First-trimester hemoglobin, haptoglobin genotype, and risk of gestational diabetes mellitus in a retrospective study among Chinese pregnant women.

BACKGROUND: This study aimed to assess whether the Haptoglobin (Hp) genotype influences the relationship between hemoglobin (Hb) levels and the development of gestational diabetes mellitus (GDM). Additionally, it sought to evaluate the interaction and joint association of Hb levels and Hp genotype with GDM risk. METHODS: This retrospective study involved 358 women with GDM and 1324 women with normal glucose tolerance (NGT). Peripheral blood leukocytes were collected from 360 individuals at 14-16 weeks' gestation for Hp genotyping. GDM was diagnosed between 24-28 weeks' gestation. Interactive moderating effect, joint analysis, and mediation analysis were performed to evaluate the crosslink of Hb levels and Hp genotype with GDM risk. RESULTS: Women who developed GDM had significantly higher Hb levels throughout pregnancy compared to those with NGT. Increase first-trimester Hb concentration was associated with a progressive rise in GDM incidence, glucose levels, glycosylated hemoglobin levels, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) values, cesarean delivery rates, and composite neonatal outcomes. Spline regression showed a significant linear association of GDM incidence with continuous first-trimester Hb level when the latter exceeded 122 g/L. Increased first-trimester Hb concentration was an independent risk factor for GDM development after adjusting for potential confounding factors in both the overall population and a matched case-control group. The Hp2-2 genotype was more prevalent among pregnant women with GDM when first-trimester Hb exceeded 122 g/L. Significant multiplicative and additive interactions were identified between Hb levels and Hp genotype for GDM risk, adjusted for age and pre-pregnancy BMI. The odds ratio (OR) for GDM development increased incrementally when stratified by Hb levels and Hp genotype. Moreover, first-trimester Hb level partially mediated the association between Hp genotype and GDM risk. CONCLUSION: Increased first-trimester Hb levels were closely associated with the development of GDM and adverse pregnancy outcomes, with this association moderated by the Hp2-2 genotype.

Prediction of chromosomal abnormalities in the screening of the first trimester of pregnancy using machine learning methods: a study protocol.

BACKGROUND: For women in the first trimester, amniocentesis or chorionic villus sampling is recommended for screening. Machine learning has shown increased accuracy over time and finds numerous applications in enhancing decision-making, patient care, and service quality in nursing and midwifery. This study aims to develop an optimal learning model utilizing machine learning techniques, particularly neural networks, to predict chromosomal abnormalities and evaluate their predictive efficacy. METHODS/ DESIGN: This cross-sectional study will be conducted in midwifery clinics in Mashhad, Iran in 2024. The data will be collected from 350 pregnant women in the high-risk group who underwent screening tests in the first trimester (between 11-14 weeks) of pregnancy. Information collected includes maternal age, BMI, smoking habits, history of trisomy 21 and other chromosomal disorders, CRL and NT levels, PAPP-A and B-HCG levels, presence of insulin-dependent diabetes, and whether the pregnancy resulted from IVF. The study follows up with the women during their clinic visits and tracks the results of amniocentesis. Sampling is based on Convenience Sampling, and data is gathered using a checklist of characteristics and screening/amniocentesis results. After preprocessing, feature extraction is conducted to identify and predict relevant features. The model is trained and evaluated using K-fold cross-validation. DISCUSSION: There is a growing interest in utilizing artificial intelligence methods, like machine learning and deep learning, in nursing and midwifery. This underscores the critical necessity for nurses and midwives to be well-versed in artificial intelligence methods and their healthcare applications. It can be beneficial to develop a machine learning model, specifically focusing on neural networks, for predicting chromosomal abnormalities. ETHICAL CODE: IR.MUMS.NURSE.REC. 1402.134.

