Miscarriage Research Articles

Histopathological evaluation of the placenta: Clues of intra-uterine fetal demise

Intrauterine fetal demise (IUFD) is a distressful event with lasting impact and risk of recurrence. However, in majority of cases, the cause remains unexplained. The aim of the present study is to evaluate the histomorphological features of placenta, the findings associated with commonly known etiologies of IUFD and other clues provided by it in establishing the cause of IUFD.: A prospective, observational study was conducted at a tertiary healthcare center in North India for a period of 3.5 years. A total of 104 placental specimen from IUFD cases were received and evaluated microscopically by 3 histopathologists. Data was tabulated and analyzed.: Majority cases of IUFD were seen in multigravida women (52.8%) in the age group of 25 to 30 years. We found that inflammatory lesions in 46.1% cases, maternal vascular malformation (MVM) in 25% cases, fetal vascular malformation in (FVM) in 16.3%, combined MVM and FVM in 2.9% while 9.7% cases were idiopathic. Presence of fibrotic villi, intervillous fibrin deposition, chorioamnionitis and calcification were the most common findings. Pregnancy induced hypertension was the most common maternal cause of IUFD identified (20.3%), while congenital anomalies were the most common fetal (72.1%) and placenta previa was the most common placental cause (33.3%). A comprehensive placental histopathological evaluation can provide clues regarding the causation and progression of IUFD, allowing clinicians to initiate early management and prevent recurrence. Patient education regarding the same may also motivate the patient to seek early and proper antenatal care in subsequent pregnancies.

Cell-cycle machinery is critical in regulating uterine steroid hormone for embryo implantation and development.

Proper embryo implantation is necessary for a successful pregnancy. In this issue of the JCI, Aljubran et al. identified the cell cycle regulatory protein cyclin A2 (CCNA2) as a factor in supporting embryo implantation and embryo development. Endometrial stromal cells showed higher levels of CCNA2 in patients undergoing assisted reproductive technology who had successful pregnancies. CCNA2 expression correlated with stromal cell proliferation and the expression of steroid hormone receptors for estrogen (ESR1, also known as ERα) and progesterone (PGR). Notably, loss of Ccna2 in mouse models resulted in infertility. The uteri of these mice were hypoplastic with reduced estrogen sensitivity, resulting in the disruption of stroma cell decidualization and loss of embryo viability after implantation. These findings demonstrate the importance of stroma cell proliferation in preparing the uterus for embryo implantation. They also identify CCNA2 as a coregulator of steroid hormone receptor signaling and suggest that impaired uterine stroma can underly early pregnancy loss.

Recurrent Early Pregnancy Loss and Congenital Thrombophilia: A Prospective Study

Background/Objectives: This study aims to investigate the role of congenital single nucleotide thrombophilia in young females with early recurrent pregnancy loss (RPL). Methods: We studied 120 pregnant females with RPL and 80 matched females as a control with no RPL. Females were aged ≤ 35 years, had at least two consecutive first-trimester RPLs, and the acquired cause of RPL was excluded. A matched control group of 80 pregnant women with no RPL was studied. Coagulation tests included prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT), a Factor XIII functional assay, and detecting IgM and IgG anti-beta2-Glycoprotein I (β2GPI) antibodies by an ELISA. The DNA samples were tested for Factor V Leiden, Factor II G20210A, Methylenetetrahydrofolate reductase (MTHFR C677T, A1298C), FXIII V34L, plasminogen activator inhibitor-1 (PAI-1) 4G/5G, endothelial protein C receptor (EPCR) A4600G, and endothelial protein C receptor (EPCR) G4678C. Results: Of the single nucleotide gene mutations investigated, the most relevant mutations were MTHFR C677T, MTHFR A1298C, heterozygous FXIII Val34Leu, and heterozygous FXIII 1694 C>T. Each of them conferred a statistically significant effect. There was a statistically significant protective role for the endothelial protein C receptor (EPCR) A2/A2, wild FXIII Val34Leu, and heterozygousFXIII1694 C>T. Conclusions: Our findings suggest the important role of congenital single nucleotide thrombophilia mutations in young Middle Eastern women with early RPL, particularly MTHFR mutations and FXIII Val34Leu. We found a protective effect of EPCR A2/A2, wild FXIIIVal34Leu, and heterozygous FXIII1694 C>T. We recommend additional studies to explore detrimental factors and protective factors.

Warmblood fragile foal syndrome: Pregnancy loss in Warmblood mares.

