Organ weights and ratios for postmortem identification of fetal growth restriction: utility and confounding factors

Man, Jessica; Hutchinson, J. Ciaran; Ashworth, Michael; Jeffrey, I; Heazell, Alexander; Sebire, Neil J.

doi:10.1002/uog.16017

Cited by 28 publications

(33 citation statements)

References 16 publications

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“…For the purposes of this study, intrauterine growth restriction (IUGR) was given as the cause of death for cases in which an antenatal diagnosis of IUGR was documented and in which surveillance was ongoing; cases in which placental pathology of maternal vascular malperfusion or other definite fetal growth restriction (FGR)‐associated pathology was identified were classified as ‘placental’. The issue of determination of FGR based on body weight and organ weight ratios is investigated in detail elsewhere.…”

Section: Resultsmentioning

confidence: 99%

“…In order to allow comparison with published data, cases were classified using ReCoDe; this resulted in many more deaths becoming ‘attributed’ to FGR (37%), based purely on fetal weight at delivery (although there are methodological flaws with this approach). Nevertheless, around one third of cases remained unexplained even using the ReCoDe classification.…”

Section: Discussionmentioning

confidence: 99%

“…There was no association between postmortem interval and determination of cause of death, demonstrating that delay between delivery and autopsy, even of many days, does not affect the likelihood of determining a cause of death, providing that bodies are refrigerated suitably; this factor should not affect decisions regarding investigation after death. In order to allow comparison with published data, cases were classified using ReCoDe; this resulted in many more deaths becoming 'attributed' to FGR (37%), based purely on fetal weight at delivery (although there are methodological flaws with this approach) 17 . Nevertheless, around one third of cases remained unexplained even using the ReCoDe classification.…”

Section: Discussionmentioning

confidence: 99%

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Stillbirth and intrauterine fetal death: factors affecting determination of cause of death at autopsy

Man

Hutchinson

Heazell

et al. 2016

Ultrasound in Obstet & Gyne

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+A: AbstractObjectives There have been many attempts to classify cause of death in stillbirth, all such systems being subjective, allowing for significant observer bias, making accurate comparisons between systems challenging. The aim of this study was to examine factors relating to determination of cause of death by using a large dataset from two specialist centres, in which observer bias has been reduced by objectively classifying findings and assigning causes of death based on predetermined criteria.Methods Detailed autopsy reports from intrauterine fetal deaths (IUFD) during [2005][2006][2007][2008][2009][2010][2011][2012][2013] in the second and third trimesters were reviewed and findings entered into a specially designed database, in which cause of death (CoD) was assigned using predefined objective criteria. Data regarding CoD categories and factors affecting determination of CoD were analysed through queries and statistical tests run using Microsoft Access, Excel, Graph Pad Prism and StatsDirect, with Mann-Whitney U-test and comparison of proportions testing as appropriate.Results There were 1,064 IUFDs, including 639 stillbirths at >23 weeks' gestation.Overall, around 40% (412 (39%)), had a definite or highly likely cause of death identified, whilst 60% (652) were classified as 'unexplained'. Of these, around half had identified risk factors, or lesions of uncertain significance present, whilst the remaining half (292 (45%)) were entirely unexplained. A stepwise increase in the proportion of unexplained deaths was observed with increasing severity of maceration. Black and Asian women had significantly greater proportions of deaths due to ascending infection whilst women aged over 40 had significantly increased placental-related causes of death. There was no significant difference in cause of death distribution by maternal 3 body mass index or with increasing post-mortem interval. Almost 20% of definitive or likely causes of death could be identified from clinical review or external examination / imaging of the fetus, with most of the remainder being determined following placental examination.Conclusions Based on objective criteria, most IUFDs across gestation remain unexplained despite autopsy examination. The rate of unexplained death varies between 30 and 60% depending on interpretation of the significance of features. The cause of death provided across studies is variable and dependent on both the classification system used and subjective interpretation such that reduction in the proportion of 'unexplained' cases across studies is largely based on speculation around mechanism of death. Novel methods to determine objectively the mechanism of death at postmortem examination are required. 4 +A: IntroductionThe primary aim of postmortem investigation of intrauterine death is determination of cause and mechanism of death, to facilitate counseling of parents, management of subsequent pregnancies and future interventions [1][2][3][4] . Over the last 50 years there have been many attempts to classify cause o...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Stillbirth and intrauterine fetal death: factors affecting determination of cause of death at autopsy

Man

Hutchinson

Heazell

et al. 2016

Ultrasound in Obstet & Gyne

Self Cite

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“…25 Similar to humans, maternal undernutrition in mice resulted in an asymmetric growth restriction, with the most significant impact on the liver. 26 The thymus and spleen are also smaller relative to body weight in SGA autopsies, 26 but were not measured in this study. Although reduced again at 6 months, 1-month relative liver weights were similar to controls, which might indicate differences in growth rate of the liver in MNR offspring.…”

Section: Discussionmentioning

confidence: 55%

Offspring from maternal nutrient restriction in mice show variations in adult glucose metabolism similar to human fetal growth restriction

Radford

Han

2018

J Dev Orig Health Dis

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Fetal growth restriction (FGR) is a pregnancy condition in which fetal growth is suboptimal for gestation, and this population is at increased risk for type 2 diabetes as adults. In humans, maternal malnutrition and placental insufficiency are the most common causes of FGR, and both result in fetal undernutrition. We hypothesized that maternal nutrient restriction (MNR) in mice will cause FGR and alter glucose metabolism in adult offspring. Pregnant CD-1 mice were subjected to MNR (70% of average ad libitum) or control (ad libitum) from E6.5 to birth. Following birth, mice were fostered by mothers on ad libitum feeds. Weight, blood glucose, glucose tolerance and tissue-specific insulin sensitivity were assessed in male offspring. MNR resulted in reduced fetal sizes but caught up to controls by 3 days postnatal age. As adults, glucose intolerance was detected in 19% of male MNR offspring. At 6 months, liver size was reduced (P = 0.01), but pAkt-to-Akt ratios in response to insulin were increased 2.5-fold relative to controls (P = 0.004). These data suggest that MNR causes FGR and long-term glucose intolerance in a population of male offspring similar to human populations. This mouse model can be used to investigate the impacts of FGR on tissues of importance in glucose metabolism.

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“…Establishing a formal autopsy research program, they undertook the mammoth task of assembling a database of over a 1000 postmortem records with over 400 data fields per case. This database provided the rich seam that the authors have mined in their series of articles that have been published together. Abigail Adams, former First Lady of the USA, stated that ‘Learning is not attained by chance, it must be sought for with ardor and attended to with diligence’.…”

mentioning

confidence: 99%

Stillbirth: a lot done… a lot more to do

McDermott

2016

Ultrasound in Obstet & Gyne

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Organ weights and ratios for postmortem identification of fetal growth restriction: utility and confounding factors

Abstract: Objectives The postmortem fetal brain:liver weight ratio is commonly used as a marker of nutrition for diagnosis of fetal growth restriction (FGR).

Cited by 28 publications

References 16 publications

Stillbirth and intrauterine fetal death: factors affecting determination of cause of death at autopsy

Stillbirth and intrauterine fetal death: factors affecting determination of cause of death at autopsy

Offspring from maternal nutrient restriction in mice show variations in adult glucose metabolism similar to human fetal growth restriction

Stillbirth: a lot done… a lot more to do

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