Cases Of Stillbirth Research Articles

Causes of Different Types of Abortion in Women Referring To Educational and Medical Centers in Shiraz, Iran

Background & aim: Abortion in Iran, like some countries in the world, has long been a culturally, socially, politically and religiously sensitive issue. So the present study was conducted to investigate the causes of abortions in pregnant women referring to Shiraz educational and medical centers.Methods: : In this cross-sectional study, 437 woman who had an abortion, were selected by examining 5176 pregnant women using sequential sampling method during 4 months from educational and forensic medicine centers in Shiraz, Iran, in 2017. A self-structured questionnaire including demographic characteristics and obstetric data was completed for each mother. Data analysis was carried out using descriptive statistics.Results: Out of 88 abortions with a legal permission from the forensic medicine, 9.1% were due to maternal illness and 90.9% were due to fetal disease, the most common cause of which was fetal cranial and cerebral disorders (17.1%). Out of 105 cases of spontaneous abortion, 8 cases were due to maternal cause (the most common cause of uterine defects (4.8%) and 97 cases were due to fetal cause. Out of 244 induced abortions with obstetric indication, the most common cause was missed abortion (32%).Conclusion: In all three types of abortion, fetal causes were the most common cause of abortion. It seems that education, access to information and awareness raising activities involving the whole community will have a significant effect on preventing the occurrence of abnormalities. Emphasis is placed on the importance of conducting prenatal screening before 20 weeks of gestation.

Fetal Complications in COVID-19 Infected Pregnant Woman: A Systematic Review and Meta-Analysis.

Background Pregnancy is an immunocompromised state and, for this reason, a pregnant woman is at a higher risk of getting infected as compared with a healthy individual. There is limited data available regarding the impact of COVD-19 on pregnancy; however, the case of miscarriage due to placental infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in second trimester has already been reported. Methods We searched for all published articles in PubMed, Science Direct, Cochrane, Scopus, and Embase. The literature search produced 167 relevant publications; 67 manuscripts were further excluded because they did not satisfy our inclusion criteria. Out of the remaining 100 articles, 78 were excluded after full text screening. Therefore, a total of 22 articles were eligible for review in our study. Results Overall, these 22 studies included a total of 7,034 participants: 2,689 (38.23%) SARS-CoV-2 positive pregnant women, of which 2,578 (95.87%) were laboratory confirmed and 111 (4.13%) were clinically diagnosed. Among the positive patients, there were 174 (6.47%) cases of abortion, of them 168 (96.55%) were spontaneous abortions and 6 (3.45%) were missed. Most patients either reported mild symptoms of fever, cough, fatigue, and anosmia or they presented asymptomatic. Conclusion Additional investigation and rigorous research are warranted to confirm placental pathology mechanisms concerning COVID-19 to protect maternal and fetal health.

The hemostatic parameters in pregnant women with different types of diabetes mellitus

BACKGROUND: The prevalence of diabetes mellitus (DM) in pregnancy is on the rise. Despite that gestational hypercoagulability is a physiological condition, diabetic pregnancy is associated with a high risk of venous thromboembolic complications (VTEC). There are many surveys related to the hemostatic parameters in non-pregnant women, but studies in pregnant women are not enough.AIMS: To assess the coagulation and vascular-platelet hemostasis parameters in pregnant women with various types of diabetes mellitus, taking into account its correction method. The data were compared with these indicators in women with preeclampsia and healthy pregnant women at the same gestational age.MATERIALS AND METHODS: An observational, single-center, retrospective cohort study was carried out at D.O. Ott ­Research Institute of Obstetrics, Gynecology, and Reproductive Medicine. The study included 1994 pregnant women who presented several groups taking into account the type of DM and its correction method, a group of women with preeclampsia (PE), and healthy women. The analysis of clinical data was carried out at 28–32 gestational weeks from 2012 to 2017. The study’s primary endpoint was taken as indicators of fibrinogen content, prothrombin index, thrombin time, activated partial thromboplastin time (APTT), and international normalized ratio (INR) antithrombin III, D-dimer, von Willebrand factor, and fibronectin. Additionally, the incidence of VTEC during pregnancy and within six weeks after delivery, gestational arterial hypertension, preeclampsia, fetal growth restriction, premature birth, and stillbirth cases was assessed.RESULTS: in pregnant women with various types of diabetes mellitus and preeclampsia, a state of pathological hypercoagulation was observed compared to the control group. These changes were characterized by an increase and activation of the following blood parameters: fibrinogen, the degree and rate of platelet aggregation, D-dimer, homocysteine, von Willebrand factor, and fibronectin. At the same time, the content of antithrombin III was significantly reduced in patients with DM. Correlation analysis established a direct relationship between the range of the studied factors with the degree of glycemic control and the frequency of obstetric complications.CONCLUSIONS: Diabetes mellitus in pregnancy is associated with a hypercoagulation condition and overexpression in the synthesis of endothelial dysfunction markers. Moreover, the severity of these processes depends on the type of DM and the severity of metabolic disorders. In diabetic pregnancy, exceptional attention to coagulation indicators, regular monitoring, and preventive treatment is required in order to improve the perinatal outcomes.

