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Background: Understanding the potential risk factors for failure of pregnancy termination is crucial for informed clinical decision making. Such insights can assist clinicians in adjusting the dosage or route of various regimens, as well as in counseling patients and predicting the likelihood of successful outcomes. However, research on these risk factors has been limited, and existing studies have yielded inconsistent results. To address this gap, we conducted a study with a large sample size, focusing on identifying the potential risk factors for failure of second-trimester termination using misoprostol as a single agent, specifically between 14 and 28 weeks of gestation. Methods: A secondary analysis based on a database of second-trimester terminations was conducted. The inclusion criteria were a singleton pregnancy, gestational age between 14 and 28 weeks, an unfavorable cervix, no spontaneous labor pain, intact membranes, and termination with misoprostol alone. Potential risk factors for failure of termination, defined as no abortion within 48 h, were analyzed using univariate and multivariate analyses. Results: A total of 1094 cases were included in the analysis, consisting of 991 successful cases and 103 (9.4%) cases of failure. The significant risk factors for failure of termination included early gestational age, live fetuses, sublingual regimen of 400 mcg every 6 h, and high maternal pre-pregnancy BMI. Previous cesarean sections and lower Bishop scores tended to increase the risk but did not reach a significant level. Conclusions: Second-trimester termination with misoprostol as a single agent was highly effective, with a failure rate of 9.4%. The risk factors for failure included gestational age, fetal viability, misoprostol regimen, and maternal pre-pregnancy BMI, suggesting that these factors should be taken into consideration for second-trimester terminations with misoprostol.

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Maternal obesity during pregnancy is associated with adverse pregnancy outcomes. This might be due to undesired obesity-induced changes in the maternal gut microbiota and related changes in the maternal immune adaptations during pregnancy. The current study examines how obesity affects gut microbiota and immunity in pregnant obese and lean mice during mid-pregnancy (gestational day 12 (GD12)). C57BL/6 mice were fed a high-fat diet or low-fat diet from 8 weeks before mating and during pregnancy. At GD12, we analyzed the gut microbiota composition in the feces and immune responses in the intestine (Peyer's patches, mesenteric lymph nodes) and the peripheral circulation (spleen and peripheral blood). Maternal obesity reduced beneficial bacteria (e.g., Bifidobacterium and Akkermansia) and changed intestinal and peripheral immune responses (e.g., dendritic cells, Th1/Th2/Th17/Treg axis, monocytes). Numerous correlations were found between obesity-associated bacterial genera and intestinal/peripheral immune anomalies. This study shows that maternal obesity impacts the abundance of specific bacterial gut genera as compared to lean mice and deranges maternal intestinal immune responses that subsequently change peripheral maternal immune responses in mid-pregnancy. Our findings underscore the opportunities for early intervention strategies targeting maternal obesity, ideally starting in the periconceptional period, to mitigate these obesity-related pregnancy effects.

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Objective: To explore the feasibility of transvaginal ultrasound measurement of uterocervical angle (UCA) and cervical length (CL) in early and mid-pregnancy and evaluate their combined prediction of spontaneous preterm birth (sPTB) in singleton pregnancies. Patients and Methods: This retrospective study comprised 274 pregnant women who underwent transvaginal ultrasound measurement of CL in mid-pregnancy (15-23+6 weeks); in 75 among them, CL also had been measured in early-pregnancy (<14 weeks). These 274 pregnant women were further divided into a preterm group (n = 149, <37 weeks gestation) and a control group (n = 125, >37 weeks gestation) according to delivery before or after 37 weeks, respectively. In the preterm group, 35 patients delivered before 34 weeks and the remaining 114 delivered between 34 and 37 weeks. Results: The optimal threshold of CL to predict preterm birth risk in women with <37 weeks gestation was 3.38 cm, and the optimal threshold of the UCA to predict preterm birth risk in the same group of women was 96°. The optimal threshold of CL to predict preterm birth risk in women with <34 weeks gestation was 2.54 cm, while that of the UCA in the same group of patients was 106°. The area under the curve for predicting preterm birth by combining the UCA and CL measurements was greater than that by using the UCA or CL alone (p < 0.01). The sensitivity and specificity for predicting preterm birth at <34 weeks gestation was 71.7% and 86.4%, respectively; and the sensitivity and specificity for predicting preterm birth at <37 weeks gestation was 87.6% and 80.6%, respectively. The difference between the two groups in CL and UCA were not significant in early pregnancy (p > 0.01), but only in mid-pregnancy (p < 0.01). There was a negative correlation between UCA and gestational week at delivery (r = -0.361, p < 0.001) and a positive correlation between CL and gestational week at delivery (r = 0.346, p < 0.001) in mid-pregnancy. The proportion of deliveries at <34 weeks was highest when the UCA was >105°, and the proportion of deliveries between 35 and 37 weeks was highest when the UCA was between 95° and 105°. The proportion of deliveries at <34 weeks was highest when the CL was <2.5 cm. Conclusion: The combination of UCA and CL has a better ability to predict preterm birth than either measurement alone. A more obtuse UCA or a shorter CL is associated with an earlier spontaneous preterm birth. The UCA increases from early to mid-pregnancy, while the CL decreases from early to mid-pregnancy.

