Late Miscarriage Research Articles

Трансформація поглядів на ведення жінок з істміко-цервікальною недостатністю

Cervical cerclage is an obstetric procedure used to prevent late term spontaneous abortions and preterm birth in women at high risk of miscarriage. Taking into consideration existance of insufficient effectiveness of methods for preventing spontaneous preterm labor, as evidenced by the lack of significant changes in statistical data over the past 10 years, further research is needed to improve the tactics of managing pregnant women, especially from the group of high risk of this complication. Cervical cerclage allows to mechanically stop the process of spontaneous opening of the cervix, however, although the method is minimally invasive, when using it, there is still a risk of complications, such as infection or trauma to the cervix. Taking this into account, determining the groups of patients who will benefit the most from this intervention is essential. Today, this issue is undergoing a number of transformations and updates which we tried to analyze in this work. Aim - determining changes in the recommendations for surgical management of women with isthmico-cervical insufficiency based on the analysis of the latest recommendations of the National Institute for Health and Care Excellence and the Royal College of Obstetricians and Gynecologists. Results and conclusions. According to the 2022 guidelines, along with slightly changed approaches to the classification and terminology of cervical cerclage, there has been some transformation in views about the groups of women who will benefit the most from the procedure. First of all, according to anamnestic data, cervical suture is recommended for three anamnestic episodes of miscarriage instead of two in the previous recommendations. On ultrasound examination, a wedge-shaped transformation of the cervix and incidental detection of cervical shortening after 20 weeks is not an indication for applying a cerclage, since the effectiveness of the intervention in this case is unproven. In addition, new techniques, such as abdominal cerclage, have been invented to more effectively prevent episodes of miscarriage. No conflict of interests was declared by the authors.

Improved estimation of the relationship between fetal growth and late stillbirth in the United States, 2014–15

In the United States the rate of stillbirth after 28 weeks’ gestation (late stillbirth) is 2.7/1000 births. Fetuses that are small for gestational age (SGA) or large for gestational age (LGA) are at increased risk of stillbirth. SGA and LGA are often categorized as growth or birthweight ≤ 10th and ≥ 90th centile, respectively; however, these cut-offs are arbitrary. We sought to characterize the relationship between birthweight and stillbirth risk in greater detail. Data on singleton births between 28- and 44-weeks’ gestation from 2014 to 2015 were extracted from the US Centers for Disease Control and Prevention live birth and fetal death files. Growth was assessed using customized birthweight centiles (Gestation Related Optimal Weight; GROW). The analyses included logistic regression using SGA/LGA categories and a generalized additive model (GAM) using birthweight centile as a continuous exposure. Although the SGA and LGA categories identified infants at risk of stillbirth, categorical models provided poor fits to the data within the high-risk bins, and in particular markedly underestimated the risk for the extreme centiles. For example, for fetuses in the lowest GROW centile, the observed rate was 39.8/1000 births compared with a predicted rate of 11.7/1000 from the category-based analysis. In contrast, the model-predicted risk from the GAM tracked closely with the observed risk, with the GAM providing an accurate characterization of stillbirth risk across the entire birthweight continuum. This study provides stillbirth risk estimates for each GROW centile, which clinicians can use in conjunction with other clinical details to guide obstetric management.

Preconception anti-annexin A5 antibodies are associated with subsequent live birth in women with recurrent miscarriage: A retrospective study from China.

To evaluate the correlation between the antiannexin A5 antibodies (aAnxA5) multiples of median (MOM) and subsequent pregnancy outcomes in women with recurrent miscarriage (RM). Totally, 310 RM women were included in this study and grouped into tertiles according to their MOM of preconception aAnxA5 circulating levels determined by ELISA. The effect of aAnxA5 on the pregnancy outcomes was performed using multiple logistic regression. The outcomes included early miscarriage (before 10weeks of gestation), late miscarriage (between 10 and 24weeks), ongoing pregnancy (beyond 10weeks), and live birth (after 24weeks) characterized by pregnancy with fetal heartbeat. For each unit increase in aAnxA5 MOM, the odds of live birth after 24weeks and ongoing pregnancy were reduced by 40.2% (OR= .598; 95%CI 0.406-0.882, P= .010) and 38.1% (OR= .619; 95%CI 0.424-0.904, P= .013), respectively, after adjusting for demographic and clinical characteristics. The rise in aAnxA5 MOM was associated with an increased risk of early miscarriage (OR=1.616; 95%CI 1.106-2.361, P= .013) and miscarriage (early + late miscarriage) (OR=1.671; 95%CI 1.134-2.464, P= .010). Further subgroup analyses showed a decreased risk of live birth rates after 24weeks of gestation in the two subgroups: maternal age ≥35 years (OR= .131; 95%CI 0.026-0.652), and previous pregnancy loss ≥ 3 (OR= .381; 95%CI 0.173-0.837). Higher preconception aAnxA5 MOM levels in women with RM may be linked with a decreased risk of live birth after 24weeks and an increased risk of early miscarriage, especially in individuals aged ≥35 years or with previous pregnancy losses ≥3.

