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

OBJECTIVE: To identify prenatal predictors of poor perinatal outcome in fetuses with isolated sacrococcygeal teratoma (SCT). METHODS: 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. RESULTS: 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%. CONCLUSIONS: 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.

Intrauterine Fetal Demise, Spontaneous Abortion and Congenital Cytomegalovirus: A Systematic Review of the Incidence and Histopathologic Features.

The objective was to review the existing literature reporting on spontaneous abortion (SA) and intrauterine fetal demise (IUFD) associated with cytomegalovirus (CMV) infection. A review using standardized terminology such as 'intrauterine fetal death', 'congenital cytomegalovirus' and 'CMV' was performed using PubMed and Embase (Medline) using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Twenty-one studies met inclusion criteria. CMV was identified as a potential or likely factor in a median of 7.1% of SA or IUFD in study cohorts. Of the studies, 11 used fetal remains, 18 used placenta, 6 used serum, and 1 used post-mortem dried blood spot as specimens for testing for CMV. Features commonly observed were fetal thrombotic vasculopathy, hydrops fetalis and chronic villitis. CMV is frequently noted in studies evaluating viral etiologies of SA or IUFD. Large population-based studies are needed to estimate the incidence of CMV-associated SA or IUFD. CMV and congenital CMV should be included on the differential diagnosis in all cases of SA or IUFD of unknown etiology.

[Group A-streptococcal infection during pregnancy]. / Groep A-streptokokkeninfectie tijdens de zwangerschap.

Group A-streptococcal (GAS) infection can lead to various clinical presentations and is fulminant when it reaches the deep tissues, leading to a high morbidity and mortality. The severity of postpartum GAS infections is widely known. In this case report we describe the course of disease in a pregnant patient with GAS toxic shock syndrome with initial complaints of abdominal pain, diarrhea and fetal demise at first presentation. Within 10 hours this patient died. It is important to stay vigilant for a fulminant GAS infection in pregnant patients, to recognize it quickly and treat it adequately.

Temporal trend in fetal mortality according to two death avoidability classifications.

OBJECTIVE: To analyze the temporal trend of fetal mortality and its components, of avoidable and ill-defined causes according to two avoidability classifications in Recife, Pernambuco, 2010-2021. METHOD: Ecological study of temporal trends of fetal mortality in Recife, 2010-2021. The Brazilian List of Avoidable Causes of Death for fetal deaths (LBE-OF) and Brazilian List of Avoidable Causes of Death for children under five years of age (LBE < 5) were used. The Joinpoint regression model was applied to analyze the temporal trends. RESULTS: Trends in fetal mortality and its components were stationary. The group of avoidable causes presented higher mortality rates in both classifications, with an increasing trend according to the LBE-OF (Annual Percentage Change-APC: 2,1; p = 0,018) and stationary according to the LBE < 5. There was a decreasing trend in mortality from ill-defined causes only according to the LBE-OF (APC: -12,3; p < 0,001). CONCLUSION: The results showed the stagnation of the temporal trend in fetal mortality, the avoidability of most deaths, and the potential of LBE-OF in monitoring the quality of information on the basic causes and avoidability of fetal deaths.

[Fetal death: Expert consensus from the College of French Gynecologists and Obstetricians]. / Mort fœtale : consensus formalisé d'experts du Collège national des gynécologues et obstétriciens français.

