Risk Of Adverse Pregnancy Outcomes Research Articles

Effect of remission, clinical remission with active serology, and glucocorticoid dosage on the pregnancy outcome of pregnant patients with systemic lupus erythematosus

BackgroundRemission is a key treatment target in systemic lupus erythematosus (SLE) management. Given the direct correlation between lupus flares and elevated risks of adverse pregnancy outcomes (APOs), securing remission before conception becomes crucial. However, the association between clinical remission with active serology, and the risk of APOs is not thoroughly understood. Additionally, determining the optimal glucocorticoid dosage during pregnancy to mitigate APO risks remains under-researched. This study investigated the risk of APOs in relation to remission/serological activity status in patients in clinical remission/glucocorticoid dosage.MethodsPregnant patients with SLE, who were followed up at two Japanese tertiary referral centers, and had their remission status assessed at conception, were included in this study. We categorized the patients into two groups based on whether they achieved Zen/Doria remission at conception and analyzed the APO ratio. We also examined the influence of serological activity in pregnant patients with clinical remission and analyzed the optimal glucocorticoid dosage to minimize the APO ratio.ResultsOf the 96 pregnancies included, 59 achieved remission at conception. Pregnant patients who achieved remission showed a significant decrease in the APO ratio compared with those who did not. (overall APO: odds ratio (OR) 0.27, 95% confidence interval (CI) 0.11–0.65, p < 0.01, maternal APO: OR 0.34, 95%CI 0.13–0.85, p = 0.021, neonatal APO: OR 0.39, 95%CI 0.17–0.90, p = 0.028). Conversely, no statistical difference was observed in the APO ratio based on serological activity in pregnant patients with clinical remission. (overall APO: OR 0.62, 95%CI 0.21–1.79, p = 0.37, maternal APO: OR 1.25, 95%CI 0.32–4.85, p = 0.75, neonatal APO: OR 0.83, 95%CI 0.29–2.39, p = 0.73). A glucocorticoid dose of prednisolone equivalent ≥ 7.5 mg/day at conception correlated with increased APO. (overall APO: OR 3.01, 95%CI 1.23–7.39, p = 0.016, neonatal APO: OR 2.98, 95% CI:1.23–7.22, p = 0.016).ConclusionsEven with active serology, achieving clinical remission can be a clinical target for reducing APOs in patients who wish to conceive. In addition, if clinically feasible, reducing the glucocorticoid dosage to < 7.5 mg/day before conception could be another predictive factor.

The impact of gut microbiota on autoimmune thyroiditis and relationship with pregnancy outcomes: a review.

Autoimmune thyroiditis (AITD) is a T-cell-mediated, organ- specific autoimmune disease caused by interactions between genetic and environmental factors. Patients with AITD show thyroid lymphocyte infiltration and an increase in the titer of thyroid autoimmune antibodies, thereby altering the integrity of thyroid follicle epithelial cells and dysregulating their metabolism and immune function, leading to a decrease in multi-tissue metabolic activity. Research has shown that patients with AITD have a significantly higher risk of adverse pregnancy outcomes, such as infertility and miscarriage. Levothyroxine(LT4) treatment can improve the pregnancy outcomes of normal pregnant women with thyroid peroxidase antibodies(TPOAb) positivity, but it is not effective for invitro fertilization embryo transfer (IVF-ET) in women with normal thyroid function and positive TPOAb. Other factors may also influence pregnancy outcomes of patients with AITD. Recent studies have revealed that the gut microbiota participates in the occurrence and development of AITD by influencing the gut-thyroid axis. The bacterial abundance and diversity of patients with Hashimoto thyroiditis (HT) were significantly reduced, and the relative abundances of Bacteroides, fecal Bacillus, Prevotella, and Lactobacillus also decreased. The confirmation of whether adjusting the composition of the gut microbiota can improve pregnancy outcomes in patients with AITD is still pending. This article reviews the characteristics of the gut microbiota in patients with AITD and the current research on its impact in pregnancy.

