Materiały źródłowe

• #1 Management of Stillbirth | ACOG

  https://www.acog.org/clinical/clinical-guidance/obstetric-care-consensus/articles/2020/03/management-of-stillbirth

  Stillbirth is one of the most common adverse pregnancy outcomes, occurring in 1 in 160 deliveries in the United States. […] The study of specific causes of stillbirth has been hampered by the lack of uniform protocols to evaluate and classify stillbirths and by decreasing autopsy rates. In any specific case, it may be difficult to assign a definite cause to a stillbirth. A significant proportion of stillbirths remains unexplained even after a thorough evaluation. Evaluation of a stillbirth should include fetal autopsy; gross and histologic examination of the placenta, umbilical cord, and membranes; and genetic evaluation. […] The method and timing of delivery after a stillbirth depend on the gestational age at which the death occurred, maternal obstetric history (eg, previous hysterotomy), and maternal preference. […] The study of specific causes of stillbirth has been hampered by the lack of uniform protocols to evaluate and classify stillbirths and by decreasing autopsy rates. […] A significant proportion of stillbirths remains unexplained even after a thorough evaluation.

• #1 Mechanisms of Death of Structurally Normal Stillbirths

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6349478/

  Hypoxia, secondary to placental dysfunction, was found to be the mechanism of death in the majority of fetal deaths of structurally normal fetuses. […] Ninety-one percent of hypoxic fetal deaths sustained brain, myocardial or both brain and myocardial injuries in utero. […] An attributable mechanism of death in 70% of the cases is circulatory failure and cardiac arrest secondary to hypoxic myocardial injury. […] A histopathological explanation for placental dysfunction was found in 74% of these cases.

• #1 Mechanisms of death in structurally normal stillbirths

  https://www.degruyterbrill.com/document/doi/10.1515/jpm-2018-0216/html?lang=en&srsltid=AfmBOoqe_EfZ9ZAa5w4WQ78wD48fVpO3S0SgaViQtgoqu3B22LmvuodE

  Hypoxia, secondary to placental dysfunction, was found to be the mechanism of death in the majority of fetal deaths among structurally normal fetuses. Ninety-one percent of hypoxic fetal deaths sustained brain, myocardial or both brain and myocardial injuries in utero. An attributable mechanism of death in 70% of the cases is circulatory failure and cardiac arrest secondary to hypoxic myocardial injury. […] The study indicated that 88% (53/60) of fetal deaths were hypoxic; that 91% (48/53) of hypoxic fetal deaths had sustained brain, myocardial or both brain and myocardial injuries in utero; and that circulatory failure and cardiac arrest, secondary to hypoxic myocardial damage, were the mechanisms of death in 70% (42/60) of cases. […] Hypoxia, secondary to placental dysfunction, is the mechanism of death in the majority of structurally normal fetuses after 20 weeks of gestation.

• #1 Chapter 5 Stillbirth & Asphyxia | obstetrical pathology

  https://obstetricalpathology.com/stillbirth-asphyxia/

  After all of the autopsy evidence on a stillborn infant is finally gathered, there may be a profound disappointment in that there is no answer. Nothing really explains the death of this normally formed, normally grown infant from an uncomplicated pregnancy. Still, there are clues, often subtle anatomic findings, that potentially tell us something about the mechanism of death. […] The first group is the equivalent of sudden acute asphyxia usually achieved experimentally by clamping the umbilical cord or the maternal uterine arteries. Fetal respiration comes to a sudden stop. […] A reasonable argument is that intrathoracic petechiae that are not in the context of shock with disseminated intravascular coagulation and diffuse petechiae, are evidence of gasping most likely in response to acute asphyxia. This is confirmed by the lack of such petechiae in the cases of partial separation that would be expected to become acidotic and apneic over a longer period of time. […] By exclusion, the most likely explanation of these deaths involves an occlusion of the fetal circulation most likely in the umbilical cord, although cardiac asystole is conceivable.

• #1

  https://journals.lww.com/ogopen/fulltext/2024/09000/addressing_barriers_to_autopsy_and_genetic_testing.7.aspx

  Placental pathology is the single most useful test in stillbirth workup, closely followed by fetal autopsy and genetic testing. Unfortunately, there are multiple barriers to pathology and genetic testing, leading to incomplete workups in most stillbirths in the United States. […] Most experts, including the American College of Obstetricians and Gynecologists, emphasize the importance of placental pathology and fetal autopsy in stillbirth workup. These two tests have the highest utility in determining cause of death. Placental pathology provided useful information in 65% of cases and fetal autopsy in 42% in the SCRN (Stillbirth Collaborative Research Network) study, a population-level assessment of 512 stillbirths. […] Genetic testing is a key part of stillbirth workup. An abnormal karyotype is found in 6-13% of stillbirths and more than 20% of stillbirths with structural anomalies. Chromosomal microarray (CMA) has increased yield over traditional karyotype in stillbirth, because CMA can be performed with direct DNA, whereas karyotype requires cultured cells.

• #1

  https://link.springer.com/article/10.1007/s00404-024-07522-1

  The study aimed to evaluate the causes of death and associated factors in cases of stillbirth, using post-mortem examination and applying a rigorous, evidence-based holistic approach. […] After applying our proposed methodology, 138 cases of stillbirth were classified into eight categories based on the causes of death. A definitive cause of death was observed in 100 (72%) cases, while 38 (28%) cases were considered unexplained. The leading cause of death was placental lesions (n=39, 28%) with maternal vascular malperfusion (MVM) lesions being the most common (54%). Ascending infection was the second most common cause of fetal death (n=24, 17%) and was often seen in the setting of preterm labor and cervical insufficiency. […] The largest category of cause of death was attributed to placental pathology. Using rigorous detailed up-to-date criteria that incorporate pathological and clinical factors may help in objectively classifying the cause of death.

• #1

  https://link.springer.com/article/10.1007/s40556-017-0133-3

  Placental weight is thought to reflect function and the feto-placental weight ratio has been suggested as a possible indicator of placental reserve capacity in IUGR. […] Placental function may be compromised by ischemia and/or infarction and thus any infarct seen in the pre-term placenta or at term anything more than 5% or peripheral infarction should be described and evaluated by volume. […] Maternal vascular malperfusion may also be seen in inherited thrombophilias which have a recognised association with stillbirth. […] It can be difficult to assign causation to FVM as many of the changes may be seen in involution of the placenta. […] Villitis of unknown etiology (VUE) with stem villitis and avascular villi (obliterative fetal vasculopathy) is regarded as a distinct process where the primary pathology relates to inflammation and damage of the vessel wall.

• #1 What Causes Stillbirth? Placenta Problems, Infection & MoreCloseleft-arrowleft-arrowleft-arrowleft-arrowleft-arrowleft-arrowCloseReconfirm cookies choice

  https://www.tommys.org/baby-loss-support/stillbirth-information-and-support/causes-stillbirth

  Bacterial infections can move from the vagina into the womb, for example, Group B strep, chlamydia, klebsiella, enterococcus, haemophilus influenza, mycoplasma or ureaplasma and escherichia coli (E.coli). These can sometimes cause inflammation of the placenta and membranes around the baby (called chorioamnionitis) or the umbilical cord (funisitis). […] Reduced fetal movements is not a cause of stillbirth but it is one of the signs that a baby may not be getting enough food or oxygen. Reduced fetal movements were noticed in around 55% of stillbirths. […] There are some other conditions that have been linked to stillbirth: intrahepatic cholestasis of pregnancy (ICP) or obstetric cholestasis – a liver disorder that can affect pregnancy, pre-existing diabetes, gestational diabetes, genetic defect in the baby (the reason for around 10% of stillbirths), excessive blood loss (haemorrhage) before or during labour, issues with the umbilical cord – the cord can come out of the entrance of the womb before the baby is born (cord prolapse), be wrapped around the baby or become knotted, premature birth – when a baby is born before 37 weeks of pregnancy.

