Adverse Pregnancy Outcomes In Women Research Articles

Predictors of adverse outcomes in pregnant women with intrauterine hematoma

To investigate the relationship between clinical features evaluated at presentation and the presence of adverse maternal or perinatal outcomes in pregnant women with intrauterine hematoma (IUH). Pregnant women aged 18 years and over who were diagnosed with IUH and had a single live fetus of six to 12 weeks at that time were retrospectively reviewed for the period from January 1, 2019 to July 30, 2021. The patients were divided into two groups according to the presence or absence of adverse pregnancy outcomes after IUH. The clinical features of the patients were evaluated. The effect of clinical factors on adverse pregnancy outcomes was determined using the logistic regression analysis. We found adverse pregnancy outcomes in 31.6% (n=42) of 133 patients included in the study. According to the multiple logistic regression analysis, age≥35 years [odds ratio (OR): 2.62, 95% confidence interval (CI): 1.16-4.37, p<0.001], presence of vaginal bleeding (OR: 2.53, 95% CI: 1.34-3.89, p=0.001), hematoma size≥4 cm (OR: 2.38, 95% CI: 1.08-4.15, p=0.023) and presence of retroplacental hematoma (OR: 2.44, 95% CI: 1.68-3.56, p<0.001) were risk factors for adverse pregnancy outcomes. In the presence of IUH, pregnant women aged ≥35 years and those with vaginal bleeding, hematoma size of ≥4 cm, and retroplacental hematoma are at risk of adverse pregnancy outcomes. These factors can help identify pregnant women who require close monitoring.

Rs868058 in the Homeobox Gene HLX Contributes to Early-Onset Fetal Growth Restriction.

Simple SummaryFetuses with hypotrophy (FGR, fetal growth restriction) are too small for their gestational age and may be prone to various diseases and loss of life. This study aimed to determine the role of single nucleotide polymorphisms (SNPs), located in two homeotic and two angiogenesis-related genes, in the occurrence of FGR, by analyzing blood samples from 380 women in singleton pregnancies. We found that the AT heterozygotes in HLX rs868058 were significantly associated with an approximately two-fold increased risk of FGR, diagnosed before 32 weeks of gestation (early-onset FGR). AT heterozygotes were significantly more frequent in women with early-onset FGR than in those with late-onset FGR (diagnosed from 32 weeks of gestation) and compared with healthy subjects. In conclusion, the AT genotype in HLX rs868058 may be a significant risk factor for the development of early-onset FGR. So far, the only therapeutic strategy for the management of early-onset FGR is to monitor and terminate pregnancy when the risk of fetal immaturity is lower than the risk of intrauterine death. Therefore, the disclosure of the mechanisms of action of the heterozygous AT state in HLX rs868058 would be important to identify plausible targets for new therapeutic approaches to treat the condition.Fetal growth restriction (FGR) is a condition that characterizes fetuses as too small for their gestational age, with an estimated fetal weight (EFW) below the 10th percentile and abnormal Doppler parameters and/or with EFW below the 3rd percentile. We designed our study to demonstrate the contribution of single nucleotide polymorphisms (SNPs) from DLX3 (rs11656951, rs2278163, and rs10459948), HLX (rs2184658, and 868058), ANGPT2 (−35 G > C), and ITGAV (rs3911238, and rs3768777) genes in maternal blood in FGR. A cohort of 380 women with singleton pregnancies consisted of 190 pregnancies with FGR and 190 healthy full-term controls. A comparison of the pregnancies with an early-onset FGR and healthy subjects showed that the AT heterozygotes in HLX rs868058 were significantly associated with an approximately two-fold increase in disease risk (p ≤ 0.050). The AT heterozygotes in rs868058 were significantly more frequent in the cases with early-onset FGR than in late-onset FGR in the overdominant model (OR 2.08 95% CI 1.11–3.89, p = 0.022), and after being adjusted by anemia, in the codominant model (OR 2.45 95% CI 1.23–4.90, p = 0.034). In conclusion, the heterozygous AT genotype in HLX rs868058 can be considered a significant risk factor for the development of early-onset FGR, regardless of adverse pregnancy outcomes in women.

Pregnancy Complications and Neonatal Mortality in a Serotonin Transporter Null Mouse Model: Insight Into the Use of Selective Serotonin Reuptake Inhibitor During Pregnancy.