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OBJECTIVE: The study aims to investigate the levels of serum NLRP3 along with its effector molecules (Caspase-1, IL-1ß, and IL-18) in the mid-pregnancy in pregnant women with hyperglycemia, and explore the relationship between NLRP3, along with its effector molecules (Caspase-1, IL-1ß, and IL-18) and insulin resistance, as well as pregnancy outcomes. METHODS: The levels of serum NLRP3 along with its effector molecules (Caspase-1, IL-1ß, and IL-18) in three groups of pregnant women with gestational diabetes mellitus (GDM), pregestational diabetes mellitus (PGDM) and normal glucose tolerance (NGT) were measured in mid-pregnancy, and their relationship with insulin resistance and pregnancy outcomes was analyzed. The ROC curve was also used to evaluate the predictive value of serum NLRP3 inflammasome and its effector molecules for pregnancy outcomes. RESULTS: There were no statistical differences in the general clinical data of the three groups, and the concentrations of serum NLRP3 along with its effector molecules were higher in the GDM and PGDM groups than in the NGT group, and NLRP3 along with its effector molecules were positively correlated with fasting blood glucose, fasting insulin, and insulin resistance index in both groups (r > 0, p < .05). The incidence of preterm delivery, hypertensive disorders of pregnancy, premature rupture of membranes, neonatal hypoglycemia and macrosomia was significantly higher in both groups than in the NGT group (p < .05). The value of the combined serum NLRP3 and its effector molecules in mid-pregnancy to predict adverse pregnancy outcomes was highest, and the AUCs for the combined prediction of late hypertensive disorders of pregnancy, premature rupture of membranes, preterm delivery, neonatal hypoglycemia and macrosomia were 0.84 (95% CI 0.79-0.88, p < .001), 0.81 (95% CI 0.75-0.85, p < .001), 0.76 (95% CI 0.70-0.81, p < .001), 0.76 (95% CI 0.70-0.81, p < .001) and 0.72 (95% CI 0.63-0.81, p < .001), respectively. CONCLUSIONS: Increased serum NLRP3 along with its effector molecules in pregnant women with hyperglycemia are associated with the levels of insulin resistance and the subsequent development of adverse pregnancy outcomes.

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BACKGROUND: This study aims to investigate the relationship between gestational metabolic syndrome (GMS) and the Chinese Healthy Eating Index (CHEI) in mid-pregnancy, and to identify potentially beneficial or high-risk dietary habits. We have developed a mid-pregnancy version of CHEI-2022, adapting the Chinese Healthy Eating Index to align with the food quantity recommendations outlined in the 2022 Dietary Guidelines for Chinese Residents for mid-pregnancy. METHODS: Using the inclusion and exclusion criteria, data from 2411 mid-pregnant individuals were collected through interviews. The Total CHEI score and its component scores were determined through analysis of responses from the food frequency questionnaire. GMS diagnosis involved conducting physical examinations and performing blood biochemical tests. A logistic regression model was employed to analyze the relationship between GMS or related indices and both the total CHEI score and its component scores. RESULTS: The study identified an overall GMS prevalence of 21.65% (522 out of 2411 participants). During mid-pregnancy, participants diagnosed with GMS exhibited higher BMI, FBG, 1hPBG, 2hPBG, TC, TG, HDL, SBP, as well as higher educational levels and daily activity, compared to those without GMS (P < 0.001). After adjusting for potential confounders, participants with higher total CHEI scores (≥ 80) were found to have lower odds of GMS or related indices (P < 0.05). Increasing dietary intake of potatoes, whole grains, beans, dark green vegetables, and fruits, as per the CHEI recommendations, was associated with reduced odds of GMS or related indices (P < 0.05). CONCLUSION: A high-quality diet, as indicated by a total CHEI score of 80 or higher, and increased consumption of specific dietary components, namely potatoes, beans, dark green vegetables, and fruits, were found to effectively reduce the odds of GMS or related indices during mid-pregnancy.