• #1

  https://link.springer.com/article/10.1007/s40556-017-0133-3

  Impaired glucose tolerance/diabetes mellitus is known to be associated with increased morbidity during pregnancy and an increased risk of stillbirth. […] Massive perivillous fibrin deposition has an association with fetal death, preterm birth and intrauterine growth restriction and may recur in subsequent pregnancies. […] Examination of the placenta alone may help to define causation and indicate treatment options in subsequent pregnancies.

• #1 Stillbirth Investigations: An Iconographic and Concise Diagnostic Workup in Perinatal Pathology – Journal of Laboratory Physicians

  https://jlabphy.org/stillbirth-investigations-an-iconographic-and-concise-diagnostic-workup-in-perinatal-pathology/

  One of the most important findings is placental abruption, which is the early separation of a healthy placenta from the uterine wall before delivery. […] Infection may masquerade as asphyxia. […] The current Amsterdam Placental Workshop Group Consensus Statement includes Staging and Grading of the Maternal and Fetal Inflammatory Responses in Ascending Intra-Uterine Infection. […] Chronic villitis is chronic inflammation constituted by lymphocytes and histiocytes with or without plasma cells involving the chorionic villi. […] Finally, two important aspects that need to be tackled in a placenta pathology report is the presence of features suggesting maternal vascular malperfusion and/or fetal vascular malperfusion.

• #1 Placental inflammation and overweight or obesity in term singleton stillbirths in Stockholm County 2002–2018; a case control study | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0284525

  Stillbirth is a severe pregnancy complication. Maternal obesity is one of the most important modifiable risk factors of stillbirth, yet the biological mechanisms behind this association remain unclear. The adipose tissue is an endocrine organ which, in persons with obesity, causes a hyperinflammatory state. […] Both acute and chronic inflammatory placental lesions were more common in cases of stillbirth compared to pregnancies with live born infants. There were increased proportions of both acute and chronic placental inflammation (vasculitis, chronic villitis, funisitis and overall fetal and maternal inflammatory response) with increasing BMI among cases with term stillbirth, however no differences among controls with term live born infants. […] A placental inflammatory process contributes to the risk of stillbirth and that contribution is potentially more pronounced in women with overweight or obesity.

• #1 Involvement of oxidative stress in placental dysfunction, the pathophysiology of fetal death and pregnancy disorders in: Reproduction Volume 166 Issue 2 (2023)

  https://rep.bioscientifica.com/view/journals/rep/166/2/REP-22-0278.xml

  Placental oxidative stress contributes to both normal and abnormal placentation during pregnancy. This review discusses the potential consequence of oxidative stress-induced placental dysfunction on pregnancies complicated by fetal death and pregnancies with a high risk of fetal death. […] The placenta is a source of reactive oxygen free radicals due to the oxidative metabolism required to meet the demands of the growing fetus. […] However, poorly controlled oxidative stress can cause aberrant placentation, immune disturbances and placental dysfunction. Abnormal placental function and immune disturbances are linked to many pregnancy-related disorders, including early and recurrent pregnancy loss, fetal death, spontaneous preterm birth, preeclampsia and fetal growth restriction. […] Finally, based on previously published work, this review presents multiple lines of evidence for the strong association between oxidative stress and adverse pregnancy outcomes, including fetal death and pregnancies with a high risk of fetal death.

• #1 Involvement of oxidative stress in placental dysfunction, the pathophysiology of fetal death and pregnancy disorders in: Reproduction Volume 166 Issue 2 (2023)

  https://rep.bioscientifica.com/view/journals/rep/166/2/REP-22-0278.xml

  Evidence supports the role of placental oxidative stress in the pathology of many unexplained stillbirth cases. […] Oxidative stress generated by ROS can trigger DNA damage (both telomeric and genomic DNA) and activate the DNA damage response. […] These data suggest that AOX1 may be involved in regulating ROS generation and 4HNE production in stillbirth pregnancies. […] However, it is still not clear whether increased oxidative stress is the actual cause or consequence of impaired placenta function in stillbirth pregnancies. […] The increased lipid oxidation that is observed under oxidative stress condition is blocked when the explants are treated with the AOX1 inhibitor, raloxifene, suggesting that AOX1 play a causative role in placental oxidative damage in pregnancy pathologies. […] Together, these data strongly support the role of oxidative stress in the pathophysiology of spontaneous abortions and recurrent miscarriage.

• #1 Cardio-pathogenic variants in unexplained intrauterine fetal death: a retrospective pilot study | Scientific Reports

  https://www.nature.com/articles/s41598-021-85893-0

  To describe the prevalence and spectrum of cardio-pathogenic variants in singleton fetuses after unexplained intrauterine fetal death (IUFD). […] Unexplained stillbirth may be caused by cardio-genetic pathologies, yet a high number of variants of uncertain significance merit a more detailed post-mortem examination including family segregation analysis. […] Previous studies have suggested the influence of cardiac arrhythmias as a possible cause for fetal death in phenotypically normal fetuses and without detectable myocardial or brain lesions in autopsy. […] By this study, we aimed to elucidate the prevalence and spectrum of cardio-pathogenic variants in fetuses whose cause of death had remained unknown despite thorough post-mortem investigation, including placental histology, fetal autopsy, microarray and chromosomal analysis, as well as maternal tests.

• #1 Cardio-pathogenic variants in unexplained intrauterine fetal death: a retrospective pilot study | Scientific Reports

  https://www.nature.com/articles/s41598-021-85893-0

  In this study involving ethnically diverse singleton fetuses after unexplained late IUFD, we aimed to investigate the prevalence of underlying cardio-pathogenic variants by targeted sequencing. […] Although our sample size was too small to be conclusive, the scope over 122 cardiac genes revealed a high prevalence of variants of unknown significance in up to 75% fetuses, mainly involving genes which mutations most frequently would lead to cardiomyopathy. […] Cardio-genetic pathologies might be a potentially underexplored etiology contributing to fetal death and therefore warrant further consideration within the frame of fetal post-mortem investigation with attentive appraisal for variants of uncertain significance.

• #1 Diabetes and stillbirth – O&G Magazine

  https://www.ogmagazine.org.au/15/4-15/diabetes-and-stillbirth/

  A chronic hypoxia could be further aggravated later in pregnancy with placental changes induced by diabetes. […] Further evidence implicating the heart in stillbirth of diabetic pregnancy is provided by studies of the peptide B-type natriuretic protein (BNP), a known product of cardiac muscle cells in response to stress. […] Since maternal diabetes is so strongly associated with stillbirth, strategies of pre-pregnancy care, multidisciplinary pregnancy care, timing of delivery and intrapartum care are vital in optimising neonatal outcomes and reducing perinatal mortality. […] Diabetes is a common and important cause of stillbirth and perinatal death, among other adverse outcomes of pregnancy. Both pre-pregnancy care and close attention to the optimisation of glycaemic control during pregnancy are critical to reducing the risk of stillbirth.