Selective serotonin reuptake inhibitors (SSRI) are widely prescribed to pregnant woman. Although some SSRI compounds are known to cause pregnancy loss and fetal malformations, other SSRI continue to be used by pregnant women. However, several studies have associated the use of SSRI with adverse pregnancy outcomes: intrauterine growth restriction, preterm birth, and neonatal morbidity. Nonetheless, interpretation of studies in humans are typically complicated by the adverse pregnancy outcomes caused by depression itself. Therefore, we used a mutant mouse model with genetic ablation of the serotonin transporter, the target site for SSRI, to unravel the role of the serotonin transporter on pregnancy outcomes. The serotonin transporter null mice had increased pregnancy loss (17.5 vs. 0%), decreased number of pups born (6.6 ± 0.2 vs. 7.5 ± 0.2), and increased neonatal mortality (2.3-fold). Furthermore, preterm birth, dystocia, and fetal malformations were only observed in serotonin transporter null mice. This genetically ablated serotonin transporter mouse recapitulates several adverse pregnancy outcomes similar to those in women undergoing SSRI treatment during gestation. Additionally, neonatal loss in the present study reproduced a sudden infant death phenotype as in humans and mice with altered serotonergic signaling. In conclusion, findings from this study demonstrate a role for serotonin transporter in pregnancy maintenance and neonatal health. Additionally, it suggests that the adverse pregnancy outcomes in women taking SSRI during gestation might be due to altered serotonin transporter function caused by SSRI independent of underlying depression. This is a critical finding, given the number of women prescribed SSRI during pregnancy, and provides the framework for critical research in this area.

Short-Term Adverse Pregnancy Outcomes in Women with Subclinical Hypothyroidism: A Comparative Approach of Iranian and American Guidelines

Introduction Subclinical hypothyroidism during pregnancy can be associated with numerous adverse outcomes. The purpose of this study was to compare short-term adverse pregnancy outcomes in treated versus nontreated patients who fall within the numerical range of thyroid-stimulating hormone (TSH) between the Iranian and American reference ranges. Materials and Methods Eighty pregnant women with a known level of antithyroid peroxidase (anti-TPO) and TSH levels of 2.5–3.9 mIu/L in the first trimester and 3–4.1 mIu/L in the second and third trimesters were enrolled in the study and randomly assigned into two groups including 41 patients in the intervention group and 39 in the control group. The intervention group was treated with levothyroxine at least 50 μg/day and the control group received no treatment. The data were analyzed by SPSS software version 23. Results The only significant findings were a correlation between pregnancy loss frequency (p − 0.011) and/or increased TSH level in the follow-up period (p = 0.008) with anti-TPO antibody positivity. Forty-four percent of mothers with positive anti-TPO Ab needed treatment initiation with levothyroxine, based on Iranian guidelines, due to increased TSH level during the follow-up period. Conclusion Untreated pregnant women with subclinical hypothyroidism, who were placed in the intermediate range of TSH, recommended by Iranian and American guidelines, did not show any significant difference in short-term adverse pregnancy outcomes compared to the treated patients. Positive anti-TPO Ab may play a role in the development of short-term complications in mothers with subclinical hypothyroidism or it may increase the likelihood of an increase in TSH level during pregnancy.

Examining family planning and adverse pregnancy outcomes for women with active tuberculosis disease: a systematic review

Objectives(1) Summarise and evaluate the current evidence of tuberculosis (TB)-associated pregnancy outcomes, (2) evaluate the state of the science of family planning during TB treatment and (3) provide recommendations to...

A machine-learning–based algorithm improves prediction of preeclampsia-associated adverse outcomes