Approximately 3% of newborns are affected by congenital abnormalities and genetic diseases, leading to disability and death. Among live births, around 3000 cases of Down syndrome (trisomy 21) can be expected based on the country's birth rate. Pregnant women carrying fetuses with Down syndrome face an increased risk of pregnancy complications. Artificial intelligence methods, such as machine learning and deep learning, are being used in nursing and midwifery to improve decision-making, patient care, and research. Nurses need to actively participate in the development and implementation of AI-based decision support systems. Additionally, nurses and midwives should play a key role in evaluating the effectiveness of artificial intelligence-based technologies in professional practice.

Mid-upper arm circumference predicts the risk of gestational diabetes in early pregnancy.

BACKGROUND: The present work aimed to assess the value of mid-upper arm circumference (MUAC) at 8 to 12 weeks in predicting the occurrence of gestational diabetes mellitus (GDM). METHODS: According to eligibility criteria, 328 women with singleton pregnancies who underwent routine antenatal check-ups at Qinhuangdao Maternal and Child Health Hospital from September 2017 to September 2020 were included. The patients were divided into the gestational diabetes mellitus (GDM) and non-GDM groups according to oral glucose tolerance test (OGTT) data from gestation weeks 24 to 28. Clinical data were compared between the two groups. Logistic regression analysis was performed to determine factors independently predicting GDM. Receiver operating characteristic (ROC) curve analysis was employed to analyze the value of MUAC in predicting the occurrence of GDM. The optimal cut-off points were calculated. RESULTS: In logistic regression analysis, pre-pregnancy weight, waist circumference, MUAC, UA, TG, and HDL-C independently predicted the occurrence of GDM (P < 0.05). MUAC retained statistical significance upon adjustment for various confounders (OR = 8.851, 95%CI: 3.907-20.048; P < 0.001). ROC curve analysis revealed good diagnostic potential for MUAC in GDM (AUC = 0.742, 95%CI: 0.684-0.800, P < 0.001), with a cut-off of 28.5 cm, sensitivity and specificity were 61% and 77%, respectively. CONCLUSION: Pregnant women with MUAC >28.5 cm are prone to develop GDM during pregnancy, indicating that MUAC as an important predictive factor of GDM in early pregnancy.

Cephalopagus twins diagnosed at 7 weeks gestational age following IVF/ICSI.

A patient in her 30s who was a G0 proceeded with in vitro fertilisation (IVF) for a history of male factor infertility. Following single embryo transfer, the patient was diagnosed with a conjoined twin pregnancy. During her IVF cycle, the patient was stimulated with an antagonist protocol for 13 days followed by a gonadotropin-releasing hormone agonist trigger. 13 eggs were retrieved, 9 were mature and 5 fertilised with intracytoplasmic sperm injection. Of those, two were cryopreserved. She had a successful frozen blastocyst embryo transfer. The patient's 7-week ultrasound demonstrated a single gestational sac, yolk sac and fetal pole. However, the crown-rump length appeared visually abnormal and two heartbeats were visualised. She was referred to maternal-fetal medicine (MFM) for a first-trimester ultrasound. Her ultrasound with MFM was notable for a fluid-filled chest, foreshortened limbs and early sacral agenesis. She was subsequently diagnosed with cephalopagus twins and underwent an induced abortion following consultation with MFM.

[Association between early pregnancy maternal blood pressure and risk of congenital heart disease in offspring].

Objective: To analyze the association between maternal blood pressure and congenital heart disease (CHD) in offspring. Methods: From February 2018 to December 2020, pregnant women who participated in the China birth cohort study in Beijing Obstetrics and Gynecology Hospital, Shenzhen Maternal and Child Healthcare Hospital and Chengdu Women's and Children's Central Hospital were enrolled in this study. The baseline and follow-up information were collected using an electronic data collection system. Stepwise logistic regression model was used to analyze the association between maternal blood pressure including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure difference (PP) in the first trimester of pregnancy and the risk of CHD in the offspring. A restrictive cubic spline curve was used to draw the dose-response curve between maternal blood pressure and CHD. Results: A total of 55 552 participants were included in this study. Of them, 31 038, 15 375 and 9 139 pregnant women were enrolled in Beijing Obstetrics and Gynecology Hospital, Shenzhen Maternal & Child Healthcare Hospital and Chendu Women's and Children's Central Hospital, respecitively. The age of pregnant women was (31.3±4.0) and the incidence of CHD in the offspring was 0.78% (435/55 552). Multivariable logistic regression model analysis showed that the increase of SBP (OR=1.01, 95%CI: 1.00-1.02), DBP (OR=1.01, 95%CI: 1.00-1.03) and MAP (OR=1.02, 95%CI: 1.00-1.03) in the first trimester were significantly associated with the risk of CHD in the offspring. The restrictive cubic spline analysis showed a positive linear association of SBP (Ptotal<0.001; Pnon-liear=0.315), DBP (Ptotal<0.001; Pnon-liear=0.928) and MAP (Ptotal<0.001; Pnon-liear=0.929) with the risk of CHD in the offspring. Conclusion: Maternal SBP, DBP and MAP in the first trimester of pregnancy were positively associated with the risk of CHD in the offspring.