To Study the Efficacy of Intrauterine Device and Endometrial Regeneration Therapy versus Endometrial Regeneration Therapy Alone in the Prevention of Adhesions after Hysteroscopic Resection of Uterine Septum

Abstract Background: Septate uterus is a very common defect of the female reproductive system. Septate anomalies are associated with diminished fertility and increased risks for adverse pregnancy outcomes. Treatment must aim for optimization of pregnancy outcomes with minimum adverse effects. The aim of this study was to compare the presence or absence of adhesions and assess the efficacy of intrauterine device (IUD) along with endometrial regeneration therapy (ERT) vis-a-vis ERT alone in the prevention of adhesions after hysteroscopic resection of septum. Objectives: (1) To compare the two groups with respect to their efficacy. (2) To analyze the side effects of therapy in each group, e.g., intermittent spotting/bleeding and cyclical pain. (3) To assess endometrial thickness after 3 months, i.e., preovulatory endometrium without therapy. This was a prospective observation study. Materials and Methods: A sample size of 42 was calculated for each study group for comparative analysis and subjects were randomly allocated into one of the two groups using computer-generated randomization tables. Group 1 received IUD and ERT while group 2 received ERT alone. Results: In first group receiving IUD + ERT therapy, 10 patients reported side effects in the form of hypomenorrhea, amenorrhea, severe pelvic pain and prolonged spotting as compared to only 8 patients developing side effects in the second group which received ERT alone therapy.: The rates of postsurgical intrauterine adhesion and other complications were not statistically significant in both groups (P = 0.457). There was no statistically significant difference between the groups with respect to preovulatory endometrial thickness. Conclusion: The findings from this clinical study reconfirm the results of already published efficacy and safety studies of the use of IUD and ERT preventive therapies following hysteroscopic metroplasty.

The Impact of Environmental Benzene, Toluene, Ethylbenzene, and Xylene Exposure on Blood-Based DNA Methylation Profiles in Pregnant African American Women from Detroit.

African American women in the United States have a high risk of adverse pregnancy outcomes. DNA methylation is a potential mechanism by which exposure to BTEX (benzene, toluene, ethylbenzene, and xylenes) may cause adverse pregnancy outcomes. Data are from the Maternal Stress Study, which recruited African American women in the second trimester of pregnancy from February 2009 to June 2010. DNA methylation was measured in archived DNA from venous blood collected in the second trimester. Trimester-specific exposure to airshed BTEX was estimated using maternal self-reported addresses and geospatial models of ambient air pollution developed as part of the Geospatial Determinants of Health Outcomes Consortium. Among the 64 women with exposure and outcome data available, 46 differentially methylated regions (DMRs) were associated with BTEX exposure (FDR adjusted p-value < 0.05) using a DMR-based epigenome-wide association study approach. Overall, 89% of DMRs consistently exhibited hypomethylation with increasing BTEX exposure. Biological pathway analysis identified 11 enriched pathways, with the top 3 involving gamma-aminobutyric acid receptor signaling, oxytocin in brain signaling, and the gustation pathway. These findings highlight the potential impact of BTEX on DNA methylation in pregnant women.

Assessment of women’s needs, wishes and preferences regarding interprofessional guidance on nutrition in pregnancy – a qualitative study

BackgroundA healthy nutrition in pregnancy supports maternal health and fetal development, decreasing the risk for adverse pregnancy outcomes. Guidance by prenatal care professionals can increase women’s awareness regarding the importance of nutrition in pregnancy and thereby contribute to a reduced risk for adverse pregnancy outcomes. The aim of this study was to assess the needs, wishes and preferences of pregnant women regarding the interprofessional guidance on nutrition in pregnancy.MethodsUsing a qualitative approach and a purposive maximum variation sampling strategy, 25 pregnant women were recruited to participate in six semi-structured, guideline-oriented online focus groups. In addition, two semi-structured, guideline-oriented interviews, with a midwife and an obstetrician, were conducted. The focus groups and interviews were audio-recorded and transcribed. Transcripts were analysed using a systematic deductive-inductive approach to qualitative content analysis according to Kuckartz.ResultsFocus group participants covered diverse perspectives in terms of their age, different models of prenatal care as well as dietary forms from omnivorous to vegan. The majority of women perceived the guidance on nutrition during pregnancy as insufficient. Involved healthcare professionals, namely midwives and obstetricians, should provide more consistent information, especially to avoid uncertainties exacerbated by the internet and social media. There is a need for individual nutrition information regarding dietary supplements and the specifics of different dietary forms during pregnancy, such as a vegan diet. The majority of participants supported the integration of a free-of-charge professional nutrition counselling in prenatal care. Interviews with experts identified time pressure and the complexity of nutrition as a topic as the main obstacles in consultation settings. Both midwife and obstetrician emphasised the need for improved professional education on nutrition in pregnancy in their respective studies.ConclusionProfessional guidance for pregnant women on nutrition and uncertainties going along with certain forms of diet during pregnancy could alleviate the burden and overwhelming amount of web-based information. Additionally, information adapted to the needs, wishes and preferences of pregnant women would improve prenatal care through a more personalised approach. The quality of nutrition guidance in pregnancy should be improved by the implementation of this topic in the education of involved healthcare professionals.

