJECTIVE: Prevalence of pre-pregnancy obesity and excessive gestational weight gain (GWG) are higher among women of color with low SES. Dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis and its end-product, cortisol, during pregnancy is hypothesized to be associated with excessive GWG. However, past studies have produced inconsistent findings and often did not include health disparities populations. This study examined the association between pre-pregnancy body mass index (BMI), third trimester diurnal cortisol, and GWG in low-income, predominantly Hispanic women. SUBJECTS/METHODS: The MADRES study is an ongoing prospective cohort study of primarily Hispanic, low-income pregnant women and their children in Los Angeles, California. Data from 176 participants were included in this study. Total cortisol secretion (area under the curve, AUC) was quantified using four salivary cortisol samples (awakening, 30 min after awakening, afternoon, and bedtime) that were collected at home on one day during the third trimester of pregnancy. Moderation of the association between total cortisol and GWG by pre-pregnancy BMI was tested using multiple linear regression with a multiplicative interaction term. RESULTS: There was no association between total cortisol secretion and GWG overall (p = 0.82), but the association between total cortisol and GWG was stronger for women with class 1 pre-pregnancy obesity compared to women with normal pre-pregnancy BMI (interaction term p = 0.04). CONCLUSIONS: Results suggest that obesity status before pregnancy may be exacerbating the physiological impact of cortisol on GWG.

Maternal Body Mass Index, Early-Pregnancy Metabolite Profile, and Birthweight.

CONTEXT: Maternal prepregnancy body mass index (BMI) has a strong influence on gestational metabolism, but detailed metabolic alterations are unknown. OBJECTIVE: First, to examine the associations of maternal prepregnancy BMI with maternal early-pregnancy metabolite alterations. Second, to identify an early-pregnancy metabolite profile associated with birthweight in women with a higher prepregnancy BMI that improved prediction of birthweight compared to glucose and lipid concentrations. DESIGN, SETTING, AND PARTICIPANTS: Prepregnancy BMI was obtained in a subgroup of 682 Dutch pregnant women from the Generation R prospective cohort study. MAIN OUTCOME MEASURES: Maternal nonfasting targeted amino acids, nonesterified fatty acid, phospholipid, and carnitine concentrations measured in blood serum at mean gestational age of 12.8 weeks. Birthweight was obtained from medical records. RESULTS: A higher prepregnancy BMI was associated with 72 altered amino acids, nonesterified fatty acid, phospholipid and carnitine concentrations, and 6 metabolite ratios reflecting Krebs cycle, inflammatory, oxidative stress, and lipid metabolic processes (P-values < 0.05). Using penalized regression models, a metabolite profile was selected including 15 metabolites and 4 metabolite ratios based on its association with birthweight in addition to prepregnancy BMI. The adjusted R2 of birthweight was 6.1% for prepregnancy BMI alone, 6.2% after addition of glucose and lipid concentrations, and 12.9% after addition of the metabolite profile. CONCLUSIONS: A higher maternal prepregnancy BMI was associated with altered maternal early-pregnancy amino acids, nonesterified fatty acids, phospholipids, and carnitines. Using these metabolites, we identified a maternal metabolite profile that improved prediction of birthweight in women with a higher prepregnancy BMI compared to glucose and lipid concentrations.

Circulating Insulin and IGF-1 and Frequency of Food Consumption during Pregnancy as Predictors of Birth Weight and Length.

The aim of the study was to assess the relationships between maternal insulin and insulin-like growth factor-1 (IGF-1) concentration and food consumption frequency and the birth parameters of the newborn. A total of 157 mother-newborn pairs participated in the study. The study showed that more frequent consumption of sweet and salty snacks as well as fruit and fruit or vegetable juices may promote greater weight gain in pregnancy and higher newborn birth weight. A significantly higher insulin concentration was found among overweight women according to body mass index (BMI), and a significantly lower concentration of IGF-1 was demonstrated among women ≥35 years of age. There was no significant correlation between the concentration of insulin and IGF-1 in the mother's blood plasma and the birth weight and length of the newborn. A significant relationship was only found between the concentration of IGF-1 in the mother's blood and the Ponderal index of the newborn. A woman's eating habits during pregnancy have a significant impact on the mother's health and on the proper growth and development of the foetus.

Maternal Serum Albumin Redox State Is Associated with Infant Birth Weight in Japanese Pregnant Women.