Fragile foal syndrome (FFS) or warmblood FFS Type 1 (WFFS) is a recessive, autosomal, hereditary, genetic defect causing late abortions, stillbirths and non-viable foals. Whether early pregnancy losses occur is unknown. To investigate how WFFS affects pregnancies and whether early pregnancy losses occur in WFFS matings and if there is a difference in pregnancy success between matings where both parents were allele carriers and those where only mare or stallion were WFFS carriers. Retrospective cohort study. Breeding records from a Warmblood stud farm were evaluated (2016-2019) and 2682 cycles of 177 mares analysed. Matings were assigned to four study groups, depending on the WFFS carrier status of the mare and stallion: N/WFFS × N/WFFS (n = 46), N/WFFS (mares) × N/N (n = 511), N/N × N/WFFS (stallions) (n = 191) and N/N × N/N (n = 2149). There were no differences in pregnancy rates between matings with only one WFFS carrier and those with non-carriers. When comparing N/WFFS × N/WFFS matings to those with only one or no WFFS-carrier, there were no increased pregnancy losses in the embryonic phase (day <42). By contrast, the N/WFFS × N/WFFS group had significantly more abortions (53.8%) than the other three study groups (7.9-9.2%; adjusted p < 0.0001). The higher losses were evenly distributed between the early (D42-150: 22.7% losses, n = 5) and late (D150-300: 29.4% losses, n = 5) foetal phase. The live foal rate per pregnancy for N/WFFS × N/WFFS matings was lowest (34.5%) and differed significantly (other groups 81%-84%; adjusted p < 0.0001); the peri- and postnatal mortality was higher (25%) compared with the other study groups (2.6%-3%). Low sample size in N/WWFS × N/WFFS matings, unbalanced study design, outcomes are descriptive, all mares from one stud farm. The mating of two WFFS carriers may lead to increased risks of pregnancy and foal loss.

Case Series of Listeria monocytogenes in Pregnancy: Maternal–Foetal Complications and Clinical Management in Six Cases

Background: Listeria monocytogenes, a Gram-positive intracellular bacillus, causes listeriosis, which is primarily transmitted through contaminated food and vertical transmission. The incidence of the disease is estimated to be between one and ten cases per million globally, with pregnant women being particularly vulnerable. Objective: The aim was to describe the clinical characteristics, management, and outcomes of cases of gestational listeriosis at Hospital Materno Infantil de Málaga in order to improve our understanding, diagnosis, and treatment of this disease. Methods: A retrospective analysis of six confirmed cases of listeriosis was performed in pregnant women or neonates. Diagnostic confirmation was achieved using analytic and microbiological methodologies, including blood cultures and the measurement of C-reactive protein (CRP). Ethical approval was obtained, and clinical data were reviewed for reasons related to consultation, treatment approaches, and complications. Results: The most frequently observed symptoms were fever and abdominal pain, with complications such as intrauterine death and suspected chorioamnionitis. Four patients were treated with antibiotics, leading to improved outcomes. No severe complications such as neurolisteriosis were observed. Conclusions: Pregnant women are more susceptible to L. monocytogenes, which can cause mild maternal symptoms but severe foetal outcomes, including prematurity, foetal death, or neonatal infections. Early diagnosis and prompt treatment are crucial for improving maternal–foetal outcomes.

Abstract 4122486: Multicenter Study of Primary Fetal Cardiomyopathy: Clinical Outcomes And Genetic Etiologies, A Fetal Heart Society Research Collaborative Study

Background: Fetal cardiomyopathy (FCM) affects 8 per 100,000 live births, often with unknown etiology. Progress in fetal cardiac screening, genetic testing and management may have impacted historically poor outcomes. Aims: We sought to investigate genetic associations and clinical outcomes of FCM in the current era. Methods: This was a retrospective Fetal Heart Society Research Collaborative cohort study of FCM cases diagnosed from January 2017-December 2021 in 39 centers. Cases of fetal myocardial disease attributable to maternal diabetes, structural heart disease, arrhythmia or extra-cardiac conditions were excluded. Data including outcomes to 1 year after birth were collected. Significance of genetic testing results and FCM subtype were classified by each center. Results: There were 138 FCM cases diagnosed at a median gestational age of 27 +4 weeks (range 13-39 weeks). Suspected fetal heart disease (41%, 56/138) was the most common referral indication. There was a known family history of CM in 19% (26/138). FCM phenotypes included 38% (52/138) dilated, 24% (33/138) hypertrophic, 17% (24/138) non-compacted, 10% (14/138) mixed, 5% (7/138) restrictive, 3% (4/138) ventricular aneurysm, 3% (4/138) unspecified. Hydrops was present at diagnosis in 15% (20/138) and by delivery or at fetal demise in 26% (36/138). Of 128 continued pregnancies, 7% (9/128) had a fetal demise, 92% (118/128) a live birth and one was lost to follow-up. Among live births, 10% (12/118) received only palliative care. Of 106 actively treated, 75% (80/106) survived to 1 year; 7% (7/106) required ECMO, and 22% (23/106) were listed for transplant with 18 of these successfully transplanted. Of the cohort, a total of 80% (110/138) had genetic testing (including 30 with invasive prenatal testing), with 38% (52/138) having a confirmed genetic etiology and 28% (38/138) with a variant of uncertain significance (VUS) (Figure 1). Transplant-free survival to 1 year was similar for those with and without a genetic diagnosis (40%,21/52 vs 47%,40/86, p=0.48). Conclusion: Outcomes remain poor in FCM, with &lt;50% 1-year survival overall. Confirmed genetic etiologies are now identified in nearly 40%, highlighting the importance of genetic testing.