Fetal death is defined as the spontaneous cessation of cardiac activity after fourteen weeks of amenorrhea. In France, the prevalence of fetal death after 22 weeks is between 3.2 and 4.4/1000 births. Regarding the prevention of fetal death in the general population, it is not recommended to counsel for rest and not to prescribe vitamin A, vitamin D nor micronutrient supplementation for the sole purpose of reducing the risk of fetal death (Weak recommendations; Low quality of evidence). It is not recommended to prescribe aspirin (Weak recommendation; Very low quality of evidence). It is recommended to offer vaccination against influenza in epidemic periods and against SARS-CoV-2 (Strong recommendations; Low quality of evidence). It is not recommended to systematically look for nuchal cord encirclements during prenatal screening ultrasounds (Strong Recommendation; Low Quality of Evidence) and not to perform systematic antepartum monitoring by cardiotocography (Weak Recommendation; Very Low Quality of Evidence). It is not recommended to ask women to perform an active fetal movement count to reduce the risk of fetal death (Strong Recommendation; High Quality of Evidence). Regarding evaluation in the event of fetal death, it is suggested that an external fetal examination be systematically offered (Expert opinion). It is recommended that a fetopathological and anatomopathological examination of the placenta be carried out to participate in cause identification (Strong Recommendation. Moderate quality of evidence). It is recommended that chromosomal analysis by microarray testing be performed rather than conventional karyotype, in order to be able to identify a potentially causal anomaly more frequently (Strong Recommendation, moderate quality of evidence); to this end, it is suggested that postnatal sampling of the placental fetal surface for genetic purposes be preferred (Expert Opinion). It is suggested to test for antiphospholipid antibodies and systematically perform a Kleihauer test and a test for irregular agglutinins (Expert opinion). It is suggested to offer a summary consultation, with the aim of assessing the physical and psychological status of the parents, reporting the results, discussing the cause and providing information on monitoring for a subsequent pregnancy (Expert opinion). Regarding announcement and support, it is suggested to announce fetal death without ambiguity, using simple words and adapting to each situation, and then to support couples with empathy in the various stages of their care (Expert opinion). Regarding management, it is suggested that, in the absence of a situation at risk of disseminated intravascular coagulation or maternal vitality, the patient's wishes should be taken into account when determining the time between the diagnosis of fetal death and induction of birth. Returning home is possible if it's the patient wish (Expert opinion). In all situations excluding maternal life-threatening emergencies, the preferred mode of delivery is vaginal delivery, regardless the history of cesarean section(s) history (Expert opinion). In the event of fetal death, it is recommended that mifepristone 200mg be prescribed at least 24hours before induction, to reduce the delay between induction and delivery (Low recommendation. Low quality of evidence). There are insufficient data in the literature to make a recommendation regarding the route of administration (vaginal or oral) of misoprostol, neither the type of prostaglandin to reduce induction-delivery time or maternal morbidity. It is suggested that perimedullary analgesia be introduced at the start of induction if the patient asks, regardless of gestational age. It is suggested to prescribe cabergoline immediately in the postpartum period in order to avoid lactation, whatever the gestational age, after discussing the side effects of the treatment with the patient (Expert opinion). The risk of recurrence of fetal death after unexplained fetal death does not appear to be increased in subsequent pregnancies, and data from the literature are insufficient to make a recommendation on the prescription of aspirin. In the event of a history of fetal death due to vascular issues, low-dose aspirin is recommended to reduce perinatal morbidity, and should not be combined with heparin therapy (Low recommendation, very low quality of evidence). It is suggested not to recommend an optimal delay before initiating another pregnancy just because of the history of fetal death. It is suggested that the woman and co-parent be informed of the possibility of psychological support. Fetal heart rate monitoring is not indicated solely because of a history of fetal death. It is suggested that delivery not be systematically induced. However, induction can be considered depending on the context and parental request. The gestational age will be discussed, taking into account the benefits and risks, especially before 39 weeks. If a cause of fetal death is identified, management will be adapted on a case-by-case basis (expert opinion). In the event of fetal death occurring in a twin pregnancy, it is suggested that the surviving twin be evaluated as soon as the diagnosis of fetal death is made. In the case of dichorionic pregnancy, it is suggested to offer ultrasound monitoring on a monthly basis. It is suggested not to deliver prematurely following fetal death of a twin. If fetal death occurs in a monochorionic twin pregnancy, it is suggested to contact the referral competence center, in order to urgently look for signs of acute fetal anemia on ultrasound in the surviving twin, and to carry out weekly ultrasound monitoring for the first month. It is suggested not to induce birth immediately.

The pregnancy rescue case versus typical abortion.

Hendricks' pregnancy rescue case (PRC) tries to show that abortion is typically morally wrong. I argue here that there are at least two morally relevant differences between the abortion in PRC and the typical abortion so that the latter isn't morally wrong even if the former is morally wrong. I develop five modifications to PRC to show that these two differences are morally important. First, in PRC we don't know whether the person gives informed consent to the abortion, nor does the medical professional who will perform the abortion, and so the abortion can't be performed because the patient gives informed consent to it. Second, not preventing the death of the fetus in PRC brings about the death of an additional fetus gestating in a separate pregnant person, whereas most abortions don't entail the termination of another's pregnancy.

Fetal and neonatal post-mortem imaging referral template: recommendations from the European Society of Paediatric Radiology Post-mortem Task Force.