• #1

  https://biomedres.us/fulltexts/BJSTR.MS.ID.006780.php

  Of particular relevance in the context of the demographic crisis is the timely diagnosis and correction of potentially preventable causes of stillbirth and perinatal mortality, which include umbilical cord abnormalities. […] The results of the study revealed a significant contribution of umbilical cord abnormalities to the development of acute intranatal fetal asphyxia (23.5%), the birth of children in a state of severe asphyxia and perinatal mortality, as well as an extremely low prenatal diagnosis of umbilical cord abnormalities (17.7%). […] Increasing the efficiency of prenatal diagnosis of umbilical cord abnormalities will make it possible to correctly determine the obstetric tactics of delivery, which will help reduce the likelihood of developing acute intranatal fetal asphyxia, severe neonatal asphyxia, stillbirth and perinatal mortality.

• #1

  https://biomedres.us/fulltexts/BJSTR.MS.ID.006780.php

  Despite the constant improvement of medical technologies and an increase in the quality of obstetric and perinatal care, acute intrapartum fetal asphyxia and stillbirth continue to remain urgent problems of modern medicine. […] Such causes include umbilical cord abnormalities, which, according to various scientific data, account for about 10% of the possible or probable causes of stillbirth, and are more common after 32 weeks of pregnancy. […] The aim of the study was to identify the role of umbilical cord abnormalities in the development of acute intrapartum fetal asphyxia and perinatal mortality in singleton term delivery in cephalic presentation. […] The highest specific gravity of severe intrapartum fetal asphyxia was found in cases of umbilical cord abnormalities (40.4%). […] Multiple umbilical cord abnormalities were detected 2.6 times significantly more often than single ones (72.3%). […] Prenatal diagnosis of umbilical cord abnormalities using ultrasound was 17.7%.

• #1 Intrauterine Fetal Demise – Causes, Risk Factors, Symptoms

  https://www.cerebralpalsyguide.com/birth-injury/intrauterine-fetal-demise/

  Intrauterine fetal demise (also called IUFD or stillbirth) occurs when a child dies in the womb at or after the 20th week of pregnancy. […] Intrauterine fetal demise can be caused by infection, genetic diseases, and more. […] Stillbirth has many causes, such as infections, issues with the umbilical cord and/or placenta, and overall complications with labor. It is important to note some cases of IUFD may not have any apparent cause. […] Common causes of stillbirth include: Birth defects (congenital abnormalities of the fetus), Blood transfer from baby to mother (feto-maternal hemorrhage), Fetal infection, Genetic disorder of the fetus, Maternal infection, Placenta separated from the inner uterine wall (placental abruption), Umbilical cord issues, Underdeveloped or damaged placenta (placental dysfunction).

• #1 An invitation to study stillbirth | obstetrical pathology

  https://obstetricalpathology.com/an-invitation-to-study-stillbirth/

  A reasonable conclusion is that petechiae were associated with severe intrauterine asphyxia. […] The pathological evidence has led to the hypothesis that some stillbirth without a cause of death are due to asphyxia. […] A meta-analysis of published reports of umbilical cord and stillbirth found very few acceptable papers for analysis. […] There is some indirect evidence that decreased umbilical blood flow may be involved in unexplained stillbirth. […] A reasonable argument going back to Virchows triad for thrombosis, namely, stasis, vascular injury, and thrombophilia, is that decreased umbilical blood flow led to the thrombi in the fetal circulation in the placenta similar to that of deep vein thrombosis in the legs. […] A surprising conclusion from these observations is the implication that the conditions of fetal asphyxia had been present for days or even weeks before death based on estimates of the development of similar lesions with postmortem retention.

• #1 Intrauterine Fetal Demise – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK557533/

  Stillbirth has many causes: intrapartum complications, hypertension, diabetes, infection, congenital and genetic abnormalities, placental dysfunction, and pregnancy continuing beyond forty weeks. […] There is currently a limited understanding of the pathophysiology responsible for fetal demise. Globally, unexplained stillbirth is reported in 76% of cases. […] The main causes of stillbirth in the US were obstetrical, including abruption and multifetal gestation complications, and spontaneous labor or rupture of membranes before viability. This study showed that the cause of stillbirth could be assigned in 75% of cases when a systematic evaluation is performed. […] Fetal growth restriction and placental abnormalities are the most prevalent findings in stillbirth. […] The risk of stillbirth is relative to the degree of growth restriction, with the highest stillbirth risk for those delivering the most growth-restricted fetuses.

• #1 Causes and risk factors for singleton stillbirth in Japan: Analysis of a nationwide perinatal database, 2013–2014 | Scientific Reports

  https://www.nature.com/articles/s41598-018-22546-9

  SGA infants had a significant increase in risk, consistent with previous studies. About 30% of SGA infants had an antenatal diagnosis of FGR, but the remaining 70% did not. The analysis of the interaction between SGA and FGR showed that SGA infants without antenatal diagnosis of FGR had a much higher risk of stillbirth compared with those with the diagnosis. This is comparable with the study by Gardosi and colleagues, who reported a reduced risk when FGR was detected antenatally to when it was not. Clinical FGR is a well-established risk factor for perinatal mortality. Once it is detected, the fetus is carefully monitored and often delivered before severe deterioration is observed on Doppler ultrasound or cardiotocography.

• #1 Stillbirth: How Common, Causes, Symptoms & Support

  https://my.clevelandclinic.org/health/diseases/9685-stillbirth

  A stillbirth happens when the fetus dies after week 20 of pregnancy. Stillbirths can have multiple causes, including problems with the placenta or umbilical cord, genetic conditions that affect the fetus or pregnancy complications. […] In 1 in 3 stillbirths, healthcare providers dont know why the fetus passed. Causes can be complex. Issues primarily affecting the mother, the fetus or the tissues and organs connecting them can all lead to stillbirth. […] Infections from a virus, parasite, bacteria or another pathogen (germ) cause up to 50% of stillbirths in developing countries. They cause up to 25% of stillbirths in developed countries. […] A problem with these lifelines can prevent the fetus from receiving the oxygen, blood and nutrients needed to thrive. […] Sometimes, theres an issue with how the fetus develops, or a congenital disability (birth defect). The fetus may have a genetic condition.

• #1

  https://journals.lww.com/greenjournal/fulltext/2019/12000/stillbirth_associated_with_infection_in_a_diverse.9.aspx?generateEpub=Article%7Cgreenjournal:2019:12000:00009%7C%7C

  To better characterize infection-related stillbirth in terms of pathogenesis and microbiology. […] For 66 (12.9%) cases of stillbirth, infection was identified as a probable or possible cause of death. […] Infection-related stillbirth occurred earlier than noninfection-related stillbirth (median gestational age 22 vs 28 weeks, P=.001). […] Of infection-related stillbirth cases in a large U.S. cohort, E coli, GBS, and enterococcus species were the most common bacterial pathogens and CMV the most common viral pathogen. […] Most cases of infection-related stillbirth are due to bacterial pathogens, of which Escherichia coli, group B streptococcus, and enterococcus species are the most common.