Preeclampsia presents a highly prevalent burden on pregnant women with an estimated incidence of 2% to 5%. Preeclampsia increases the maternal risk of death 20-fold and is one of the main causes of perinatal morbidity and mortality. Novel biomarkers, such as soluble fms-like tyrosine kinase-1 and placental growth factor in addition to a wide span of conventional clinical data (medical history, physical symptoms, laboratory parameters, etc.), present an excellent basis for the application of early-detection machine-learning models. This study aimed to develop, train, and test an automated machine-learning model for the prediction of adverse outcomes in patients with suspected preeclampsia. Our real-world dataset of 1647 (2472 samples) women was retrospectively recruited from women who presented to the Department of Obstetrics at the Charité - Universitätsmedizin Berlin, Berlin, Germany, between July 2010 and March 2019. After standardization and data cleaning, we calculated additional features regarding the biomarkers soluble fms-like tyrosine kinase-1 and placental growth factor and sonography data (umbilical artery pulsatility index, middle cerebral artery pulsatility index, mean uterine artery pulsatility index), resulting in a total of 114 features. The target metric was the occurrence of adverse outcomes throughout the remaining pregnancy and 2 weeks after delivery. We trained 2 different models, a gradient-boosted tree and a random forest classifier. Hyperparameter training was performed using a grid search approach. All results were evaluated via a 10× 10-fold cross-validation regimen. We obtained metrics for the 2 naive machine-learning models. A gradient-boosted tree model was performed with a positive predictive value of 88%±6%, a negative predictive value of 89%±3%, a sensitivity of 66%±5%, a specificity of 97%±2%, an overall accuracy of 89%±3%, an area under the receiver operating characteristic curve of 0.82±0.03, an F1 score of 0.76±0.04, and a threat score of 0.61±0.05. The random forest classifier returned an equal positive predictive value (88%±6%) and specificity (97%±1%) while performing slightly inferior on the other available metrics. Applying differential cutoffs instead of a naive cutoff for positive prediction at ≥0.5 for the classifier's results yielded additional increases in performance. Machine-learning techniques were a valid approach to improve the prediction of adverse outcomes in pregnant women at high risk of preeclampsia vs current clinical standard techniques. Furthermore, we presented an automated system that did not rely on manual tuning or adjustments.

Effects of Thyroperoxidase Antibody and Thyroglobulin Antibody on Maternal and Neonatal Outcomes in Pregnant Women.

The aim of the study was to evaluate the effects of thyroperoxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) on maternal and neonatal adverse outcomes in pregnant women. A total of 296 singleton pregnant women were classified into four groups according to the thyroid auto-antibody in the first trimester. Finally, there were 97 women in TPOAb positive group (TPOAb+/TgAb-), 35 in TgAb positive group (TPOAb-/TgAb+), 85 in TPOAb and TgAb positive group (TPOAb+/TgAb+), and 79 in TPOAb and TgAb negative group (TPOAb-/TgAb-). Thyroid function, TPOAb, and TgAb were checked during pregnancy and followed up at 6 weeks, 3 months, 6 months, 9 months, and 12 months postpartum. Levothyroxine sodium tablets could be taken to maintain euthyroid antepartum. Thyroid function of women with postpartum thyroiditis (PPT) were followed up at 2 and 3 years postpartum. We observed the incidence of PPT, premature rupture of membranes (PROM), placental abruption, placenta previa, polyhydramnios, oligohydramnios, postpartum hemorrhage, preterm birth, and low birth Weight in the four groups. 19.93% of the women had PPT. The incidence of PPT in TPOAb+/TgAb-, TPOAb-/TgAb+, TPOAb+/TgAb+groups was significantly higher than that in TPOAb-/TgAb- group, respectively (16.49 vs. 6.33%, 22.86 vs. 6.33%, 35.29 vs. 6.33%, p <0.05). The incidence of PPT in TPOAb+/TgAb+group was significantly higher than that in TPOAb+/TgAb- group (35.29 vs. 16.49%, p <0.01). PPT occurred as early as 6 weeks postpartum, but mainly at 3 and 6 months postpartum in the four groups (62.50%, 75.00%, 70.00%, 80.00%). All PPT in TPOAb-/TgAb- group occurred within 6 months postpartum, while it was found at 9 months or 12 months postpartum in other three groups. There was no classical form of PPT in TPOAb-/TgAb- group, while in the other three groups, all three types (classical form, isolated thyrotoxicosis, isolated hypothyroidism) existed. At 2 years postpartum of the women with PPT, the rate of euthyroidism in TPOAb+/TgAb+group was significantly lower than that in TPOAb-/TgAb- group (p <0.05). At 3 years postpartum of the women with PPT, the rate of euthyroidism in TPOAb+/TgAb-, TPOAb-/TgAb+, and TPOAb+/TgAb+groups were significantly lower than that in TPOAb-/TgAb- group (p <0.05). The values of TPOAb and TgAb postpartum were significantly higher than those during pregnancy (p <0.05). The incidence of PROM in TPOAb+/TgAb- group was significantly higher than that in TPOAb-/TgAb- group (32.99 vs. 17.72%, p <0.05). The binary logistic regression for PPT showed that the OR value of TPOAb was 2.263 (95% CI 1.142-4.483, p=0.019). The OR value of TgAb was 3.112 (95% CI 1.700-5.697, p=0.000). In conclusion, pregnant women with positive thyroid auto-antibodies had an increased risk of PPT and a reduced rate of euthyroidism at 2 and 3 years postpartum. TPOAb is associated with the incidence of PROM. Both of TPOAb and TgAb were independent risk factors for PPT. TgAb deserves more attention when studying autoimmune thyroid disease (AITD) combined with pregnancy.