BACKGROUND: In post-mortem (PM) fetal and neonatal imaging, relevant clinical information is crucial for accurate interpretation and diagnosis; however, it is usually incomplete. OBJECTIVE: To propose a standardized template for PM fetal and neonatal imaging referrals to enhance communication between referring clinicians and reporting radiologists. MATERIALS AND METHODS: A modified Delphi approach was conducted amongst members of the European Society of Paediatric Radiology (ESPR) PM Task Force and other recommended PM imaging specialists worldwide to determine consensus on necessary information. These were based on three pre-existing referral templates already in use across a variety of centers. The study ran for 4 months (December 2023-April 2024). RESULTS: Nineteen specialists from 17 centers worldwide formed our expert panel. The final agreed referral template information includes the patient's identification details (mother and fetus when available), fetal/neonatal information (gestational age, sex, type of demise (including type of termination of pregnancy (i.e., surgical or medical)), date and time of fetal demise (+ delivery) or neonatal death, singleton/multiple pregnancy, clinical information (obstetrical history, prenatal imaging findings, amniocentesis findings, physical external examination findings), provisional clinical diagnosis, and ordering physician's information. CONCLUSION: A comprehensive referral template has been created, representing expert consensus on the minimum data required for the conduct of quality PM fetal and neonatal imaging, with the goal of facilitating accuracy of image interpretation.

A rare case of maternal foetal death caused by uterine rupture in the placenta accreta.

Background: Fetal death has various causes, among the most common are problems relating to the placenta, such as placental abruption or placental malformations such as placenta accreta. From the literature, it emerges that placental analysis at autopsy can allow for greater resolution of cases compared to clinical history and external examination of the fetus alone. Case Report: We report the case of a woman at the eleventh week of pregnancy who died in hospital. The medical history revealed two further previous pregnancies, both with births by cesarean section. The autopsy identified the cause of maternal death as acute cardiorespiratory arrest secondary to hemorrhagic shock from spontaneous uterine rupture. Hemorrhagic infiltrate was found in the intervillous placental spaces with rupture of the uterus due to placenta previa and accreta. Discussion: Placenta accreta is a condition in which a pathological adherence and/or invasion of the myometrium by the placenta is observed. This condition poses a problem during recovery with potential for severe bleeding. Therefore, we emphasize the macroscopic and histological analysis of the placenta, uterus and the ovaries in all cases of maternal-fetal death, suggesting however that the organs be analyzed both by gross analysis and after permanence in formaldehyde. Furthermore, in these cases, it is important to evaluate the clinical history and data, especially ultrasound scans performed in life, or insertion anomalies during instrumental investigations. For this reason, we recommend to collaborate with a multidisciplinary team in these cases, including the gynecologist and the forensic pathologist.

Sudden Intrauterine Unexplained Death (SIUD) and Oxidative Stress: Placental Immunohistochemical Markers.

BACKGROUND: Intrauterine fetal death and perinatal death represent one of the most relevant medical scientific problems since, in many cases, even after extensive investigation, the causes remain unknown. The considerable increase in medical legal litigation in the obstetrical field that has witnessed in recent years, especially in cases of stillborn births, has simultaneously involved the figure of the forensic pathologist in scientific research aimed at clarifying the pathophysiological processes underlying stillbirth. METHODS: our study aims to analyze cases of sudden intrauterine unexplained death syndrome (SIUD) to evaluate the role of oxidative stress in the complex pathogenetic process of stillbirth. In particular, the immunohistochemical expression of specific oxidative stress markers (NOX2, NT, iNOS, 8-HODG, IL-6) was evaluated in tissue samples of placentas of SIUDs belonging to the extensive case series (20 cases), collected from autopsy cases of the University of Ferrara and Politecnica delle Marche between 2017 and 2023. RESULTS: The study demonstrated the involvement of oxidative stress in intrauterine fetal deaths in the placenta of the cases examined. In SIUD, the most expressed oxidative stress markers were NOX2 and 8-HODG. CONCLUSIONS: The study contributes to investigating the role of oxidative stress in modulating different pathways in unexplained intrauterine fetal death (SIUD) tissues.

Maternal Morbidity following Trial of Labor after Cesarean in Women Experiencing Antepartum Fetal Death.