The Impact of Military Trauma Exposures on Servicewomen's Pregnancy Outcomes: A Scoping Review.

Active-duty servicewomen and veterans make up nearly 20% of the United States military and may experience trauma specific to military service. Military-specific trauma includes combat deployment and military sexual trauma, exposure to which may result in posttraumatic stress disorder (PTSD). The purpose of this scoping review is to examine the extent to which military trauma exposures impact the pregnancy outcomes of active-duty servicewomen and women veterans. A systematic search of OVID MEDLINE, OVID Embase, and OVID PsycINFO from inception to September 25, 2023, identified studies examining associations between military trauma exposures and perinatal outcomes. Of the 614 studies identified, 464 were reviewed for relevance, with 16 meeting inclusion criteria. Of the 16 included studies, 14 found associations between military trauma exposure and adverse pregnancy outcomes including preterm birth, gestational diabetes, hypertensive disorders of pregnancy, low birth weight, and perinatal mood and anxiety disorders. The risks of adverse pregnancy outcomes increased with the severity of PTSD, the recency of combat deployment, and repetitive deployment. This scoping review strengthens the link between trauma exposures and adverse pregnancy outcomes for current and former military servicewomen. A gap in the literature persists regarding trauma exposure among active-duty servicewomen, which differs significantly from women veterans. As mental health conditions are the leading underlying cause of maternal mortality, standardized screening during the perinatal period for military-specific trauma exposures and PTSD is recommended for this population. Black servicewomen of junior enlisted rank carry disproportionate burdens of PTSD diagnosis and adverse pregnancy outcomes. Comprehensive prenatal and postpartum management may improve perinatal and neonatal outcomes for military servicewomen and provide an innovative approach to reducing existing racial disparities.

Metabolomic and genetic architecture of gestational diabetes subtypes.

Physiological gestational diabetes mellitus (GDM) subtypes that may confer different risks for adverse pregnancy outcomes have been defined. The aim of this study was to characterise the metabolome and genetic architecture of GDM subtypes to address the hypothesis that they differ between GDM subtypes. This was a cross-sectional study of participants in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study who underwent an OGTT at approximately 28 weeks' gestation. GDM was defined retrospectively using International Association of Diabetes and Pregnancy Study Groups/WHO criteria, and classified as insulin-deficient GDM (insulin secretion <25th percentile with preserved insulin sensitivity) or insulin-resistant GDM (insulin sensitivity <25th percentile with preserved insulin secretion). Metabolomic analyses were performed on fasting and 1h serum samples in 3463 individuals (576 with GDM). Genome-wide genotype data were obtained for 8067 individuals (1323 with GDM). Regression analyses demonstrated striking differences between the metabolomes for insulin-deficient or insulin-resistant GDM compared to those with normal glucose tolerance. After adjustment for covariates, 33 fasting metabolites, including 22 medium- and long-chain acylcarnitines, were uniquely associated with insulin-deficient GDM; 23 metabolites, including the branched-chain amino acids and their metabolites, were uniquely associated with insulin-resistant GDM; two metabolites (glycerol and 2-hydroxybutyrate) were associated with the same direction of association with both subtypes. Subtype differences were also observed 1h after a glucose load. In genome-wide association studies, variants within MTNR1B (rs10830963, p=3.43×10-18, OR 1.55) and GCKR (rs1260326, p=5.17×10-13, OR 1.43) were associated with GDM. Variants in GCKR (rs1260326, p=1.36×10-13, OR 1.60) and MTNR1B (rs10830963, p=1.22×10-9, OR 1.49) demonstrated genome-wide significant association with insulin-resistant GDM; there were no significant associations with insulin-deficient GDM. The lead SNP in GCKR, rs1260326, was associated with the levels of eight of the 25 fasting metabolites that were associated with insulin-resistant GDM and ten of 41 1h metabolites that were associated with insulin-resistant GDM. This study demonstrates that physiological GDM subtypes differ in their metabolome and genetic architecture. These findings require replication in additional cohorts, but suggest that these differences may contribute to subtype-related adverse pregnancy outcomes.