Metabolic characteristics and adverse pregnancy outcomes for women with hyperglycaemia in pregnancy as a function of insulin resistance

Aim. Recent studies have shown that women with hyperglycaemia in pregnancy and insulin resistance have a greater risk of adverse pregnancy outcomes than women with normoglycaemic pregnancies. This study aimed to determine adverse pregnancy outcomes of women with hyperglycaemia in pregnancy only as a function of insulin resistance.Methods. From a prospective cohort study, we included 1,423 women with hyperglycaemia in pregnancy whose insulin resistance was evaluated using homoeostatic model assessment for insulin resistance (HOMA-IR) when care was first provided for this condition. We compared the adverse pregnancy outcomes for different tertiles of HOMA-IR (intertertile range 1.9 and 3.3).Results. Increasing HOMA-IR tertiles were positively associated with the rate of insulin therapy (tertile 1, 2 and 3: 32.7, 47.0 and 58.7%, P < 0.0001), caesarean section (23.7, 26.0 and 32.2%, respectively, P < 0.01), gestational hypertension (1.3, 2.8 and 5.4% respectively, P < 0.01), preeclampsia (1.5, 2.8 and 4.5% respectively, P < 0.05), large-for-gestational-age infant (13.3, 10.4 and 17.6% respectively, P < 0.05), and neonatal hypoglycaemia (0.8, 1.5 and 3.2% respectively, P < 0.05). Women in the 3rd HOMA-IR tertile were more likely to have insulin therapy (odds ratio 2.09 (95% interval confidence 1.61–2.71)), hypertensive disorders (2.26 (1.42–3.36)), and large-for-gestational-age infant (1.42 (1.01–1.99)) than those in the 1st and 2nd tertiles combined in multivariable logistic regression analyses adjusted for gestational age at HOMA-IR measurement, glycaemic status, age, body mass index, family history of diabetes, parity and ethnicity.Conclusion. Despite suitable care and increased rates of insulin therapy during pregnancy, higher insulin resistance in women with hyperglycaemia in pregnancy was associated with a greater risk of adverse pregnancy outcomes.

Impact of Scaling and Periodontal Treatment during Pregnancy on the Risk of Adverse Birth Outcomes.

Background: Adverse pregnancy outcomes (APOs) are associated with periodontal disease owing to the induction of a chronic systemic inflammatory response. Hence, knowledge of periodontal status during pregnancy is important in order to reduce the risk of APOs. The aim of this study was to compare the risk of APOs in women with and without periodontal disease to ascertain whether regular scaling performed prior to pregnancy improves the risk of APOs. Method: This case-control study enrolled1,386,887 pregnant women from the National Health Insurance Research Database who gave birth to their first child between 1 January 2004 and 31 December 2014. The study population included mothers who gave birth to low birth weight (LBW) and non-LBW newborns, totaling 86,958 and 1,299,929, respectively. Scaling and periodontal emergency treatment during and before pregnancy were assessed. Univariable and multivariable logistic regression analyses were performed to identify the associations between periodontal treatment and LBW risk. Results: Compared with the comparison cohort, the pregnant women who didnot have periodontal emergency treatment or scaling treatment during pregnancy exhibited a significantly increased risk of LBW than those who had treatment. Women who underwent scaling within the2 years before pregnancy or during pregnancy had a lower risk of delivering a LBW baby (odds ratio (OR), 0.93; 95% confidence interval (CI), 0.91–0.94). In the normal group, the mothers who had periodontal emergency treatment within the2 years before pregnancy or during pregnancy had a higher risk of delivering a LBW baby (OR, 1.05; 95% CI, 1.02–1.08). In those who had scaling treatment, a lower risk of delivering a LBW baby was noted (OR, 0.95; 95% CI, 0.93–0.97). Conclusion: The risk of LBW was significantly increased in women who underwent periodontal treatment, and our findings suggested that periodontal disease is an important risk factor for preterm LBW babies in an East Asian population.

Increased risk of obstetric complications in patients with adenomyosis: A narrative literature review.