This study aims to investigate whether trial of labor after cesarean delivery (TOLAC) in women with antepartum fetal death, is associated with an elevated risk of maternal morbidity. A retrospective multicenter. TOLAC of singleton pregnancies following a single low-segment incision were included. Maternal adverse outcomes were compared between women with antepartum fetal death and women with a viable fetus. Controls were matched with cases in a 1:4 ratio based on their previous vaginal births and induction of labor rates. Univariate analysis was followed by multiple logistic regression modeling. During the study period, 181 women experienced antepartum fetal death and were matched with 724 women with viable fetuses. Univariate analysis revealed that women with antepartum fetal death had significantly lower rates of TOLAC failure (4.4% vs. 25.1%, p < 0.01), but similar rates of composite adverse maternal outcomes (6.1% vs. 8.0%, p = 0.38) and uterine rupture (0.6% vs. 0.3%, p = 0.56). Multivariable analyses controlling for confounders showed that an antepartum fetal death vs. live birth isn't associated with the composite adverse maternal outcomes (aOR 0.96, 95% CI 0.21-4.44, p = 0.95). TOLAC in women with antepartum fetal death is not associated with an increased risk of adverse maternal outcomes while showing high rates of successful vaginal birth after cesarean (VBAC).

Asymptomatic acute massive abruptio placenta at 30 weeks' gestation in a primigravida with no risk factors - clinical presentation and management.

Abruptio placenta can be a catastrophic event with a high association with adverse maternal and fetal outcomes. We present a case of massive abruptio placenta occurring in a young asymptomatic mother at 30 weeks' gestation. Although electronic fetal monitoring and ultrasound allowed a prompt diagnosis of an 8 × 5 cm retroplacental hematoma, the fetus died at the time of emergency cesarean section. The fetus was intubated, but could not be resuscitated. Histologic examination of the placenta documented thinning and stacked hypercapillarized villi, with syncytial buds and foci of fibrinoid necrosis in the presence of hyaline streaks on both the maternal and fetal sides.

Intrauterine fetal death due to rupture of umbilical vessels: a rare case of furcate cord insertion.

Furcate cord insertion refers to the separation of umbilical vessels before reaching the placenta, where the branching vessels normally attach at the edge of the placental parenchyma or near the placental membranes. This is an extremely rare abnormal umbilical cord insertion. This paper reported a case of a furcate cord insertion, where the rupture of exposed umbilical vessels led to intrauterine fetal death at full term. Through literature review, we analyzed the prenatal ultrasound characteristics and pregnancy outcomes of furcate cord insertions, with the aim to improve detection rates and reduce the risk of adverse pregnancy outcomes.

Female Mice Exposed to Pyriproxyfen Since Prepuberty Showed Reproductive Impairment During Sexual Maturity and Increased Fetal Death in Their Offspring.

Pyriproxyfen (PPF) is an insecticide used in agriculture, which is approved for use in drinking water tanks for human consumption. However, some studies indicate that it may act as an endocrine disruptor and affect nontarget organisms. This study aimed to evaluate the effects of PPF on reproduction and general health status in female mice exposed from pre-puberty to adulthood. In the first experiment, females were treated by gavage from postnatal day (PND) 23 to (PND) 75 and were distributed into three experimental groups: control (vehicle), PPF 0.1 mg/kg, and PPF 1 mg/kg. Female mice were assessed for the age of puberty onset, body mass, water and food consumption, and the estrous cycle. On PDN 75, a subgroup was euthanized, when vital and reproductive organs were collected and weighed. The thyroid, ovary, and uterus were evaluated for histomorphometry. The other subgroup was assessed in relation to reproductive performance and fetal parameters. In a second experiment, the uterotrophic assay was performed with juvenile females (PND 18) using doses of 0.01, 0.1, or 1 mg/kg of PPF. PPF treatment reduced thyroid mass and increased liver mass. Furthermore, there was an increase in ovarian interstitial tissue and, in the uterus, a decrease in the thickness of the endometrial stroma with reduced content of collagen fibers. There was also a reduction of 30% in pregnancy rate in the treated groups and an increase in the frequency of fetal death. This study suggests that, based on this experimental model, the insecticide may pose a reproductive risk for females chronically exposed to the substance from the pre-pubertal period until adulthood. These results raise concerns about prolonged exposure of women to the same compound.

Acute febrile illness in pregnancy: Spectrum of disease and impact on maternal and foetal outcome.