Exploring parents’ experiences and holistic needs following late miscarriage: a narrative systematic review

ABSTRACT Background Up to 2% of all pregnancies result in pregnancy loss between 14 + 0 and 23 + 6 weeks’ gestation, which is defined as ‘late miscarriage’. Lack of consensus about definition of viability paired with existing multiple definitions of perinatal loss make it difficult to define the term ‘late miscarriage’. Parents who experience late miscarriage often have had reassuring scan-milestones, which established their confidence in healthy pregnancy progression and identity formation, which socially integrates their baby into their family. The clinical lexicon alongside the lack of support offered to parents experiencing late miscarriage may disclaim their needs, which has potential to cause adverse psychological responses. Aim To review what primary research reports about parents’ experiences and their perceived holistic needs following late miscarriage. Methods A narrative systematic review was carried out. Papers were screened based on gestational age at time of loss (i.e. between 14 + 0 and 23 + 6 weeks’ gestation). The focus was set on experience and holistic needs arising from the loss rather than its clinical care and pathophysiology. Studies were selected using PRISMA-S checklist, and quality assessed using the Critical Appraisal Skills Program (CASP) tool. Thematic analysis was used to guide the narrative synthesis of findings. Results Six studies met the inclusion criteria. Three main themes emerged: communication and information-giving; feelings post-event; and impact of support provision. Conclusion Literature about the experience of late miscarriage is scarce, with what was found reporting a lack of compassionate and individually tailored psychological follow-up care for parents following late miscarriage. Hence, more research in this arena is required to inform and develop this area of maternity care provision.

Higher Cumulative Live Birth Rate but Also Higher Late Miscarriage Risk in Non-Obese Women with Polycystic Ovary Syndrome Undergoing the First IVF/ICSI Cycle.

To determine the impact of polycystic ovary syndrome on in vitro fertilization/intracytoplasmic sperm injection and embryo transfer outcomes while analyzing the influencing factors. A retrospective cohort study comprised 4839 patients who underwent their first cycle of IVF/ICSI treatment from January 2016 to December 2021. Cumulative pregnancy rates, cumulative live birth rates, and late miscarriage rates compared between the PCOS group and control group. Subgroup analysis and binary regression were used to analyze the influence of BMI on clinical outcomes among individuals diagnosed with PCOS. Non-obese PCOS patients exhibited higher cumulative pregnancy rates, cumulative live birth rates, and late miscarriage rates compared to the control group with the normal BMI population (84.7% vs71.2%, P < 0.001; 74.1% vs 61.6%, P < 0.001; 4.1% vs 2.0%, P = 0.002), but there was no significant difference in early miscarriage rates between the two groups. Non-obese PCOS patients demonstrated a notably higher cumulative live birth rate but also a higher risk of late miscarriage compared to non-PCOS females with a normal BMI.

Mothers working to prevent early stillbirth study (MiNESS 20–28): a case–control study protocol

IntroductionIn the UK, 1600 babies die every year before, during or immediately after birth at 20–28 weeks’ gestation. This bereavement has a similar impact on parental physical and psychological well-being...

Predictors of late spontaneous miscarriages depending on the phenotype of abortion

The aim. Assessment of risk factors for late miscarriages depending on the clinical phenotype of abortion.Materials and methods. The study included 156 women. The main group consisted of 66 patients with late spontaneous abortion at a gestational age of 12,0–21,6 weeks, 47 of them with miscarriage on the background of isthmic-cervical insufficiency or premature rupture of amniotic fluid, 19 with late miscarriage against the background of blood discharge. Control group – 90 patients whose pregnancy ended in term delivery.Results. Analysis of the prevalence of extragenital pathology revealed a high incidence of anemia (31,8 %; p = 0,000), obesity (12,12 %, p = 0,013), and gastrointestinal diseases (12,12 %; p = 0,004) in women with late miscarriage. When analyzing gynecological pathology, it was revealed that surgical treatment of the cervix was 9,6 times more common in patients of the main group compared to the control group (10,6 and 1,1 %; p = 0,008; OR = 10,68 CI 1,28–89,04), the frequency of abnormalities in the development of the uterus – 7,5 times more often in the group with bleeding compared to the group of patients with isthmic-cervical insufficiency (15,8 and 2.1 %; p = 0,035; OR = 8,63 CI 0,84–88,97). Significant risk factors for late miscarriages are preterm birth (18,2 %, p = 0,000), non-developing pregnancy (18,2 %; p = 0,026), medical abortions (42,6 %; p = 0,003). When analyzing the course of pregnancy, prognostically unfavorable markers of miscarriage were identified: the threat of termination of a real pregnancy (53,0 %; p = 0,000), isthmic-cervical insufficiency (19,1 %: p = 0,000) and violations of the vaginal biocenosis (71,2 %, p = 0,000).Conclusion. Thus, the presence of extragenital pathology, aggravated obstetric anamnesis and complicated course of pregnancy is typical for patients with late spontaneous abortions, which requires monitoring of this category of patients at the stage of preconception preparation, treatment of extragenital pathology, as well as timely prevention, diagnosis and treatment of complications at different stages of pregnancy.