BackgroundReproductive‐age women occasionally face the pathological condition of adenomyosis, which is often concurrent with endometriosis. It is believed that endometriosis and adenomyosis increases the risk of obstetric complications. Although new insights into the mechanism of obstetric complications due to endometriosis are emerging, there is little information on the etiology of adverse pregnancy outcomes in pregnant women with adenomyosis.MethodsWe performed a literature review focusing on the pathophysiological pathways of obstetric complications in women with adenomyosis using currently available basic and clinical studies. We used the internet search engines PubMed and Google Scholar to search for studies published between January 2000 and June 2021. We carefully read pertinent sections within each document to ensure relevancy.Main findingsThe prevalence of adverse pregnancy outcomes in women with adenomyosis is increased after adjusting for conceiving by assisted reproductive technology. Thus, adenomyosis emerges as a relevant factor associated with several obstetric complications such as preterm birth, preterm premature rupture of membranes, placental abruption, small for gestational age/fetal growth restriction, and preeclampsia.ConclusionIt is plausible that the impact of adenomyosis on pregnancy outcomes is not always the same; rather it is dependent on the degree of uterine involvement and subtypes.

Adverse pregnancy outcomes in women with celiac disease: a systematic review and meta-analysis.

The aim of this meta-analysis was to evaluate the risk of adverse pregnancy outcomes in women affected with celiac disease (CD), and to further estimate the impact of early disease diagnosis and subsequent adherence to a gluten-free diet (GFD) on obstetric complications. A systematic search for English language observational studies was conducted in Medline, Scopus, and the Cochrane Library, from inception till April 2022, to identify relevant studies reporting on the incidence of adverse pregnancy outcomes in women with CD. Odds ratios (OR) and relative risks (RR) with 95% confidence intervals (CIs) were used to combine data from case-control and cohort studies, respectively. The quality of the included studies was assessed using the Newcastle-Ottawa scale. In total, 14 cohort and 4 case-control studies were included and our analysis demonstrated that the risk for spontaneous abortion (RR 1.35, 95%CI 1.10-1.65), fetal growth restriction (RR 1.68, 95%CI 1.34-2.10), stillbirth (RR 1.57, 95%CI 1.17-2.10), preterm delivery (RR 1.29, 95%CI 1.12-1.49), cesarean delivery (RR 1.10, 95%CI 1.03-1.16) and lower mean birthweight (mean difference -176.08, 95%CI -265.79 to -86.38) was significantly higher in pregnant women with CD. The subgroup analysis demonstrated that only undiagnosed CD increased risk for fetal growth restriction, stillbirth, preterm delivery and lower mean birthweight, whereas early diagnosis of CD was not linked to any adverse pregnancy outcomes. Undiagnosed CD is associated with a higher risk of adverse pregnancy outcomes. Early CD diagnosis and appropriate management with GFD may ameliorate these associations.

Increased levels of soluble fms-like tyrosine kinase-1 are associated with adverse outcome in pregnant women withCOVID-19.

ABSTRACTObjectiveIn addition to the lungs, the placenta and the endothelium can be affected by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and placental growth factor (PlGF) are markers of endothelial dysfunction and could potentially serve as predictors of severe coronavirus disease 2019 (COVID‐19). We aimed to investigate the association of serum concentrations of sFlt‐1 and PlGF with the severity of COVID‐19 in pregnancy.MethodsThis was a prospective cohort study carried out in a tertiary care hospital in Mexico City, Mexico. Symptomatic pregnant women with a positive reverse‐transcription quantitative polymerase chain reaction test for SARS‐CoV‐2 infection who fulfilled the criteria for hospitalization were included. The primary outcome was severe pneumonia due to COVID‐19. Secondary outcomes were intensive care unit (ICU) admission, viral sepsis and maternal death. sFlt‐1 levels were expressed as multiples of the median (MoM). The association between sFlt‐1 and each adverse outcome was explored by logistic regression analysis, adjusted for gestational age for outcomes occurring in more than five patients, and the predictive performance was assessed by receiver‐operating‐characteristics‐curve analysis.ResultsAmong 113 pregnant women with COVID‐19, higher sFlt‐1 MoM was associated with an increased probability of severe pneumonia (adjusted odds ratio (aOR), 1.817 (95% CI, 1.365–2.418)), ICU admission (aOR, 2.195 (95% CI, 1.582–3.047)), viral sepsis (aOR, 2.318 (95% CI, 1.407–3.820)) and maternal death (unadjusted OR, 5.504 (95% CI, 1.079–28.076)). At a 10% false‐positive rate, sFlt‐1 MoM had detection rates of 45.2%, 66.7%, 83.3% and 100% for severe COVID‐19 pneumonia, ICU admission, viral sepsis and maternal death, respectively. PlGF values were similar between women with severe and those with non‐severe COVID‐19 pneumonia.ConclusionsFlt‐1 MoM is higher in pregnant women with severe COVID‐19 and has the capability to predict serious adverse pregnancy events, such as severe pneumonia, ICU admission, viral sepsis and maternal death. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Melanin nanoparticles for safe and effective iron chelation therapy for Beta-thalassemia during pregnancy

Iron toxicity is a major contributor to adverse pregnancy outcomes in women with transfusion-dependent thalassemia. Currently used chelators are not recommended during pregnancy, as they can cross the placenta causing potential risk to the foetus. Ceasing medication may adversely affect the mother’s health even long after delivery.