Genetic Factors Associated With Adverse Pregnancy Outcomes in Chronic Pancreatitis.

The effects of genetic factors on pregnancy outcomes in chronic pancreatitis (CP) patients remain unclear. We evaluated the impacts of clinical features and mutations in main CP-susceptibility genes ( SPINK1 , PRSS1 , CTRC , and CFTR ) on pregnancy outcomes in Chinese CP patients. This was a prospective cohort study with 14-year follow-up. The sample comprised female CP patients with documented pregnancy and known genetic backgrounds. Adverse pregnancy outcomes were compared between patients with and without gene mutations. Univariate and multivariate analyses were performed to determine the impact factors for adverse pregnancy outcomes. Totally, 160 female CP patients with a pregnancy history were enrolled; 59.4% of patients carried pathogenic mutations in CP-susceptibility genes. Adverse pregnancy outcomes occurred in 38 patients (23.8%); the prevalence of adverse outcomes was significantly higher in those harboring gene mutations than those without (30.5% vs 13.8%, P = 0.015). Notably, the rates of preterm delivery (12.6% vs 3.1%, P = 0.036) and abortion (17.9% vs 4.6%, P = 0.013) were remarkably higher in patients with gene mutations (especially SPINK1 mutations) than those without. In multivariate analyses, both CP-susceptibility gene mutations (odds ratio, 2.52; P = 0.033) and SPINK1 mutations (odds ratio, 2.60; P = 0.037) significantly increased the risk of adverse pregnancy outcomes. Acute pain attack during pregnancy was another risk factor for adverse pregnancy outcomes. Pathogenic mutations in CP-susceptibility genes, especially SPINK1 , were independently related to adverse pregnancy outcomes in CP patients. Significant attention should be paid to pregnant females harboring CP-susceptibility gene mutations (ClinicalTrials.gov: NCT06055595).

Effects of glycated serum protein, homocysteine, and cystatin-C levels on pregnancy outcomes in patients with gestational diabetes mellitus.

To explore the effects of serum glycated serum protein (GSP), homocysteine (Hcy) and cystatin-C (Cys-C) levels on pregnancy outcomes in patients with gestational diabetes mellitus (GDM). Retrospective selection of 247 pregnant women who underwent normal prenatal examinations in The Yan'an People's Hospital from January 2020 to May 2022 were included in this retrospective study. Among them, 119 were pregnant women with diabetes (GDM-group) and 128 were pregnant women with normal blood glucose (Normal-group). The levels of serum GSP, HCY, CYS-C, and incidence of adverse pregnancy outcomes were compared between the two groups. The clinical value of levels of serum GSP, Hcy, and Cys-C in predicting adverse pregnancy outcomes were analyzed. Compared with the Normal-group, the overall incidence of adverse pregnancy outcomes, serum GSP, Hcy, and Cys-C levels in the GDM-group were significantly higher (p<0.05). Logistic regression analysis showed that the levels of GSP, Hcy, and Cys-C were independent risk factors for adverse pregnancy outcomes in the GDM-group (p<0.05). Receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) for diagnosing adverse pregnancy outcomes in pregnant women with GDM using serum GSP, Hcy, and CysC levels alone were 0.817, 0.843, and 0.775, respectively. The AUC of the three indicators combined was 0.921, indicating that this combination has a good predictive value for diagnosing adverse outcomes in GDM-complicated pregnancies. GDM is associated with a high risk of adverse pregnancy outcomes. Levels of serum GSP, Hcy, and Cys-C are higher in patients with GDM. The higher the levels of GSP, Hcy, and Cys-C, the greater the risk of adverse pregnancy outcomes. Combining these three indicators can effectively predict maternal pregnancy outcomes.

Melatonin alleviates high temperature exposure induced fetal growth restriction via the gut-placenta-fetus axis in pregnant mice