BACKGROUND: Plasma albumin (ALB) reflects protein nutritional status in rats, but it is not clear whether it is associated with dietary protein insufficiency in pregnant women and/or their risk of low birth weight delivery. This study aimed to investigate whether maternal serum ALB redox state reflects maternal protein nutritional status and/or is associated with infant birth weights. METHODS: The relationship between the serum reduced ALB ratio and infant birth weight was examined in an observational study of 229 Japanese pregnant women. A rat model simulating fetal growth restriction, induced by protein-energy restriction, was used to elucidate the relationship between maternal nutritional status, maternal serum ALB redox state, and birth weight of the offspring. RESULTS: In the human study, serum reduced ALB ratio in the third trimester was significantly and positively correlated with infant birth weight. In the rat study, serum reduced ALB ratio and birth weight in the litter decreased as the degree of protein-energy restriction intensified, and a significant and positive correlation was observed between them in late pregnancy. CONCLUSIONS: Maternal serum reduced ALB ratio in the third trimester is positively associated with infant birth weight in Japanese pregnant women, which would be mediated by maternal protein nutritional status.

Vitamin D in gestational diabetes mellitus and its association with hyperglycaemia, insulin sensitivity and other factors.

We investigated if vitamin D is independently associated with hyperglycaemia in gestational diabetes mellitus (GDM). Serum 25 hydroxy vitamin D (25OHD), fasting blood glucose (FBG), HbA1c, fructosamine, insulin sensitivity (QUICKI equation), body mass index, clothing style and outdoor activity were measured in 58 pregnant women with GDM during the third trimester. 25OHD was also measured in 20 women with normal pregnancies. There was no significant difference in mean 25OHD concentrations between GDM (14.43 ± 5.27 ng/ml) and normal (15.45 ± 5.29 ng/ml) pregnancies, p = .354. However, a higher percentage of GDM subjects had 25OHD concentration <19.8 ng/ml (86 versus 65%, p = .003). 25OHD did not correlate with FBG, HbA1c, fructosamine, insulin sensitivity or insulin dosage (p > .05). On multivariate analysis, only ethnicity (p = .006) and outdoor activity (p = .004) were associated with 25OHD. We conclude that the lower 25OHD levels in our GDM patients were related to ethnicity and outdoor activity (Study FF-2017-111, National University of Malaysia, 16 March 2017).IMPACT STATEMENTWhat is already known on this subject? Vitamin D deficiency in pregnancy is widespread and particularly in certain ethnic groups. Low vitamin D levels may be an aetiological factor for gestational diabetes mellitus (GDM) but previous studies provide conflicting results perhaps due to confounding factors.What do the results of this study add? In this study of pregnant women with GDM from different ethnic backgrounds, we analysed serum 25-hydroxy vitamin D (25OHD) levels together with other confounding factors, that is, body mass index, ethnicity and sunlight exposure. Furthermore, instead of using consensus values, we determined cut-offs for different vitamin D status from normal pregnancies matched for gestational age and ethnicity. We found that a higher percentage of GDM subjects had lower vitamin D status but there was no correlation with hyperglycaemia or insulin sensitivity. The study showed that lower vitamin D levels in GDM was associated with ethnicity and less outdoor activity.What the implications are of these findings for clinical practice and/or further research? In GDM patients, low vitamin D levels may be modifiable by supplementation or lifestyle change. Longitudinal studies are needed to determine whether this would impact on the occurrence of GDM.

Circulating angiogenic profiles and histo-morphological placental characteristics of uncomplicated post-date pregnancies.