Bacterial vaginosis as a factor associated with adverse pregnancy outcomes

Bacterial vaginosis is the most common disease of the genitals and affects 20–70% of women. This non-inflammatory syndrome is characterized by dysbiosis of the vaginal microbiota and is accompanied by a decrease in the number of lactobacilli. Bacterial vaginosis in 60% of pregnant women is asymptomatic, but can lead to obstetric complications such as late miscarriage, premature birth, fetal growth restriction, premature rupture of membranes, choriominionitis, postpartum endometritis, and sepsis. The clinical picture of bacterial vaginosis in pregnant women is the same as in non-pregnant women, namely homogeneous whitish-gray discharge from the genital tract, often with an unpleasant “fishy” smell, rarely itching and/or burning in the genital area and urethra, as well as soreness during urination (dysuria), with no signs of an inflammation detected in the genitals. Diagnosis of bacterial vaginosis in pregnant women, as well as in non-pregnant women, is based on the use of clinical and laboratory methods. Multiplex tests based on the nucleic acid amplification method, such as real-time polymerase chain reaction, are very popular for the diagnosis of bacterial vaginosis in this country. The Femoflor-16 Reagent Kit (DNA Technology CJSC, Moscow, Russia) is designed to detect the DNA of opportunistic microorganisms, lactobacilli DNA and human genomic DNA (as a control for taking biological material). Examination of pregnant women, especially in case of complaints of vaginal discharge, should be carried out when registering for pregnancy in order to start treatment early and prevent adverse pregnancy outcomes for the mother and fetus. Biofilms formed by microorganisms in bacterial vaginosis, especially G. vaginalis, limit the penetration of antibacterial agents to bacteria, their concentration being lower than therapeutic one, which leads to ineffective treatment. There remain many unexplored issues related to changes in the epidemiology of bacterial vaginosis, an increase in the frequency of relapses against the background of increasing resistance of microorganisms associated with bacterial vaginosis to antibiotics, and the development of agents that affect bacterial films.

Role of Bacterial and Viral Infections and Co-Infections in Miscarriages

Abstract Aim To investigate the potential role of the following bacterial/viral panel (Chlamydia trachomatis, Ureaplasma urealyticum/parvum, Mycomplasma hominis/genitalium, Gardnerella vaginalis, HSV1/2, EBV, CMV, VZV, HHV6, HHV7, HHV8) as causative factors for miscarriages in women by testing endometrial biopsies. Anaerobic and aerobic microorganisms causing dysbiosis and endometrial bacterial colonization by unbalanced growth were additionally tested. Materials and methods In total, 65 patients with a history of early and late miscarriages were analyzed. DNA extractions, real-time qPCR, agarose gel-electrophoresis were applied. Comparative analysis of the current with previously obtained data on the described panel in menstrual tissue samples was performed. Results In 64,6% of all tested endometrial biopsies bacterial and/or viral pathogens were detected. In 49,23% of all tested samples we found bacterial, while in 15,3% – viral pathogens. These results are similar to our previous data on menstrual tissue samples of infertile women – 61,1% infected, as 48,8% had bacterial and 22,2% had viral pathogens. Gardnerella vaginalis and Ureaplasma parvum were detected in 31,25% and 3,12% of all bacterial infected endometrial biopsies, significantly lower in comparison to the estimated rate of 69,31% and 61,36% on menstrual tissue. Anaerobic and aerobic dysbiosis were detected in 53,33% and 27% of the bacterial infected endometrial samples. In 13,33% a dysbiosis with a mixed etiology was found, while in 7% a dysbiotic condition with a totally absent findings of targeted bacteria and Lactobacillus was observed. EBV, CMV, HHV6 and HHV7 were detected in 30%, 30%, 20% and 20% of the positive for viral factors endometrial biopsies and in 40%, 7,5%, 10% and 42,5% in menstrual tissue samples. In the current study 62,5% bacterial co-infection and 12,5% bacterial/viral co-infection variants were found. Infections with the rest of the target pathogens were not detected in the endometrial biopsies. In contrast to the endometrial biopsy results, Mycomplasma hominis, Ureaplasma urealyticum and HSV2 were detected in our previous research on menstrual tissue samples. Conclusions Our research suggests a possible dysbiosis as a consequence of bacterial/viral endometrial colonization, associated with miscarriages. We prove that menstrual tissue, containing parts of the functional endometrial layer, is a reliable and accurate noninvasive sample for infectious screening of the upper genital tract.