Relationship between exposure to air pollutants in the first trimester and spontaneous abortion in pregnant women in the river valley city.

Purpose The relationship between exposure doses of 2.5-micrometer Particulate Matter (PM2.5), Inhalable particles (PM10), Sulfur Dioxide (SO2), Nitrogen Dioxide (NO2) and Ozone (O3) in the first trimester and spontaneous abortion of pregnant women was evaluated by global average method and nearest monitoring station method, respectively. Method Retrospective analysis of the clinical data of pregnant women with spontaneous abortion and full-term pregnant women in the Department of Obstetrics and Gynecology of two third-class hospitals in a valley city in Northwest China. According to the age factor, the eligible pregnant women were matched at a ratio of 1 : 4. The global average method and the nearest monitoring station method were used to evaluate the exposure of pollutants. The rank-sum test and conditional logistic regression were used to analyze the correlation between air pollutants and spontaneous abortion. Results Although the global average method and the nearest monitoring station method are slightly different in the assessment of exposure dose, they do not affect the correlation evaluation with spontaneous abortion. The exposure of pregnant women to PM2.5(OR1 = 1.156, OR2 = 1.036), SO2 (OR1 = 1.432, OR2 = 1.429) and NO2 (OR1 = 1.121, OR2 = 1.159) in the first trimester is related to the occurrence of spontaneous abortion.(OR1: the global average method, OR2: the nearest monitoring station method) Conclusion The exposure of PM2.5, SO2 and NO2 in the first trimester in valley cities is associated with the occurrence of spontaneous abortion in pregnant women.

Manual Uterine Aspiration Simulation for Emergency Medicine Learners.

Manual uterine aspiration is a potentially lifesaving procedure for treating patients with hemorrhagic complications of early pregnancy loss. While early pregnancy loss is a common diagnosis seen in the emergency department, manual uterine aspiration education is lacking for emergency medicine physicians. We designed a 90-minute procedural skills training session for 30 emergency medicine learners. The session included a brief lecture and video demonstration, followed by two micro-skills stations before finally completing the simulated procedure in its entirety. At each station, learners were asked to verbalize the steps and landmarks for the procedure before performing them on models. Participants completed a combined pre-post survey evaluating their perceived knowledge of the procedure and self-efficacy in performing the procedure. Thirty learners who participated in the workshop were surveyed, with a 100% response rate. All participants reported increased comfort with the procedure and knowledge about the procedure. All participants completed a successful simulated procedure. Participants also indicated increased interest in learning more about manual uterine aspiration and its potential application within the emergency medicine physician's scope of practice. We developed a workshop to train emergency medicine learners in manual uterine aspiration to stop life-threatening hemorrhage in the setting of early pregnancy loss. The workshop was well received by learners and increased their self-efficacy and desire for additional training with this procedure. Similar curricula should be tried at other institutions.

Comparative Safety of Antipsychotic Medications and Mood Stabilizers During Pregnancy: A Systematic Review and Network Meta-analysis of Congenital Malformations and Prenatal Outcomes.

A network meta-analysis was performed to evaluate the risk of congenital malformations and other prenatal outcomes in fetuses after exposure to antipsychotic medications and mood stabilizers during pregnancy. We searched the PubMed, EMBASE, and Cochrane CENTRAL databases up to 15 December 2023, to identify experimental and observational studies comparing antipsychotic and mood stabilizer treatments with control treatments (no exposure). The primary outcome of the study was the incidence of congenital malformations and the secondary outcomes were preterm birth and spontaneous abortion. Additionally, two authors independently assessed the risk of bias in each domain of the included studies using the ROBINS-I tool and evaluated the quality of evidence using the CINeMA rating tool. The literature search identified 18,334 potential records, and 22 studies involving 3,042,997 pregnant women were ultimately included. Compared with the unexposed group, quetiapine [odds ratio (OR), 1.19; 95% credible interval (CrI), 1.01-1.39], aripiprazole (OR, 1.30; 95% CrI 1.10-1.65), olanzapine (OR, 1.33; 95% CrI 1.11-1.64), risperidone (OR, 1.43; 95% CrI 1.18-1.77), and lithium (OR, 1.61; 95% CrI 1.07-2.30) were associated with a slightly increased risk of congenital malformations. In contrast, lamotrigine (OR, 1.21; 95% CrI 0.86-1.64), ziprasidone (OR, 1.14; 95% CrI 0.73-1.72), and haloperidol (OR, 1.26; 95% CrI 0.90-1.75) did not show significant differences compared with the unexposed group, with narrower credible intervals. The evidence from this analysis suggests that, overall, quetiapine has the lowest teratogenic risk when used during pregnancy, making it thesaferoption for pregnant women. Lamotrigine and haloperidol follow closely behind. At the same time, the use of lurasidone and ziprasidone should be approached with caution, and further clinical studies are necessary to better assess their safety. PROSPERO CRD4201811373.