• #1 Intrauterine Fetal Demise – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK557533/

  Diabetes increases stillbirth risk up to 5 times. […] The risk of stillbirth is augmented by advanced maternal age due to an increased risk for aneuploidy and medical complications of pregnancy. […] Chronic hypertension increases stillbirth risk 3 times. […] Infection as a cause of stillbirth may be underrepresented because signs and symptoms of infection are often undetected, and evaluation for infection is often not conducted. […] Antiphospholipid syndrome (APS), in addition to thrombotic events, has been linked to stillbirth since 1984. […] The survival of a fetus in utero is dependent on several factors. These factors can be broken down into the well-being of the host in its environment, the function of the uteroplacental unit, the condition of the environment in which the fetus lives, and the absence of lethal fetal factors. A single insult or a combination of factors may affect the function of these life-sustaining factors and lead to a stillbirth. […] Structure, function, genetic anomalies, or insults such as hemorrhage or infection may compromise the integrity of the uteroplacental unit. Placental findings could include various abnormalities that may lead to stillbirth.

• #1 What Causes Stillbirth? Placenta Problems, Infection & MoreCloseleft-arrowleft-arrowleft-arrowleft-arrowleft-arrowleft-arrowCloseReconfirm cookies choice

  https://www.tommys.org/baby-loss-support/stillbirth-information-and-support/causes-stillbirth

  In most cases there isn’t a clear reason why placental abruption has happened. Placental abruption can be caused by a blow or impact to the stomach such as following a care accident. Or it sometimes linked to a condition such as pre-eclampsia or IUGR or FGR. […] Pre-eclampsia is a condition that occurs typically after 20 weeks of pregnancy and causes high blood pressure and protein in urine. If you’re told you have pre-eclampsia, it’s important that you attend appointments to check your blood pressure and wellbeing. You may be offered the option of having an early birth to prevent complications. […] Sometimes it’s not clear that you have pre-eclampsia until after your baby has died or even after you have given birth. […] 4.2% of stillbirths happened because of an intrauterine (womb) infection.

• #1 Association between maternal sleep practices and risk of late stillbirth: a case-control study | The BMJ

  https://www.bmj.com/content/342/bmj.d3403

  Objectives To determine whether snoring, sleep position, and other sleep practices in pregnant women are associated with risk of late stillbirth. […] The prevalence of late stillbirth in this study was 3.09/1000 births. […] However, women who slept on their back or on their right side on the previous night (before stillbirth or interview) were more likely to experience a late stillbirth compared with women who slept on their left side (adjusted odds ratio for back sleeping 2.54 (95% CI 1.04 to 6.18), and for right side sleeping 1.74 (0.98 to 3.01)). […] Women who regularly slept during the day in the previous month were also more likely to experience a late stillbirth than those who did not (2.04 (1.26 to 3.27)). […] This is the first study to report maternal sleep related practices as risk factors for stillbirth, and these findings require urgent confirmation in further studies.

• #1 Risk for Stillbirth Among Women With and Without COVID-19 at Delivery Hospitalization — United States, March 2020–September 2021 | MMWR

  https://www.cdc.gov/mmwr/volumes/70/wr/mm7047e1.htm

  Among 1,249,634 delivery hospitalizations during March 2020September 2021, U.S. women with COVID-19 were at increased risk for stillbirth compared with women without COVID-19 (adjusted relative risk [aRR] = 1.90; 95% CI = 1.692.15). […] COVID-19 documented at delivery was associated with increased risk for stillbirth, with a stronger association during the period of Delta variant predominance. […] A previous study of pregnancies complicated by SARS-CoV-2 infection identified placental histopathologic abnormalities, suggesting that placental hypoperfusion and inflammation might occur with maternal COVID-19 infection; these findings might, in part, explain the association between COVID-19 and stillbirth. […] Additional studies are warranted to investigate the role of maternal complications from COVID-19 on the risk for stillbirth.

• #1 Pathophysiology of the Unexplained Stillbirth

  https://brieflands.com/articles/ijp-55946

  Although with the introduction of better management of high-risk pregnancies, the stillbirth rate has been notably reduced during the last decades, intrauterine fetal death remains a major health problem, accounting for a large part of perinatal mortality in developed countries. […] However, despite extensive clinical and anatomopathological examinations, a specific cause of death continues to be unidentified in almost half of cases. These deaths are classified as unexplained stillbirths. […] The anatomopathological protocol developed by the Lino Rossi Research Center for this specific purpose, concerns above all the analysis of the main centers that control the vital functions, prevalently located in the brainstem. […] Thanks to this methodology of study, the „Lino Rossi” Research Center has identified subtle developmental anomalies, prevalently hypoplasia, of many nuclei of vital importance in sudden unexplained deaths, not observable in age-matched victims who died of known cause. These alterations, as reported in numerous publications, have offered a plausible explanation of the pathogenetic mechanism leading to sudden death in utero.

• #1 Pathophysiology of the Unexplained Stillbirth

  https://brieflands.com/articles/ijp-55946

  Very interesting is the observation, in the great part of unexplained stillbirths, of hypoplasia of the parafacial nucleus, a roundish cluster of large polygonal neurons in the caudal pons, so called for its position adjacent to the facial nucleus. […] An hypothesis, could be that, in the last weeks of pregnancy, advancing towards the birth, a general check of all the brainstem nuclei that coordinate the essential functions for the extra-uterine life, and in particular the respiratory activity, occurs. Unexpected fetal death could therefore be ascribed to a selective process of self-suppression in presence of developmental alterations of the respiratory network components, particularly of the parafacial nucleus, to avoid the most devastating event of a sudden infant death after birth. […] Since the hypoplasia of the parafacial nucleus has never been found in our large series of SIDS, we suppose that the normal development of this nucleus is essential for extra-uterine life, and that its hypodevelopment can be considered a specific marker of unexplained stillbirths, or at least of a great subset of unexplained stillbirths.

• #1 Pregnancy loss – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/pregnancy-loss/

  Fetoplacental factors include intrauterine growth restriction, placental abnormalities, infection, chromosomal abnormalities, congenital malformations, and umbilical cord complications. […] The cause of stillbirth is unknown in some studies, with more than half of all stillbirths being of unknown etiology. […] Ultrasonography is used to confirm the absence of fetal cardiac activity. […] Evaluation of underlying cause is indicated in all cases, including maternal and family history, examination of the placenta, fetal membranes, and umbilical cord, fetal autopsy, and genetic analysis. […] Spontaneous labor usually begins within 2 weeks of intrauterine fetal death. […] Method of delivery for stillbirth typically involves spontaneous or induced vaginal delivery, which is usually safer than cesarean delivery.