IntroductionGlobal warming augments the risk of adverse pregnancy outcomes in vulnerable expectant mothers. Pioneering investigations into heat stress (HS) have predominantly centered on its direct impact on reproductive functions, while the potential roles of gut microbiota, despite its significant influence on distant tissues, remain largely unexplored. Our understanding of deleterious mechanisms of HS and the development of effective intervention strategies to mitigate the detrimental impacts are still limited. ObjectivesIn this study, we aimed to explore the mechanisms by which melatonin targets gut microbes to alleviate HS-induced reproductive impairment. MethodsWe firstly evaluated the alleviating effects of melatonin supplementation on HS-induced reproductive disorder in pregnant mice. Microbial elimination and fecal microbiota transplantation (FMT) experiments were then conducted to confirm the efficacy of melatonin through regulating gut microbiota. Finally, a lipopolysaccharide (LPS)-challenged experiment was performed to verify the mechanism by which melatonin alleviates HS-induced reproductive impairment. ResultsMelatonin supplementation reinstated gut microbiota in heat stressed pregnant mice, reducing LPS-producing bacteria (Aliivibrio) and increasing beneficial butyrate-producing microflora (Butyricimonas). This restoration corresponded to decreased LPS along the maternal gut-placenta-fetus axis, accompanied by enhanced intestinal and placental barrier integrity, safeguarding fetuses from oxidative stress and inflammation, and ultimately improving fetal weight. Further pseudo-sterile and fecal microbiota transplantation trials confirmed that the protective effect of melatonin on fetal intrauterine growth under HS was partially dependent on gut microbiota. In LPS-challenged pregnant mice, melatonin administration mitigated placental barrier injury and abnormal angiogenesis via the inactivation of the TLR4/MAPK/VEGF signaling pathway, ultimately leading to enhanced nutrient transportation in the placenta and thereby improving the fetal weight. ConclusionMelatonin alleviates HS-induced low fetal weight during pregnancy via the gut-placenta-fetus axis, the first time highlighting the gut microbiota as a novel intervention target to mitigate the detrimental impact of global temperature rise on vulnerable populations.

Association between tuberculosis and pregnancy outcomes: a retrospective cohort study of women in Cape Town, South Africa

BackgroundTuberculosis (TB) remains a leading cause of mortality among women of childbearing age and a significant contributor to maternal mortality. Pregnant women with TB are at high risk of adverse...

Parental genetically predicted liability for coronary heart disease and risk of adverse pregnancy outcomes: a cohort study

BackgroundAdverse pregnancy outcomes (APO) may unmask or exacerbate a woman’s underlying risk for coronary heart disease (CHD). We estimated associations of maternal and paternal genetically predicted liability for CHD with lifelong risk of APOs. We hypothesized that associations would be found for women, but not their male partners (negative controls).MethodsWe studied up to 83,969‬ women (and up to 55,568‬ male partners) from the Norwegian Mother, Father and Child Cohort Study or the Trøndelag Health Study with genotyping data and lifetime history of any APO in their pregnancies (1967–2019) in the Medical Birth Registry of Norway (miscarriage, stillbirth, hypertensive disorders of pregnancy, gestational diabetes, small for gestational age, large for gestational age, and spontaneous preterm birth). Maternal and paternal genetic risk scores (GRS) for CHD were generated using 148 gene variants (p-value < 5 × 10−8, not in linkage disequilibrium). Associations between GRS for CHD and each APO were determined using logistic regression, adjusting for genomic principal components, in each cohort separately, and combined using fixed effects meta-analysis.ResultsOne standard deviation higher GRS for CHD in women was related to increased risk of any hypertensive disorders of pregnancy (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.05–1.10), pre-eclampsia (OR 1.08, 95% CI 1.05–1.11), and small for gestational age (OR 1.04, 95% CI 1.01–1.06). Imprecise associations with lower odds of large for gestational age (OR 0.98, 95% CI 0.96–1.00) and higher odds of stillbirth (OR 1.04, 95% CI 0.98–1.11) were suggested. These findings remained consistent after adjusting for number of total pregnancies and the male partners’ GRS and restricting analyses to stable couples. Associations for other APOs were close to the null. There was weak evidence of an association of paternal genetically predicted liability for CHD with spontaneous preterm birth in female partners (OR 1.02, 95% CI 0.99–1.05), but not with other APOs.ConclusionsHypertensive disorders of pregnancy, small for gestational age, and stillbirth may unmask women with a genetically predicted propensity for CHD. The association of paternal genetically predicted CHD risk with spontaneous preterm birth in female partners needs further exploration.