Evaluation of pitolisant, sodium oxybate, solriamfetol, and modafinil for the management of narcolepsy: a retrospective analysis of the FAERS database

ObjectiveNarcolepsy, a rare neurological disorder believed to have an autoimmune etiology, necessitates lifelong management. This study aimed to provide evidence supporting the safety of pharmacological treatment for narcolepsy.MethodsFive-year data on pitolisant, sodium oxybate, solriamfetol, and modafinil were extracted from the FDA Adverse Event Reporting System (FAERS) self-reporting database for the period spanning from 2019 to 2023. Various statistical methods, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network analysis (BCPNN), and multi-item gamma Poisson shrinker (MGPS), were employed to quantify the signals. Finally, a comparative analysis was conducted between demographic data, outcomes, and inherent associations among the medications and the signals.ResultsAfter data analysis, we obtained 50 signals (a cumulative count of 762 cases) for pitolisant, 640 signals (corresponding to 46,962 cases) for sodium oxybate, 40 signals (equivalent to 1,228 cases) for solriamfetol, and finally, 72 signals (representing 632 cases) for modafinil. The majority of these patients were female. Psychiatric and nervous system disorders were identified as the predominant adverse drug events (ADEs). For sodium oxybate, it is crucial to consider psychiatric disorders (such as suicidal ideation), respiratory disorders (including sleep apnea syndrome and respiratory depression), and signs of pregnancy and congenital familial diseases. For solriamfetol, noteworthy new ADEs include drug inefficacy, suicidal ideation, restless legs syndrome, and somnambulism. Furthermore, a relationship has been observed between modafinil use and restricted fetal growth, spontaneous abortion, cognitive disorders, and drug inefficacy and abuse.ConclusionThe majority of observed adverse reactions in this study were consistent with those listed in the product instructions. However, potential novel or notable ADE signals were identified through real-world pharmacovigilance analysis. It is anticipated that this paper will offer additional information regarding safe and rational medication for narcolepsy.

Compromised C3b-VSIG4 axis between decidual NK cells and macrophages contributes to recurrent spontaneous abortion.

NK cells and macrophages constitute the predominant immune cell subsets in the decidua during the first trimester of pregnancy, with macrophages typically adopting an anti-inflammatory phenotype. Conversely, in the third trimester, macrophages undergo a shift towards a pro-inflammatory phenotype concurrent with a reduction in NK cell numbers. The direct regulatory impact of NK cells on macrophage phenotype remains poorly explored. In our investigation, we observed that ICAM1+ macrophages stimulate the expression of intracellular C3 in LFA1+ decidual NK cells. Notably, Cathepsin W within NK cells exhibit the potential to generate active C3b fragments, effectively inhibit the proinflammatory phenotype of macrophages by binding to VSIG4. Our study unveils a direct regulatory mechanism orchestrated by decidual NK cells over macrophages, providing a potential pathogenic explanation for recurrent spontaneous abortion.

Comparative study on pregnancy complications: PGT-A vs. IVF-ET with gender-specific outcomes

The safety and clinical effectiveness of preimplantation genetic testing for aneuploidy (PGT-A) in improving pregnancy outcomes for sub-fertile patients remains controversial. Potential sex-based differences in the relationship between PGT-A and pregnancy complications have not been investigated, which could guide the appropriate clinical application of PGT-A. In this secondary analysis of data from a multicenter, randomized, controlled, non-inferiority trial (NCT03118141), 940 women who achieved singleton live birth during the trial were included to estimate the between-group differences in pregnancy complications following PGT-A versus conventional in vitro fertilization (IVF) vary with fetal sex. Logistic regression analysis was used to adjust for possible confounders, and subgroup analysis was also performed. Among male fetuses, the risk of maternal preeclampsia was significantly lower after PGT-A compared to conventional IVF treatment (3.37% vs. 7.88%; adjusted OR, 0.40; 95% CI, 0.17-0.92; P = 0.032). However, this protective effect was not observed in pregnancies with female fetuses (3.63% vs. 3.38%; adjusted OR, 1.04; 95% CI, 0.36-3.00; P = 0.937). In addition, no significant sex-dependent differences in the risks of other pregnancy complications or neonatal outcomes were detected between PGT-A and conventional IVF groups (P &amp;gt; 0.05). In summary, PGT-A was associated with a decreased risk of maternal preeclampsia in singleton pregnancies with male fetuses, highlighting its potential utility in preeclampsia prevention in addition to spontaneous abortion rate reduction.

