Late Intrauterine Fetal Death Research Articles

Chronic Inflammatory Placental Disorders Associated With Recurrent Adverse Pregnancy Outcome.

Chronic inflammatory placental disorders are a group of rare but devastating gestational syndromes associated with adverse pregnancy outcome. This review focuses on three related conditions: villitis of unknown etiology (VUE), chronic histiocytic intervillositis (CHI) and massive perivillous fibrin deposition (MPFD). The hallmark of these disorders is infiltration of the placental architecture by maternal immune cells and disruption of the intervillous space, where gas exchange between the mother and fetus occurs. Currently, they can only be detected through histopathological examination of the placenta after a pregnancy has ended. All three are associated with a significant risk of recurrence in subsequent pregnancies. Villitis of unknown etiology is characterised by a destructive infiltrate of maternal CD8+ T lymphocytes invading into the chorionic villi, combined with activation of fetal villous macrophages. The diagnosis can only be made when an infectious aetiology has been excluded. VUE becomes more common as pregnancy progresses and is frequently seen with normal pregnancy outcome. However, severe early-onset villitis is usually associated with fetal growth restriction and recurrent pregnancy loss. Chronic histiocytic intervillositis is characterised by excessive accumulation of maternal CD68+ histiocytes in the intervillous space. It is associated with a wide spectrum of adverse pregnancy outcomes including high rates of first-trimester miscarriage, severe fetal growth restriction and late intrauterine fetal death. Intervillous histiocytes can also accumulate due to infection, including SARS-CoV-2, although this infection-induced intervillositis does not appear to recur. As with VUE, the diagnosis of CHI requires exclusion of an infectious cause. Women with recurrent CHI and their families are predisposed to autoimmune diseases, suggesting CHI may have an alloimmune pathology. This observation has driven attempts to prevent CHI with a wide range of maternal immunosuppression. Massive perivillous fibrin deposition is diagnosed when >25% of the intervillous space is occupied by fibrin, and is associated with fetal growth restriction and late intrauterine fetal death. Although not an inflammatory disorder per se, MPFD is frequently seen in association with both VUE and CHI. This review summarises current understanding of the prevalence, diagnostic features, clinical consequences, immune pathology and potential prophylaxis against recurrence in these three chronic inflammatory placental syndromes.

Timing of hospital admission for stillbirth delivery on maternal and obstetric outcome: a retrospective cohort study

The effect of timing of hospital admission for stillbirth delivery following late intrauterine fetal death (IUFD) has not yet been described. By this study, we aimed to gain an understanding of the impact of “immediate” (i.e., on the same day of IUFD diagnosis) versus “delayed” hospital admission (i.e., on the subsequent day or two days after IUFD diagnosis) on maternal and delivery outcome parameters. This retrospective cohort study comprised all women who suffered a singleton IUFD ≥ 21 gestational weeks and delivered the stillborn at our tertiary referral center between 2003 and 2019. We excluded all terminations of pregnancy and women presenting with acute symptoms on the day of IUFD diagnosis. In total, 183 women were included of whom 69.4% (n = 127) were immediately admitted and 30.6% (n = 56) had delayed admission. Median gestational age of IUFD was 30+3 (21+0–41+3) weeks. Whilst women with early signs of labor were more frequently admitted immediately (87.5%; 14/16), neither maternal demographic and obstetric parameters, nor day of the week or presenting symptoms influenced the timing of hospital admission. 77.6% (142/183) of women after IUFD diagnosis delivered within the first 3 days after admission. Women after immediate admission equally often delivered on admission day and the day after (26.0%; 33/127 each), women after delayed admission most commonly delivered the day after admission (39.3%; 22/56). Stillbirth delivery on the day of diagnosis was more common upon immediate admission (p = 0.006), especially in early gestational weeks (p = 0.003) and with small fetal weight (p < 0.001), requiring less induction of labor. No significant difference regarding delivery mode, labor duration, use of intrapartum analgesia, need for episiotomy and risk of perineal injury was observed between the groups. Also rate of intrapartum hemorrhage was independent of admission timing, although immediately admitted women experienced greater median blood loss after vaginal delivery. Maternal laboratory parameters (hemoglobin, thrombocytes and CRP) were independent of admission timing, except for higher levels of leucocytes, neutrophils and lymphocytes in immediately admitted women. Our study shows no clinical superiority of immediate hospital admission for stillbirth delivery. Under stable medical circumstances, it, therefore, seems feasible to allow the woman delayed admission for labor and delivery.