P956 Pregnancy outcomes after maternal or paternal exposure in the tofacitinib ulcerative colitis clinical programme

Abstract Background Pregnant women with ulcerative colitis (UC) have a higher risk of adverse pregnancy outcomes vs age-matched controls.1 Tofacitinib is an oral Janus kinase inhibitor for the treatment of UC. There are no well-controlled studies on tofacitinib use in pregnant women. It was shown to be teratogenic in rats and rabbits at approximately 73 and 6.3 times, respectively, the maximum recommended human dose of 10 mg twice daily. Tofacitinib affects female fertility, parturition and peri/postnatal development in rats and was secreted into the milk of lactating rats; it had no effects on male fertility or sperm motility/concentration. Methods We report pregnancy outcomes in the tofacitinib UC clinical programme: 4 randomised, placebo-controlled Phase (P)2/3 studies (NCT00787202/NCT01465763/NCT01458951/NCT01458574),2,3 an open-label, long-term extension study (NCT01470612)4 and a randomised P3b/4 study (NCT03281304) were analysed.5 Study protocols excluded pregnant women, required females of childbearing potential to use effective contraception and regularly tested for urine β-hCG. Study drug was discontinued in female patients who became pregnant. Pregnancy outcomes after maternal or paternal tofacitinib exposure were identified from Pfizer’s internal safety database up to March 2023 and categorised as healthy newborn, medical termination, foetal death, congenital malformation, spontaneous abortion or lost to follow-up. Results There were 40 pregnancies with exposure to tofacitinib: 16 cases of maternal exposure (median age 29.5 [range: 24−41] years), all during the 1st trimester (10 [62.5%] healthy newborns, 2 [12.5%] medical terminations, 2 [12.5%] spontaneous abortions, 2 [12.5%] lost to followup); and 24 cases of paternal exposure (18 [75.0%] healthy newborns, 2 [8.3%] spontaneous abortions, 4 [16.7%] lost to follow-up). There were no cases of foetal death or congenital malformation. Conclusion Most known outcomes for maternal and paternal tofacitinib exposure were healthy newborns, similar to previous analyses in other tofacitinib clinical study populations and the general UC population.6,7 Limitations included the low number of reported pregnancies and available follow-up. Tofacitinib should not be used during pregnancy unless necessary.

Impact of inherited bleeding disorders on maternal bleeding and other pregnancy outcomes: A population-based cohort study.

Increasing rate of postpartum haemorrhage (PPH) has been observed between 2003 and 2010 in Canada. Inherited bleeding disorders contribute to the risk of PPH. To identify the trend in PPH in the last decade, assess the impact of bleeding disorders on pregnancy outcomes and evaluate their coagulation workup during pregnancy. We conducted a population-based retrospective cohort study using the Alberta Pregnancy Birth Cohort from 2010 to 2018. We included women with von Willebrand disease (VWD) and haemophilia, identified by previously validated algorithm and matched with controls. Logistic regression was used to compute odds of PPH and other pregnancy outcomes. We identified 311,330 women with a total of 454,400 pregnancies with live births. The rate of PPH did not change significantly from 10.13 per 100 deliveries (95% CI 10.10-10.16) in 2010-10.72 (95% CI 10.69-10.75) in 2018 (p for trend=.35). Women with bleeding disorders were significantly more likely to experience PPH (odds ratio [OR] 2.3; 95% CI 1.5-3.6), antepartum haemorrhage (OR 2.9; 95% CI 1.5-5.9) and red cell transfusion (OR 2.8; 95% CI 1.1-7.0). We observed a nonsignificant rise in the rate of PPH in women with VWD and haemophilia. Only 49.5% pregnancies with bleeding disorders had third trimester coagulation factor levels checked. Higher odds of PPH and antepartum haemorrhage were observed even with factor levels ≥0.50IU/mL in third trimester. Despite comprehensive care in women with bleeding disorders, they are still at higher risk of adverse pregnancy outcomes compared to population controls.

Leptin and Leptin Receptor Polymorphisms in Infants and Their Parents: Correlation with Preterm Birth.

It has been proven that single-nucleotide polymorphisms (SNPs) in LEP and LEPR genes could predispose individuals to an increased risk of pregnancy adverse outcomes (PAOs) such as recurrent pregnancy loss (RPL) and pre-eclampsia. Preterm birth (PTB) is the leading cause of infant mortality. We decided to investigate the correlation between PTB and LEP and LEPR SNPs. The study cohort included families who underwent spontaneous PTB and control samples of families who had at-term-born (≥37 weeks of gestational age) children. Swabs were performed by rubbing the sticky end for about 30 s on the gum and on the inside of the cheek, allowing us to collect the flaking cells of the oral mucosa. Genotyping of the three SNPs-LEPRA668G, LEPG2548A and A19G-was carried out via an ARMS-MAMA real-time PCR procedure, as previously described. Regarding LEPG2548A, we found that the most expressed genotype in infants both in the preterm and the at-term group was AG; however, we did not discover any statistically significant difference (p = 0.97). Considering LEPA19G, none among the infants and parents were found to carry the AA genotype. No statistically significant differences were found between children, mothers and fathers belonging to preterm and at-term groups. We did not find a statistically significant association in newborns and their mother, but our results show a statistical correlation with the LEPRA668G genotype GG of the father. This fact can contribute to defining genetic risk factors for PTB. Further studies are certainly needed to better clarify the role of genetics in influencing preterm delivery.