Exposure to a mixture of metal(loid)s and sleep quality in pregnant women during early pregnancy: A cross-sectional study.

Biological characteristics of pregnant women during early pregnancy make them susceptible to both poor sleep quality and metal/metalloid exposure. However, the effects of metal(loid) exposure on sleep quality in pregnant women remain unknown and unexplored. We aimed to examine the relationship between exposure to a mixture of metal(loid)s and pregnant women's sleep quality during early pregnancy. We recruited 493 pregnant women in the first trimester from prenatal clinics in Jinan, Shandong Province, China, and collected their spot urine samples. All urine specimens were assessed for eight metal(loid)s: arsenic (As), cadmium (Cd), iron (Fe), zinc (Zn), molybdenum (Mo), lead (Pb), selenium (Se), and mercury (Hg). We used the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality. Linear regression, logistic regression, generalized additive models (GAMs), quantile g-computation, and Bayesian kernel machine regression (BKMR) were applied to investigate the relationships between metal(loid) exposure and sleep quality. The results from single metal(loid) models, quantile g-computation models, and BKMR models consistently suggested that Fe was positively related to women's sleep quality. Moreover, in the quantile g-computation models, As was the most critical contributor to the negative effects of the metal(loid) mixture on sleep quality. In addition, we found significant As by Fe interaction for scores of PSQI and habitual sleep efficiency, Pb by Fe interaction for PSQI and sleep latency, and Hg by Fe interaction for PSQI, suggesting the interactive effects of As and Fe, Pb and Fe, Hg and Fe on sleep quality and specific sleep components. Our study provided the first-hand evidence of the effects of metal(loid) exposure on pregnant women's sleep quality. The underlying mechanisms need to be explored in the future.

Pregnancy outcomes and risk factors analysis in patients with systemic lupus erythematous.

BACKGROUND: The management of systemic lupus erythematosus (SLE) during pregnancy remains a challenge currently. Identifying early predictors of adverse pregnancy outcomes in SLE patients can help to develop treatment plan and improve prognosis. The aim of this study is to explore the clinical and laboratory variables in the early pregnancy that can predict adverse neonatal and maternal outcomes, thereby facilitating the grading management of SLE. METHODS: A retrospective analysis was conducted on 126 pregnant women with SLE who were admitted to Zhongnan Hospital of Wuhan University between January 2017 and December 2022. All enrolled patients were diagnosed (including newly diagnosed and previously diagnosed) during first trimester of pregnancy and their clinical records, laboratory results and pregnancy outcomes were reviewed. The association between the clinical and laboratory characteristics of patients at 12 gestational age and the adverse neonatal (ANOs) as well as maternal outcomes (AMOs) were analyzed. RESULTS: A total of 117 live births (92.8%) were recorded in the study. ANOs occurred in 59 (46.8%) cases, including fetal loss in 9 cases (7.1%), preterm birth in 40 cases (31.7%), small for gestational (SGA) in 15 cases (11.9%), and complete heart block in 2 cases (1.5%). Univariate analysis showed that disease activity index (P < 0.0001), lupus nephritis (P = 0.0195), anti-SSB positivity (P = 0.0074) and hypocomplementemia (P = 0.0466) were related to ANOs. However, multivariate analysis showed that only disease activity during early pregnancy was an independent predictor for ANOs (OR = 7.053, 95% CI: 1.882 to 26.291, P = 0.004). In addition, 48 patients experienced AMOs during subsequent trimester, including 24 (19.0%) patients with disease flare and 23 (18.3%) patients with pre-eclampsia. Unplanned pregnancy (P = 0.010), active disease (P = 0.0004), new onset SLE (P = 0.0044) and lupus nephritis (P = 0.0009) were associated with AMOs in univariate analysis, while disease activity was identified as an independent risk factor for AMOs (OR = 2.553, 95% CI: 1.012-6.440, P = 0.047). CONCLUSION: Active disease in early pregnancy is associated with adverse pregnancy outcomes. For patients with high risk factor for ANOs and AMOs, more intensive treatment and follow-up should be a wise measure. Especially for those who suffer from active disease, they should be fully informed and given the option to terminate or continue their pregnancy.