Prospective risk of stillbirth and neonatal complications for monochorionic diamniotic and dichorionic diamniotic twins after 24 weeks of gestation.

Our study compared the prospective risks of intrauterine fetal death (IUFD), neonatal death (NND), perinatal death (PND), and neonatal morbidities in monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin pregnancies. This retrospective cohort study included twin pregnancies who had antenatal care and delivery in a public hospital from 2011 to 2018. Exclusion criteria included monoamnionicity, one/both twin miscarriage, twin-twin transfusion syndrome, or lethal congenital abnormalities. All twins were managed in multiple pregnancy clinic with standardized protocols. Gestational age-specific IUFD, NND, PND, and neonatal morbidity rates were compared according to chorionicity. Three hundred seventy-eight MCDA and 1282 DCDA twins were included. MCDA twins had higher risks of PND (1.9% vs. 0.7% in DCDA twins, p=0.05), composite neonatal morbidity (p=0.01), preterm delivery (p < 0.01), and low birth weight (p < 0.01). The prospective risk of IUFD was 0.6% and 0.4% for MCDA and DCDA twins, respectively after 34 weeks' gestation. No NND occurred among deliveries after 30 weeks. The risk of neonatal morbidity of MCDA twins fell from 22.7% at 34 weeks to 2.7% at 37 weeks (p < 0.01). For DCDA twins, the risk of morbidity fell insignificantly from 36 to 38 weeks (4.0% vs. 3.4%, p=0.60). Logistic regression analysis suggested that the increased risk of perinatal morbidities was related to the higher rate of preterm delivery in MCDA twins rather than chorionicity. With close fetal monitoring, the risk of late IUFD in twin pregnancies without major complications is low. Perinatal morbidity can be minimized by avoiding late preterm deliveries in twin pregnancies.

A COMPARATIVE STUDY OF MIFEPRISTONE AND MISOPROSTOL VERSUS MISOPROSTOL ALONE IN INDUCTION OF LABOUR IN LATE INTRAUTERINE FETAL DEATH

Objective: To compare efficacy, safety and tolerance of combination of Mifepristone and Misoprostol versus Misoprostol alone in induction of labour in late intrauterine fetal death (&gt;24 weeks).&#x0D; Methods: This prospectively study included 160 women with late intrauterine fetal death (IUFD) after 24 weeks of gestation and divided the women randomly into two groups each containing 80 women. In Group-A : Mifepristone 200 mg single dose was given and after 24 hrs Tab Misoprostol (intravaginally) administered and repeated 4 hourly upto a maximum of 5 doses, while in Group-B : Only Tab Misoprostol administered intravaginally 4 hourly upto maximum 5 doses. Induction-delivery interval and number of doses of Misoprostol was calculated. &#x0D; Results: The mean induction-delivery interval in Group-A was 13.02 ± 3.74 hours and in Group-B was 16.09 ± 2.99 hours (p-value &lt;0.0001). Mean doses of Misoprostol required in Group-A was 3.36 ± 1.08 hours and in Group-B was 4.32 ± 0.65 hours (p-value &lt;0.0001).&#x0D; Conclusion: Combination of Mifepristone and Misoprostol is more effective as comparison to Misoprostol in terms of induction-delivery interval and number of doses of misoprostol required. &#x0D; Keywords: IUFD, mifepristone, misoprostol, induction of labour, induction-delivery interval.

Factors Related to Late Intrauterine Fetal Death in a Tertiary Referral Center: A Retrospective Study

Backgroun: Intrauterine fetal death (IUFD) is a contributor of perinatal outcome and is an important indicator of the quality of antenatal care. Despite efforts, risk factors cannot be identified in cases of intrauterine fetal deaths. This study aims to identify the maternal, fetal, placental and cord related factors related to it. &#x0D; Methods: It is a retrospective cross-sectional study conducted analyzing patients admitted with IUFDs after 28 weeks of pregnancy at Tribhuwan University Teaching Hospital from April 2019 to March 2020. It was conducted after taking ethical approval from Institutional Review Committee (IRC) of Institute of Medicine. Data were collected from review of charts of individual patients in MS Excel and was analyzed using SPSS.&#x0D; Results: There were 5496 births and 46 intrauterine fetal deaths during the study period giving stillbirth rate of 8 per 1000 births. It was common in the age group of 26-30 years (34.8%), 62.2% were from inside Kathmandu valley,43.5% were just literate, 13% were illiterate, 84.8% were housewives, 56.5% were primigravida and 69.57% of the babies were preterm. Only four percent had previous history of intra uterine fetal deaths. Hypertensive disorders complicating pregnancy were found in 30.5% followed by heart disease in 10.9% of the mothers. There were no known co-morbidities in 26.1% of the patients. Out of total 46 cases, 62% were female. Two had Rh isoimmunization and four had congenital malformations. Placenta previa was seen in four percent and abruptio placenta in two percent. Twin pregnancy with diamniotic dichorionic placenta was present in four percent. Seventeen percent of the babies had cord around the neck and two percent had thrombosis of the umbilical cord. &#x0D; Conclusion: Low level of maternal education and maternal comorbidities like hypertensive disorders complicating pregnancy were found to be most common factors seen in cases of intrauterine fetal deaths.