Low PAPPA and Its Association with Adverse Pregnancy Outcomes in Twin Pregnancies: A Systematic Review of the Literature and Meta-Analysis

Background: It is well established in the literature that pregnancy-associated plasma protein-A (PAPP-A) is linked to several adverse pregnancy outcomes, including pre-eclampsia (PE), fetal growth restriction (FGR), and preterm birth (PTB) in singleton pregnancies. However, data regarding such an association in twin pregnancies are lacking. The primary goal of this systematic review and meta-analysis was to assess the potential value of low PAPP-A levels in the prediction of the subsequent development of hypertensive disorders of pregnancy (HDPs), PTB, and small for gestational age (SGA)/FGR fetuses in twin pregnancies and investigate its association with the development of gestational diabetes, intrauterine death (IUD) of at least one twin, and birth weight discordance (BWD) among the fetuses. Methods: Medline, Scopus, CENTRAL, Clinicaltrials.gov, and Google Scholar databases were systematically searched from inception until 31 July 2024. All observational studies reporting low PAPP-A levels after the performance of the first-trimester combined test as part of the screening for chromosomal abnormalities with reported adverse pregnancy outcomes were included. Results: The current systematic review encompassed a total of 11 studies (among which 6 were included in the current meta-analysis) that enrolled a total of 3741 patients. Low PAPP-A levels were not associated with HDPs (OR 1.25, 95% CI 0.78, 2.02, I-square test: 13%). Low PAPP-A levels were positively associated with both the development of preterm birth prior to 32 (OR 2.85, 95% CI 1.70, 4.77, I-square test: 0%) and 34 weeks of gestational age (OR 2.09, 95% CI 1.34, 3.28, I-square test: 0%). Furthermore, low PAPP-A levels were positively associated with SGA/FGR (OR 1.58, 95% CI 1.04, 2.41, I-square test: 0%). Prediction intervals indicated that the sample size that was used did not suffice to support these findings in future studies. Conclusions: Our study indicated that low PAPP-A levels are correlated with an increased incidence of adverse perinatal outcomes in twin pregnancies. Identifying women at elevated risk for such adversities in twin pregnancies may facilitate appropriate management and potential interventions, but additional studies are required to identify the underlying mechanism linking PAPP-A with those obstetrical complications.

A Narrative Review of Congenital Syphilis in the United States: Innovative Perspectives on a Complex Public Health and Medical Disease.

Over the past two decades, congenital syphilis cases have risen 11-fold in the United States. While disparities across geography, race, and ethnicity exist, lack of timely screening or treatment is identified in 88% of cases nationally. Congenital syphilis is a public health and medical problem rooted in systematic and societal structural determinants of health and healthcare limitations. Early syphilis in pregnancy leads to congenital syphilis if untreated in 50 - 70% of cases, with risk for fetal demise, and among survivors, congenital anomalies, organ damage, and central nervous system disease. Prevention of congenital syphilis lies in early detection and treatment in pregnant persons. In this narrative review, we describe the evolving epidemiology of syphilis and congenital syphilis, highlighting unique aspects among women. We explore the role of novel screening and treatment strategies, public health policy, and medical considerations in terms of congenital syphilis prevention. Readers of this review will understand CS as a complex public health and medical disease that can be prevented through innovative and coordinated strategies in public health policy, expanded screening and research opportunities.

Maternal and Fetal Outcomes of Aplastic Anemia During Pregnancy and Delivery: Systematic Review and Meta-Analysis.