Antiphospholipid antibody-induced trophoblast responses are differentially modulated by viral dsRNA and viral ssRNA.

Women with antiphospholipid antibodies (aPL) are at increased risk for pregnancy loss and preeclampsia. aPL target the trophoblast and induce a pro-inflammatory, anti-angiogenic and anti-migratory profile. Since infection during pregnancy can increase the risk for preeclampsia, a viral infection could further increase this in women with aPL. The goal of this study was to characterize the effect of viral components on trophoblast responses to aPL. A human first trimester trophoblast cell line was treated with or without aPL or control IgG in the presence of media, viral dsRNA or viral ssRNA. Supernatants were measured for inflammatory IL-1β and IL-8; inflammasome-associated uric acid and caspase-1 activity; and anti-angiogenic sFlt-1. Trophoblast migration was measured using a two-chamber assay. Viral dsRNA augmented aPL-induced trophoblast caspase-1 activity, and IL-1β and IL-8 secretion in an additive manner. Viral ssRNA inhibited aPL-induced uric acid, IL-1β and sFlt-1 secretion, and further exacerbated aPL-inhibition of trophoblast migration. While viral ssRNA may have some protective effects on aPL-induced inflammation and anti-angiogenic responses, viral dsRNA exacerbated aPL-mediated inflammation and viral ssRNA further limited cell migration, which could prove detrimental to placentation. Thus, viral infections may contribute to adverse pregnancy outcomes in women with aPL.

The predicted risk of adverse pregnancy outcomes as a result of treatment-associated obesity in a hypothetical population receiving tenofovir alafenamide/emtricitabine/dolutegravir, tenofovir disoproxil fumarate/emtricitabine/dolutegravir or tenofovir disoproxil fumarate/emtricitabine/efavirenz.

Integrase inhibitors, including dolutegravir (DTG), are associated with weight gain and obesity, especially when combined with tenofovir alafenamide (TAF). Obesity increases the risk of adverse pregnancy outcomes (APOs). This study aimed to predict the risk of APOs caused by treatment-associated obesity, using a hypothetical sample based on the ADVANCE trial. Risk prediction. Firstly, a meta-analysis was performed to determine the relative risk (RR) for APOs in women with obese (≥30) versus normal prepregnancy BMIs (18.5-24.9). For the hypothetical sample, 3000 nonpregnant women with normal BMIs at Week 0 of treatment were evenly allocated across the following treatment arms: TAF/FTC+DTG, TDF/FTC+DTG, TDF/FTC/EFV. The treatment-associated obesity rates from ADVANCE were used to calculate the number of women with obese and normal BMIs expected at Week 96 in our sample. This was combined with the APO RRs to predict the number of women at risk of APOs, in each treatment arm, assuming they conceived at Week 96. At Week 96, the percentage of women predicted to be obese was 14.1% with TAF/FTC+DTG, 7.9% with TDF/FTC+DTG and 1.5% with TDF/FTC/EFV. The RR in women with obese versus normal BMIs was significantly higher for most APOs. Therefore, the number of women at risk of APOs was higher with TAF/FTC+DTG than TDF/FTC+DTG and TDF/FTC/EFV. For example, 11/1000 additional gestational hypertension cases were predicted with TAF/FTC+DTG, 6/1000 with TDF/FTC+DTG and 1/1000 with TDF/FTC/EFV. Treatment-associated obesity increased the APO risk in women. This risk is likely to increase, as preliminary data from ADVANCE demonstrates ongoing weight gain beyond Week 96.

Adverse pregnancy outcomes in women with diabetes-related microvascular disease and risks of disease progression in pregnancy: A systematic review and meta-analysis.