Dihydroergotamine and triptan use to treat migraine during pregnancy and the risk of adverse pregnancy outcomes

Migraine is prevalent during pregnancy. Antimigraine medications such as dihydroergotamine (DHE) and triptans have been associated with adverse pregnancy outcomes in individual studies but lack of consensus remains. We compared the risk of prematurity, low birth weight (LBW), major congenital malformations (MCM), and spontaneous abortions (SA) associated with gestational use of DHE or triptans. Three cohort and one nested-case–control analyses were conducted within the Quebec Pregnancy Cohort to assess the risk of prematurity, LBW, MCM, and SA. Exposure was defined dichotomously as use of DHE or triptan during pregnancy. Generalized estimation equations were built to quantify the associations, adjusting for potential confounders. 233,900 eligible pregnancies were included in the analyses on prematurity, LBW, and MCM; 29,104 cases of SA were identified. Seventy-eight subjects (0.03%) were exposed to DHE and 526 (0.22%) to triptans. Adjusting for potential confounders, DHE and triptans were associated with increased risks of prematurity, LBW, MCM, and SA but not all estimates were statistically significant. DHE was associated with the risk of prematurity (aRR: 4.12, 95% CI 1.21–13.99); triptans were associated with the risk of SA (aOR: 1.63, 95% CI 1.34–1.98). After considering maternal migraine, all antimigraine specific medications increased the risk of some adverse pregnancy outcomes, but estimates were unstable.

Disease Reactivation after Fingolimod Discontinuation in Pregnant Multiple Sclerosis Patients

Recent studies estimated an incidence of 4–25% of disease rebound after withdrawal of fingolimod (FTY) for any reason, but specific data on disease reactivation after FTY withdrawal due to pregnancy are limited. The aim of the study was to evaluate the frequency and predictors of disease reactivation in patients who stopped FTY for pregnancy. A multicentre retrospective cohort study was conducted in four Italian MS centres in 2013–2019. Both planned and unplanned pregnancies were included. The annualized relapse rate (ARR) was calculated before FTY treatment, during FTY treatment, during pregnancy and during the year after delivery. In total, 27 patients (mean age 29 years) were included. The ARR 1 year before FTY treatment was 1.3. Patients were exposed to FTY for a median of 2.9 years. The ARR was 0.04 during the last year before conception (p < 0.001 compared with the ARR before FTY treatment). Eleven patients became pregnant after a mean of 88 days following FTY discontinuation, whereas 16 patients stopped FTY after pregnancy confirmation. Relapses were observed in 22% of patients during pregnancy and in 44% in the postpartum period. ARR increased both during pregnancy (0.49; p = 0.027) and in the first year after delivery (0.67; p < 0.001) compared to the last year before pregnancy. Compared with radiological assessment before pregnancy, more patients showed new or enlarging T2 lesions (63% vs 30%; p = 0.02) and gadolinium-enhancing lesions (44% vs 0; p = 0.0001) on brain Magnetic Resonance Imaging. Relapses during pregnancy were the only significant predictor for postpartum relapses (OR 1.9, 95% CI 1.11–3.1). One case of spontaneous abortion and no cases of abnormal foetal development were observed. Despite adequate and prolonged control of disease activity, women who discontinue FTY because of pregnancy are at risk for disease reactivation. In patients who relapsed during pregnancy, the initiation of high-efficacy disease modifying drugs (DMDs) soon after delivery is advisable to prevent postpartum relapses.

How to investigate a stillbirth on farm

Background: Bovine stillbirth is a common presentation in farm practice, but its investigation is complex and so a structured approach is recommended to aid diagnosis. This, in turn, will help practitioners to provide targeted advice to farmers, with the aim of reducing incidence in the future.Aim of the article: This article outlines a structured approach to follow when investigating stillbirth cases that can lead to a firm evidence base for giving the best advice on farm.

Global warming increases the risk of the stillbirth: a ten years follow-up study in Taiwan

BACKGROUND AND AIM: Few studies have examined heat with respect to the risk of stillbirth. This study explored the association between ambient temperature and stillbirth in Taiwan. METHODS: This study collected monthly stillbirths, air pollution, and meteorological variables in Taiwan from 2009 to 2018. We apply time-series analysis and use exponential smoothing to predict the risk of stillbirth in the next five years. The distributed hysteresis nonlinear model (DLNM) is used to study the associated hysteresis effect of temperature on stillbirth. RESULTS:A total of 22,769 cases of stillbirth were reported, with a mean stillbirth rate of 1.13±0.14%. Risks were elevated during the warm season (May—July). There is an increasing trend of stillbirth together with ambient temperature. Chronic exposure to warm temperatures (27—30℃) (RR = 1.08, 95% CI 1.05, 1.12) and high temperature (30℃) significantly increased the risk of stillbirth (RR = 1.15, 95% CI 1.04, 1.24). The effects of heat on stillbirth were observed in the first month of pregnancy at lag 10 and one month before delivery at lag 1. CONCLUSIONS:Pregnant women in subtropical Asia countries are at increased risk of stillbirth during the hot season. The government should take the thermal effect on stillbirth seriously and formulate effective preventive strategies to mitigate the health burden of global warming. KEYWORDS: stillbirth, temperature, DLNM