УСПЕШНОЕ ПРИМЕНЕНИЕ МЕТОДА ПОЛИМИКСИНОВОЙ СОРБЦИИ ЭНДОТОКСИНА В КОМПЛЕКСНОЙ ТЕРАПИИ ПАЦИЕНТКИ С ГРАМОТРИЦАТЕЛЬНЫМ СЕПСИСОМ ПРИ ПОЗДНЕМ ИНФИЦИРОВАННОМ ВЫКИДЫШЕ

Abstract. Introduction. Sepsis is one of the most serious problems of modern obstetrics, accounting for 11% of the overall structure of maternal mortality. One of the main initial causes of sepsis is endotoxin having diverse biological effects. Moreover, during sepsis development, endotoxin directly or indirectly leads to irreversible and often life-incompatible damage to organs. Columns for direct hemoperfusion with polymyxin B are used for extracorporeal endotoxin removal. Aim: Reviewing the literature on using columns with polymyxin B in sepsis treatment and describing our own clinical observation of maternal sepsis. Materials and Methods. Review of publications in electronic resources, such as PubMed, eLibrary, EMBASE, and Google Scholar. This article presents a clinical case of successful sepsis treatment during late infected miscarriage in a young patient. Results and Discussion. Currently published systematic reviews and meta- analyses prove the reduction of mortality in patients with sepsis/septic shock. A 39-year-old patient was admitted with signs of chorioamnionitis and incipient miscarriage at 20-21 weeks of pregnancy. After the delivery of a dead fetus, the picture of sepsis and septic shock developed. Removal of the uterus as the primary source of infection did not improve the woman’s condition. Positive changes were only observed after having applied the polymyxin sorption of endotoxin. This new advanced technology in medicine, thanks to the timely use, correct dose, and duration of hemoperfusion with polymyxin B, made it possible to remove bacterial endotoxins safely and effectively from the blood, which led to the successful sepsis therapy. Conclusions. Thanks to the coordinated actions of a multidisciplinary team of highly qualified specialists and the timely administration of adequate therapy, it was possible to save the patient’s life, thus preventing her from maternal mortality.

Subsequent pregnancy outcomes after second trimester miscarriage or termination for medical/fetal reason: A systematic review and meta-analysis of observational studies.

Women with a prior stillbirth or a history of recurrent first trimester miscarriages are at increased risk of adverse pregnancy outcomes. However, little is known about the impact of a second trimester pregnancy loss on subsequent pregnancy outcome. This review investigated if second trimester miscarriage or termination for medical reason or fetal anomaly (TFMR/TOPFA) is associated with future adverse pregnancy outcomes. A systematic review of observational studies was conducted. Eligible studies included women with a history of a second trimester miscarriage or termination for medical reasons and their pregnancy outcomes in the subsequent pregnancy. Where comparative studies were identified, studies which compared subsequent pregnancy outcomes for women with and without a history of second trimester loss or TFMR/TOPFA were included. The primary outcome was livebirth, and secondary outcomes included: miscarriage (first and second trimester), termination of pregnancy, fetal growth restriction, cesarean section, preterm birth, pre-eclampsia, antepartum hemorrhage, stillbirth and neonatal death. Studies were excluded if exposure was nonmedical termination or if related to twins or higher multiple pregnancies. Electronic searches were conducted using the online databases (MEDLINE, Embase, PubMed and The Cochrane Library) and searches were last updated on June 16, 2023. Risk of bias was assessed using the Newcastle-Ottawa scale. Where possible, meta-analysis was undertaken. PROSPERO registration: CRD42023375033. Ten studies were included, reporting on 12 004 subsequent pregnancies after a second trimester pregnancy miscarriage. No studies were found on outcomes after second trimester TFMR/TOPFA. Overall, available data were of "very low quality" using GRADE assessment. Meta-analysis of cohort studies generated estimated outcome frequencies for women with a previous second trimester loss as follows: live birth 81% (95% CI: 64-94), miscarriage 15% (95% CI: 4-30, preterm birth 13% [95% CI: 6-23]).The pooled odds ratio for preterm birth in subsequent pregnancy after second trimester loss in case-control studies was OR 4.52 (95% CI: 3.03-6.74). Very low certainty evidence suggests there may be an increased risk of preterm birth in a subsequent pregnancy after a late miscarriage. However, evidence is limited. Larger, higher quality cohort studies are needed to investigate this potential association.