Subchorionic hematoma: Research status and pathogenesis (Review).

Subchorionic hematoma (SCH) is a hematoma in which blood accumulates between the chorion and decidua basalis due to the separation of the chorion and decidua basalis. It is common in patients with threatened abortion in early pregnancy and is mainly detected by ultrasound. SCH mainly manifests as an hypoechoic or anechoic crescent-shaped fluid dark area on ultrasound images. Although there are numerous studies on SCH, its pathogenesis and etiology remain unclear, and its influence on pregnancy outcomes is also controversial; there are also no uniform clinical treatment guidelines. Current studies suggest that the occurrence of SCH may be related to several factors, such as abnormal coagulation function, autoimmune factors of pregnant women, assisted reproduction, drug use during pregnancy and reproductive tract infection; however, its exact etiology remains unclear. Some studies suggest that SCH is associated with adverse pregnancy outcomes such as miscarriage, preterm birth, preeclampsia and fetal growth restriction, although other studies have found that SCH does not increase the risk of adverse pregnancy outcomes. Therefore, the present review mainly discusses the pathogenesis, etiology and treatment of SCH in an aim to provide a reference for the clinical treatment of this condition in pregnant women.

Nitrate in drinking water and pregnancy outcomes: A narrative review of epidemiological evidence and proposed biological mechanisms

There is emerging evidence of an association between nitrate contamination in drinking water and adverse pregnancy outcomes. Few studies have discussed the evidence in the context of plausible biological mechanisms. We performed a narrative review of the current evidence investigating associations between nitrate in drinking water and the risk of adverse pregnancy outcomes with a focus on congenital anomalies (CA) and preterm birth (PTB). We also reviewed evidence and discuss several biological mechanisms that may explain the observed associations. We reviewed cohort and case-control epidemiological studies assessing associations between maternal nitrate exposure and adverse pregnancy outcomes published until January 2023. Three plausible mechanisms may explain how maternal exposure to nitrate may impact pregnancy outcomes, which include the formation of N-nitroso compounds (NOC), thyroid dysfunction and oxidative stress. For CA, seven studies were included (two cohort and five case-control studies). The strongest associations observed in epidemiological studies were for neural tube defects. Inconsistent positive and negative associations were observed for anomalies of the limb, eye, ear, face and neck. Of the four PTB studies (all cohort studies), three of the largest cohort studies observed associations between PTB with nitrate levels &gt;5 mg/L while one small cohort study did not. Emerging epidemiological evidence has observed a potential increased risk of adverse pregnancy outcomes with elevated maternal nitrate exposure in drinking water. There are also plausible biological mechanisms to support this association. However, the current evidence lacks homogeneity and additional longitudinal evidence with robust exposure asssessments is required. Given the increasing concentrations of nitrate contamination in drinking water in many countries, and the adverse effects observed at concentrations below the current regulatory standard, a further precautionary approach should be adopted until futher evidence emerges.

The association between plasma angiopoietin-like protein 4, glucose and lipid metabolism during pregnancy, placental function, and risk of delivering large-for-gestational-age neonates

BackgroundLarge-for-gestational-age (LGA) neonates have increased risk of adverse pregnancy outcomes and adult metabolic diseases. We aimed to investigate the relationship between plasma angiopoietin-like protein 4 (ANGPTL4), a protein involved in lipid and glucose metabolism during pregnancy, placental function, growth factors, and the risk of LGA. MethodsWe conducted a prospective cohort study and recruited women with singleton pregnancies at the National Taiwan University Hospital between 2013 and 2018. First trimester maternal plasma ANGPTL4 concentrations were measured. ResultsAmong 353 pregnant women recruited, the LGA group had higher first trimester plasma ANGPTL4 concentrations than the appropriate-for-gestational-age group. Plasma ANGPTL4 was associated with hemoglobin A1c, post-load plasma glucose, plasma triglyceride, plasma free fatty acid concentrations, plasma growth hormone variant (GH-V), and birth weight, but was not associated with cord blood growth factors. After adjusting for age, body mass index, hemoglobin A1c, and plasma triglyceride concentrations, plasma ANGPTL4 concentrations were significantly associated with LGA risk, and its predictive performance, as measured by the area under the receiver operating characteristic curve, outperformed traditional risk factors for LGA. ConclusionsPlasma ANGPTL4 is associated with glucose and lipid metabolism during pregnancy, plasma GH-V, and birth weight, and is an early biomarker for predicting the risk of LGA.