Acute febrile illness (AFI) in pregnancy is a neglected cause of maternal and foetal mortality and morbidity in low-and middle-income countries. This prospective cohort studied antenatal and postpartum women admitted with acute fever to a tertiary care university teaching hospital from July 2014 to March 2015 for aetiology, maternal and foetal complications, and the impact on maternal mortality ratio (MMR) and perinatal mortality rate. Among the 180 women admitted with AFI, urinary tract infection 54(30%) was the commonest cause, followed by airborne infections (67; 37.2%), peripartum or wound infections (25; 13.8%) and vector-borne diseases (21; 11.6%). Maternal deaths were 4 (2%) and foetal deaths 9 (5%). Post-operative gram-negative sepsis was the most common cause of maternal mortality. The MMR was ten times higher with AFI 2778 against 197 (p < 0.0001) among the other hospital deliveries during the same period. Screening for asymptomatic bacteriuria , maintaining aseptic precautions, and vaccination may impact maternal and foetal morbidity significantly.

Stillbirth in women with Type 1 Diabetes mellitus-still a current topic.

PURPOSE: Compared to the general stillbirth rate in Germany for term deliveries of 0.12% the risk in type 1 diabetes mellitus is reported to be up to ten times higher. The reasons for this excess risk of intrauterine demise are still not fully elucidated. Risk factors named in the literature include poor glycemic control before and during pregnancy and the occurrence of ketoacidosis. Additionally there might be a diabetes related type of placental dysfunction leading to organ failure in late pregnancy. Understanding the underlying causes is mandatory to develop strategies to reduce the incidences. The Purpose of this publication is to point out the difficulties in prediction of intrauterine death in pregnant type 1 diabetes patients and thus emphasizing the necessity of constant awareness to all caregivers. METHODS: We present a case series of four cases of stillbirth that occurred in patients with type 1 diabetes mellitus at our tertiary care obstetric unit during a five-year period. RESULTS: In all four presented cases the underlying cause of intrauterine demise was different and we could not find a common mechanism or risk profile. Furthermore, established monitoring tools did not become peculiar to raise awareness. We compared our cases to published data. Underlying causes of intrauterine death in type 1 diabetes are discussed in the light of the current literature. CONCLUSIONS: The main risk factors of stillbirth in diabetic pregnancies are high maternal blood glucose levels including pre-conceptional HbA1c and diabetic ketoacidosis. Late acute placental insufficiency are associated with intrauterine death in type 1 diabetes. Despite the elevated risk of near term intrauterine demise there are currently no guidelines on how to monitor pregnancies in type 1 diabetes for fetal distress during the third trimester. Established thresholds for fetal Doppler data indicating fetal distress in normal and growth restricted fetuses may not be applicable for overgrown fetuses. Future research on how to monitor the diabetic fetus needs to be initiated.

Criteria and non-criteria antiphospholipid autoantibodies screening in patients with late pregnancy morbidity: A cross-sectional study.

INTRODUCTION: Antiphospholipid syndrome (APS) is a cause of pregnancy morbidity. We aim to determine the frequency of criteria and non-criteria anti-phospholipid (aPL) autoantibodies in patients admitted for unexplained fetal death (UFD), pre-eclampsia (PE) and/or fetal growth restriction (FGR). METHODS: All consecutive patients with UFD, PE and/or FGR followed in the department of Obstetrics, Bichat Hospital, University of Paris, Paris, between January 2019 and December 2021 were screened. Patients with available serum stored from the index pregnancy were included. Patients with previously known APS or twin pregnancy were excluded. Testing for aPL autoantibodies included anti-cardiolipin (aCL), anti-ß2GPI (aß2GPI), anti-phosphatidylethanolamine (aPE), anti-phosphatidylserine/prothrombin (aPS/PT) IgG/IgM and anti-annexin V IgG. When available, placenta specimens were analyzed by a pathologist blinded to the aPL status. All clinical characteristics, pregnancy features, and comorbidities were extracted from electronic medical records. RESULTS: Overall 167 (32 (28.8-35.7) years) patients with UFD (n = 28; 16.8 %), PE (n = 60; 35.9 %) and/or FGR (n = 105; 62.9 %) were screened for aPL autoantibodies. Moderate titers of aPL autoantibodies were detected in 33 (n = 33/167, 19.8 %) patients. aPL autoantibodies were non-criteria aPE IgG/IgM in most cases (n = 28/33, 84.8 %). aPS/PT IgG/IgM were found in 11 (n = 11/33, 33.3 %) cases and aCL or aß2GP1 IgG/IgM in 4 (n = 4/33, 12.1 %). Multivariable logistic regression showed that aPL autoantibodies were mostly associated with UFD (OR 4.37 [1.72-11.20], p = 0.002), PE ≤ 34th week of gestation (3.22 [0.86-11.90], p = 0.070) and chronic deciduitis (8.03 [0.89-67.2], p = 0.060) DISCUSSION: The frequency of aPL autoantibodies, mostly aPE, is high in patients with late pregnancy morbidity and may qualify obstetrical APS.

