Stillbirth evaluation: a stepwise assessment of placental pathology and autopsy

Miller, Emily S.; Minturn, Lucy; Linn, Rebecca L.; Weese‐Mayer, Debra E.; Ernst, Linda M.

doi:10.1016/j.ajog.2015.08.049

Cited by 49 publications

(48 citation statements)

References 17 publications

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“…The placenta is considered to be a record of fetal life 64 , and by examining it histologically, one can often glean the intrauterine pathological processes that may have led to obstetrical complications such as fetal death 32 . The pathologic processes implicated in fetal death include: infection 65–84 , placental abruption, 5, 37, 70, 85–92 vascular lesions of the placenta, 28, 35, 93–100 preeclampsia, 41, 101–105 fetal growth restriction 9, 106–114 , maternal anti-fetal rejection, 35, 115–120 metabolic disorders, 121–133 genetic disorders, 80, 131, 134–137 umbilical cord accident, 97, 138–145 trauma 146–148 , and placental senescence 22 ; however, most of the 47,000 stillbirths reported from developed countries in 2015 149 were classified as unknown etiology.…”

Section: Discussionmentioning

confidence: 99%

The prediction of fetal death with a simple maternal blood test at 24-28 weeks: a role for angiogenic index-1 (PlGF/sVEGFR-1 ratio)

Chaiworapongsa

Romero

Erez

et al. 2017

American Journal of Obstetrics and Gynecology

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Objective To determine if maternal plasma concentrations of angiogenic and anti-angiogenic factors measured at 24–28 weeks of gestation can predict subsequent fetal death. Methods A case-cohort study was designed to include 1000 randomly selected subjects and all remaining fetal deaths (cases) from a cohort of 4006 women with a singleton pregnancy, enrolled at 6–22 weeks of gestation, in a pregnancy biomarker cohort study. The placentas of all fetal deaths were histologically examined by pathologists who used a standardized protocol and were blinded to patient outcomes. Placental growth factor (PlGF), soluble endoglin (sEng), and soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) concentrations were measured by ELISA assays. Quantiles of the analyte concentrations (or concentration ratios) were estimated as a function of gestational age among women who delivered live neonates but did not develop preeclampsia or deliver small-for-gestational–age (SGA) newborns. A positive test was defined as analyte concentrations (or ratios) <2.5th and 10th centiles [PlGF, PlGF/sVEGFR-1 (angiogenic index-1), and PlGF/sEng)] or >90th and 97.5th centiles (sVEGFR-1 and sEng). Inverse probability weighting was used to reflect the parent cohort when estimating the relative risk. Results There were 11 fetal deaths and 829 controls with samples available for analysis between 24–28 weeks of gestation. Three fetal deaths occurred prior to 28 weeks and eight at or after 28 weeks of gestation. The rate of placental lesions consistent with maternal vascular underperfusion was 33.3% (1/3) among those who had a fetal death before 28 weeks and 87.5% (7/8) of those who had this complication at or after 28 weeks of gestation. The maternal plasma angiogenic index-1 value was below the 10th centile in 63.6% (7/11) of the fetal death group and in 11.1% (92/829) of the controls. The angiogenic index-1 value was <2.5th centile in 54.5% (6/11) of the fetal death group and in 3.7% (31/829) of the controls. An angiogenic index-1 value <2.5th centile had the largest positive likelihood ratio for predicting fetal death >24 weeks (14.6; 95% CI, 7.7–27.7) and a relative risk of 29.1 (95% CI, 8.8–97.1), followed by sEng >97.5thcentile and PlGF/sEng <2.5th, both with a positive likelihood ratio of 13.7 (95% CI, 7.3–25.8) and a relative risk of 27.4 (95% CI, 8.2–91.2). Among women without a fetal death whose plasma angiogenic index-1 concentration ratio was below the 2.5th centile, 61% (19/31) developed preeclampsia or delivered an SGA neonate; when the 10th centile was used as the cut-off, 37% (34/92) of women had these adverse outcomes. Conclusions 1) A maternal plasma angiogenic index-1 value below the 2.5th centile (0.126) at 24–28 weeks of gestation carries a 29-fold increase in the risk of subsequent fetal death and identifies 55% of subsequent fetal deaths with a false-positive rate of 3.5%; and 2) 61% of women who have a false-positive test result will subsequently experience adverse pregnancy outcomes.