Mediating Factors in the Association of Maternal Educational Level With Pregnancy Outcomes

Lower educational attainment is associated with increased risk of adverse pregnancy outcomes, but it is unclear which pathways mediate this association. To investigate the association between educational attainment and pregnancy outcomes and the proportion of this association that is mediated through modifiable cardiometabolic risk factors. In this 2-sample mendelian randomization (MR) cohort study, uncorrelated (R2 < 0.01) single-nucleotide variants (formerly single-nucleotide polymorphisms) associated with the exposure (P < 5 × 10-8) and mediators and genetic associations with the pregnancy outcomes from genome-wide association studies were extracted. All participants were of European ancestry and were largely from Finland, Iceland, the United Kingdom, or the US. The inverse variance-weighted method was used in the main analysis, and the weighted median, weighted mode, and MR Egger regression were used in sensitivity analyses. In mediation analyses, the direct effect of educational attainment estimated in multivariable MR was compared with the total effect estimated in the main univariable MR analysis. Data were extracted between December 1, 2022, and April 30, 2023. Genetically estimated educational attainment. The mediators considered were genetically estimated type 2 diabetes, body mass index, smoking, high-density lipoprotein cholesterol level, and systolic blood pressure. Ectopic pregnancy, hyperemesis gravidarum, gestational diabetes, preeclampsia, preterm birth, and offspring birth weight. The analyses included 3 037 499 individuals with data on educational attainment, and those included in studies on pregnancy outcomes ranged from 141 014 for ectopic pregnancy to 270 002 with data on offspring birth weight. Each SD increase in genetically estimated educational attainment (ie, 3.4 years) was associated with an increased birth weight of 42 (95% CI, 28-56) g and an odds ratio ranging from 0.53 (95% CI, 0.46-0.60) for ectopic pregnancy to 0.81 (95% CI, 0.71-0.93) for preeclampsia. The combined proportion of the association that was mediated by the 5 cardiometabolic risk factors ranged from -17% (95% CI, -46% to 26%) for hyperemesis gravidarum to 78% (95% CI, 10%-208%) for preeclampsia. Sensitivity analyses accounting for pleiotropy were consistent with the main analyses. In this MR cohort study, intervening for type 2 diabetes, body mass index, smoking, high-density lipoprotein cholesterol level, and systolic blood pressure may lead to reductions in several adverse pregnancy outcomes associated with lower levels of education. Such public health interventions would serve to reduce health disparities attributable to social inequalities.

Cardiogenic Shock and Utilization of Mechanical Circulatory Support in Pregnancy.

Maternal mortality rates are rising in the United States, a trend which is in contrast to that seen in other high-income nations. Cardiovascular disease and hypertensive disorders of pregnancy are consistently the leading causes of maternal mortality both in the United States and globally, accounting for about one-quarter to one-third of maternal and peripartum deaths. A large proportion of cardiovascular morbidity and mortality stems from acquired disease in the context of cardiovascular risk factors, which include obesity, pre-existing diabetes and hypertension, and inequities in care from maternal care deserts and structural racism. Patients may also become pregnant with preexisting structural heart disease, or acquire disease throughout pregnancy (ex: spontaneous coronary artery dissection, peripartum cardiomyopathy), and be at higher risk of pregnancy-related cardiovascular complications. While risk-stratification tools including the modified World Health Organization (mWHO) classification, Cardiac Disease in Pregnancy (CARPREG II) and Zwangerschap bij Aangeboren HARtAfwijking/Pregnancy in Women with Congenital Heart Disease (ZAHARA) have been designed to help physicians identify patients at increased risk for adverse pregnancy outcomes and who may therefore benefit from referral to a tertiary care center, the limitation of these scores is their predominant focus on patients with known preexisting heart disease. As such, identifying patients at risk for pregnancy complications presents a significant challenge, and it is often patients with high-risk cardiovascular substrates prior to or during pregnancy who are at a highest risk for adverse pregnancy outcomes including cardiogenic shock.