P–374 Investigating causality of risk factors for miscarriage – a Mendelian randomization analysis

Abstract Study question Do modifiable risk factors such as smoking, alcohol or coffee consumption, and adiposity causally increase the risk of sporadic or recurrent miscarriage? Summary answer We found evidence for a causal relationship between smoking initiation and sporadic miscarriage, but not for any other risk factor tested. What is known already Miscarriage is estimated to end between 10–25% of clinically confirmed pregnancies, and many observational studies have suggested numerous lifestyle factors, such as coffee and alcohol consumption, smoking and increased adiposity, may increase miscarriage risk. However, results are not always consistent across studies, and definitive causal relationships between various risk factors and miscarriage have not yet been demonstrated. Mendelian randomization utilizes genetic variants significantly associated with heritable risk factors (i.e. at P-values &amp;lt;5x10–8 in large genome-wide association studies) as instrumental variables to investigate causality of risk factors in population health outcomes. Study design, size, duration We conducted two-sample Mendelian randomization analyses to investigate causality of smoking (initiation and quantity), alcohol and coffee consumption (quantity), and adiposity (body mass index and waist-hip ratio) in sporadic and recurrent miscarriage. Data included in this study were taken from previously published summary genetic association statistics (betas, standard errors and P-values) from large-scale genome-wide association studies (GWAS) for each risk factor, and from our recently published GWAS of sporadic and recurrent miscarriage. Participants/materials, setting, methods Instrumental variables were constructed using 5–306 genetic variants significantly associated with the listed risk factors in published GWAS (minimum N = 178,000 individuals). Two instrumental variables were constructed per risk factor using data from different GWAS. Associations of the instrumental variables with miscarriage were investigated using summary association data from women of European ancestry included in our miscarriage GWAS, including 49,996 sporadic miscarriage cases and 174,109 female controls, and 750 recurrent miscarriage cases and 150,215 female controls. Main results and the role of chance We found a significant association between sporadic miscarriage and the instrumental variables for two smoking measures: smoking initiation (inverse variance weighted Odds Ratio = 1.17, 95% confidence intervals = 1.10–1.24, P = 2.7 x 10–07) and lifetime smoking (inverse variance weighted Odds Ratio = 1.22, 95% confidence intervals 1.11–1.35, P = 4.2x10–5). No other risk factors (smoking quantity, coffee or alcohol consumption, or BMI or waist-hip ratio) were associated with either sporadic or recurrent miscarriage. A priori power calculations considering the amount of phenotypic variance in each risk factor explained by the associated SNPs suggested our analysis to have at least 75% power to detect an association with Odds Ratio of 1.2 with sporadic miscarriage for analyses of body mass index, waist hip ratio and smoking initiation, quantity and the lifetime smoking measure, but that the alcohol and coffee consumption analyses were underpowered (4.9% and 48%, respectively). All analyses were underpowered for recurrent miscarriage given the small case sample size (N = 750). Limitations, reasons for caution While data utilised here come from large-scale GWAS including 1000s of individuals, genetic variants significantly associated with each risk factor currently explain small percentages (0.02–6%) of the variance in each trait. Larger GWAS for specific risk factors, and for sporadic and recurrent miscarriage, are required to clarify some published associations. Wider implications of the findings: We find no evidence of a causal link between adiposity and miscarriage, indicating that observational findings of increased miscarriage risk with increasing body mass index require further explanation. Significant associations between measures of ever-smoking and sporadic miscarriage highlights that no amount of smoking is safe in regards to miscarriage risk. Trial registration number Not applicable

P–357 The risk factors for early pregnancy loss based on a logistic model following 13,977 infertile patients after in vitro fertilization