Little scientific evidence exists on maternal and fetal outcomes in aplastic anemia (AA) during pregnancy. The review was conducted to assess the maternal and fetal outcomes due to AA during pregnancy. Web of Science, EMBASE, PubMed, Scopus, Cochrane CENTRAL, and registries until May 5, 2024. Studies (prospective, retrospective cohort, cross-sectional, one arm, survey, follow-up studies) evaluating AA during pregnancy were searched as per PROSPERO registered protocol (CRD42024506668). Case reports, case series, expert opinion letters, and studies assessing less than or equal to 10 pregnant women were not considered. The primary outcome was the prevalence of preeclampsia in AA pregnancies. The secondary outcomes included spontaneous abortion, preterm premature rupture of membranes, premature rupture of membranes, fetal growth restriction, type of delivery, intrauterine fetal death, maternal and neonatal mortality, and pre and post-pregnancy remission status comparison. The quality of research was checked using the New Castle-Ottawa risk-of-bias tool. A meta-analysis model with a random effect distribution, coupled with meta-regression, sensitivity analysis, and publication bias assessment, was used in the statistical software R. Standard Equator network study reporting guidelines were followed. Seven (one prospective and six retrospective cohort) studies included patients with confirmed AA diagnosis in 248 pregnancies. The pooled prevalence of preeclampsia was 13% (95% CI, 8%-20%). Heterogeneity was low in the present meta-analysis (I2 = 26%). The secondary outcome evaluation showed a pooled prevalence of 5% (95% CI, 3%-11%) for spontaneous abortion, 4% (95% CI, 1%-11%) for preterm premature rupture of membranes, 10% (95% CI, 3%-28%) for premature rupture of membranes, 6% (95% CI, 3%-11%) for fetal growth restriction, 5% (95% CI, 2%-13%) for intrauterine fetal death, 12% (95% CI, 5%-26%) for post-partum hemorrhage, 74% (95% CI, 45%-91%) for intrapartum transfusion requirement, and 55% (95% CI, 27%-80%) for the cesarean delivery opting. The maternal mortality in pregnancies with AA was 4% (95% CI, 0.01-0.14), whereas neonatal mortality was 7% (95% CI, 0.03-0.18). The odds of AA complete remission were better in pre-pregnancy than post-pregnancy (OR = 0.36; 95% CI = 0.08-1.66), although the results remain insignificant. The leave-one-out sensitivity analysis did not change the pooled estimates for the primary outcome. A risk of developing preeclampsia was observed in every eighth pregnant woman with an AA diagnosis. AA remission status might worsen after undergoing pregnancy, considering the significant obstetric morbidity and mortality burden.

Prediction of perinatal mortality in early-onset fetal growth restriction: A post hoc analysis of the Dutch STRIDER trial to predict perinatal mortality in early-onset fetal growth restriction

ObjectiveEarly-onset fetal growth restriction affects about 0.3% of pregnancies, posing high perinatal risks due to placental insufficiency. Early-onset fetal growth restriction often coincides with early-onset pre-eclampsia, associated with significant mortality and morbidity. Clinical management varies among clinicians, with emphasis on intensive monitoring and timely delivery. Our objective was to improve clinical prediction of perinatal mortality in early-onset fetal growth restriction for parental counseling. Study designThis was a secondary analysis of prospective cohort data from the Dutch STRIDER trial. The study included 215 pregnant women diagnosed with severe early-onset fetal growth restriction between 20 + 0 and 29 + 6 weeks of gestation, from tertiary and secondary antenatal care centers in The Netherlands. Maternal and fetal characteristics were collected at inclusion, including sonographic and laboratory measurements. Analysis was performed using univariable and multivariable binary logistic regression to create a prediction model for perinatal mortality. The main outcome measures were fetal demise and neonatal mortality up to discharge. Results215 Participants were included for this analysis. Perinatal mortality occurred in 84 (39 %) cases; 51 (24 %) were fetal and 33 (15 %) neonatal. Fetal abdominal circumference, gestational age at diagnosis, estimated fetal weight Multiple of Median, absent or reversed end-diastolic flow of the umbilical artery, umbilical artery pulsatility index Multiple of Median, non-Caucasian ethnicity, male sex, placental growth factor level and uterine artery pulsatility index were independent predictors of perinatal mortality. Randomization allocation (sildenafil or placebo) had no predictive value for mortality. The prediction model including gestational age at diagnosis, estimated fetal weight Multiple of Median and umbilical artery pulsatility index Multiple of Median showed an area under the receiver operating characteristic curve of 0.840 (P < 0.01). Placental growth factor was measured in a subset of patients and was an independent prognostic factor and performed significantly better within the predictive model, however it did not improve the predictive value of the model. ConclusionsPrediction of perinatal mortality in early-onset fetal growth restriction is feasible with commonly available tests and measurements and could support decision making in management of pregnancy. However, implementation in practice requires further studies.