• #1 Stillbirth – Gynecology and Obstetrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/gynecology-and-obstetrics/antenatal-complications/stillbirth

  Stillbirth is fetal death (fetal demise) at 20 weeks gestation (28 weeks in some definitions). Management is delivery and postpartum care. Maternal and fetal testing is done to determine the cause. […] Fetal death during late pregnancy may have maternal, placental, or fetal anatomic or genetic causes. […] If a fetus dies during late pregnancy or near term but remains in the uterus for weeks, consumptive coagulopathy or even disseminated intravascular coagulation (DIC) may occur. […] The diagnosis of stillbirth is clinical. […] Testing for hereditary thrombophilia is controversial and is not routinely recommended. The association between stillbirth and hereditary thrombophilia is not clear but does not appear to be strong, except for possibly factor V Leiden mutation. […] Uterine evacuation may have spontaneously occurred. If not, evacuation should be done using drugs (eg, oxytocin) or a surgical procedure (eg, dilation and evacuation [D E], preceded by preabortion osmotic dilators to prepare the cervix, with or without misoprostol), depending on the gestational age. […] Disseminated intravascular coagulation may develop secondarily if uterine evacuation is delayed. […] Do tests to determine the cause; however, the cause often cannot be determined.

• #1 Prior Stillbirth – Brigham and Women’s Hospital

  https://www.brighamandwomens.org/obgyn/maternal-fetal-medicine/pregnancy-complications/prior-stillbirth

  For women and families who have experienced a prior stillbirth, we monitor subsequent pregnancies more closely. This monitoring plan is unique to each pregnancy, depending on the circumstances of the prior stillbirth, but can involve: Specialized genetic testing, Ultrasound detection of congenital abnormalities, Serial ultrasound examination to track fetal growth, Antenatal surveillance to assess fetal well-being (including ultrasounds to look at amniotic fluid volume and fetal movements, and non-stress testing to assess fetal heart rate patterns), Careful monitoring for pregnancy complications (such as high blood pressure or diabetes), Delivery timing. […] The Prior Stillbirth Clinic will make individualized care plans, especially regarding antenatal surveillance and delivery timing, taking into account the reasons for the prior stillbirth and the growth and well-being of the current pregnancy. […] We strive to provide families with prior stillbirth excellent outcomes in future pregnancies, including not only healthy babies but the emotional and social support needed to make it through challenging pregnancies.

• #1 Diabetes and stillbirth – O&G Magazine

  https://www.ogmagazine.org.au/15/4-15/diabetes-and-stillbirth/

  This article explores the risk factors for stillbirth in diabetic pregnancy, the underlying pathophysiology of diabetes in pregnancy relating to potential mechanisms of fetal death and the important roles of optimised glycaemic control as well as careful fetal surveillance in reducing stillbirth risk. […] The increased rate of stillbirth and neonatal death in the offspring of mothers with pre-existing diabetes is well recognised, with rates of stillbirth increased by up to five times compared to non-diabetic pregnancies. […] It has been concluded that, the single most important factor to reduce the risk of stillbirth is to achieve and maintain good glycaemic control during pregnancy. […] The pathophysiology of diabetic effects on the fetus in later pregnancy are summarised by the Pederson hypothesis: maternal hyperglycaemia results in fetal hyperglycaemia, which in turn overstimulates the fetal pancreatic beta cells to cause fetal hyperinsulinaemia.

• #1 Stillbirth and neonatal mortality in a subsequent pregnancy following stillbirth: a population-based cohort study | BMC Pregnancy and Childbirth | Full Text

  https://bmcpregnancychildbirth.biomedcentral.com/articles/10.1186/s12884-021-04355-7

  A history of stillbirth is a risk factor for recurrent fetal death in a subsequent pregnancy. […] Risk factors, etiology and the underlying mechanism of the prior stillbirth may influence the risk of recurrent fetal death in a subsequent pregnancy. […] The highest risk of recurrence occurred in the group of women with a stillbirth in early gestation between 22 and 28 weeks of gestation, while after 32 weeks the risk decreased. […] A history of stillbirth remains an important risk for recurrent stillbirth especially in early gestation (22-28 weeks). […] The recurrence of stillbirth compared to women with a previous live birth, was higher in the group of women with expectant management. […] The risk of neonatal death is higher in the group of women with a history of stillbirth compared to women with a previous live birth, both in expectant management group and in the group of women with a planned delivery.

• #1

  https://journals.lww.com/ogopen/fulltext/2024/09000/addressing_barriers_to_autopsy_and_genetic_testing.7.aspx

  The cause of death in many stillbirths remains unexplained, in part because of systematic barriers to complete workup. We review the importance of placental pathology, fetal autopsy, and genetic testing in stillbirth workup. Placental pathology is useful in 65% of stillbirths, and fetal autopsy is useful in 42%. Currently, only 21% of stillbirths in the United States undergo autopsy. Barriers to complete stillbirth workup include cost of autopsy and genetic testing, availability of perinatal pathology expertise, health care professional knowledge about workup, and availability of skilled counseling to support bereaved parents in making decisions about autopsy and genetic workup. We propose solutions to overcome these barriers, including policy changes to expand access and a framework for high-quality patient counseling and decision support.

• #1 Pathophysiology of the Unexplained Stillbirth

  https://brieflands.com/articles/ijp-55946

  In conclusion, a systematic evaluation of the brainstem, possibly performed by experienced, reliable pathologists, associated to the analysis of all the potential risk factors, is extremely important to highlight any possible pathogenic mechanism in unexplained stillbirth and to establish appropriate preventive programs.

• #1 Meeting abstracts from the International Stillbirth Alliance Conference 2017 | BMC Pregnancy and Childbirth | Full Text

  https://bmcpregnancychildbirth.biomedcentral.com/articles/10.1186/s12884-017-1457-7

  Intrauterine fetal demise due to utero-placental insufficiency usually occurs between obstetric evaluations when the gestation is not being actively monitored. […] It is hoped that improved monitoring can help to reduce preventable fetal damage and stillbirths. […] Stillbirth is a major health burden and is twice as common as neonatal death in developed countries. […] Identifying potentially modifiable risk factors for stillbirth may reduce the prevalence of this tragic condition. […] The overall risk of supine going-to-sleep position is 3.67 (adjusted odds ratio (aOR), 95% confidence interval (CI) 1.74-7.78). […] The magnitude of risk associated with supine going-to-sleep position may be greater for term pregnancies compared with those between 28 and 36 weeks. […] Understanding the causes globally is key to prevention.

• #2 Stillbirth – Gynecology and Obstetrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/gynecology-and-obstetrics/antenatal-complications/stillbirth

  Stillbirth is fetal death (fetal demise) at 20 weeks gestation (28 weeks in some definitions). Management is delivery and postpartum care. Maternal and fetal testing is done to determine the cause. […] Fetal death during late pregnancy may have maternal, placental, or fetal anatomic or genetic causes. […] If a fetus dies during late pregnancy or near term but remains in the uterus for weeks, consumptive coagulopathy or even disseminated intravascular coagulation (DIC) may occur. […] The diagnosis of stillbirth is clinical. […] Testing for hereditary thrombophilia is controversial and is not routinely recommended. The association between stillbirth and hereditary thrombophilia is not clear but does not appear to be strong, except for possibly factor V Leiden mutation. […] Uterine evacuation may have spontaneously occurred. If not, evacuation should be done using drugs (eg, oxytocin) or a surgical procedure (eg, dilation and evacuation [D E], preceded by preabortion osmotic dilators to prepare the cervix, with or without misoprostol), depending on the gestational age. […] Disseminated intravascular coagulation may develop secondarily if uterine evacuation is delayed. […] Do tests to determine the cause; however, the cause often cannot be determined.