Abstract Study question What are the risk factors for early pregnancy loss (EPL) after in vitro fertilization-embryo transfer (IVF-ET)? Summary answer The maternal age, gestational sac diameter, embryonic length, yolk sac diameter, heart rate of day 27–29 and endometrium thickness on transfer day were risk factors. What is known already: The first routine ultrasound scan is commonly arranged on day 27–29 after IVF-ET in most reproductive centers in China to determine the location and viability of the embryo. Individual maternal factors, such as a high maternal age (MA) and abnormal ultrasound parameters such as embryonic bradycardia and excessively large or small yolk sac diameter (YSD) have been shown to be associated with pregnancy failures. However, few studies focused on the risk factors of the IVF population, and little is known about the clinical meaning of ultrasound indicators of 27–29 days after transplantation. Study design, size, duration This was a retrospective study in a single reproductive centre. The infertile patients included in this study underwent IVF treatment between June 2016 to December 2017. Participants/materials, setting, methods: During this period, 13,977 women were identified with a singleton pregnancy by TVS at day 27–29 after IVF-ET. The gestational sac diameter (GSD), embryonic length (EL), embryonic heart rate (EHR) and YSD and the presence of intrauterine hematoma (IUH) were measured. The clinical characteristics were also collected. The first trimester pregnancy outcome of these women was noted at 12 weeks of gestation. A backward Wald logistic regression model was established to screen the risk factors. Main results and the role of chance 1,926 cases of spontaneous miscarriage ≤12 weeks of gestation, which were assigned as EPL and 12,051 women with an ongoing pregnancy for &amp;gt;12 weeks of gestation. When compared with the ongoing pregnancy group, the MA, infertility duration and transfer cycle were significantly higher, and the day–14 human chorionic gonadotrophin and the endometrium (EM) thickness on transfer day were significantly lower in the EPL group (p &amp;lt; 0.001). Based on the TVS measurements, the GSD (18.5±3.6 vs. 13.2±4.8 mm), EL (3.5±0.9 vs. 1.2±1.6 mm), YSD (3.6±0.4 vs. 2.6±1.5 mm) and EHR (114.5±12.2 vs. 42.4±53.5 bpm) were significantly greater in the ongoing pregnancy group than those in the EPL group (p &amp;lt; 0.001). The incidence of IUH (16.0% vs. 18.8%, P = 0.002) was also markedly higher in the EPL group MA, GSD, EL, YSD, EHR and EM on transfer day finally entered the logistic model after stepwise screening. The probability of EPL was: exp(z)/(1 + exp(z)), where z = 2.432 + (0.092 × MA) - (0.074 × EM) - (0.114 ×GSD) - (0.245 × EL) - (0.034 × HR) - (0.159 × YSD). Limitations, reasons for caution Data on smoking and clinical symptoms such as vaginal bleeding or abdominal pain were not included in the final analysis which might be possible risk factors. These predictors were derived from an IVF population, the situation may not be the same in the general population. Wider implications of the findings: The risk factors for EPL after IVF-ET are clearly identified in this study. The logistic model which incorporates readily available data that are routinely collected in clinical practice could be used for calculating the risk of EPL and effectively guide subsequent medical plans. Trial registration number None

O-139 Complete removal of uterine septum tissue as a wedge, an alternative method for patients suffering from recurrent pregnancy loss or infertility, a retrospective cohort study

Abstract Study question Is hysteroscopic wedge septectomy (HWS) an effective and safe method for reducing the risk of miscarriage and improving the reproductive outcome in patients with recurrent pregnancy loss or infertility history? Summary answer HWS is a safe and effective method for RPL and infertility cases with statistically significant improvement in pregnancy chances and reproductive outcomes. What is known already With regard to the persisting uncertainty around the effectiveness of septum resection in recurrent miscarriage and infertility cases, there may be alternative methods to better address the pathophysiology of septum. There are different explanations for the poor reproductive performance with uterine septum: poor vascularisation of a highly fibrous implantation site, low sensitivity of endometrial receptors covering the septa, its “myoma-like” composition, and finally higher uterine vascular resistance. Complete removal of this abnormal tissue rather than just incising it may not only enhance challenging the pathogenesis but also expand the endometrial volume, an objective parameter by which to predict endometrial receptivity. Study design, size, duration In this retrospective cohort study, 214 consecutive patients, aged 33.3±4.8, diagnosed with a septate uterus based on ESHRE classification who had been under HWS between April 2017 and January 2020 due to recurrent miscarriage or at least one failed embryo transfer, met the enrollment criteria. With 11 to 36 months follow up, gathering of follow up data was managed between August till the end of Nov 2020, when the last new information was included. Participants/materials, setting, methods Patients with a history of RPL or at least one failed ET who were diagnosed as septate uterus by 2D, 3D, or hysteroscopy have been under HWS in a tertiary infertility and recurrent abortion treatment/educational setting. Those with BMI≥32, day 3 FSH≥13 mIU/mL, acquired or hereditary thrombophilia, thyroid disease, and myomatous uterus were excluded. HWS’s goal was to remove the septum as a wedge, cutting with 7Fr scissors, in its entirety as much as possible. Main results and the role of chance 39 patients who experienced 1 to 8 failed ET and 175 with 2 to 10 miscarriages, were enrolled in the study. The average septum size based on the depth of the removed wedge was 1.73±0.86 cm. There was an increase of 1.68±0.9 cm in uterine depth and 2.28±0.6 ml in uterine capacity measured by uterine sound and inflation of 8F Folley catheter balloon inside the cavity, respectively. The procedure took 35.75±8.7 minutes. Intraoperative, postoperative, or late complications during the next pregnancies were not reported. 7 patients (17.9%) in failed ET group, conceived spontaneously, before another embryo transfer attempt. Embryo transfer in the remaining 32 cases resulted in 25 (78.1%) clinical pregnancies. 2 miscarried (6.2%), 5(15.6%) are ongoing after 20 weeks of gestation and 25 (78.1%) have resulted in live births. Among 126 clinical pregnancies in RPL group, 16 patients (12.6%) experienced another miscarriage; 6%, 11.3%, and 25% in patients with a previous history of 2, 3, and 4 or more miscarriages, respectively. There was a significant drop in odds of post-procedure miscarriage from 22.7% to 6% (p:0.005) and from 27.8% to 11.3% (p:0.27) with 2 and 3 miscarriage history, respectively. This reduction was not significant with more than 3 losses. Limitations, reasons for caution We acknowledge the inherent limitations of this retrospective observational study, confining direct inferences. Our goal is to encourage future prospective studies to compare the effectiveness of different methods of hysteroscopy with or without involving the removal of septal tissue. An RCT comparing metroplasty vs expectant management seems infeasible, though. Wider implications of the findings Our findings suggest that timely removal of the uterine septal tissue with hysteroscopy will result in favorable reproductive outcomes in patients with RPL and/or infertility. Also, a history of a normal term pregnancy before subsequent successive losses does not rule out the uterine septum and calls for a thorough assessment. Trial registration number not applicable