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Objective To investigate the relationship between combined plasma ferritin and triglyceride (TG) concentrations in early pregnancy and the risk of gestational diabetes mellitus (GDM). Methods A total of 1 000 pregnant women who had antenatal care at the Sixth Hospital of Wuhan from January 2021 to January 2023 were selected as the research subjects. The cut-offs of ferritin and TG were analyzed by using unrestricted cube splines. All participants were divided into 4 groups according to the cut‐off values of ferritin and TG. Associations between combined ferritin and TG concentrations and GDM risk were estimated using multivariable logistic regression models. Results A total of 158 (15.8%) participants were diagnosed with GDM. The ferritin and TG levels in early pregnancy of pregnant women in the GDM group were significantly higher than those in the non-GDM group (P<0.05). After adjusting for potential confounders, the OR for the risk of developing GDM after combining ferritin with TG was 2.35 (1.65, 3.35). Couclusion The increase in plasma ferritin and TG concentrations in early pregnancy is positively correlated with the increased risk of GDM. Pregnant women with high plasma ferritin (˃65.7 ng/mL) and high TG (˃1.9mmoL/L) have the greatest risk of GDM.

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Background: Effectively predicting the risk of adverse pregnancy outcome (APO) in women with systemic lupus erythematosus (SLE) during early and mid-pregnancy is a challenge. This study was aimed to identify potential markers for early prediction of APO risk in women with SLE. Methods: The GSE108497 gene expression dataset containing 120 samples (36 patients, 84 controls) was downloaded from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA) was performed, and differentially expressed genes (DEGs) were screened to define candidate APO marker genes. Next, three individual machine learning methods, random forest, support vector machine-recursive feature elimination, and least absolute shrinkage and selection operator, were combined to identify feature genes from the APO candidate set. The predictive performance of feature genes for APO risk was assessed using area under the receiver operating characteristic curve (AUC) and calibration curves. The potential functions of these feature genes were finally analyzed by conventional gene set enrichment analysis and CIBERSORT algorithm analysis. Results: We identified 321 significantly up-regulated genes and 307 down-regulated genes between patients and controls, along with 181 potential functionally associated genes in the WGCNA analysis. By integrating these results, we revealed 70 APO candidate genes. Three feature genes, SEZ6, NRAD1, and LPAR4, were identified by machine learning methods. Of these, SEZ6 (AUC = 0.753) showed the highest in-sample predictive performance for APO risk in pregnant women with SLE, followed by NRAD1 (AUC = 0.694) and LPAR4 (AUC = 0.654). After performing leave-one-out cross validation, corresponding AUCs for SEZ6, NRAD1, and LPAR4 were 0.731, 0.668, and 0.626, respectively. Moreover, CIBERSORT analysis showed a positive correlation between regulatory T cell levels and SEZ6 expression (P < 0.01), along with a negative correlation between M2 macrophages levels and LPAR4 expression (P < 0.01). Conclusions: Our preliminary findings suggested that SEZ6, NRAD1, and LPAR4 might represent the useful genetic biomarkers for predicting APO risk during early and mid-pregnancy in women with SLE, and enhanced our understanding of the origins of pregnancy complications in pregnant women with SLE. However, further validation was required.