OA07 Upadacitinib exposure during pregnancy in seronegative Rheumatoid arthritis

Abstract Introduction Targeted therapies have become increasingly prevalent in the management of rheumatoid arthritis (RA), with Janus kinase inhibitors (JAK inhibitors) gaining traction in clinical practice. Upadacitinib, a selective JAK1 inhibitor, is widely used for its efficacy in controlling RA. However, preclinical studies have demonstrated teratogenic effects associated with JAK inhibitors, raising concerns about their safety during pregnancy. Given the limited data on human exposure, current guidelines recommend the immediate discontinuation of JAK inhibitors upon pregnancy detection. This case report details an instance of Upadacitinib exposure during pregnancy. Case description A 36-year-old woman was diagnosed with seronegative RA in January 2020. Her medical history is otherwise unremarkable. She has two children, aged four and two, both of whom were born after uneventful pregnancies. She has no history of spontaneous abortions. At the time of her RA diagnosis, the patient was considering pregnancy and was initially started on sulfasalazine. However, due to the development of a rash, her treatment was switched to certolizumab injections. Despite this treatment, she exhibited only a partial response with ongoing disease activity, leading to a change to etanercept in August 2021. When etanercept proved ineffective, adalimumab was considered in January 2022. Unfortunately, her response to adalimumab was limited. Consequently, she was started on Upadacitinib in July 2022. The patient responded well to Upadacitinib, achieving remission with normal inflammatory markers. In April 2024, the patient reported being six weeks pregnant while on Upadacitinib. Upon confirmation of her pregnancy, Upadacitinib was discontinued at approximately four weeks of gestational age. The parents were informed about the potential risks of teratogenicity. After a detailed discussion with the high-risk pregnancy team, who provided reassurance, the patient decided to continue the pregnancy. She was subsequently started on certolizumab. Unfortunately, the patient experienced a miscarriage at 11 weeks of gestation. Discussion Currently, there are no published human studies available in the literature regarding the effects of upadacitinib during pregnancy. It is crucial to encourage adequate contraception for women of childbearing potential and to verify a negative pregnancy status before initiating therapy. Women with reproductive potential should be advised to use effective contraception during upadacitinib therapy and for at least four weeks after discontinuation. If a patient becomes pregnant while on the drug, they should be informed of the potential risks to the foetus. According to the 2019 product information on upadacitinib, animal studies have shown that the drug, when administered at exposures equal to or greater than approximately 1.6 to 15 times the maximum recommended human dose, resulted in dose-related increases in skeletal and cardiovascular malformations, increased post-implantation loss, and decreased foetal body weights. There are no controlled data on upadacitinib use during human pregnancy, and it is unknown whether the drug can cause foetal harm or adversely affect reproductive capacity in humans. Data about pregnancy while on upadacitinib is limited. There are some unpublished data from the clinical trials and it was noted most of the patients had live births without congenital anomaly. Spontaneous abortions, elective terminations and ectopic pregnancies were among the other outcomes noted. Key learning points • Due to issues such as primary or secondary treatment failures, hypersensitivity reactions, and adverse events, patients often require sequential trials of different agents in management of Rheumatoid Arthritis (RA). Janus kinase inhibitors (JAK inhibitors) have shown remarkable efficacy in managing RA over the last decade. Despite their widespread use, there is limited literature on the safety of upadacitinib exposure during pregnancy in humans. Most of the available data come from unexpected pregnancies documented during clinical trials. • Animal studies indicate that upadacitinib can be harmful to a developing foetus. Furthermore, data suggest that women with RA who experience increased disease activity are at a heightened risk for adverse pregnancy outcomes, including preterm delivery, low birth weight, and infants who are small for gestational age. • It is crucial to emphasize pregnancy contraindications during follow-up appointments for patients on these medications. Access to a medical obstetrician team is invaluable in managing such cases. • While some case reports have documented positive pregnancy outcomes with other JAK inhibitors, such as tofacitinib and baricitinib, there remains a significant gap in knowledge regarding upadacitinib. This case report adds to the limited data on the potential risks associated with upadacitinib exposure during pregnancy. Comprehensive and targeted studies are necessary to better understand the safety of this class of drugs during pregnancy and lactation.

Spontaneous uterine rupture in pregnancy after treatment of Asherman syndrome

Study objectiveWomen with Asherman syndrome are at high risk of recurrent adhesions and pregnancy complications. Spontaneous uterine rupture is a rare but life-threatening complication, associated with severe maternal and fetal morbidity and mortality. Uterine ruptures can occur after extended induction of labor or a history of cesarean section, whereas spontaneous uterine rupture in an unscarred uterus is rare. Aim of this study is to evaluate the incidence of spontaneous uterine rupture among women with Asherman syndrome treated by hysteroscopy and without a history of cesarean section. DesignProspective cohort study. SettingAsherman Expertise Center of the Spaarne Gasthuis, the Netherlands. PatientsWomen were defined by as patients with Asherman syndrome when they had one or more clinical features and the presence of hysteroscopically confirmed intrauterine adhesions. InterventionsHysteroscopic adhesiolysis and a second-look hysteroscopy two months after the initial procedure. Measurements and resultsData on the severity of adhesions and ongoing pregnancy after treatment were collected prospectively. A total of 428 women with Asherman syndrome were included, 4 women (0.9%) experienced spontaneous uterine rupture. The timing varied, none of the affected women were in active labor and the occurrence of uterine rupture was not related to the severity of adhesions. Ruptures were all found in the fundus. One woman had a history of perforation of the uterine wall located in the fundus. Neonatal outcomes were poor, two cases had intrauterine neonatal death and two cases had long-term lifelong disability. One woman had a second uterine rupture. ConclusionWomen with Asherman syndrome are at risk of uterine rupture, a pregnancy complication with significant consequences that is challenging to predict and may also be associated with history of uterine perforation. Clinicians should be aware of this risk in women treated with hysteroscopic adhesiolysis and consider counseling these patients accordingly prior to treatment.