P–408 Inadequate increase in Tim–3 on peripheral NK cells after blastocyst transfer is associated with early miscarriage

Abstract Study question Whether the changing peripheral levels of Tim–3/Galectin–9 (Gal–9) and PD–1/PL–1 over 4 weeks after ET in ongoing pregnancies is different from pregnancies destined to miscarry. Summary answer A significant and sustained increase of Tim–3 in pNK cells was observed in pregnancies which were ongoing but not in pregnancies which later miscarried. What is known already The importance of maternal immune adaptation and tolerance to the implanting embryo, an allograft, has been extensively investigated for decades. Immune checkpoint molecules, like T-cell immunoglobulin mucin–3 (Tim–3) and programed cell death–1 (PD–1), are co-stimulatory receptors negatively regulating immune responses. During pregnancy, Tim–3 and PD–1 are expressed by several immune cells in the decidua and participate in the maternal-fetal immune interactions to mediate maternal immune tolerance through binding to their ligands Gal–9 and progressed death-ligand 1 (PD-L1) produced by trophoblast and immune cells. In addition to the implantation site, Tim–3 and PD–1 expressions in peripheral lymphocytes are modified during pregnancy. Study design, size, duration A prospective observational study includes 81 women who achieved ongoing pregnancy and 17 women who suffered from miscarriage after single day–5 blastocyst transfer. All the subjects were recruited from November 2018 to January 2020 in a university teaching hospital. Participants/materials, setting, methods Women undergoing single blastocyst transfer after in-vitro-fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment were recruited on the day of ET following informed, written consent. They had serial blood samples taken on the day of ET, and 4, 5, 6 and 7 weeks of gestation for measurement of (1) membranous Tim–3 and PD–1 expression on various peripheral lymphocytes by flow cytometry; and (2) serum concentrations of ligands Gal–9 and PD-L1 by ELISA. Main results and the role of chance The comparisons between two groups showed there was no significant difference between the 2 groups in baseline levels among all the parameters measured. In women who achieved ongoing pregnancy, a significant and sustained increase of Tim–3 in either peripheral NK (pNK) subsets was observed at 4-week, 5-week, 6-week and 7-week gestations compared to the baseline (Tim–3+CD56dimNK 39.14±1.51%, 41.14±1.62%, 41.34±1.94%, and 41.69±2.12% vs. 30.27±1.49%; Tim–3+CD56brihgtNK cells, 24.54±1.71%, 25.43±1.54%, 27.26±1.88% and 24.70±1.64% vs. 19.08±1.13%), and the concentration of serum PD-L1 was significantly increased at 6-week and 7-week gestations (48.33±17.78 pg/ml, 52.53±20.60 pg/ml) when compared to the day of blastocyst transfer (41.40±16.01 pg/ml). The expressions of Tim–3 in T, NKT cells and PD–1 in NK, T, NKT cells were not significantly changed across the 5 time points. In women who conceived but later miscarried, all the parameters examined from 4–7 weeks of gestation were not significantly different when compared with the baseline measurement. The only measurement which showed a significant difference between the 2 groups and across all time points after ET was the proportion of Tim–3+CD56dimNK cells which was significantly higher in women who achieved ongoing pregnancies compared with women who destined to miscarry from 4 to 7 weeks of gestation. Limitations, reasons for caution It is uncertain if the observation would be different between miscarriage associated with aneuploid embryo or euploid embryo as we had not been able to obtain karyotyping result in most of the miscarriage cases. Wider implications of the findings: Our preliminary observation suggests that the proportion of Tim–3+pNK cells as early as 4-week gestation could be a potential immuno-bio-marker to predict if a pregnancy is likely to progress normally or result in a miscarriage. Clearly, the finding in this study needs to be confirmed in a larger cohort study Trial registration number not applicable.

Iodine and thyroid status during pregnancy and risk of stillbirth: A population-based nested case-control study.