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The aim of this study was to compare the diagnostic values of red blood cell distribution width-coefficient of variation (RDW-CV) and red blood cell distribution width-standard deviation (RDW-SD) in mid-pregnancy women with iron deficiency anemia (IDA). To obtain the results, 115 mid-pregnancy women with IDA, defined as the IDA group, and 142 healthy mid-pregnancy women, selected as the control group, were enrolled in this study. Hematological parameters and ferritin concentrations in the serum were analyzed. The efficiency of RDW-CV and RDW-SD to distinguish IDA from mid-pregnancy women was evaluated using receiver operating characteristic (ROC) curves. The RDW-SD value in the IDA group was significantly higher than that in the control group (p < 0.05), while the RDW-CV value did not differ between them (p = 0.84). Significantly negative correlations were found between RDW-CV (r = -0.297, p = 0.001), RDW-SD (r = -0.404, p = 0.000), and serum ferritin in the IDA group but not in the control group. For the diagnosis of IDA, RDW-CV and RDW-SD produced areas under the ROC curves of 0.58 and 0.84. To conclude, our results suggest that RDW-SD, but not RDW-CV, can be used as a diagnostic index of IDA for mid-pregnancy women.

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Folate status for women during early pregnancy has been investigated, but data for women during mid-pregnancy, late pregnancy or lactation are sparse or lacking. Between May and July 2014, we conducted a cross-sectional study in 1211 pregnant and lactating women from three representative regions in China. Approximately 135 women were enrolled in each stratum by physiological periods (mid-pregnancy, late pregnancy or lactation) and regions (south, central or north). Plasma folate concentrations were measured by microbiological assay. The adjusted medians of folate concentration decreased from 28·8 (interquartile range (IQR) 19·9, 38·2) nmol/l in mid-pregnancy to 18·6 (IQR 13·2, 26·4) nmol/l in late pregnancy, and to 17·0 (IQR 12·3, 22·5) nmol/l in lactation (Pfor trend < 0·001). Overall, lower folate concentrations were more likely to be observed in women residing in the northern region, with younger age, higher pre-pregnancy BMI, lower education or multiparity, and in lactating women who had undergone a Caesarean delivery or who were breastfeeding exclusively. In total, 380 (31·4 %) women had a suboptimal folate status (folate concentration <13·5 nmol/l). Women in late pregnancy and lactating, residing in the northern region, having multiparity and low education level had a higher risk of suboptimal folate status, while those with older age had a lower risk. In conclusion, maternal plasma folate concentrations decreased as pregnancy progressed, and were influenced by geographic region and maternal socio-demographic characteristics. Future studies are warranted to assess the necessity of folic acid supplementation during later pregnancy and lactation especially for women at a higher risk of folate depletion.

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OBJECTIVES: To assess risk of fetal growth restriction (FGR) by combined screening in early and mid-pregnancy. METHODS: Pregnant women who received prenatal examinations and delivered in our hospital from January 2015 to January 2019 were selected and retrospectively analyzed. All women completed two ultrasonographic examinations during pregnancy, i.e. Down's screening during early pregnancy (11-13 + 6 weeks) and prenatal color Doppler screening during mid-pregnancy (20-24 weeks). A total of 33 FGR cases were screened out, and there were 1,507 normal pregnant women. The clinical, ultrasonographic and serological indices in early and mid-pregnancy were recorded. When the false positive rate was 5%, logistic regression analysis and receiver operating characteristic (ROC) curve were used to evaluate the influencing factors and predictive values of individual and combined indices for FGR in corresponding gestational weeks. The sensitivity and specificity of the optimal cutoff value of each index as well as the combination of optimal predictive indices were found by the area under ROC curve (AUC). RESULTS: When the false positive rate was 5% in the single-index screening during early pregnancy, the parity, BPD, AC, HC, and FL had statistical significances. Multivariate analysis showed that the parity and BPD had statistical significances. During mid-pregnancy, univariate analysis revealed that the parity, BMI, BPD, AC, HC, FL, UTA-PI, UTA-RI, UA-PI and UA-RI had statistical significances. BMI, AC, UTA-PI, UTA-RI, UA-PI and UA-RI had statistical significances in multivariate analysis. BMI, UTA-PI and UA-PI were risk factors for FGR, with UTA-PI being most dangerous. AUC for combined screening exceeded those for individual screenings. The best combined screening program was BPD in early pregnancy + BMI + AC + UTA-PI + UTA-RI + UA-PI + UA-RI in mid-pregnancy. The optimal cutoff value was 0.015, with the sensitivity of 83.1% and the specificity of 61.3%. CONCLUSION: The predictive efficiency of combined FGR screening in early and mid-pregnancy surpasses that of simple mid-pregnancy screening. It is recommended to use the integrated screening program in early and mid-pregnancy to predict FGR.