Growth velocity of fetal sacrococcygeal teratoma as predictor of perinatal morbidity and mortality: multicenter study.

To identify prenatal predictors of poor perinatal outcome in fetuses with isolated sacrococcygeal teratoma (SCT). This was a retrospective study of fetuses with isolated (non-syndromic) SCT managed at one of five pediatric surgery and/or fetal medicine centers between January 2007 and December 2017. The primary outcome was the occurrence of poor perinatal outcome, defined as prenatal death (including termination), or neonatal death or severe compromise (hemorrhagic shock). Data regarding prenatal diagnosis (sonographic features both at referral and at the last ultrasound examination before pregnancy outcome, assessment of SCT growth velocity), perinatal complications and outcome, and neonatal course were analyzed to determine prenatal SCT characteristics associated with adverse perinatal outcome. Fifty-five fetuses were included, diagnosed with isolated SCT at a median gestational age of 22 (interquartile range, 18-23) weeks. There was a poor perinatal outcome in 31% (n = 17) of these cases, including intrauterine fetal demise (4%, n = 2), pregnancy termination (13%, n = 7) and neonatal severe compromise (15%, n = 8), leading to neonatal death in five cases. The overall survival rate after prenatal diagnosis of isolated SCT was 75% (n = 41 of 55). Earlier gestational age at diagnosis (P = 0.02), large tumor volume at referral (P < 0.001), presence of one or more hemodynamic complications (P = 0.02), fast tumor growth velocity (P < 0.001) and high tumor grade (highest tumor grade ≥ 3) (P = 0.049) were associated with poor perinatal outcome on univariate analysis. On stepwise logistic regression analysis, tumor growth velocity was the only remaining independent factor associated with poor perinatal outcome (odds ratio (OR) (per 1-mm/week increase), 1.48 (95%CI, 1.22-1.97), P = 0.001). The best predictive cut-off of tumor growth velocity for poor perinatal outcome was 7 mm/week (OR, 25.7 (95%CI, 5.6-191.3), P < 0.001), yielding a sensitivity of 88% and a specificity of 77%. Approximately 30% of fetuses with a diagnosis of isolated SCT have poor perinatal outcome. Tumor growth velocity ≥ 7 mm/week appears to be an appropriate discriminative cut-off for poor perinatal outcome. These results could help to inform prenatal management and counseling of parents with an affected pregnancy. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Service evaluation of an early pregnancy loss support clinic in an inner London early pregnancy unit

BackgroundEarly pregnancy loss (EPL) can have profound implications for physical and psychological health. In the UK, significant variation in service provision exists for women affected by EPL. There is very little guidance on what hospital-based follow-up support services should entail, and how these can be implemented and integrated into current care provision to meet the needs of women who experience EPL. This service evaluation (SE) reports on an Early Pregnancy Loss Support Clinic (EPLSC) in an inner-city Hospital Trust.MethodsThis SE gathered both quantitative and qualitative feedback from women to assess the value of a locally implemented Early Pregnancy Loss Support Clinic (EPLSC). Quantitative feedback was collected using the Short Assessment of Patient Satisfaction (SAPS) questionnaire and the Visual Anxiety Scale (VAS-A), both administered to women attending the EPLSC. Qualitative feedback was collected through semi-structured interviews and focused on four pre-determined themes based on EPL literature - physical health, mental health, role of the bereavement midwife and overall service user experience. Quantitative feedback was summarised using descriptive statistics, while qualitative feedback was analysed using framework analysis.ResultsA total of 127 women were invited to the EPLSC, with 110 (87%) attending, and 17 (13%) not attending their appointment. SAPS scores ranged from 21 to 28, indicating that women were either satisfied or very satisfied with the care they received at the EPLSC. Results from VAS-A scores showed that 76 (69%) women reported a decrease in anxiety immediately after attending the EPLSC, compared to 8 (7%) who reported no change or a small increase in anxiety. Qualitative findings highlighted women’s concerns around future fertility, the importance of emotional support and the value of connecting with the bereavement midwife.ConclusionAn EPLSC that focuses on providing emotional support and reassurance, particularly regarding future fertility, is important to women. Further rigorous evaluation of national disparities in EPL follow-up is urgently needed to assess the gaps in clinical care delivery.