Prior research suggests that severe iodine deficiency in pregnancy may be associated with stillbirth. However, the relationship between mild to moderate iodine insufficiency, which is prevalent even in developed countries, and risk of stillbirth is unclear. We thus examined associations of iodine status and risk of stillbirth in a prospective population‐based nested case–control study in Finland, a mild to moderately iodine insufficient population. Stillbirth cases (n = 199) and unaffected controls (n = 249) were randomly selected from among all singleton births in Finland from 2012 to 2013. Serum samples were collected between 10 and 14 weeks gestation and analysed for iodide, thyroglobulin (Tg) and thyroid‐stimulating hormone (TSH). Odds ratios (ORs) and 95% confidence intervals (CIs) for stillbirth were estimated using logistic regression. After adjusting for maternal age, prepregnancy body mass index, socio‐economic status and other factors, neither high nor low serum iodide was associated with risk of stillbirth (Q1 vs. Q2–Q3 OR = 0.92, 95% CI = 0.78–1.09; Q4 vs. Q2–Q3 OR = 0.78; 95% CI = 0.45–1.33). Tg and TSH were also not associated with risk of stillbirth in adjusted models. Maternal iodine status was not associated with stillbirth risk in this mildly to moderately iodine‐deficient population. Tg and TSH, which reflect functional iodine status, were also not associated with stillbirth risk. The lack of associations observed between serum iodide, TSH and Tg and risk of stillbirth is reassuring, given that iodine deficiency in pregnancy is prevalent in developed countries.

Associations between the exposure to organophosphate flame retardants during early pregnancy and the risk of spontaneous abortion based on metabolomics combined with tandem mass spectrometry.

BackgroundAs potential substitutes for polybrominated diphenyl ethers (PBDEs), organophosphate flame retardants (OPFRs) have been frequently detected in the environment. They have been suggested to impair fetal growth and development in toxicological studies. However, there are few studies on their maternal effects before or during early pregnancy.MethodsThis study was designed to investigate whether exposure to OPFRs before or during early pregnancy is associated with the risk of spontaneous abortion (SAB), using a nested case-control design based on the case data from clinical examinations in Shanghai, China. A total of 110 cases from this cohort project in 2019–2020 were included. The concentrations of OPFRs in maternal urine samples collected in early pregnancy were determined using Ultra high performance liquid chromatography- triple quadrupole mass spectrometer (UHPLC-MS/MS), and pregnancy outcomes were extracted from the medical records. Meanwhile, ultra high performance liquid chromatography time-of-flight mass spectrometer (UHPLC-Q-TOF/MS)-based metabonomics was used to obtain urine metabolic profiles of 110 women in early pregnancy.ResultsAccording to the quantitative results, the content of bis(1-chloro-2-propyl)phosphate (BCIPP) in urine was significantly different between the SAB patients and the healthy pregnant women. Besides, metabolic profile analysis showed a significant difference in the urine metabolism profile in early pregnancy between SAB cases and controls. Twenty-five different metabolites were screened out, which showed different degrees of correlation with the urinary BCIPP concentration.ConclusionsBased on these results, it suggests that there may be a certain correlation between BCIPP concentration in the urine and the risk of SAB from a metabolomics perspective, and its effect may be related to the metabolism of tryptophan and fatty acids.

Evaluation of the role of CD56 cells in unexplained recurrent spontaneous abortion

Objective: To determine whether peripheral natural killer (NK) cells play a role in recurrent miscarriage by evaluating the percentage of these cells using flow cytometry and comparing it with the percentages in normal multiparous women and women who experienced miscarriage only once. Methods: This case-control study was carried out on a total of 108 women. The study participants consisted of two groups of cases: unexplained recurrent miscarriage cases (n=36) and explained recurrent miscarriage cases (n=36). Additionally, a control group of normal multiparous women or women with only one previous miscarriage (n=36) was included. Detailed clinical assessments, laboratory investigations, and flow cytometry analysis were conducted to collect relevant data. Flow cytometry was used to determine the percentage of CD56+ NK cells in peripheral blood samples. Results: The mean age of the participants ranged from 26.72 to 28.33 years, with no significant difference among the three groups. Parity showed a statistically significant difference, with a higher proportion of nulliparous women in the unexplained abortion group. The number of previous abortions did not differ significantly between the unexplained and explained groups. Among the causes of abortion, endocrine and immunological factors were prominent.

Preventable stillbirths in India and Pakistan: a prospective, observational study.