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Discovering pathophysiologic networks in a blood-based approach may help to generate valuable tools for early treatment or preventive measures in autism. To date targeted or untargeted metabolomics approaches to identify metabolic features and pathways affecting fetal neurodevelopment have rarely been applied to pregnancy samples, that is, an early period potentially relevant for the development of autism spectrum disorders (ASD). We conducted a population-based study relying on autism diagnoses retrieved from California Department of Developmental Services record. After linking cases to and sampling controls from birth certificates, we retrieved stored maternal mid-pregnancy serum samples collected as part of the California Prenatal Screening Program from the California Biobank for children born 2004 to 2010 in the central valley of California. We retrieved serum for 52 mothers whose children developed autism and 62 population controls originally selected from all eligible children matched by birth year and child's sex. Also, we required that these mothers were relatively low or unexposed to air pollution and select pesticides during early pregnancy. We identified differences in metabolite levels in several metabolic pathways, including glycosphingolipid biosynthesis and metabolism, N-glycan and pyrimidine metabolism, bile acid pathways and, importantly, C21-steroid hormone biosynthesis and metabolism. Disturbances in these pathways have been shown to be relevant for neurodevelopment in rare genetic syndromes or implicated in previous studies of autism. This study provides new insight into maternal mid-pregnancy metabolic features possibly related to the development of autism and an incentive to explore whether these pathways and metabolites are useful for early diagnosis, treatment, or prevention. LAY SUMMARY: This study found that in mid-pregnancy the blood of mothers who give birth to a child that develops autism has some characteristic features that are different from those of blood samples taken from control mothers. These features are related to biologic mechanisms that can affect fetal brain development. In the future, these insights may help identify biomarkers for early autism diagnosis and treatment or preventive measures. Autism Res 2020, 13: 1258-1269. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

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@#Objective To study the distribution of sleep duration in mid－pregnancy women and examine its association with prehypertension ( PHT) ． Methods In the baseline survey of a prospective cohort study，943 women in mid－pregnancy were recruited in Guangzhou，China in 2017－2018． A standardized questionnaire was used to assess demographic characteristics，sleep duration and other lifestyles． We obtained maternal blood pressure values，weights，heights，and medical histories from medical records． Multivariate logistic regression was conducted to examine the association between sleep duration and PHT． Ｒesults The average daily sleep duration of women in mid －pregnancy was ( 10. 41 ± 1. 67 ) hours，and it was negatively related to age and educational level． Overall，98. 33% of pregnant women had a daily sleep duration ≥ 7 h and the distribution was related to passive smoking． The average night time sleep duration was ( 9. 48±1. 21 ) hours，and it was negatively related to age and educational level． The daytime sleep duration was ( 0. 93 ± 0. 69 ) hours，and it was positively associated with physical activity． The average bedtime was( 22 ∶ 42 ± 1．24) ，and it was positively associated with passive smoking． The prevalence of PHT was 9. 61%． We did not observe any significant association between sleep duration and PHT． Conclusions The mid－pregnancy women in Guangzhou had relatively long sleep duration， and it differed by maternal age，educational level，physical activity，and passive smoking． There was no significant association between sleep duration and PHT．