• #2 Intrauterine Fetal Demise – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK557533/

  Stillbirth has many causes: intrapartum complications, hypertension, diabetes, infection, congenital and genetic abnormalities, placental dysfunction, and pregnancy continuing beyond forty weeks. […] There is currently a limited understanding of the pathophysiology responsible for fetal demise. Globally, unexplained stillbirth is reported in 76% of cases. […] The main causes of stillbirth in the US were obstetrical, including abruption and multifetal gestation complications, and spontaneous labor or rupture of membranes before viability. This study showed that the cause of stillbirth could be assigned in 75% of cases when a systematic evaluation is performed. […] Fetal growth restriction and placental abnormalities are the most prevalent findings in stillbirth. […] The risk of stillbirth is relative to the degree of growth restriction, with the highest stillbirth risk for those delivering the most growth-restricted fetuses.

• #2 Mechanisms of death in structurally normal stillbirths

  https://www.degruyterbrill.com/document/doi/10.1515/jpm-2018-0216/html?lang=en&srsltid=AfmBOoqe_EfZ9ZAa5w4WQ78wD48fVpO3S0SgaViQtgoqu3B22LmvuodE

  Hypoxia, secondary to placental dysfunction, was found to be the mechanism of death in the majority of fetal deaths among structurally normal fetuses. Ninety-one percent of hypoxic fetal deaths sustained brain, myocardial or both brain and myocardial injuries in utero. An attributable mechanism of death in 70% of the cases is circulatory failure and cardiac arrest secondary to hypoxic myocardial injury. […] The study indicated that 88% (53/60) of fetal deaths were hypoxic; that 91% (48/53) of hypoxic fetal deaths had sustained brain, myocardial or both brain and myocardial injuries in utero; and that circulatory failure and cardiac arrest, secondary to hypoxic myocardial damage, were the mechanisms of death in 70% (42/60) of cases. […] Hypoxia, secondary to placental dysfunction, is the mechanism of death in the majority of structurally normal fetuses after 20 weeks of gestation.

• #2 Mechanisms of Death of Structurally Normal Stillbirths

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6349478/

  Hypoxia, secondary to placental dysfunction, was found to be the mechanism of death in the majority of fetal deaths of structurally normal fetuses. […] Ninety-one percent of hypoxic fetal deaths sustained brain, myocardial or both brain and myocardial injuries in utero. […] An attributable mechanism of death in 70% of the cases is circulatory failure and cardiac arrest secondary to hypoxic myocardial injury. […] A histopathological explanation for placental dysfunction was found in 74% of these cases.

• #2 An invitation to study stillbirth | obstetrical pathology

  https://obstetricalpathology.com/an-invitation-to-study-stillbirth/

  An interpretation of the findings is that they are the result of relatively brief cardiac failure, but longer than expected in sudden cessation of cardiac contractions. […] The findings do not reflect prolonged heart failure in the fetus which results in anasarca (fetal hydrops) and large pleural effusions often with pulmonary hypoplasia. […] The current understanding of SIDS is that the infant exhales and then on trying to inhale, the airway is blocked by a foreign object like a blanket. […] To complete the analogy, there needs to be an equivalent to the obstructing blanket. […] The answer can be seen in the results of early experiments of birth asphyxia in newborn monkeys. […] A fetus with complete occlusion of the umbilical cord, or complete separation of the placenta from the maternal blood supply or even the death of the mother, would all cause in utero the hypoxic stimulus for gasping analogous to the plastic bag after birth.

• #2

  https://www2.hse.ie/conditions/stillbirth/diagnosis-causes/

  Many stillbirths are linked to complications with the placenta. The placenta is the organ that links the baby’s blood supply to the mother’s and nourishes the baby in the womb. […] With more research, it’s hoped that placental causes may be better understood, leading to improved detection and better care for these babies. […] A detailed examination of your placenta is one of the most important investigations to get information about what caused your baby to die. It can give vital information in many cases. […] If your baby has a post-mortem examination, then examination of the placenta will also be a very important part of the post-mortem examination.

• #2

  https://link.springer.com/article/10.1007/s00404-024-07522-1

  In our study, the leading cause of death was attributed to placental pathologies (28%), which were revealed by a post-mortem histopathological examination of the placenta. […] In conclusion, the pathophysiological mechanisms of stillbirth have yet to be sufficiently described. In our study, the largest category of cause of death was attributed to placental pathology, with MVM lesions being the most common. A rigorous up-to-date criteria that incorporates pathological findings and clinical reports may help objectively classify the cause of death and lower the cases of unexplained fetal death.

• #2 Stillbirth Investigations: An Iconographic and Concise Diagnostic Workup in Perinatal Pathology – Journal of Laboratory Physicians

  https://jlabphy.org/stillbirth-investigations-an-iconographic-and-concise-diagnostic-workup-in-perinatal-pathology/

  One of the most important findings is placental abruption, which is the early separation of a healthy placenta from the uterine wall before delivery. […] Infection may masquerade as asphyxia. […] The current Amsterdam Placental Workshop Group Consensus Statement includes Staging and Grading of the Maternal and Fetal Inflammatory Responses in Ascending Intra-Uterine Infection. […] Chronic villitis is chronic inflammation constituted by lymphocytes and histiocytes with or without plasma cells involving the chorionic villi. […] Finally, two important aspects that need to be tackled in a placenta pathology report is the presence of features suggesting maternal vascular malperfusion and/or fetal vascular malperfusion.

• #2 What Causes Stillbirth? Placenta Problems, Infection & MoreCloseleft-arrowleft-arrowleft-arrowleft-arrowleft-arrowleft-arrowCloseReconfirm cookies choice

  https://www.tommys.org/baby-loss-support/stillbirth-information-and-support/causes-stillbirth

  In most cases there isn’t a clear reason why placental abruption has happened. Placental abruption can be caused by a blow or impact to the stomach such as following a care accident. Or it sometimes linked to a condition such as pre-eclampsia or IUGR or FGR. […] Pre-eclampsia is a condition that occurs typically after 20 weeks of pregnancy and causes high blood pressure and protein in urine. If you’re told you have pre-eclampsia, it’s important that you attend appointments to check your blood pressure and wellbeing. You may be offered the option of having an early birth to prevent complications. […] Sometimes it’s not clear that you have pre-eclampsia until after your baby has died or even after you have given birth. […] 4.2% of stillbirths happened because of an intrauterine (womb) infection.

• #2 Placental inflammation and overweight or obesity in term singleton stillbirths in Stockholm County 2002–2018; a case control study | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0284525

  The results indicate that the effect of an inflammatory placental process on term stillbirth is greater with increasing BMI. However, to be able to use that knowledge to decrease the risk in future pregnancies a biomarker would be needed. […] Placental inflammatory processes are more pronounced in cases of term stillbirth compared to term live births. In addition, both vasculitis, funisitis, chronic villitis as well as an overall fetal and maternal inflammatory response were found more frequently in placentas from women with overweight or obesity in pregnancies complicated by term singleton stillbirth. Both acute and chronic inflammation may contribute to the increased risk of stillbirth of women with increased BMI.

• #2 Involvement of oxidative stress in placental dysfunction, the pathophysiology of fetal death and pregnancy disorders in: Reproduction Volume 166 Issue 2 (2023)

  https://rep.bioscientifica.com/view/journals/rep/166/2/REP-22-0278.xml

  The involvement of oxidative stress in FGR and preeclampsia has also been investigated in the laboratory using in vivo models. […] Collectively, evidence of elevated oxidative stress and diminished antioxidant defence in both humans and using in vivo models supports the concept that oxidative stress plays a part in the pathology of preeclampsia and FGR.