Stillbirths occur 10-20 times more frequently in low-income settings compared with high-income settings. We created a methodology to define the proportion of stillbirths that are potentially preventable in low-income settings and applied it to stillbirths in sites in India and Pakistan. Prospective observational study. Three maternity hospitals in Davangere, India and a large public hospital in Karachi, Pakistan. All cases of stillbirth at ≥20weeks of gestation occurring from July 2018 to February 2020 were screened for participation; 872 stillbirths were included in this analysis. We prospectively defined the conditions and gestational ages that defined the stillbirth cases considered potentially preventable. Informed consent was sought from the parent(s) once the stillbirth was identified, either before or soon after delivery. All information available, including obstetric and medical history, clinical course, fetal heart sounds on admission, the presence of maceration as well as examination of the stillbirth after delivery, histology, and polymerase chain reaction for infectious pathogens of the placenta and various fetal tissues, was used to assess whether a stillbirth was potentially preventable. Whether a stillbirth was determined to be potentially preventable and the criteria for assignment to those categories. Of 984 enrolled, 872 stillbirths at ≥20weeks of gestation met the inclusion criteria and were included; of these, 55.5% were deemed to be potentially preventable. Of the 649 stillbirths at ≥28weeks of gestation and ≥1000g birthweight, 73.5% were considered potentially preventable. The most common conditions associated with a potentially preventable stillbirth at ≥28weeks of gestation and ≥1000g birthweight were small for gestational age (SGA) (52.8%), maternal hypertension (50.2%), antepartum haemorrhage (31.4%) and death that occurred after hospital admission (15.7%). Most stillbirths in these sites were deemed preventable and were often associated with maternal hypertension, antepartum haemorrhage, SGA and intrapartum demise. Most stillbirths are preventable by better care for women with hypertension, growth restriction and antepartum haemorrhage.

Anti-hypertensive use for non-severe gestational hypertension in Botswana: A case-control study.

The fetal risks and benefits of antihypertensives to treat gestational hypertension in pregnancy are understudied, particularly in low- and middle-income countries. We performed a nested case-control study within a retrospective cohort of obstetrical patients in Botswana from 2014 to 2019. We included women carrying singletons who developed new onset non-severe hypertension (140-159mmHg systolic or 90-109mmHg diastolic blood pressure) after 20weeks of pregnancy. Cases were defined as women with either small-for-gestational-age (SGA) infants or stillbirth, analyzed separately; controls were otherwise similar women without the adverse outcome in each analysis. We identified 1932 cases of SGA (7925 controls) and 316 cases of stillbirth (9619 controls). Cases with SGA were more likely to have used an anti-hypertensive than controls (33% vs 29%, adjusted odds ratio [aOR] 1.28, 95% confidence interval [CI] 1.15-1.43). Cases with stillbirth were more likely to have used an anti-hypertensive than controls (42% versus 29%, aOR 1.45, 95% CI 1.14-1.83). Anti-hypertensive use for new-onset gestational hypertension was associated with an increased risk of having an SGA infant or a stillbirth among women who never developed severe hypertension. These data support conduct of a randomized clinical trial to determine the appropriate use of anti-hypertensives in non-severe gestational hypertension.

Non-lethal Raine Syndrome Report Lacking Characteristic Clinical Features

Raine syndrome is a rare, often lethal autosomal recessive condition marked by congenital malformations that range in severity. Considering that several case reports of this syndrome describe cases of stillbirth or perinatal death, information about the clinical presentation and development of this condition in mild, non-lethal cases is lacking. With that in mind, in this case report, we describe the clinical, oro-dental, and skeletal findings of a 14-year-old Brazilian patient diagnosed with a mild form of non-lethal Raine syndrome. This patient has very mild facial dysmorphia, not displaying hypoplastic nose, micrognathia, low set ears or depressed nasal bridge, which is uncommon even in other mild, non-lethal cases of RS. Furthermore, this patient has bilateral brain calcifications and a series of oro-dental abnormalities, such as amelogenesis imperfecta and recurrent periodontal abcesses. Sanger sequencing of genomic DNA identified a homozygous missense variant c.1487C > T at exon 9 of FAM20C (NM_020223.4) in the patient. The patient's mother carries the same variant but is heterozygous. This variant predicts a proline to leucine substitution in position 496 (p.P496L, NP_064608.2) previously reported, which allows for the phenotypic comparison between these cases. This way, this case report calls attention to how differently RS can appear, highlighting the importance of new non-lethal Raine syndrome case reports to help further determine the phenotypic spectrum of this condition.

Pregnancy Outcomes With COVID-19 Lessons Learned From the Pandemic.

BackgroundSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that causes Coronavirus disease has caused one of the most damaging pandemics in the recorded human history.ObjectiveTo assess pregnancy outcomes with COVID-19 lessons learned from the pandemic.Study designThis retrospective observational study was conducted at Teerthanker Mahaveer Medical College and Research Centre, Moradabad, a level 3 COVID hospital in Northern India, with a patient pool of all the antenatal females diagnosed COVID 19 positive via a positive quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) test of maternal pharyngeal and nasal swab samples in the given time period of three months and ten days, i.e., May 25, 2020 to September 3, 2020. In conjunction with maternal outcomes, neonatal outcomes including evidence of perinatal transmission of SARS-CoV-2 was assessed by testing neonatal pharyngeal swab samples.ResultsOut of 100 COVID-19 positive patients, the average age of women was 26.2 years, 73 women (73%) were asymptomatic, and 50 patients (50%) women had associated co-morbidities such as anaemia in 38 (38%) women, gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) in four patients (4%) each, respectively. No case of spontaneous abortion in early gestation was reported. Out of 100 patients, 32 (32%) patients delivered during their stay, out of which 17 women (53.1%) delivered via cesarean section which was performed mainly due to obstetric indications. One maternal death was reported due to antepartum eclampsia which was unrelated to COVID-19 complications. Five neonates were born prematurely, out of which three were delivered followed by spontaneous premature preterm rupture of membranes (PPROM).The Appearance Pulse Grimace Activity Respiration (APGAR) score was recorded to be ≥9 at the five minutes mark in 28 out of 30 live babies (93.3%) and the birth weight of the babies ranged from 1.8 to 3.5 kg) with an average birth weight of 2.71 kg. Two neonatal deaths were reported due to respiratory distress. There were two documented intrauterine demise (IUD) cases both due to PIH. Furthermore, all 30 live neonates tested for SARS CoV-2 had negative results.ConclusionThe spectrum of Coronavirus infection leans more towards asymptomatic and mild symptomatic clinical presentation. Favourably, the likelihood of spontaneous preterm birth was not escalated in our current study and remained low. The rate of intrauterine fetal demise and neonatal death were less. As none of the neonates tested positive for COVID-19, there is no corroborative proof of vertical perinatal transmission.