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INTRODUCTION: Placenta previa is a severe pregnancy complication with considerable maternal and neonatal morbidity. Placenta previa can be defined as major or minor by location. Major placenta previa is associated with higher complication rates. Management of women with minor placenta previa has not been well defined. The primary goal of the study was to evaluate the accuracy of our existing screening protocol for placenta previa. Secondly, we wanted to compare pregnancy and delivery outcomes by the type of placenta previa. METHODS: The study was conducted at the Helsinki University Hospital between June 2010 and September 2014. The study population consisted of all women with the antenatal ultrasound diagnosis of placenta previa during delivery. Data were retrospectively collected and analysed. RESULTS: Altogether 176 women had placenta previa at delivery (major 129, minor 47). Placenta previa remained undiagnosed at second trimester screening ultrasound in 32 women (18.2%). Twenty (62.5%) of these cases had minor placenta previa and 12 (37.5%) had major placenta previa. Five (15.6%) of the undiagnosed cases developed life-threatening hemorrhage (≥2500 ml) during the delivery and two had abnormally invasive placenta followed by hysterectomy. Women with major placenta previa had significantly more blood loss and delivered earlier than women with minor placenta previa. The groups were otherwise similar, including the rate of abnormally invasive placenta. DISCUSSION: The existing protocol for placenta previa missed almost one fifth of cases. Both major and minor placenta previa are risk factors for abnormally invasive placenta and should be treated as severe conditions.

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Fetal exposure to general anesthetics may pose significant neurocognitive risks but methods to mitigate against these detrimental effects are still to be determined. We set out, therefore, to assess whether single or repeated in utero exposure to sevoflurane triggers long-term cognitive impairments in rat offspring. Since maternal exercise during pregnancy has been shown to improve cognition in offspring, we hypothesized that maternal treadmill exercise during pregnancy would protect against sevoflurane-induced neurotoxicity. In the first experiment, pregnant rats were exposed to 3% sevoflurane for 2 h on gestational (G) day 14, or to sequential exposure for 2 h on G13, G14 and G15. In the second experiment, pregnant rats in the exercise group were forced to run on a treadmill for 60 min/day during the whole pregnancy. The TrkB antagonist ANA-12 was used to investigate whether the brain-derived neurotrophic factor (BDNF)/TrkB/Akt signaling pathway is involved in the neuroprotection afforded by maternal exercise. Our data suggest that repeated, but not single, exposure to sevoflurane caused a reduction in both histone acetylation and BDNF expression in fetal brain tissues and postnatal hippocampus. This was accompanied by decreased numbers of dendritic spines, impaired spatial-dependent learning and memory dysfunction. These effects were mitigated by maternal exercise but the TrkB antagonist ANA-12 abolished the beneficial effects of maternal exercise. Our findings suggest that repeated, but not single, exposure to sevoflurane in pregnant rats during the second trimester caused long-lasting learning and memory dysfunction in the offspring. Maternal exercise ameliorated the postnatal neurocognitive impairment by enhancing histone acetylation and activating downstream BDNF/TrkB/Akt signaling.

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OBJECTIVE: This study was to explore the link between gamma-glutamyl transferase (GGT), alanine transaminase (ALT) and aspartate transaminase (AST) levels during early-middle pregnancy and subsequent risk of gestational diabetes mellitus (GDM). METHODS: In a prospective cohort study, pregnant women enrolled prior to 16 weeks of gestation were followed up until delivery. GGT, AST and ALT levels were tested during weeks 14-18 of gestation and oral glucose tolerance test was conducted during 24-28 weeks to screen GDM. RESULTS: The GDM rate was 8.1% (122/1512). Mean GGT level was higher in GDM than non-GDM women (18.7 ± 13.0 vs 14.5 ± 7.0, P < .001). The higher GGT level was 26.9~74.0 U/L, which was significantly associated with increased risk of GDM. The adjusted RR (95% CI) comparing higher GGT level versus lower was 5.40 (3.36-8.68). No significant correlation was found between ALT or AST levels and the risk of GDM. CONCLUSIONS: The results suggest that pregnant women with higher serum GGT during early-middle pregnancy have higher risk of developing GDM. A GGT level >26.9 U/L may indicate an increased risk of developing GDM later and should be further concerned.