Maternal Weight Gain in Early Pregnancy with Healthy Live Offspring: Based on the China Birth Cohort Study.

BACKGROUND: Research on maternal weight gain in early pregnancy with healthy live offspring is lacking for Chinese women. Based on the China birth cohort study (CBCS), we aimed to explore maternal weight gain in different groups. METHODS: Singleton pregnancies of 6 + 0~13 + 6 weeks of gestation from the CBCS were considered, not including missing data or outliers, those lost at follow-up, or those with non-typical conditions of the offspring. Maternal first-trimester weight and body mass index (BMI) gain was considered as the early pregnancy weight minus the pre-pregnancy weight. Using Pearson's or Spearman's correlation and linear regression models to explore the relationship between maternal weight and BMI gain and gestational age (GA), stratified and sensitivity analyses were carried out to identify the study's robustness. RESULTS: There were 25,292 singleton pregnancies with healthy live offspring who were ultimately enrolled, and there was a linear correlation between GA and maternal weight gain (=0.55 + 0.05 × GA (weeks), p < 0.001, r2 = 0.002) and BMI change (=0.21 + 0.02 × GA (weeks), p < 0.001, r2 = 0.002). The association remained robust in the stratified and sensitivity analyses of the subgroups. CONCLUSIONS: Although the association between GA and maternal pre-pregnancy weight and BMI gain is weak, a slight correlation was shown, especially in pregnant women with a typical or low pre-pregnancy BMI, Han ethnicity, moderate levels of physical activity, natural conception, and folic acid (FA) and/or multivitamin supplementation.

Correlation of Maternal Vitamin D Status in Early Pregnancy and Vitamin D Supplementation during Pregnancy with Atopic Dermatitis in Infants: A Prospective Birth Cohort Study.

OBJECTIVE: This study aimed to investigate the association of maternal first-trimester vitamin D levels and vitamin D supplementation during pregnancy with infant atopic dermatitis (AD) and to determine the effect of variables such as mode of conception on the association. METHODS: This study was based on the Shanghai sub-cohort of the International Birth Cohort of China. A total of 4051 woman-infant pairs with singleton pregnancies were recruited. Vitamin D deficiency and insufficiency were defined as serum 25-hydroxyvitamin D concentrations of 25 and 50 nmol/L, respectively. AD in infants was assessed during the first six months using a standardized questionnaire based on the British Working Party criteria. Modified Poisson regression estimated the association between maternal vitamin D status and infant AD. RESULTS: The risk of AD in infants was higher in women with deficient 25-hydroxyvitamin D levels in the first trimester (RR: 1.77, 95% CI: 1.41-2.23). This increased risk was seen in naturally conceived pregnancies, but not in those conceived using assisted reproductive technology (ART). The incidence of AD decreased in infants of mothers who took multi-vitamin (RR: 0.79, 95% CI: 0.67-1.98) and vitamin D supplements (RR: 0.51, 95% CI: 0.37-0.71) compared to those whose mothers did not take any supplements. Maternal vitamin D deficiency had varying effects on AD risk based on passive smoking exposure and breastfeeding patterns. CONCLUSIONS: Our findings highlight the importance of monitoring and supplementing vitamin D during pregnancy, especially in specific maternal populations, to reduce the risk of AD in offspring.