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Section: Discussionmentioning

confidence: 99%

The prediction of fetal death with a simple maternal blood test at 24-28 weeks: a role for angiogenic index-1 (PlGF/sVEGFR-1 ratio)

Chaiworapongsa

Romero

Erez

et al. 2017

American Journal of Obstetrics and Gynecology

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“…Placental examination alone changed subsequent clinical management in 36% of cases. In 6% of all cases, medical recommendations for the management in a subsequent pregnancy changed, based on overall autopsy findings [47]. In another cohort with 230 fetuses, including miscarriages <20 weeks of gestation, SBs, and neonatal deaths, prenatal findings were confirmed in 23% of cases, and in 37% additional findings were observed.…”

Section: Fetal Autopsymentioning

confidence: 99%

“…This is well illustrated by the effect of classifying the same SB case in different classification systems [49]. In cases with impaired antenatal visualization by ultrasound in pregnancy, such as with maternal obesity or reduced amniotic fluid, fetal autopsy may be of particular value, whereas in others e for example, antenatally diagnosed aneuploidy e autopsy examination adds little in terms of management of future pregnancies [47]. However, there has been a consistent fall in the proportion of parents who consent to fetal autopsy.…”

Section: Considerations Regarding Autopsymentioning

confidence: 99%

“…Clinicians reported workload, negative publicity, religion, and cultural issues as important barriers [50]. In one study more than 30% of parents who declined fetal autopsy subsequently regretted their decision [50] therefore it is necessary to explain to the family the potential additional value of fetal autopsy, including the value of 'negative' findings for future discussions [47]. To help parents with their decision about fetal autopsy, it is necessary to provide clear and consistent user-friendly information.…”

Section: Considerations Regarding Autopsymentioning

confidence: 99%

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Perinatal death investigations: What is current practice?

Nijkamp

Sebire

Bouman

et al. 2017

Seminars in Fetal and Neonatal Medicine

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Perinatal death (PD) is a devastating obstetric complication. Determination of cause of death helps in understanding why and how it occurs, and it is an indispensable aid to parents wanting to understand why their baby died and to determine the recurrence risk and management in subsequent pregnancy. Consequently, a perinatal death requires adequate diagnostic investigation. An important first step in the analysis of PD is to identify the case circumstances, including relevant details regarding maternal history, obstetric history and current pregnancy (complications are evaluated and recorded). In the next step, placental examination is suggested in all cases, together with molecular cytogenetic evaluation and fetal autopsy. Investigation for fetal-maternal hemorrhage by Kleihauer is also recommended as standard. In cases where parents do not consent to autopsy, alternative approaches such as minimally invasive postmortem examination, postmortem magnetic resonance imaging, and fetal photographs are good alternatives. After all investigations have been performed it is important to combine findings from the clinical review and investigations together, to identify the most probable cause of death and counsel the parents regarding their loss.

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“…A number of lesions have been recognised in association with stillbirth C 24 week gestation [15]. 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.…”

Section: Placental Lesionsmentioning

confidence: 99%

Placental Pathology and Stillbirth: A Review of the Literature and Guidelines for the Less Experienced

Kulkarni¹,

Palaniappan

Evans

2017

Journal of Fetal Medicine

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The aim of this review is to examine the role of placental pathology in the understanding of singleton stillbirth. The placenta may be regarded as the ''black box'' of pregnancy and detailed examination may afford insight into the fetal and maternal events leading to this tragic outcome. In the UK, 1 in 200 to 1 in 240 pregnancies end in stillbirth whilst India accounts for the majority of global stillbirths. Between 2010 and 2013, India showed a decline in the stillbirth rate and it continues to fall-a recent report felt that the majority of deaths in the third trimester were preventable. However, in order to prevent such deaths we need to understand their cause. Postmortem studies may cast light on the many factors which lead to stillbirth or early neonatal death but there is anecdotal evidence that certain groups are reluctant to authorise postmortem examination and in a religiously diverse and observant country such as India, postmortem may not be acceptable to families. However, if the purpose of the postmortem study is properly explained, many families would agree to such an examination. In this paper the authors aim to look at how examination of the singleton placenta alone may provide valuable information regarding the causation of stillbirth and indicate potential treatment options for its prevention in future pregnanices. The authors will consider the more commonly encountered lesions, clinically and pathologically and provide guidelines for those less experienced in this field.

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Stillbirth evaluation: a stepwise assessment of placental pathology and autopsy

Cited by 49 publications

References 17 publications

The prediction of fetal death with a simple maternal blood test at 24-28 weeks: a role for angiogenic index-1 (PlGF/sVEGFR-1 ratio)

The prediction of fetal death with a simple maternal blood test at 24-28 weeks: a role for angiogenic index-1 (PlGF/sVEGFR-1 ratio)

Perinatal death investigations: What is current practice?

Placental Pathology and Stillbirth: A Review of the Literature and Guidelines for the Less Experienced

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