COVID-19 outbreak and decreased hospitalisation of pregnant women in labour

COVID-19 outbreak and decreased hospitalisation of pregnant women in labour

Role of combination of mifepristone and misoprostol versus misoprostol alone in induction of labor in late intrauterine fetal death: A randomized trial

Role of combination of mifepristone and misoprostol versus misoprostol alone in induction of labor in late intrauterine fetal death: A randomized trial

Why fetuses die - A retrospective observational study in a tertiary care center

Background: Late intrauterine fetal death (IUFD) and stillbirth are a cause of concern and not widely reported though it contributes a large chunk in perinatal mortality. It is a traumatic experience for the family and obstetrician. If the cause of fetal deaths can be ascertained, preventive strategies can be formulated. Objectives: This study was done to estimate the incidence and suspected causes leading to IUFD and stillbirth. Materials and Methods: The present study was conducted in the Department of Obstetrics and Gynecology of Veer Chandra Singh Garhwali Government Institute of Medical Science and Research (VCSGGIMS&R) and RI and its attached hospital. Retrospective data of all the cases of IUFD were recorded in a predesigned performa from for April 2016–March 2017. Data was compiled and analyzed statistically using simple statistical measures such as percentage and proportions. Results: The incidence of stillbirth in our study was 24.8/1000 live birth. Among all factors responsible for IUFD, hypertensive disorder of pregnancy was present in 14 (18.42%) of the patients; placental abruption was present in 10 (13.2%) cases. In 28.95% of cases, no apparent cause of IUFD could be ascertained. Conclusion: Poor socioeconomic background, illiteracy, and late seeking of antenatal care are the predisposing factors for IUFD. Many of the causes of intrauterine deaths are preventable such as placental abruption, hypertensive disorders, and diabetes which can be avoided by proper antenatal care. Early detection of high-risk pregnancy and timely referral to equipped center will help in decreasing IUFD.

Impact of management protocols of intrauterine fetal death on perceived stress: A comparative study

Background: Pregnancy loss is a distressing problem and retention of dead fetus in utero has its own ill effects on physical, psychological, and social aspects, and hence, it is better to recommend medical induction, provided this can be safely undertaken. Aims: The aim of this study is to compare the efficacy, tolerability, induction-delivery interval, and perceived stress scores between induction methods in late intrauterine fetal death (IUFD) with misoprostol alone and mifepristone with misoprostol combination in a rural population of Eastern India. Materials and Methods: This pilot study was conducted on 125 patients after taking institutional ethical clearance and informed consent of the patients in a time span of 1 year. Group 2 patients received 200 mg of mifepristone per orally and observed for 48 h, followed by 50 μg misoprostol administered in the posterior vaginal fornix, and repeated 6th hourly up to a maximum of four doses. Group 1 received 50 μg misoprostol per vaginally 6 hourly for four doses. Induction-delivery interval was calculated. Perceived stress level was calculated on admission and before discharge. Results: Significantly lower induction-delivery interval was observed in Group 2 as compared to Group 1 with P < 0.001. There was no significant difference of Cohen's perceived stress scores on admission, but the difference was significantly lower in Group 2 on discharge with the value of P = 0.03. Group 1 had significantly lower hospital stay in days as compared to Group 2 of patients with P < 0.001. Conclusions: Patients with IUFD administered misoprostol per vaginally only may require shorter hospital stay as compared to patients administered with oral mifepristone followed by misoprostol vaginally but the delivery induction time increases significantly and may increase perceived stress levels which may have short- and long-term negative psychological impact.