Association between Disgust Sensitivity during Pregnancy and Endogenous Steroids: A Longitudinal Study.

The emotion of disgust protects individuals against pathogens, and it has been found to be elevated during pregnancy. Physiological mechanisms discussed in relation to these changes include immune markers and progesterone levels. This study aimed to assess the association between steroids and disgust sensitivity in pregnancy. Using a prospective longitudinal design, we analyzed blood serum steroid concentrations and measured disgust sensitivity via text-based questionnaires in a sample of 179 pregnant women during their first and third trimesters. We found positive correlations between disgust sensitivity and the levels of C19 steroids (including testosterone) and its precursors in the Δ5 pathway (androstenediol, DHEA, and their sulfates) and the Δ4 pathway (androstenedione). Additionally, positive correlations were observed with 5α/ß-reduced C19 steroid metabolites in both trimesters. In the first trimester, disgust sensitivity was positively associated with 17-hydroxypregnanolone and with some estrogens. In the third trimester, positive associations were observed with cortisol and immunoprotective Δ5 C19 7α/ß-hydroxy-steroids. Our findings show that disgust sensitivity is positively correlated with immunomodulatory steroids, and in the third trimester, with steroids which may be related to potential maternal-anxiety-related symptoms. This study highlights the complex relationship between hormonal changes and disgust sensitivity during pregnancy.

Evaluating the predictive efficacy of first trimester biochemical markers (PAPP-A, fß-hCG) in forecasting preterm delivery incidences.

In this investigation, we explored the correlation between first-trimester biochemical markers and the incidence of preterm birth (PTB), irrespective of the cause, spontaneous preterm birth (sPTB), and preterm premature rupture of membranes (pPROM) within a cohort comprising 1164 patients. It was discovered that diminished levels of Pregnancy-Associated Plasma Protein-A (PAPP-A) between 11 and 13 + 6 weeks of gestation significantly contributed to the risk of preterm deliveries both before 35 and 37 weeks, as well as to pPROM instances. Furthermore, women experiencing sPTB before the 37th week of gestation also exhibited lower concentrations of PAPP-A. Moreover, reduced first-trimester concentrations of free beta-human chorionic gonadotropin (fb-HCG) were identified as a risk factor for deliveries preceding 37 weeks, pPROM, and sPTB before 35 weeks of gestation. Despite these correlations, the area under the curve for these biochemical markers did not surpass 0.7, indicating their limited diagnostic potential. The most significant discriminatory capability was noted for PAPP-A levels, with a threshold of < 0.71 multiples of the median (MoM) predicting PTB before 37 weeks, yielding an odds ratio of 3.11 (95% Confidence Interval [CI] 1.97-4.92). For sPTB, the greatest discriminatory potential was observed for PAPP-A < 0.688, providing an OR of 2.66 (95% CI 1.51-4.66). The cut-off points corresponded to accuracies of 76.05% and 79.1%, respectively. In regression analyses, the combined predictive models exhibited low explanatory power with R2 values of 9.2% for PTB and 7.7% for sPTB below 35 weeks of gestation. In conclusion, while certain biochemical markers demonstrated associations with outcomes of preterm birth, their individual and collective predictive efficacies for foreseeing such events were found to be suboptimal.

Elevated serum uric acid to creatinine ratio is associated with adverse pregnancy outcomes: a prospective birth cohort study.