INTRODUCTION: The objectives of this study were to describe the histo-morphology of post-date placentas in clinically uncomplicated pregnancies without adverse delivery outcomes and the association with maternal circulating pre-delivery Placental Growth Factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1), as well as the sFlt-1/PlGF ratio. METHODS: Post-date placentas (gestational week ≥40+2, n = 87) were macroscopically and histo-morphologically assessed according to the international, standardized Amsterdam Workshop Consensus Group criteria. Inter-rater agreement was evaluated by percentage of agreement. PlGF and sFlt-1 concentrations were available from maternal serum sampled close to delivery, and were compared by Mann-Whitney U test. Linear regression analyses were adjusted for predefined potential confounders. RESULTS: The majority of the post-date placentas showed morphological signs of delayed maturation. About half of the placentas showed increased syncytial knotting and fibrin. In placentas with increased presence of intervillous fibrin, median maternal PlGF level was significantly lower (p = 0.004), median sFlt-1 level higher and sFlt-1/PlGF ratio significantly higher (p = 0.002) compared to those with normal fibrin amounts. Increased placental syncytial knotting was associated with lower levels of PlGF, higher sFlt-1 and higher sFlt-1/PlGF ratio compared to those with normal knotting. DISCUSSION: Our standardized morphological study of post-date placentas in clinically healthy women with uncomplicated pregnancies and delivery outcomes revealed delayed maturation in the majority of placentas. Increased pre-delivery circulating anti-angiogenic profile was associated with increased intervillous fibrin and syncytial knotting. We propose that circulating maternal angiogenic biomarkers may be of future use in clinical post-date pregnancy assessment, as they reflect important aspects of placental health and function.

Establishment of assay method- and trimester-specific reference intervals for thyroid hormones during pregnancy in Chengdu, China.

BACKGROUND: The reference intervals of thyroid hormone will change at different stages of pregnancy because of physiological alterations. On the other hand, the reference intervals of thyroid hormone will also change in different detection systems due to the manufacturer's methodology as well as a different race. The objective of this study was to establish the assay method- and trimester-specific reference intervals for thyroid-stimulating hormone, free thyroxine and free triiodothyronine for pregnant women in Chengdu. METHODS: A prospective, population-based cohort study involved 23,701 reference samples of pregnant women during the three trimesters and 8646 non-pregnant women with pre-pregnancy clinical and laboratory tests. The 2.5th and 97.5th percentiles were calculated as the reference intervals for thyroid-stimulating hormone, free thyroxine and free triiodothyronine at each trimester of pregnant women according to ATA Guidelines. RESULTS: The reference interval of thyroid-stimulating hormone in the 2.5th and 97.5th percentiles has a significant increasing trend from the first trimester, to second trimester and to third trimester, which was 0.08-3.79 mIU/L for the first trimester, and 0.12-3.95 mIU/L for the second trimester and 0.38-4.18 mIU/L for the third trimester, respectively (p < 0.001). However, the reference intervals of free thyroxine and free triiodothyronine in the 2.5th and 97.5th percentiles have significant decreasing trends from the first trimester, to second trimester and to third trimester, which were 11.87-18.83 pmol/L and 3.77-5.50 pmol/L for the first trimester, and 11.22-18.19 pmol/L and 3.60-5.41 pmol/L for the second trimester, and 10.19-17.42 pmol/L and 3.37-4.79 pmol/L for the third trimester, respectively (both p < 0.001). CONCLUSION: It is necessary to establish assay method- and trimester-specific reference intervals for thyroid-stimulating hormone, free thyroxine, and free triiodothyronine because the reference intervals of these thyroid hormones are significantly different at different stages of pregnancy.

Impact of gestational diabetes mellitus diagnosed during the third trimester on pregnancy outcomes: a case-control study.

BACKGROUND: In 2010, the International Association of Diabetes and Pregnancy Study Group (IADPSG) proposed new criteria indicating that gestational diabetes mellitus (GDM) can be diagnosed if the fasting threshold of ≤92 mg/dL, 1-h threshold of ≤180 mg/dL, or 2-h threshold of ≤153 mg/dL are exceeded during the 75-g 2-h oral glucose tolerance test (OGTT) performed at 24-28 weeks of gestation. The World Health Organization (WHO) recommends using the proposed diagnostic threshold values of the IADPSG to diagnose GDM; however, it does not limit the timing of the 75-g OGTT. Since 2010 in Japan, GDM has been diagnosed using the same criteria as that proposed by the WHO. However, neither the JSOG nor the WHO has provided any evidence that it is appropriate to use a threshold beyond the range recommended by the IADPSG. METHODS: This was a single-centre retrospective study based on the medical records and delivery registry database of our centre. We included women who underwent a 50-g glucose challenge test (GCT) with results < 140 mg/dL at 24-28 weeks of gestation and subsequently underwent a 75-g OGTT after 29 weeks of gestation with abnormal glucose tolerance suspected based on clinical findings. The reference values for the 75-g OGTT followed the IADPSG criteria. Subjects were classified into the normal glucose tolerance (NGT) group and the GDM group. The type of delivery and neonatal outcomes of the two groups were compared. A multivariable analysis was performed to match the backgrounds of both groups. RESULTS: In total, the NGT and GDM group comprised 189 and 49 women, respectively. Emergency caesarean delivery rates were similar in the GDM and NGT groups (10.6 and 12.2%, respectively; adjusted odds ratio [OR], 1.25; 95% confidence interval [CI], 0.43-3.64; p = 0.74); however, the elective caesarean delivery rate was higher in the GDM group than in the NGT group (16.3 and 5.3%, respectively, adjusted OR, 3.60; 95% CI, 1.27-10.19; p = 0.01). No significant differences were observed in other maternal and neonatal outcomes between both groups. CONCLUSION: Although a diagnosis of GDM during the third trimester does not improve pregnancy outcomes, it increases the elective caesarean delivery rate.