Oral misoprostol with mifepristone versus misoprostol alone for inducing labor in intrauterine fetal death: A randomized placebo-controlled trial

Context: Intrauterine fetal death (IUFD) causes emotional distress and could result in intrauterine infection. In view of these complications, medical induction is recommended, if it is safe. Aim: The aim of this study was to compare the efficacy and safety of a combination of mifepristone and misoprostol with oral misoprostol alone for induction of labor in IUFD. Settings and Design: This is a randomized placebo-controlled trial conducted at a tertiary care teaching hospital in southern India. Patients and Methods: We recruited 72 women with IUFD in a singleton pregnancy after 28 weeks with intact membranes. Thirty-six women received oral placebo followed by misoprostol. In other group, 36 women received 200 mg oral mifepristone followed by misoprostol (both groups received 50 μg orally 4th hourly up to 5 doses). The interval between mifepristone/placebo and the first dose of misoprostol was 24 h. Results: Successful delivery occurred within 72 h in 31 of 36 (86%) women who received mifepristone before misoprostol and in 28 of 36 (78%) women who received only misoprostol (P = 0.541). Median (interquartile range) induction to delivery interval was 3.5 (2–5) and 4 (3–5) h in the combination group and misoprostol group, respectively (P = 0.465). Conclusions: Addition of mifepristone to misoprostol appears to be marginally more effective than misoprostol alone for induction of labor in intermediate and late IUFD, although the differences were not statistically significant.

Re: The use of mifepristone and misoprostol in the management of late intrauterine fetal death

Re: The use of mifepristone and misoprostol in the management of late intrauterine fetal death

The use of mifepristone and misoprostol in the management of late intrauterine fetal death

Key content A combination of mifepristone and misoprostol is the gold standard treatment for induction of labour in women with late intrauterine fetal death. This article attempts to review the current best available evidence as well as provide an insight based on the available evidence regarding the dosing regimens and safety in women with a previous caesarean section. Learning objectives To review the pharmacokinetics, mode of action, efficacy, adverse effects, dose and route of administration of mifepristone and misoprostol. To review the safety of misoprostol in women with previous caesarean section and other uterine scars. Ethical issues To identify the most effective regimen with the fewest adverse effects. To balance the desire to achieve a quick and successful induction with the risk of complications including uterine rupture in women with previous uterine scars. To provide a sympathetic approach to women who are already emotionally stressed.

Induction of Labor Using Misoprostol With or Without Mifepristone in Intrauterine Deat

Rapid expulsion of fetus in intrauterine fetal death is usually requested without any medical grounds for it. So an efficient, safe method for induction of labor is required. The objective of this study is to determine if pre-treatment with mifepristone followed by induction of labor with misoprostol in late intrauterine fetal death is more efficacious. We conducted a randomized controlled trial in 100 patients in B.P.Koirala Institute of Health Sciences, Nepal from June 2011 to May 2013. Group A women received single oral dose of 200 mg mifepristone, followed by induction with vaginal misoprostol after 24 hours. Group B women were induced only with vaginal misoprostol. In each group, five doses of misoprostol was used four hourly. If first cycle was unsuccessful, after break of 12 hour, second course of misoprostol was started. The primary outcome was a measure of induction to delivery time and vaginal delivery within 24 hours. Secondary outcome was to measure need of oxytocin and complications. Maternal age, parity and period of gestation were comparable between groups. Number of misoprostol dose needed in group A was significantly less than group B. Mann Whitney U test showed, women in group A had significantly earlier onset of labor, however total induction to delivery interval was not significant. In group A, 85.7% delivered within 24 hours of first dose of misoprostol while in group B 70% delivered within 24 hours (p=0.07). More women in Group B required oxytocin. Pretreatment with mifepristone before induction of labor following late intrauterine fetal death is an effective and safe regimen. It appears to shorten the duration of induction to onset of labor.

PPO.37 Snapshot of Post-Mortem Examinations following Stillbirths at a University Hospital

IntroductionStillbirth incidence is 1 in 200 births. 2.6 million 3rd trimester stillbirths occur worldwide every year. Parents should be offered full post-mortem (PM) examination to elicit the cause of the...