The rise in the global prevalence of diabetes, particularly among younger people, has led to an increase in the number of pregnant women with preexisting diabetes, many of whom have diabetes-related microvascular complications. We aimed to estimate the magnitude of the risks of adverse pregnancy outcomes or disease progression in this population. We undertook a systematic review and meta-analysis on maternal and perinatal complications in women with type 1 or 2 diabetic microvascular disease and the risk factors for worsening of microvascular disease in pregnancy using a prospective protocol (PROSPERO CRD42017076647). We searched major databases (January 1990 to July 2021) for relevant cohort studies. Study quality was assessed using the Newcastle-Ottawa Scale. We summarized the findings as odds ratios (ORs) with 95% confidence intervals (CIs) using random effects meta-analysis. We included 56 cohort studies involving 12,819 pregnant women with diabetes; including 40 from Europe and 9 from North America. Pregnant women with diabetic nephropathy were at greater risk of preeclampsia (OR 10.76, CI 6.43 to 17.99, p < 0.001), early (<34 weeks) (OR 6.90, 95% CI 3.38 to 14.06, p < 0.001) and any preterm birth (OR 4.48, CI 3.40 to 5.92, p < 0.001), and cesarean section (OR 3.04, CI 1.24 to 7.47, p = 0.015); their babies were at higher risk of perinatal death (OR 2.26, CI 1.07 to 4.75, p = 0.032), congenital abnormality (OR 2.71, CI 1.58 to 4.66, p < 0.001), small for gestational age (OR 16.89, CI 7.07 to 40.37, p < 0.001), and admission to neonatal unit (OR 2.59, CI 1.72 to 3.90, p < 0.001) compared to those without nephropathy. Diabetic retinopathy was associated with any preterm birth (OR 1.67, CI 1.27 to 2.20, p < 0.001) and preeclampsia (OR 2.20, CI 1.57 to 3.10, p < 0.001) but not other complications. The risks of onset or worsening of retinopathy were increased in women who were nulliparous (OR 1.75, 95% CI 1.28 to 2.40, p < 0.001), smokers (OR 2.31, 95% CI 1.25 to 4.27, p = 0.008), with existing proliferative disease (OR 2.12, 95% CI 1.11 to 4.04, p = 0.022), and longer duration of diabetes (weighted mean difference: 4.51 years, 95% CI 2.26 to 6.76, p < 0.001) compared to those without the risk factors. The main limitations of this analysis are the heterogeneity of definition of retinopathy and nephropathy and the inclusion of women both with type 1 and type 2 diabetes. In pregnant women with diabetes, presence of nephropathy and/or retinopathy appear to further increase the risks of maternal complications.

First Trimester Anticoagulant Exposure and Adverse Pregnancy Outcomes in Women with Preconception Venous Thromboembolism: A Nationwide Cohort Study

ObjectiveThe purpose of this study was to investigate first trimester anticoagulant exposure and risks of adverse pregnancy-related and fetal outcomes. MethodsUsing Danish nationwide registries, we identified all pregnant women with preconception venous thromboembolism, 2000-2017, and linked data on exposure to low-molecular-weight heparin (LMWH), vitamin K antagonist (VKA), or non-VKA oral anticoagulant (NOAC) during pregnancy. We assessed pregnancy-related and fetal outcomes associated with first trimester anticoagulant exposure. ResultsAmong 4490 pregnancies in women with preconception venous thromboembolism (mean age 31 years, 40% nulliparous) during the first trimester, 63.1% were unexposed, 25.9% were exposed to LMWH, 10.4% VKA, and 0.6% NOAC. Adverse outcomes were lowest in unexposed and LMWH exposed. Compared with unexposed, VKA was associated with higher risks of preterm (adjusted odds ratio [OR] 2.26; 95% confidence interval [CI], 1.70-2.99) and very preterm birth (adjusted OR 3.78; 95% CI, 1.91-7.49), shorter mean gestational age was associated with VKA (−7.5 days; 95% CI, −9.1 to −5.9 days) or NOAC (−2.3 days; 95% CI, −8.4-3.8), and lower mean birthweight with VKA (−55 g; 95% CI, −103.1 to −8.5) or NOAC (−190 g; 95% CI, −364.1 to −16.4). Adjusted ORs for small-for-gestational-age infants were 1.07 (95% CI, 0.77-1.50) with VKA, and 3.29 (95% CI, 1.26-7.95) with NOAC. Mean 5-minute Apgar score (9.8) and congenital defect prevalence (8.4%-10%) varied little across exposure groups. ConclusionsFetal risk was lowest in unexposed and LMWH-exposed pregnancies, supporting the recommendation of LMWH during pregnancy. NOAC safety during pregnancy is unclear due to the rarity of NOAC exposure.