Purpose: This study evaluated the association between maternal serum uric acid-to-creatinine ratio (SUA/SCr) in the first trimester and adverse maternal and neonatal outcomes. Methods: A prospective birth cohort study was conducted between 2018 and 2021. Logistic regression models and restricted cubic splines were utilized to estimate the associations between the SUA/SCr ratio and feto-maternal pregnancy outcomes. Women were stratified according to maternal age and pre-pregnancy body mass index. Results: This study included 33,030 pregnant women with live singleton pregnancies. The overall prevalence of gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), cesarean delivery, preterm birth, large-for-gestational age (LGA), small-for-gestational age, and low Apgar scores were 15.18%, 7.96%, 37.62%, 4.93%, 9.39%, 4.79% and 0.28%, respectively. The highest quartile of SUA/SCr was associated with the highest risk of GDM (odds ratio [OR] 2.14, 95% CI 1.93-2.36), PIH (OR 1.79, 95% CI 1.58-2.04), cesarean delivery (OR 1.24, 95% CI 1.16-1.33), and preterm birth (OR 1.30, 95% CI 1.12-1.51). The associations between SUA/SCr with adverse pregnancy outcomes showed linear relationships except for GDM (P < 0.001 for all, P < 0.001 for non-linearity). Subgroup analyses revealed that the associations between the SUA/SCr ratio and the risks of PIH and LGA were significantly stronger in younger pregnant women (P = 0.033 and 0.035, respectively). Conclusion: Maternal SUA/SCr levels were associated positively with the risk of adverse pregnancy outcomes. Timely monitoring of SUA and SCr levels during early pregnancy may help reduce the risk of adverse pregnancy outcomes and provide a basis for interventions.

Covid-19 infection and vaccination during first trimester and risk of congenital anomalies: Nordic registry based study.

OBJECTIVES: To evaluate the risk of major congenital anomalies according to infection with or vaccination against covid-19 during the first trimester of pregnancy. DESIGN: Prospective Nordic registry based study. SETTING: Sweden, Denmark, and Norway. PARTICIPANTS: 343 066 liveborn singleton infants in Sweden, Denmark, and Norway, with an estimated start of pregnancy between 1 March 2020 and 14 February 2022, identified using national health registries. MAIN OUTCOME MEASURE: Major congenital anomalies were categorised using EUROCAT (European Surveillance of Congenital Anomalies) definitions. The risk after covid-19 infection or vaccination during the first trimester was assessed by logistic regression, adjusting for maternal age, parity, education, income, country of origin, smoking, body mass index, chronic conditions, and estimated date of start of pregnancy. RESULTS: 17 704 (5.2%) infants had a major congenital anomaly. When evaluating risk associated with covid-19 infection during the first trimester, the adjusted odds ratio ranged from 0.84 (95% confidence interval 0.51 to 1.40) for eye anomalies to 1.12 (0.68 to 1.84) for oro-facial clefts. Similarly, the risk associated with covid-19 vaccination during the first trimester ranged from 0.84 (0.31 to 2.31) for nervous system anomalies to 1.69 (0.76 to 3.78) for abdominal wall defects. Estimates for 10 of 11 subgroups of anomalies were less than 1.04, indicating no notable increased risk. CONCLUSIONS: Covid-19 infection and vaccination during the first trimester of pregnancy were not associated with risk of congenital anomalies.

The predictive value of ultrasound markers for pregnancy outcomes in recurrent pregnancy loss: a retrospective study.

Establishing prediction models of pregnancy outcomes for recurrent pregnancy loss women at specific gestational weeks will provide patients and physicians with more precise information, ultimately leading to time and cost savings associated with unnecessary revisits. Therefore, our aim was to develop a prediction model for first trimester pregnancy loss in RPL patients. We used ultrasound indices during the first trimester of pregnancy in combination with demographic characteristics and commonly used serum markers. The independent risk factors for each week were as follows: age and P in the fifth week; age, mGSD and CRL in the sixth week; age, hCG and CRL in the seventh week; CRL in the eighth week; mGSD and CRL in ninth week. The corresponding AUC was 0.671, 0.796, 0.872, 0.871, 0.813, respectively. There is a linear relationship between age and first trimester pregnancy loss. hCG < 69,636.6 mIU/ml was associated with a higher risk of pregnancy loss in the seventh gestation week. An mGSD < 18.3 mm, adjusted for age, BMI, and previous pregnancy loss in the sixth week, was linked to an increased risk of first trimester pregnancy loss. A small CRL measurement (less than 2.4 mm, 9.9 mm, 16.9 mm, and 18.6 mm) in the sixth, seventh, eighth and ninth week was closely correlated with higher risk of first trimester pregnancy loss. Furthermore, an mGSD < 33.3 mm and > 48.3 mm in ninth gestational week was associated with a higher risk of pregnancy loss. These models and thresholds may help physicians and patients make more informed decisions together. Further studies are needed to confirm the results.