Analysis of perinatal consequences against the background of the proposed treatment complex in pregnant women after the application of assisted reproductive technologies

The course of pregnancy that occurs as a result of the application of assisted reproductive technologies is accompanied by numerous complications that affect the indicators of perinatal morbidity and mortality. Nowadays in Ukraine, there is no unified approach to the management of women whose pregnancy occurred as a result of ART application, which determined the direction of this work.The objective: to assess perinatal consequences against the background of the introduction of the proposed treatment complex in women whose pregnancy occurred as a result of the application of assisted reproductive technologies.Materials and methods. 249 pregnant women were examined, which were divided into: group I – 94 women with tubo-peritoneal, group II – 87 women with endocrine and group III – 68 women with male types of infertility. Depending on the prescribed therapy, women of groups I, II and III are divided into: subgroup IA – 49 pregnant women with tubo-peritoneal, subgroup IIA – 48 pregnant women with endocrine, subgroup IIIA – 36 pregnant women with male factor of infertility who received the proposed therapeutic and preventive complex; subgroup IB – 45 pregnant women with tubo-peritoneal, subgroup IIB – 39 pregnant women with endocrine, subgroup IIIB – 32 pregnant women with male factor of infertility, which were observed in accordance with generally accepted standards of obstetric care.Results. Against the background of prescribing the proposed complex, there was a significant decrease in the frequency of threatened miscarriage in women of Group I by 41.6%, in women of Group II by 37.1% (p&lt;0.05). In the second and third trimesters, there was a significant decrease in the number of cases of threatening late spontaneous miscarriages, threatening premature birth, placental dysfunction, preeclampsia, and fetal growth retardation syndrome (p&lt;0.05). A significant indicator of the effectiveness of the proposed treatment complex is a significant increase in the proportion of urgent labor in women of subgroups IA and IIA. Thus, 46 (93.8%) women of subgroup IA and 46 (95.8%) women of subgroup IIA had urgent labor.Assessing the pathological conditions of newborns, it should be noted that in children from women in labor of subgroups who received the proposed complex, respiratory disorders syndrome (p&lt;0.05), intraventricular hemorrhages (p&lt;0.05), hypoxic-ischemic encephalopathy (p&lt;0.05), and cases of antenatal infection (p&lt;0.05) were determined in a significantly smaller number of cases.Conclusions. The effectiveness of the proposed treatment complex and the complex of psychoemotional correction in pregnant women after the use of assisted reproductive technologies is confirmed by a reliably better course of the first, second and third trimesters of pregnancy, a reliably better course of Labor, which was reflected in an increase in cases of urgent labor and a decrease in cases of complications in childbirth, which was reflected in a significant decrease in the number of cesarean sections.Improvement of perinatal consequences against the background of the use of the proposed treatment complex and the complex of psychoemotional correction in newborns from women in labor after the use of assisted reproductive technologies is confirmed by a significantly larger mass of newborns, a significantly smaller number of newborns with low gestational weight, a significantly higher Apgar score, a significantly smaller number of cases of pathological and transient conditions, and a significantly shorter duration of stay of women in labor and newborns in an obstetric hospital, as well as the absence of cases of early neonatal and perinatal mortality among newborns.

Визначення особливостей перебігу вагітності та пологів, стану плода і новонародженого у вагітних після застосування допоміжних репродуктивних технологій (дані ретроспективного аналізу)

The rapid growth in the number of infertile couples leads to the development of assisted reproductive technologies (ART). Among the most common forms of infertility are tubo-peritoneal, endocrine, and caused by the male factor, and prevention of pregnancy complications caused by ART treatment cycles becomes one of the main tasks of practicing clinicians. Purpose - to determine the features of the course of pregnancy and childbirth; to assess the condition of the fetus and newborn in pregnant women after the application of ART to improve the perinatal outcomes of pregnancy and childbirth. Materials and methods. A retrospective clinical and statistical analysis of 334 histories of pregnancy and childbirth of women, as well as medical records of newborns from women, was conducted over the past five years, which formed the ART group - 221 history of pregnancy and childbirth, and the group of spontaneous pregnancy - 113 history of pregnancy and childbirth. Results. The structure of the subjects was statistically significant dominated by pregnant women over the age of 35 years and pregnant women in late reproductive age. The main characteristics of women after the ART application were a statistically significant predominance of somatic and gynecological pathology. The structure of pregnancy complications in women after ART application was dominated by threatening late spontaneous miscarriages, isthmic-cervical insufficiency and vaginitis, and in the structure of labor complications - anomalies of labor activity and premature rupture of fetal membranes. Among newborns from women in the ART group, perinatal mortality was 18.0%. Conclusions. The revealed features of somatic and gynecological anamnesis, as well as aspects of the course of pregnancy and childbirth and the condition of newborns in women after ART application are the basis for an in-depth examination of this category of pregnant women in order to improve approaches to predicting, diagnosing and optimizing preventive measures, as well as to improve the perinatal consequences of pregnancy and childbirth. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. No conflict of interests was declared by the authors.