The impact of prenatal depression and diabetes management self-efficacy on postpartum stress and depression in women with gestational diabetes mellitus.

The study aimed to examine the impact of prenatal depression and diabetes management self-efficacy on postpartum stress and postpartum depression in women with gestational diabetes mellitus. Poor perinatal mental health is linked to various adverse pregnancy outcomes in women with gestational diabetes mellitus. A predictive study design and the guidelines forthe STROBE checklist were used for the study. A total of 119 pregnant women with a positive 75g-glucose challenge test were recruited at a medical centre. The Taiwanese depression questionnaire (TDQ), the diabetes management self-efficacy scale (DMSES) and the Hung postpartum stress scale (Hung PSS) were used for data collection at the 24th week of pregnancy and the first week after childbirth. Diabetes management self-efficacy was correlated with postpartum stress in women with gestational diabetes mellitus. Moreover, prenatal depression was a predictor of postpartum stress and postpartum depression, respectively, in women with gestational diabetes mellitus. Healthcare providers should assess those women's diabetes management self-efficacy and mood status during prenatal visits and offer the needed intervention to reduce the levels of postpartum stress and postpartum depression of those women after childbirth. A holistic care approach integrated diabetic care and mental health for women with gestational diabetes mellitus in a timely manner is warranted to promote perinatal mental health in women with gestational diabetes mellitus.

Impact of COVID-19 on Pregnancy and Maternal Health: An Update

The current pandemic caused by the novel coronavirus disease 2019 (COVID-19) is spreading at an accelerated rate globally. Global concerns were raised following its discovery in December 2019, as previous similar diseases. Diseases such as the severe acute respiratory syndrome-related coronavirus (SARS-CoV) and the Middle East respiratory syndrome-related coronavirus (MERS-CoV) are known to lead to adverse outcomes in pregnant women and those in early maternal stages, with significantly higher rates of complication and mortality compared to other groups of individuals. The anatomical, physiological, and immunological changes that occur during pregnancy lead to higher risks associated with respiratory infections for pregnant women, as they can directly affect the well-being of pregnant women and infants. Vertical transmission of COVID-19 from mother to child was a concern, as such transmission could endanger a child. Three mechanisms of vertical transmission have been suggested: intrauterine transmission, placental blood transmission, and intrapartum transmission. This review discusses the impact and pathogenicity of COVID-19 on the well-being of pregnant and early maternal women, both the clinical aspect, health aspects, and diagnostic and therapeutic options. It will also discuss the adverse outcomes among pregnant women and newborn infants who contract the disease and the different mechanisms of vertical transmission from infected mother to child. The diagnostic and therapeutic approaches of COVID- 19 that have been recently used have also been highlighted, in addition to the challenges faced by pregnant women who have contracted the virus during the pandemic.

OC15.02: Increased levels of soluble FMS‐like tyrosine kinase‐1 are associated with adverse outcomes in pregnant women with COVID‐19

This study aimed to investigate the association between serum concentrations of soluble FMS-like tyrosine kinase-1 sFlt-1 and the severity of COVID-19 among pregnant women. Prospective cohort study. Inclusion criteria were pregnant women with positive rt-PCR COVID-19 between July 2020-January 2021. The outcome was severe COVID-19, defined as a composite adverse outcome of pneumonia, ICU admission, sepsis, and death. Forward and backward stepwise logistic regression analysis was performed to assess the association between independent variables and outcome. Adjusted model's performance after logistic regression was evaluated by a receiver-operating-curve (ROC) analysis along with an area under the curve (AUC). Among the 113 included women, 31 (27.43%) had severe COVID-19, including 5 (4.42%) maternal deaths. There was a statistically significant difference in the gestational age at hospital admission (35.2 vs 30.2; p = 0.002) between groups. A cut-off of 1.66 sFlt-1 MoMs had an odds ratio [OR] of 1.81 (95%CI:1.36-2.41) for a composite severe adverse outcome. The predictive performance of sFlt-1 for severe COVID-19 achieved an AUC of 0.71 (95%CI: 0.58-0.82) and maternal death of 0.97 (95%CI: 0.95-1.00) (figure 1). The detection rates for maternal death at 5% and 10% false-positive-rates were 80% and 100%, respectively. sFlt-1 is a potential predictor of COVID-19-related adverse events such as pneumonia, ICU admission, sepsis, and death. Further research in a larger prospective cohort is needed to validate the association and accuracy of sFlt-1 for the prediction of adverse events among pregnant women with COVID-19. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.