Maternal PM2.5 exposure associated with stillbirth: A large birth cohort study in seven Chinese cities

Maternal exposure to fine particulate matter (PM2.5) has been associated with a few adverse birth outcomes. However, its effect on stillbirth remains unknown in China, especially the susceptible windows and potential modifiers. This study aimed to evaluate the associations between maternal PM2.5 exposure and stillbirth in seven Chinese cities. We used birth cohort data of 1,273,924 mother-and-birth pairs in seven cities in southern China between 2014 and 2017 to examine these associations. Pregnant women were recruited in the cohort at their first visit to a doctor for pregnancy, and stillbirths were recorded at the time of birth. Air pollution exposures were assessed through linking daily air pollutant concentrations from nearby monitoring stations to the mother's residential community. Cox regression models were applied to determine the associations between PM2.5 and stillbirth for different gestational periods. Among the participants, 3150 (2.47‰) were identified as stillbirth cases. The hazard ratio (HR) of stillbirths was 1.52 (95% CI: 1.42, 1.62) for each 10μg/m3 increase in PM2.5 during the entire pregnancy after controlling for some important covariates. Relatively stronger associations were observed during the second trimester [adjusted HR=1.67 (95% CI: 1.57, 1.77)] than trimesters 1 [HR=1.44 (95% CI: 1.37, 1.52)] and trimester 3 [HR=1.23 (95% CI: 1.16, 1.30)]. Stratified analyses also showed a stronger association among pregnant women without previous pregnancy and previous delivery experiences. The study indicates that maternal exposure to PM2.5, especially during the midpoint period of pregnancy, might increase the risk of stillbirths. Maternal previous pregnancy and delivery may modify this association.

Fetoscopic compared with open repair of myelomeningocele: a 2-delivery cost-effectiveness analysis

Recent studies have compared maternal and neonatal outcomes associated with fetoscopic surgical approach for repair of myelomeningocele compared with an open approach. In this study, we compared the cost-effectiveness of these techniques in the setting of a woman seeking future pregnancies. A decision-analytical model using TreeAge software was designed to compare the costs and outcomes of fetoscopic vs open repair in patients with prenatally diagnosed myelomeningocele. We assumed a theoretical cohort of 500 women with a pregnancy affected by myelomeningocele planning to have a future pregnancy. Our model accounted for costs and quality-adjusted life years of the woman, the neonate with myelomeningocele, and the neonate in a subsequent pregnancy. Neonatal outcomes from the incident pregnancy included motor function >2 levels better than the anatomic level, motor function <2 levels better than the anatomic level, and same motor function as the anatomic level, preterm birth in the index pregnancy, neonatal death in the index pregnancy, and major neurodevelopmental disability as a result of preterm birth in the index pregnancy. Neonatal outcomes in the subsequent pregnancy included stillbirth, preterm birth, and neonatal and major neurodevelopmental disability as a result of preterm birth. Probabilities were derived from the literature, and we used a willingness-to-pay threshold of $100,000 per quality-adjusted life year. In the index pregnancy, fetoscopic surgical technique resulted in 140 fewer cases of preterm birth and fewer cases of neurodevelopmental disability and neonatal death. Fetoscopic technique resulted in 130 more cases of functional level >2 levels better than the anatomic level, 35 fewer cases of functional level >2 levels worse than the anatomic level, and 107 fewer cases of function same as the anatomic level. In the subsequent pregnancy, fetoscopic surgery led to 22 fewer cases of delivery complications (uterine dehiscence, uterine rupture, and excessive bleeding), 24 fewer cases of stillbirth, and 22 fewer cases of preterm birth. Although the fetoscopic approach was more costly, it was cost-effective with an incremental cost-effectiveness ratio of $1029 per quality-adjusted life year in our theoretical cohort of 500 patients. Monte Carlo probabilistic sensitivity analysis showed that fetoscopic technique is cost-effective 100% of the time. In our theoretical cohort, the fetoscopic approach was more costly, but resulted in improved outcomes when a subsequent pregnancy was considered.