“I had given up on being a mother”: a survey of 183 women’s experience of transabdominal cerclage (TAC)

BackgroundTransabdominal cerclage (TAC) is a relatively uncommon intervention for preventing preterm birth. This study aimed to investigate the experience of women who had undergone this procedure.MethodsThe survey was designed in collaboration with a preterm birth studies public and patient involvement (PPI) group and ethical approval was granted by KCL BDM Research Ethics Panel (LRS-19/20-13205). Members of closed Facebook group, UK TAC Support, were invited to complete an online questionnaire about their experience of TAC, and pregnancies before and after having it placed. The survey was open between December 2019 and May 2020. Open and closed questions provided both qualitative and quantitative data for analysis, which was carried out using NVivo Pro 2020 v.1.4.1 qualitative data management software and SPSS Statistics 27 (IBM).ResultsOne hundred eighty-three participants completed the survey, having had TAC procedures carried out in 36 hospitals. Altogether, participants had experienced 287 preterm births (PTB) and late miscarriages (LM), equating to an average of 1.6 each (range 0–5), including 18 stillbirths. TAC was indicated in 123 (67%) for previous PTB and/or LM, 29 (16%) for cervical surgery and 31 (17%) for both. 151 (83%) TAC procedures were open, 32 (17%) laparoscopic. 86% (n = 157) were placed outside pregnancy. Of those placed in pregnancy, gestation at TAC ranged from 7 to 16 weeks. When comparing earliest pre- and post-TAC pregnancy gestation (excluding first trimester losses), median gestational weeks gained following TAC was 15.5 weeks (SD 6.89). Qualitative themes included: the struggle to get treatment; lack of TAC knowledge amongst clinicians; gratitude, hope and feeling protected; possible detrimental effects of TAC.ConclusionsThis very high-risk group found having a TAC gave great reassurance and hope, and were very grateful to have found the care they needed. However, they often struggled to get this support, frequently due to lack of clinician awareness. This may improve following roll-out of NHS England’s Saving Babies Live Care Bundle and NHS commissioning guidelines for care of women at risk of PTB.

Prevalence of neural tube defects in England prior to the mandatory fortification of non-wholemeal wheat flour with folic acid: a population-based cohort study

ObjectivesTo determine the baseline trends in the total birth prevalence of neural tube defects (NTDs) in England (2000–2019) to enable the impact of folic acid fortification of non-wholemeal wheat flour...

A prospective cohort study of preconception COVID-19 vaccination and miscarriage.

To what extent is preconception maternal or paternal coronavirus disease 2019 (COVID-19) vaccination associated with miscarriage incidence? COVID-19 vaccination in either partner at any time before conception is not associated with an increased rate of miscarriage. Several observational studies have evaluated the safety of COVID-19 vaccination during pregnancy and found no association with miscarriage, though no study prospectively evaluated the risk of early miscarriage (gestational weeks [GW] <8) in relation to COVID-19 vaccination. Moreover, no study has evaluated the role of preconception vaccination in both male and female partners. An Internet-based, prospective preconception cohort study of couples residing in the USA and Canada. We analyzed data from 1815 female participants who conceived during December 2020-November 2022, including 1570 couples with data on male partner vaccination. Eligible female participants were aged 21-45 years and were trying to conceive without use of fertility treatment at enrollment. Female participants completed questionnaires at baseline, every 8 weeks until pregnancy, and during early and late pregnancy; they could also invite their male partners to complete a baseline questionnaire. We collected data on COVID-19 vaccination (brand and date of doses), history of SARS-CoV-2 infection (yes/no and date of positive test), potential confounders (demographic, reproductive, and lifestyle characteristics), and pregnancy status on all questionnaires. Vaccination status was categorized as never (0 doses before conception), ever (≥1 dose before conception), having a full primary sequence before conception, and completing the full primary sequence ≤3 months before conception. These categories were not mutually exclusive. Participants were followed up from their first positive pregnancy test until miscarriage or a censoring event (induced abortion, ectopic pregnancy, loss to follow-up, 20 weeks' gestation), whichever occurred first. We estimated incidence rate ratios (IRRs) for miscarriage and corresponding 95% CIs using Cox proportional hazards models with GW as the time scale. We used propensity score fine stratification weights to adjust for confounding. Among 1815 eligible female participants, 75% had received at least one dose of a COVID-19 vaccine by the time of conception. Almost one-quarter of pregnancies resulted in miscarriage, and 75% of miscarriages occurred <8 weeks' gestation. The propensity score-weighted IRR comparing female participants who received at least one dose any time before conception versus those who had not been vaccinated was 0.85 (95% CI: 0.63, 1.14). COVID-19 vaccination was not associated with increased risk of either early miscarriage (GW: <8) or late miscarriage (GW: 8-19). There was no indication of an increased risk of miscarriage associated with male partner vaccination (IRR = 0.90; 95% CI: 0.56, 1.44). The present study relied on self-reported vaccination status and infection history. Thus, there may be some non-differential misclassification of exposure status. While misclassification of miscarriage is also possible, the preconception cohort design and high prevalence of home pregnancy testing in this cohort reduced the potential for under-ascertainment of miscarriage. As in all observational studies, residual or unmeasured confounding is possible. This is the first study to evaluate prospectively the relation between preconception COVID-19 vaccination in both partners and miscarriage, with more complete ascertainment of early miscarriages than earlier studies of vaccination. The findings are informative for individuals planning a pregnancy and their healthcare providers. This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Health [R01-HD086742 (PI: L.A.W.); R01-HD105863S1 (PI: L.A.W. and M.L.E.)], the National Institute of Allergy and Infectious Diseases (R03-AI154544; PI: A.K.R.), and the National Science Foundation (NSF-1914792; PI: L.A.W.). The funders had no role in the study design, data collection, analysis and interpretation of data, writing of the report, or the decision to submit the paper for publication. L.A.W. is a fibroid consultant for AbbVie, Inc. She also receives in-kind donations from Swiss Precision Diagnostics (Clearblue home pregnancy tests) and Kindara.com (fertility apps). M.L.E. received consulting fees from Ro, Hannah, Dadi, VSeat, and Underdog, holds stock in Ro, Hannah, Dadi, and Underdog, is a past president of SSMR, and is a board member of SMRU. K.F.H. reports being an investigator on grants to her institution from UCB and Takeda, unrelated to this study. S.H.-D. reports being an investigator on grants to her institution from Takeda, unrelated to this study, and a methods consultant for UCB and Roche for unrelated drugs. The authors report no other relationships or activities that could appear to have influenced the submitted work. N/A.