Maternal food consumption during late pregnancy and offspring risk of islet autoimmunity and type 1 diabetes.

AIMS/HYPOTHESIS: We aimed to investigate the association between maternal consumption of gluten-containing foods and other selected foods during late pregnancy and offspring risk of islet autoimmunity (IA) and type 1 diabetes in The Environmental Determinants of Diabetes in the Young (TEDDY) study. METHODS: The TEDDY study recruited children at high genetic risk for type 1 diabetes at birth, and prospectively follows them for the development of IA and type 1 diabetes (n = 8556). A questionnaire on the mother's diet in late pregnancy was completed by 3-4 months postpartum. The maternal daily intake was estimated from a food frequency questionnaire for eight food groups: gluten-containing foods, non-gluten cereals, fresh milk, sour milk, cheese products, soy products, lean/medium-fat fish and fatty fish. For each food, we described the distribution of maternal intake among the four participating countries in the TEDDY study and tested the association of tertile of maternal food consumption with risk of IA and type 1 diabetes using forward selection time-to-event Cox regression. RESULTS: By 28 February 2019, 791 cases of IA and 328 cases of type 1 diabetes developed in TEDDY. There was no association between maternal late-pregnancy consumption of gluten-containing foods or any of the other selected foods and risk of IA, type 1 diabetes, insulin autoantibody-first IA or GAD autoantibody-first IA (all p ≥ 0.01). Maternal gluten-containing food consumption in late pregnancy was higher in Sweden (242 g/day), Germany (247 g/day) and Finland (221 g/day) than in the USA (199 g/day) (pairwise p < 0.05). CONCLUSIONS/INTERPRETATION: Maternal food consumption during late pregnancy was not associated with offspring risk for IA or type 1 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00279318.

Dehydroepiandrosterone (DHEA) Serum Levels Indicate Cerebrospinal Fluid Levels of DHEA and Estradiol (E2) in Women at Term Pregnancy.

Neuroactive steroids such as dehydroepiandrosterone (DHEA), estradiol (E2), and progesterone (P4) are associated with structural and functional changes in the central nervous system (CNS). Measurement of steroid levels in the CNS compartments is restricted in accessibility. Consequently, there is only limited human data on the distributional equilibrium for steroid levels between peripheral and central compartments. While some neuroactive steroids including DHEA and E2 have been reported to convey excitatory and proconvulsant properties, the opposite was demonstrated for P4. We aimed to elucidate the correlation between peripheral and central DHEA, E2, and P4 levels in women at term pregnancy. CSF and serum samples of 27 healthy pregnant women (22-39 years) at term pregnancy were collected simultaneously under combined spinal and epidural anesthesia and used for DHEA ELISA and E2, and P4 ECLIA. All three neuroactive steroids were detected at markedly lower levels in CSF compared to their corresponding serum concentrations (decrease, mean ± SD, 97.66 ± 0.83%). We found a strong correlation for DHEA between its serum and the corresponding CSF levels (r = 0.65, p = 0.003). Serum and CSF levels of E2 (r = 0.31, p = 0.12) appeared not to correlate in the investigated cohort. DHEA serum concentration correlated significantly with E2 (r = 0.58, p = 0.0016) in CSF. In addition, a strong correlation was found between DHEA and E2, both measured in CSF (r = 0.65, p = 0.0002). Peripheral DHEA levels might serve as an indicator for central nervous levels of the neuroactive steroids DHEA and E2 in pregnant women.