• #2 Identification of putative pathogenic single nucleotide variants (SNVs) in genes associated with heart disease in 290 cases of stillbirth | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210017

  The aim of this study was to analyze DNA from 290 stillbirth cases without chromosomal abnormalities for pathogenic single nucleotide variants (SNVs) in 70 genes associated with cardiac channelopathies and cardiomyopathies. […] Our results give further support to the hypothesis that cardiac channelopathies might contribute to stillbirth. Screening for pathogenic SNVs in genes associated with heart disease might be a valuable complement for stillbirth cases where todays conventional investigation does not reveal the underlying cause of fetal demise. […] We have analyzed DNA from 290 stillbirth cases for prevalence of pathogenic SNVs in 70 genes associated with heart disease. […] The proportion was significantly higher than the corresponding proportion for the same variants in ExAC NFE, (5.3%, p0.001) as well as in SweGen (5.1%, p0.001).

• #2

  https://biomedres.us/fulltexts/BJSTR.MS.ID.006780.php

  Despite the constant improvement of medical technologies and an increase in the quality of obstetric and perinatal care, acute intrapartum fetal asphyxia and stillbirth continue to remain urgent problems of modern medicine. […] Such causes include umbilical cord abnormalities, which, according to various scientific data, account for about 10% of the possible or probable causes of stillbirth, and are more common after 32 weeks of pregnancy. […] The aim of the study was to identify the role of umbilical cord abnormalities in the development of acute intrapartum fetal asphyxia and perinatal mortality in singleton term delivery in cephalic presentation. […] The highest specific gravity of severe intrapartum fetal asphyxia was found in cases of umbilical cord abnormalities (40.4%). […] Multiple umbilical cord abnormalities were detected 2.6 times significantly more often than single ones (72.3%). […] Prenatal diagnosis of umbilical cord abnormalities using ultrasound was 17.7%.

• #2 Stillbirth | March of Dimes

  https://www.marchofdimes.org/find-support/topics/miscarriage-loss-grief/stillbirth

  We dont know what causes all stillbirths, but common causes include infections, birth defects and pregnancy complications, like preeclampsia. […] We dont know what causes many stillbirths, but common causes include: […] Infections in the mother or baby. Some infections may not cause signs or symptoms and may not be diagnosed until they cause serious complications, like preterm birth or stillbirth. Infections that can cause stillbirth include: […] Problems with the placenta or umbilical cord. Placental problems include infections, blood clots, inflammation (redness, pain and swelling), problems with blood vessels and other conditions, like placental abruption. Problems with the umbilical cord include having a knot in the cord or the cord being pinched so that your baby doesnt get enough oxygen.

• #2 What Causes Stillbirth? Placenta Problems, Infection & MoreCloseleft-arrowleft-arrowleft-arrowleft-arrowleft-arrowleft-arrowCloseReconfirm cookies choice

  https://www.tommys.org/baby-loss-support/stillbirth-information-and-support/causes-stillbirth

  If the placenta doesn’t work properly, the baby doesn’t receive enough nutrients or oxygen and fails to grow or develop. This is called intrauterine growth restriction (IUGR) or fetal growth restriction (FGR). […] If there were problems with the placenta, stillborn babies are usually born looking perfectly formed, although often small. Sometimes, a post-mortem examination can help to diagnose IUGR or FGR by comparing the size of baby’s liver and brain. If the baby’s brain is more than 4.5 times bigger than their liver, then this makes growth restriction more likely. […] Sometimes the placenta can separate from the womb before the baby is born. This is called placental abruption. It can lead to stillbirth because the placenta that has separated from the womb is not working as it should.

• #2 Stillbirth | Stillborn | MedlinePlus

  https://medlineplus.gov/stillbirth.html

  If a woman loses a pregnancy after she’s past her 20th week, it’s called a stillbirth. Stillbirths are due to natural causes. They can happen before delivery or during delivery. Causes include: […] Problems with the placenta, the organ that transports oxygen and nutrients to the fetus […] Genetic problems with the fetus […] Fetal infections […] Other physical problems in the fetus. In at least half of all cases, it is not possible to tell why the baby died.

• #2

  https://journals.lww.com/ogopen/fulltext/2024/09000/addressing_barriers_to_autopsy_and_genetic_testing.7.aspx

  Whole-genome sequencing and whole-exome sequencing also play a role in stillbirth workup. When 246 stillbirths from SCRN with negative karyotype or CMA underwent whole-exome sequencing for pathogenic variants linked to stillbirth, the diagnostic yield of whole-exome sequencing was 6.1%, or 15 of 246 cases. […] Identifying a genetic cause allows prenatal diagnosis or preimplantation genetic diagnosis in future pregnancies. Although whole-exome sequencing and whole-genome sequencing are not currently recommended as first-line tests, they are reasonable to consider in stillbirths that remain unexplained after CMA. […] Modifiable barriers to complete stillbirth workup include availability of pathologists trained in stillbirth evaluation, cost of autopsy and genetic testing, and optimized counseling that supports shared decision making on fetal autopsy.

• #2 What Causes Stillbirth? Placenta Problems, Infection & MoreCloseleft-arrowleft-arrowleft-arrowleft-arrowleft-arrowleft-arrowCloseReconfirm cookies choice

  https://www.tommys.org/baby-loss-support/stillbirth-information-and-support/causes-stillbirth

  Bacterial infections can move from the vagina into the womb, for example, Group B strep, chlamydia, klebsiella, enterococcus, haemophilus influenza, mycoplasma or ureaplasma and escherichia coli (E.coli). These can sometimes cause inflammation of the placenta and membranes around the baby (called chorioamnionitis) or the umbilical cord (funisitis). […] Reduced fetal movements is not a cause of stillbirth but it is one of the signs that a baby may not be getting enough food or oxygen. Reduced fetal movements were noticed in around 55% of stillbirths. […] There are some other conditions that have been linked to stillbirth: intrahepatic cholestasis of pregnancy (ICP) or obstetric cholestasis – a liver disorder that can affect pregnancy, pre-existing diabetes, gestational diabetes, genetic defect in the baby (the reason for around 10% of stillbirths), excessive blood loss (haemorrhage) before or during labour, issues with the umbilical cord – the cord can come out of the entrance of the womb before the baby is born (cord prolapse), be wrapped around the baby or become knotted, premature birth – when a baby is born before 37 weeks of pregnancy.

• #2 2006-2008 Transplacental Transmission of Viruses and Pathogenesis of Stillbirth, Preterm Births and Congenital Abnormalities | Red Nose Australia

  https://rednose.org.au/research/2006-2008-transplacental-transmission-of-viruses-and-pathogenesis

  A third of stillbirths are still unexplained after post-mortem examination. Viruses are the most likely candidate. CMV is the most common virus found in stillbirths to date, according to our research which was funded by SIDS and Kids. […] The project aimed to find new techniques for testing for infection among pregnant women and to determine what types of viruses cause stillbirth, preterm problems and abnormalities.