Mediation analysis quantifying the magnitude of stillbirth risk attributable to small for gestational age infants

Many risk factors for stillbirth are linked to placental dysfunction, which leads to suboptimal intrauterine growth and small for gestational age infants. Such infants also have an increased risk for stillbirth. This study aimed to investigate the effect of known causal risk factors for stillbirth, and to identify those that have a large proportion of their risk mediated through small for gestational age birth. This retrospective cohort study used data from all births in the state of Queensland, Australia between 2000 and 2018. The total effects of exposures on the odds of stillbirth were determined using multivariable, clustered logistic regression models. Mediation analysis was performed using a counterfactual approach to determine the indirect effect and percentage of effect mediated through small for gestational age. For risk factors significantly mediated through small for gestational age, the relative risks of stillbirth were compared between small for gestational age and appropriate for gestational age infants. We also investigated the proportion of risk mediated via small for gestational age for late stillbirths (≥28 weeks). The initial data set consisted of 1,105,612 births. After exclusions, the final study cohort constituted 925,053 births. Small for gestational age births occurred in 9.9% (91,859/925,053) of the study cohort. Stillbirths occurred in 0.5% of all births (4234/925,053) and 1.5% of small for gestational age births (1414/91,859). Births at ≥28 weeks occurred in 99.4% (919,650/925,053) of the study cohort and in 98.9% (90,804/91,859) of all small for gestational age births. Of the ≥28-week births, stillbirths occurred in 0.2% (2156/919,650) of all births and 0.8% (677/90,804) of the small for gestational age births. Overall, increased odds of stillbirth were significantly mediated through small for gestational age for age <20 years, low socioeconomic status, Indigenous ethnicity, birth in sub-Saharan and North Africa or the Middle East, smoking, nulliparity, multiple pregnancy, assisted conception, previous stillbirth, preeclampsia, and renal disease. Preeclampsia had the largest proportion mediated through small for gestational age (66.7%), followed by nulliparity (61.6%), smoking (29.4%), North-African or Middle Eastern ethnicity (27.6%), multiple pregnancy (26.3%), low socioeconomic status (25.8%), and Indigenous status (18.7%). Sensitivity analysis showed that for late stillbirths, the portions mediated through small for gestational age remained very similar for many of the risk factors. Although small for gestational age is an important mediator between many pregnancy risk factors and stillbirth, mitigating the risk of small for gestational age is likely to be of value only when it is a major contributor in the pathway to fetal demise.