Concomitant use of antidepressants and benzodiazepines during pregnancy and associated risk of congenital malformations: a population-based cohort study in Taiwan.

BACKGROUND: Despite the frequent co-administration of antidepressants and benzodiazepines, the association between such concomitant use during pregnancy and the risk of congenital malformations remains inadequately explored. This study aims to examine the association between concomitant use of antidepressants and benzodiazepines during the first trimester and organ-specific congenital malformations. METHODS: We conducted a population-based cohort study using Taiwan's National Birth Certificate Application database, the Maternal and Child Health database, and Taiwan's National Health Insurance database. Pregnant people aged 15-50 years with singleton births between Jan 1, 2004, and Dec 31, 2018, were included. Use of antidepressants and benzodiazepines was defined as at least one prescription during the first trimester, and concomitant use was defined as the overlapping prescription of both drugs with an overlapping prescription period. The primary outcomes were overall congenital malformations and eight organ-specific malformations, consisting of the nervous system, heart, respiratory system, oral cleft, digestive system, urinary system, genital system, and limb malformations. Logistic regression models with propensity score fine stratification weighting approach were used to control for measured confounders. Analyses controlling for confounding by indication and sibling comparison analyses were done to address unmeasured confounders. No individuals with lived experience participated in the research or writing process. FINDINGS: The cohort included 2 634 021 singleton pregnancies, and 8599 (0·3%) individuals were concomitant users of antidepressants and benzodiazepines during the first trimester (mean age at delivery was 31·8 years [SD 5·2] for pregnancies with exposure to antidepressants and benzodiazepines vs 30·7 years [SD 4·9] for pregnancies without exposure). All study participants were female, and information about ethnicity was not available. Absolute risk of overall malformations was 3·81 per 100 pregnancies with exposure, compared with 2·87 per 100 pregnancies without exposure. The propensity score-weighted odds ratios (weighted ORs) did not suggest an increased risk for overall malformations (weighted OR 1·10, 95% CI 0·94-1·28), heart defects (1·01, 0·83-1·23), or any of the other organ-specific malformations, except for digestive system malformations, for which the weighted OR remained statistically significant after adjustment (1·63, 1·06-2·51). The absence of an increased risk for overall congenital malformations associated with concomitant use of antidepressants and benzodiazepines was supported by the analyses controlling for confounding by indication and sibling-matched comparisons. INTERPRETATION: The findings of this study suggest that the concomitant use of antidepressants and benzodiazepines during the first trimester is not associated with a substantial increase in risk for most malformation subtypes. However, considering other potential adverse effects of using both medications concomitantly, a thorough assessment of the risks and benefits is crucial for clinical decision making. FUNDING: National Science and Technology Council.

Assessment of the Safety of Exposure to Cefcapene Pivoxil during the First Trimester of Pregnancy: A Prospective Cohort Study in Japan.

Cefcapene pivoxil hydrochloride is an antibiotic often used by women who are or may be pregnant. However, the safety of exposure to it during the first trimester of pregnancy has not been assessed. In this study, we aimed to clarify the effects of exposure during the first trimester of pregnancy on maternal and fetal outcomes. Data were obtained from pregnant women who were counseled on drug use during pregnancy at two Japanese facilities from April 1988 to December 2017. The incidence of major malformations in singleton pregnancy was compared between neonates born to women who took cefcapene pivoxil hydrochloride (n = 270) and control drugs (n = 1594) during their first trimester. The adjusted odds ratio of the incidence of major malformations was calculated using multivariate logistic regression analysis adjusted for smoking during pregnancy and maternal age. The incidence of major malformations was 2.6% in the cefcapene pivoxil hydrochloride group and 1.8% in the control group. There were no significant differences in the incidence between the cefcapene pivoxil hydrochloride and control groups (adjusted odds ratio: 1.48 [95% confidence interval: 0.64-3.42], p = 0.36). This prospective cohort study showed that exposure to cefcapene pivoxil hydrochloride during the first trimester of pregnancy was not associated with increased risk of major malformations in infants. Our findings will help healthcare providers in choosing appropriate medicines.