• #2 Diabetes and stillbirth – O&G Magazine

  https://www.ogmagazine.org.au/15/4-15/diabetes-and-stillbirth/

  This article explores the risk factors for stillbirth in diabetic pregnancy, the underlying pathophysiology of diabetes in pregnancy relating to potential mechanisms of fetal death and the important roles of optimised glycaemic control as well as careful fetal surveillance in reducing stillbirth risk. […] The increased rate of stillbirth and neonatal death in the offspring of mothers with pre-existing diabetes is well recognised, with rates of stillbirth increased by up to five times compared to non-diabetic pregnancies. […] It has been concluded that, the single most important factor to reduce the risk of stillbirth is to achieve and maintain good glycaemic control during pregnancy. […] The pathophysiology of diabetic effects on the fetus in later pregnancy are summarised by the Pederson hypothesis: maternal hyperglycaemia results in fetal hyperglycaemia, which in turn overstimulates the fetal pancreatic beta cells to cause fetal hyperinsulinaemia.

• #2 Association between maternal sleep practices and risk of late stillbirth: a case-control study | The BMJ

  https://www.bmj.com/content/342/bmj.d3403

  We hypothesised that sleep disordered breathing and maternal supine sleep position would be associated with increased risk of late stillbirth. […] The association between maternal sleep position and late stillbirth risk was strongest on the last night, but a trend towards significance was also seen in the earlier time periods in pregnancy. […] Women who did not sleep on their left side on the last night had a doubled risk of late stillbirth compared with those who slept on their left side. […] This is a new observation, and confirmatory studies are needed before public health recommendations can be made.

• #2 Stillbirth – Women’s Health Issues – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/women-s-health-issues/complications-of-pregnancy/stillbirth

  Stillbirth may result from a problem in the woman, placenta, or fetus. […] Problems with the placenta may also result in death of the fetus. These problems may include the following: Conditions that reduce blood flow (and thus oxygen and nutrients) to the fetus. […] Sometimes the fetus dies when it has a problem, such as A chromosome or genetic abnormality. […] To try to identify the cause of stillbirth, doctors do genetic and blood tests (such as tests for infections, diabetes, thyroid disorders, and antiphospholipid syndrome). […] If disseminated intravascular coagulation develops, women are given blood transfusions as needed.

• #2 Is There a Link Between Gestational Diabetes and Stillbirth?

  https://www.healthline.com/health/pregnancy/gestational-diabetes-and-stillbirth

  Stillbirth occurs when a baby dies in the womb at or after 20 weeks of pregnancy. […] Uncontrolled GDM poses some risks to pregnant people and their babies, including a possible increased risk of stillbirth. […] Having continually high blood sugar if you have GDM can cause abnormalities in your placenta, which is responsible for delivering nutrition and oxygen to your growing baby. Low oxygenation and placental anomalies are significant risk factors for fetal distress and stillbirth. […] Unmanaged GDM also increases your risk of conditions like pre-eclampsia (a type of high blood pressure in pregnancy), excessive amniotic fluid, and abnormal fetal growth patterns. These complications can further increase your risk of stillbirth. […] Stillbirth is more likely when GDM goes undiagnosed, remains untreated, or is unmanaged.

• #3 Etiology & prevention of stillbirth prof.salah | PPT

  https://www.slideshare.net/slideshow/etiology-prevention-of-stillbirth-profsalah/15470696

  The World Health Organization (WHO) classification of stillbirth is defined as fetal loss in pregnancies beyond 20 weeks of gestation, or, if the gestational age is not known, a birth weight of 500 g or more, which corresponds to 22 weeks of gestation in a normally developing fetus. […] Stillbirths are subclassified as antepartum (ie, the fetus died before the onset of labor) or intrapartum (ie, the fetus died after the onset of labor but before birth). […] Stillbirth is a relatively common, but often completely random occurrence. Based on statistical data, it has been found that the mean stillbirth rate in the United States is approximately 1 in 115 births, which is roughly 26,000 stillbirths each year, or one every 20 minutes. […] Common risk factors for stillbirth include maternal age, obesity, medical conditions like diabetes and hypertension, thrombophilias, infection, and multiple pregnancies.

• #3 Mechanisms of death in structurally normal stillbirths

  https://www.degruyter.com/document/doi/10.1515/jpm-2018-0216/html

  Hypoxia, secondary to placental dysfunction, was found to be the mechanism of death in the majority of fetal deaths among structurally normal fetuses. Ninety-one percent of hypoxic fetal deaths sustained brain, myocardial or both brain and myocardial injuries in utero. Hypoxic myocardial injury was an attributable mechanism of death in 70% of the cases. […] The study indicated that 88% (53/60) of fetal deaths were hypoxic; that 91% (48/53) of hypoxic fetal deaths had sustained brain, myocardial or both brain and myocardial injuries in utero; and that circulatory failure and cardiac arrest, secondary to hypoxic myocardial damage, were the mechanisms of death in 70% (42/60) of cases. […] Hypoxia, secondary to placental dysfunction, is the mechanism of death in the majority of structurally normal fetuses after 20 weeks of gestation.

• #3 An invitation to study stillbirth | obstetrical pathology

  https://obstetricalpathology.com/an-invitation-to-study-stillbirth/

  For the purpose of understanding a mechanism of stillbirth, the experiments demonstrated that partial asphyxia alone would eventually lead to hypoxia sufficient to stimulate gasping, and to cause fetal death. […] A reasonable distinction is that partial asphyxia causes an unrelenting, increase in fetal acidosis leading to cardiovascular collapse and death. […] A refinement on the definition of partial asphyxia was made in ovine studies with a doughnut like occluder wrapped around the umbilical cord with a timer set to regularly occlude the blood flow for a fixed duration at fixed intervals. […] A reasonable conclusion is that the intrathoracic petechiae and findings of acute heart failure are caused by fetal asphyxia, either complete, partial or intermittent. […] If the separation is complete, the fetus suffers acute total asphyxia. Smaller separations are equivalent to partial asphyxia.

• #3 An invitation to study stillbirth | obstetrical pathology

  https://obstetricalpathology.com/an-invitation-to-study-stillbirth/

  The role of vascular contractility in response to decreased umbilical blood flow may play a role in exacerbating fetal asphyxia. […] One explanation is that the anatomic occlusion does not harm the cord per se. […] Compression in occult prolapse of the umbilical cord is plausible cause of compromise of umbilical blood flow even prior to labor if the cord is wedged between a fetal part and the pelvis. […] These observations and thought experiments lead to the hypothesis that a functionally short cord from fetal wrapping may compromise umbilical blood flow. […] The same MRI study could also identify occult prolapse or other forms of compromised umbilical cord. […] The model of partial asphyxia and progressive fetal acidosis as sufficient to cause fetal death, provides a framework for tying other risk factors to the immediate cause of death. […] If the hypothesis of a key role for compromised umbilical blood flow is true, then an MRI will uncover a pattern such as functional short cord from wrapping or unsuspected occult cord prolapse.

• #3 Is There a Link Between Gestational Diabetes and Stillbirth?

  https://www.healthline.com/health/pregnancy/gestational-diabetes-and-stillbirth

  Research has shown that managing your GDM can reduce your risk of stillbirth to normal or near-normal levels. […] GDM is an increasingly common pregnancy-related form of glucose intolerance. Particularly when not successfully managed, GDM can increase the risk of stillbirth and other health complications for you and your baby.

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