The placental vascular component in early and late intrauterine fetal death

ObjectiveTo compare the placental histopathological findings between pregnancies complicated by early (<34weeks' gestation) and late (≥34weeks' gestation) intrauterine fetal death (IUFD) and pregnancies with live births. Material & MethodsPlacentas of patients with unexplained IUFD between 22–42weeks of gestation were analyzed for maternal vascular supply lesions that include those related to maternal underperfusion (villous changes and vascular lesions), fetal vascular supply lesions that include findings consistent with fetal thrombo-occlusive disease (villous changes and vascular lesions) and maternal and fetal inflammatory response lesions. The clinical characteristics and placental findings were compared with those from live birth controls adjusted for gestational age. ResultsIn the early IUFD group (n=28), compared to controls with early delivery, a higher rate of vascular lesions consistent with fetal thrombo-occlusive disease (28.6% vs. 0, p=0.002), villous changes consistent with fetal thrombo-occlusive disease (21.4 vs. 3.6%, p=0.043), and cord related lesions (46.4% vs. 0, p<0.001), respectively, were observed. A similar high rate of maternal vascular supply lesions was detected in both groups. In the late IUFD group (n=30), compared to controls, a higher rate of cord related lesions, 40% vs. 0, respectively, p<0.001, were found. In contrast, maternal and fetal inflammatory response lesions were more common in controls than in placentas from early and late IUFD. ConclusionsThe involvement of placental fetal vascular supply lesions is more extensive in early IUFD than in late IUFD, when compared with matched controls.

Do national guidelines affect local practice in a timely manner? assessment of the rcog guideline on the management of stillbirth

BackgroundNHS clinical effectiveness initiatives aim to promote uniform standards of high-quality, evidence-based care. Clinical practice guidelines produced by the RCOG are a principal component of such care. We aimed to...

Parental care pathway after late fetal loss and stillbirth: an audit of cases in sunderland royal hospital over a 2-year period

BackgroundRecently the RCOG published Green-Top Guideline ‘Late Intrauterine Fetal Death & Stillbirth’.1 The North East has the highest adjusted mortality for stillbirth,2 therefore an audit of the parental care pathway...

Risk of fetal hydrops and non-hydropic late intrauterine fetal death after gestational parvovirus B19 infection

Background Risk assessment of parvovirus B19 (B19)-associated fetal complications following gestational B19 infection remains controversial. Objectives To determine the risk of fetal hydrops or non-hydropic late intrauterine fetal death following acute maternal B19 infection at defined gestational weeks. Study design Observational cohort study of pregnant women with serologic evidence of acute B19 infection. If available, fetal or neonatal tissue samples from cases complicated by fetal loss or hydrops were investigated for the presence of B19 DNA by polymerase chain reaction (PCR) and/or in situ hybridization (ISH). Results Of 236 women with known pregnancy outcome, 228 had a live birth and 8 a fetal loss. The observed rate of fetal hydrops for all pregnant women was 4.2% (10/236) (95% confidence interval [CI], 2.1–7.7) and 10.6% (10/94) (95% CI, 5.2–18.7) for those infected between 9 and 20 weeks gestation. Tissue samples from 8 hydrops cases were investigated by PCR or ISH and all were B19 DNA positive. Fetal death occurring during or after gestational week 22 was only observed in one case which was associated with B19-derived fetal hydrops. Conclusions Our findings demonstrate that although adverse fetal outcome is a rare complication of gestational B19 infection, a relevant risk of fetal hydrops exists particularly for women infected between 9 and 20 weeks’ gestation. Cases of B19-derived non-hydropic late intrauterine fetal death were not observed in the present study.

288: Optimal medical management of late intra-uterine fetal death (IUFD)

288: Optimal medical management of late intra-uterine fetal death (IUFD)

Polymorphisms within the Interleukin‐1 Gene Family and Unexplained Late Intrauterine Fetal Death: A Multi‐center Study

Interleukin-1 (IL-1) mediated inflammatory processes have been proposed to be involved in the pathogenesis of late unexplained intrauterine fetal death (IUFD). We determined whether common polymorphisms within the IL-1 gene locus can serve as candidate genes for this condition. In a multi-center case-control study, we evaluated the -889 C/T polymorphism of the IL-1alpha gene (IL1A), the -511 C/T polymorphism of the IL-1beta promoter (IL1B promoter), the +3953 C/T polymorphism of IL-1beta exon 5 (IL1B exon 5), and a 86 base pair repeat in intron 2 of the IL-1 receptor antagonist gene (IL1RN) in 94 women with IUFD and 94 healthy controls using pyrosequencing. No significant associations were found between the presence of polymorphic alleles of IL1A (P = 0.9), IL1B promoter (P = 0.3), IL1B exon 5 (P = 0.9), and IL1RN intron 2 (P = 0.7) and the incidence of IUFD. In women with IUFD, polymorphisms were not associated with the timing of fetal death and birth weight. Polymorphisms within the IL1 gene family are not associated with the occurrence of IUFD overall and do not modulate the clinical characteristics of affected pregnancies in a large series of Caucasian women.