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BACKGROUND & AIMS: Gestational diabetes mellitus is associated with adverse short- and long-term consequences for both the mother and the offspring. To examine the relationship between the rates of gestational weight gain (RGWG) during early and mid-pregnancy and the risk of gestational diabetes mellitus (GDM). METHODS: 2090 singleton pregnant women from the Tongji Maternal and Child Health Cohort (TMCHC) without overt diabetes before pregnancy were analyzed in our study. Gestational weight were measured regularly in every antenatal visit. Gestational diabetes mellitus was assessed with the 75-g, 2-h oral glucose tolerance test at 24-28 weeks of gestation. Multivariable logistic regression was performed to estimate effect of RGWG on GDM. RESULTS: A total of 8.3% (n = 173) of pregnant women were diagnosed with GDM. Women with elevated rate of gestational weight gain prior to glucose screening test (RGWG-PG) increased the risk of GDM (adjusted p-trend = 0.004; odds ratios (OR) 1.64, 95% confidence intervals (CI) 1.01-2.68 and OR 2.30,95% CI 1.44-3.66 for 0.297-0.384 kg/wk and 0.385 kg/wk or more vs. 0.213 kg/wk or less, respectively). Women with greater rate of gestational weight gain in the first trimester (RGWG-F) increased the risk of GDM (adjusted p-trend = 0.048; OR 1.83, 95% CI 1.14-2.94 and OR 1.76, 95% CI 1.10-2.83 for 0.086-0.200 kg/wk and 0.201 kg/wk or more vs. -0.025 kg/wk or less, respectively). The rate of gestational weight gain in the second trimester (RGWG-S) was significantly associated with GDM only among women with RGWG-F more than 0.086 kg/wk (adjusted p-trend = 0.035; OR 2.04, 95% CI 1.16-3.59 for 0.658 kg/wk or more vs. 0.418 kg/wk or less). CONCLUSIONS: Greater early pregnancy weight gain are associated with increased risk of GDM. Elevated weight gain in mid-pregnancy increased the risk of GDM only among pregnant women with greater weight gain in the first trimester.

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OBJECTIVES: this study aimed to explore if maternal vitamin D status in early pregnancy was associated with pre-eclampsia and pregnancy-induced hypertension. Relationships between vitamin D status and blood pressure at the start of pregnancy as well as the occurrence of a mid-pregnancy drop in blood pressure were also explored. This secondary analysis was completed to investigate a possible mechanism for the association between vitamin D status and pregnancy related hypertensive disorders. DESIGN AND SETTING: data were obtained from the Amsterdam Born Children and their Development study, a prospective community-based cohort study based in Amsterdam, The Netherlands. PARTICIPANTS: a total of 2074 nulliparous women without pre-existing hypertension and with a known vitamin D status before 17 weeks gestation were included in the study. Vitamin D status was categorized into four groups: "normal" (≥50nmol/L), "insufficient" (30-49.9nmol/L) "deficient" (20-29.9nmol/L) or "severely deficient" (<20nmol/L). MEASUREMENTS: logistic regression analysis was used to investigate if vitamin D status was related to the odds of experiencing pre-eclampsia or pregnancy-induced hypertension. Models were corrected for maternal age, ethnicity, pre-pregnancy BMI, smoking and socioeconomic status. χ(2) and ANOVA tests were used to investigate relationships between vitamin D status and the blood pressure parameters. FINDINGS: when compared to women with a normal vitamin D status, women who were severely deficient had an increased risk for pre-eclampsia (OR 2.08; 95% CI, 1.05-4.13), but the association was rendered non-significant after correction (OR 1.88; 95% CI 0.79-4.48). There were no associations between vitamin D status and pregnancy-induced hypertension, starting blood pressure or the occurrence of a mid-pregnancy drop in blood pressure. KEY CONCLUSIONS: no strong evidence was found for an association between first trimester vitamin D status and pregnancy related hypertensive disorders in nulliparous women. IMPLICATIONS FOR PRACTICE: at this time, vitamin D supplementation is not warranted for the specific purpose of preventing pregnancy related hypertensive disorders.