Characteristics of unilateral and bilateral bovine twin foetuses.

Twin pregnancy in cattle is undesirable for a number of reasons, including a higher abortion risk compared to pregnancies with a single foetus. Yet, the abortion risk is significantly influenced by the intrauterine location of the foetuses, that is, the abortion risk is several times higher if they are implanted in the same uterine horn (unilateral twin pregnancy) than if they are implanted with one foetus in each uterine horn (bilateral twin pregnancy). The reason for the higher abortion risk in unilateral twin pregnancies is unknown, but it may be related to malnutrition of the outermost foetus due to a limited placental capacity, as is the case for equine twin foetuses. A slaughterhouse study was performed and the foetuses of cattle pregnant with twins were measured. We identified 65 cases of twin pregnancies, of which 35 were unilateral twin pregnancies and 30 were bilateral twin pregnancies. There was no significant difference between the outermost and the more centrally located foetus in unilateral twin pregnancies in terms of body weight and length of the metacarpal diaphysis. Growth retardation of the outermost foetus could therefore not be confirmed as the cause of the higher abortion risk in unilateral bovine twin pregnancies. Four cases of pre-slaughter foetal mortality were identified. In three of these cases, both twins were dead, of equal size and at a comparable level of degradation. In the fourth case, with approximately 40-day-old twin foetuses of equal size, only one of the foetuses showed signs of pre-slaughter death.

The association between maternal obesity and fetomaternal outcomes in twin pregnancies.

The prevalence of overweight and obese people worldwide has dramatically increased in the last decades and is yet to peak. At the same time and partly due to obesity and associated assisted reproduction, twinning rates showed a clear rise in the last years. Adverse fetomaternal outcomes are known to occur in singleton and twin pregnancies in overweight and obese women. However, the impact of the obesity levels as defined by the World Health Organization on the outcomes of twin pregnancies has not been thoroughly studied. Therefore, the purpose of this study is to examine how maternal overweight, and the level of obesity affect fetomaternal outcomes in twin pregnancies, hypothesizing a higher likelihood for adverse outcomes with overweight and each obesity level. This is a retrospective cohort study with 2,349 twin pregnancies that delivered at the Buergerhospital Frankfurt, Germany between 2005 and 2020. The mothers were divided into exposure groups depending on their pre-gestational body mass index; these were normal weight (reference group), overweight and obesity levels I, II, and III. A multivariate logistic regression analysis was performed to assess the influence of overweight and obesity on gestational diabetes mellitus, preeclampsia, postpartum hemorrhage, intrauterine fetal death, and a five-minutes Apgar score below seven. The adjusted odds ratio for gestational diabetes compared to normal weight mothers were 1.47, 2.79, 4.05, and 6.40 for overweight and obesity levels I, II and III respectively (p = 0.015 for overweight and p < 0.001 for each obesity level). Maternal BMI had a significant association with the risk of preeclampsia (OR 1.04, p = 0.028). Overweight and obesity did not affect the odds of postpartum hemorrhage, fetal demise, or a low Apgar score. While maternal overweight and obesity did not influence the fetal outcomes in twin pregnancies, they significantly increased the risk of gestational diabetes and preeclampsia, and that risk is incremental with increasing level of obesity.

Receipt of hepatitis E vaccine and fetal loss in rural Bangladesh: further analysis of a double-blind, cluster-randomised, controlled trial.