PECULIARITIES OF THE COURSE OF PREGNANCY IN WOMEN OF DIFFERENT POPULATION GROUPS BURDENED WITH ANEMIA AND HELICOBACTERIOSIS

Peculiarities of the course of pregnancy in women of different ethnic groups are burdened with anemia and helicobacteriosis in modern living conditions after the pandemic of coronavirus infection, the state of constant stress of the war in Ukraine. The purpose of the study was to determine the characteristics of the course of pregnancy in women of different population groups burdened with anemia and helicobacteriosis&#x0D; Materials and Methods. 30 pregnant women of reproductive age, burdened with anemia, residents of the city of Odesa (group I) and countries of Southeast Asia (group II) were under our observation. All women were registered at the women’s clinic. The monitoring algorithm included clinical and laboratory studies of Helicobacter pylori infection (total antibodies (IgG, IgM, IgA) to Helicobacter pylori antigens).&#x0D; Results. The presence of infectious processes in the body of women is one of the etiological factors of gestational complications, including the progression of the severity of anemia in pregnant women. The clinical severity of anemia in pregnant women was consistent with a high coefficient of positivity of total antibodies (IgG, IgM, IgA) to Helicobacter pylori antigens and a low level of hemoglobin, the level of ferritin, folic acid, cyanocobalamin, the vital trace element iron. Indicators of the clinical course of pregnancy in group I and group II had a significant difference (p&lt;0.05), respectively: early toxicosis (mild, moderate, severe) – 20.0 %, 0 %, 0 % and 26.7 %, 20.0 %, 0 %; syndrome of the threat of early miscarriage - 13.3 % and 33.3 %; late miscarriage threat syndrome – 6.7 % and 20.0 %; secondary placental dysfunction – 0 % and 20.0 %; fetal growth retardation syndrome (FGRS) – 0 % and 6.7 %; intranatal fetal distress – 0 % and 6.7 %. The postpartum period in 13.3 % of women in the 2nd group had a lochiometer.&#x0D; Conclusions. Peculiarities of the course of pregnancy in women of different population groups burdened with anemia and helicobacteriosis consisted in the progression of the severity of the clinical and laboratory course of anemia and gestational complications during the trimesters. The clinical severity of anemia in pregnant women was consistent with a high ratio of total antibodies (IgG, IgM, IgA) to Helicobacter pylori antigens and a low level of hemoglobin, the level of ferritin, folic acid, cyanocobalamin, the vital trace element iron. It is recommended to determine the ratio of total antibodies (IgG, IgM, IgA) to Helicobacter pylori antigens in the blood of pregnant women with anemia and at the stage of pregnancy planning. Positive results are an indication for examination of all family members.

Transabdominal cerclage: The journey of turning bad into good

Recurrent pregnancy loss is a challenging obstetric condition that requires thorough evaluation and vigilant antenatal care. Cervical insufficiency is a well-recognized cause of late miscarriage. Here, we are reporting a case of multiple pregnancy failures including both 1st- and 2nd-trimester losses with cervical insufficiency after ruling out all other probable causes. The patient had a history of 3 failed transvaginal cervical cerclage procedures, and hence, in her 7th pregnancy, transabdominal cervical cerclage was attempted that resulted in salvaging the pregnancy beyond viability and the patient delivered a healthy baby through an emergency cesarean section near term. The patient was reconceived with the transabdominal cerclage in situ and delivered with a successful fetal and maternal outcome despite having multiple high-risk factors. This highlights the effectiveness of transabdominal cervical cerclage to prevent spontaneous mid-trimester loss and preterm delivery when previous transvaginal cerclage has failed.

Risk factors for late (28+ weeks' gestation) stillbirth in the United States, 2014-2015.

In the United States (US) late stillbirth (at 28 weeks or more of gestation) occurs in 3/1000 births. We examined risk factors for late stillbirth with the specific goal of identifying modifiable factors that contribute substantially to stillbirth burden. All singleton births in the US for 2014-2015. We used a retrospective population-based design to assess the effects of multiple factors on the risk of late stillbirth in the US. Data were drawn from the US Centers for Disease Control and Prevention live birth and fetal death data files. There were 6,732,157 live and 18,334 stillbirths available for analysis (late stillbirth rate = 2.72/1000 births). The importance of sociodemographic determinants was shown by higher risks for Black and Native Hawaiian and Other Pacific Islander mothers compared with White mothers, mothers with low educational attainment, and older mothers. Among modifiable risk factors, delayed/absent prenatal care, diabetes, hypertension, and maternal smoking were associated with increased risk, though they accounted for only 3-6% of stillbirths each. Two factors accounted for the largest proportion of late stillbirths: high maternal body mass index (BMI; 15%) and infants who were small for gestational age (38%). Participation in the supplemental nutrition for women, infants and children program was associated with a 28% reduction in overall stillbirth burden. This study provides population-based evidence for stillbirth risk in the US. A high proportion of late stillbirths was associated with high maternal BMI and small for gestational age, whereas participation in supplemental nutrition programs was associated with a large reduction in stillbirth burden. Addressing obesity and fetal growth restriction, as well as broadening participation in nutritional supplementation programs could reduce late stillbirths.