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OBJECTIVE: Our purpose was to analyze the fetal weight and placental volume (PV) ratio in diabetic pregnancies during mid-pregnancy. METHOD: One hundred and forty nine diabetic pregnancies [75 gestational diabetes mellitus (GDM) and 74 diabetes mellitus type I (T1DM) with good glycemic control] and 232 healthy patients were analyzed by three-dimensional sonographic volumetry of the placenta, while fetal weight was estimated by two-dimensional technique. RESULTS: The gestational age-specific estimated fetal weight (EFW) [EFWGDM: 1840.8 ± 932.82 g; EFWT1DM: 1475.6 ± 914.7 g (mean ± standard deviation) and placental ratio (PR)] was significantly higher (p < 0.05) in pregnancies complicated by GDM and T1DM (PRGDM: 5.5 ± 1.67 g/cm(3), PRT1DM: 4.56 ± 3.2 g/cm(3)) compared to control group (Q) (EFWQ: 532 ± 186.49 g; PRQ: 2.2 ± 0.8 g/cm(3)), whereas PV was significantly higher (p < 0.05) only in GDM (PVGDM: 334.3 ± 111.5 cm(3)) compared to control data (PVQ: 232 ± 78.9 cm(3)). In contrast to GDM, T1DM with good glycemic control did not predispose to any changes in placental sonographic volumetric differences compared to control values. CONCLUSIONS: Fetal weight related to the PV is already elevated in second trimester in pregnancies complicated by gestational diabetes mellitus and type I diabetes mellitus compared to normal pregnancies.

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AIM: We investigated the influence of carbon dioxide (CO2) pneumoperitoneum on the growth hormone(GH)-insulin-like growth factor I (IGF-I) axis in mid- and late-pregnancy Sprague-Dawley rats. METHODS: A total of 48 mid-pregnancy rats were randomly assigned to one of three groups: anesthesia only (control group); 1-h CO2 pneumoperitoneum; or 2-h CO2 pneumoperitoneum. Blood samples were collected immediately after the procedure or in late pregnancy. Maternal concentration of serum GH and IGF-I was measured on enzyme-linked immunosorbent assay and compared between different groups. RESULTS: Under the same CO2 pneumoperitoneum pressure, serum GH and IGF-I concentration in the 2-h pneumoperitoneum group were significantly lower than those of the 1-h pneumoperitoneum group or the control group in both mid- and late pregnancy (P < 0.05), but there was no significant difference between the 1-h pneumoperitoneum group and the control group (P > 0.05). Serum GH and IGF-I concentrations were positively correlated in pregnant rats (R(2) = 0.3434, P < 0.05). CONCLUSIONS: Under the same CO2 pneumoperitoneum pressure, exposure duration was correlated with effect on maternal GH-IGF-I axis in mid- and late-pregnancy rats. Two h of exposure inhibited the GH-IGF-I axis in both mid- and late pregnancy, and therefore may restrict development of the placenta and fetus.

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Accumulating evidence documents the initiation of diverse physiologic and biochemical response subsequent to an oral glucose load. However, significant gaps in knowledge exist in the understanding of consequences of glucose load during pregnancy, a state of insulin resistance. Using high dimensional protein arrays, we conducted a pilot proof-of-concept and feasibility study to investigate profiles of 120 plasma proteins in pre- and post- 50-gram oral glucose challenge samples. Participants (N = 10) were selected from among women enrolled in a pregnancy cohort. Differences in plasma protein concentrations between pre- and post-glucose load challenge samples were evaluated using Student's T-test (paired) and mean fold change comparisons. Multiple testing adjusted p-values (i.e., false discovery rate q values) were computed using Benjamini-Hochberg (BH) corrections. Plasma haptoglobulin, epidermal growth factor, hemoglobin, thrombospondin-1, and S100 protein concentrations were two to five fold higher in post-glucose load compared with pre-glucose load samples (all q-values <0.05). Among women aged >31 years (above median), post-load S100 protein was elevated 9.92-fold above pre-load concentrations, while it was elevated 4.10-fold among women aged <31 years (below median). Similarly, among women with post-load glucose concentrations <101mg/dl (below median), S100 was elevated 8.26-fold while it was elevated 3.28 fold among women with post-load glucose concentrations >101mg/dl (above median). Our study findings suggest that post-glucose load changes in plasma biomarkers represent a diverse set of cellular responses including receptor for advanced glycation end products (RAGE), inflammation, oxidative stress and adipogenesis, during mid-pregnancy. Future studies of larger populations and longer periods of follow-up are warranted.