BACKGROUND: Vaccination constitutes an attractive control measure for hepatitis E virus (HEV), a major cause of maternal and perinatal mortality globally. Analysis of pregnant participants in an effectiveness trial of the HEV vaccine HEV239 showed possible HEV239-associated fetal losses. We aimed to conduct a detailed analysis of this safety signal. METHODS: In a double-blind, cluster-randomised trial, 67 villages in Matlab, Bangladesh, were randomly allocated (1:1) to two vaccine groups, in which non-pregnant women aged 16-39 years received either HEV239 (HEV239 group) or Hepa-B (a hepatitis B vaccine; control group). We implemented weekly surveillance for pregnancy detection, and follow-up of pregnancies once every 2 weeks, using physician-confirmed diagnoses to evaluate fetal loss outcomes (miscarriage [spontaneous abortion], stillbirth, and elective termination). Data from a parallel system of reproductive health surveillance in Matlab were used to clarify study diagnoses when necessary. Miscarriage was assessed only among participants whose first positive pregnancy test and vaccination date (for whichever dose was closest to the date of last menstrual period [LMP]) were before 20 weeks' gestation. We defined the following analysis periods of interest: from 90 days before the LMP until the pregnancy outcome (the proximal period); from the LMP date until the pregnancy outcome (the pregnancy period); from 90 days before the LMP until the LMP date (90 days pre-LMP period); and from enrolment until 90 days before the LMP (the distal period). Both Poisson and Cox regression models were used to assess the associations between receipt of HEV239 and fetal loss outcomes. The trial was registered with ClinicalTrials.gov (NCT02759991). FINDINGS: Among the 19 460 non-pregnant participants enrolled in the trial, 5011 were identified as having pregnancies within 2 years following vaccination and met the criteria for analysis (2407 in the HEV239 group and 2604 in the control group). Among participants vaccinated in the proximal period and evaluated for miscarriage, miscarriage occurred in 54 (8·9%) of 607 in the HEV239 group and 32 (4·5%) of 719 in the control group (adjusted relative risk [aRR] 2·0 [95% CI 1·3-3·1], p=0·0009). Similarly, the risk of miscarriages was increased in the HEV239 group versus the control group among participants inadvertently vaccinated during pregnancy (22 [10·5%] miscarriages among 209 participants in the HEV239 group vs 14 [5·3%] of 266 in the control group; aRR 2·1 [95% CI 1·1-4·1], p=0·036) and among those vaccinated within 90 days pre-LMP (32 [8·0%] of 398 vs 18 [4·0%] of 453; 1·9 [1·1-3·2], p=0·013). No increased risk of miscarriage was observed in those who received HEV239 in the distal period (93 [5·6%] of 1647 vs 80 [4·5%] of 1773; 1·3 [0·8-1·9], p=0·295). Stillbirth and elective termination showed no increased risk among women administered HEV239 versus those administered Hepa-B in any of the analysis periods. INTERPRETATION: HEV239 given shortly before or during pregnancy was associated with an elevated risk of miscarriage. This association poses a possible safety concern for programmatic use of HEV239 in women of childbearing age. FUNDING: Research Council of Norway and Innovax.

Fetal, neonatal, and infant death among offspring of pregnant women with HIV in Tanzania.

OBJECTIVE: Assess the risk of death for offspring of pregnant women with HIV (PWHIV) and the association with sociodemographic, pregnancy, HIV-related, and birth factors. DESIGN: We conducted a prospective cohort study of PWHIV on antiretroviral therapy (ART) and their offspring in urban Tanzania who were enrolled in a vitamin D trial conducted from June 2015 to October 2019. METHODS: We described rates of fetal, neonatal, and infant death and assessed risk factors for these outcomes with generalized estimating equations. We also estimated population-attributable risk percentages for the contribution of prematurity and small-for-gestational age (SGA) to neonatal and infant mortality. RESULTS: Among 2299 PWHIV, there were a total of 136 fetal deaths (5.6%) and the stillbirth rate was 42.0 per 1000 total births. Among 2167 livebirths, there were 57 neonatal deaths (26.3 per 1000 livebirths) and 114 infant deaths (52.6 per 1000 livebirths). Twin birth was associated with neonatal death, while maternal CD4 + T-cell count <350 cells/µl in pregnancy was associated with infant death ( P -values < 0.05). As compared to term-appropriate-for-gestational age (AGA) births, the relative risks for neonatal mortality for term-SGA, preterm-AGA, and preterm-SGA infants were 2.07 [95% confidence interval (CI): 1.00-4.28], 2.87 (95% CI 1.54-5.35), and 7.15 (95% CI: 2.11-24.30), respectively. We estimated that 42.7% of neonatal and 29.4% of infant deaths were attributable to prematurity and SGA in the cohort. CONCLUSIONS: The risk of death is high for offspring of PWHIV in Tanzania and the combination of prematurity and fetal growth restriction may account for nearly half of neonatal deaths.