[The association between visceral adipose thickness and gestational diabetes mellitus in the first trimester].

Objective: To investigate the association between visceral adipose tissue (VAT) thickness in early pregnancy and the risk of gestational diabetes mellitus (GDM). Methods: Based on the Qingdao Women and Children Health Cohort, pregnant women in the first trimester (11-13+6 weeks of gestation) were enrolled in this cohort study between May 2019 and October 2022. The VAT was measured in first trimester and determined as the distance from the inner margin of the rectus abdominis muscle to the anterior wall of the great artery using multi-functional color ultrasound. The 75 g oral glucose tolerance test (OGTT) results were followed up at 24-28 weeks and the participants were divided into GDM group and non-GDM group. The pregnant women were divided into 4 groups according to the VAT quartile. Log-binomial model and linear regression model were used to analyze the association between VAT and GDM/blood glucose. Results: A total of 3 686 pregnant women were included in this study, the mean age of participants was (30.56±4.05) years and 722 were diagnosed with GDM, with an incidence of 19.6%. The log-binomial regression model results showed that compared with VAT thickness Q1 (VAT<14.70 mm), the GDM risk in Q3 (21.65≤VAT≤29.69 mm) and Q4 (VAT ≥29.70 mm) increased by 34% [RR(95%CI): 1.34 (1.08-1.67)], and 61% [RR(95%CI): 1.61 (1.30-2.00)], respectively. Among women with gestational age<35 years old, compared with VAT thickness Q1, the risk of GDM increased by 42% in Q3 [RR(95%CI): 1.42 (1.22-1.65)] and 70% [RR(95%CI): 1.70 (1.46-1.98)] in Q4, whereas no associations were found in women with gestational age ≥35 years old (P>0.05). The association between VAT and GDM risk was only found in pregnant women with pre-pregnancy BMI <24.0 kg/m2, and the GDM risk increased by 57% [RR(95%CI): 1.57 (1.22-2.04)] in Q3 and 65% [RR(95%CI): 1.65 (1.24-2.19)] in Q4 compare with Q1. The results of multiple linear regression analysis showed that VAT was positively correlated with fasting blood glucose, 1-hour blood glucose after 75 g OGTT and 2-hours blood glucose after 75 g OGTT (all Pfor trend<0.001). Conclusion: High VAT thickness in early pregnancy is an independent risk factor for GDM, and the GDM risk increases with the raising of VAT depth.

Environmental exposures to organophosphorus flame retardants in early pregnancy and risks of gestational diabetes mellitus: a nested case-control study.

OPFRs are emerging environmental pollutants with reproductive and endocrine toxicity. This study aimed to examine the association between environmental exposure to OPFRs during early pregnancy and GDM. This nested case-control study was based on a birth cohort that was constructed at a maternal and child health hospital, including 74 cases of GDM among 512 pregnant women. The OPFRs, including TBP, TBEP, TCEP, TDCPP, TMCP, TOCP, and TPHP during 10-14 weeks of pregnancy were determined using GC-MS. The association between the OPFRs and GDM was assessed using WQS and BKMR models. The levels of OPFRs were significantly elevated in GDM patients (60) compared with the controls (90). The WQS analysis showed that mixtures of the OPFRs were significantly associated with GDM (OR 1.370, 95% CI 1.036-1.810, P = 0.027), and TBP, TPHP, and TMCP were the major contributors to the mixed exposure effect. In the BKMR model, individual exposure to TBP, TPHP, and TMCP, and the interaction of TMCP with TBP and TPHP were significantly associated with GDM. Environmental exposure to OPFRs is positively associated with GDM. These findings provide evidence for the adverse effects of OPFR exposure on the health of pregnant women.