The association of stillbirth with placental abnormalities in growth-restricted and normally grown fetuses

Alexa A. Freedman, Robert M. Silver, Karen Gibbins, Carol J. Hogue, Robert L. Goldenberg, Donald J. Dudley, Halit Pinar, Carolyn Drews-Botsch

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Stillbirth, defined as foetal death ≥20 weeks’ gestation, is associated with poor foetal growth and is often attributed to placental abnormalities, which are also associated with poor foetal growth. Evaluating inter-relationships between placental abnormalities, poor foetal growth, and stillbirth may improve our understanding of the underlying mechanisms for some causes of stillbirth. Objective: Our primary objective was to determine whether poor foetal growth, operationalised as small for gestational age (SGA), mediates the relationship between placental abnormalities and stillbirth. Methods: We used data from the Stillbirth Collaborative Research Network study, a population-based case-control study conducted from 2006-2008. Our analysis included 266 stillbirths and 1135 livebirths. We evaluated associations of stillbirth with five types of placental characteristics (developmental disorders, maternal and foetal inflammatory responses, and maternal and foetal circulatory disorders) and examined mediation of these relationships by SGA. We also assessed exposure-mediator interaction. Models were adjusted for maternal age, race/ethnicity, education, body mass index, parity, and smoking status. Results: All five placental abnormalities were more prevalent in cases than controls. After adjustment for potential confounders, maternal inflammatory response (odds ratio [OR] 2.58, 95% confidence interval [CI] 1.77, 3.75), maternal circulatory disorders OR 4.14, 95% CI 2.93, 5.84, and foetal circulatory disorders OR 4.58, 95% CI 3.11, 6.74 were strongly associated with stillbirth, and the relationships did not appear to be mediated by SGA status. Associations for developmental disorders and foetal inflammatory response diverged for SGA and non-SGA births, and strong associations were only observed when SGA was not present. Conclusions: Foetal growth did not mediate the relationships between placental abnormalities and stillbirth. The relationships of stillbirth with maternal and foetal circulatory disorders and maternal inflammatory response appear to be independent of poor foetal growth, while developmental disorders and foetal inflammatory response likely interact with foetal growth to affect stillbirth risk.

Original languageEnglish (US)
Pages (from-to)274-383
Number of pages110
JournalPaediatric and Perinatal Epidemiology
Volume33
Issue number4
DOIs
StatePublished - Jul 1 2019

Fingerprint

Stillbirth
Fetus
Fetal Development
Growth
Gestational Age
Mothers
Odds Ratio
Confidence Intervals
Fetal Death
Maternal Age
Parity
Case-Control Studies
Body Mass Index
Smoking
Parturition
Education

Keywords

  • foetal growth retardation
  • infant
  • placenta
  • small for gestational age
  • stillbirth

ASJC Scopus subject areas

  • Epidemiology
  • Pediatrics, Perinatology, and Child Health

Cite this

Freedman, A. A., Silver, R. M., Gibbins, K., Hogue, C. J., Goldenberg, R. L., Dudley, D. J., ... Drews-Botsch, C. (2019). The association of stillbirth with placental abnormalities in growth-restricted and normally grown fetuses. Paediatric and Perinatal Epidemiology, 33(4), 274-383. https://doi.org/10.1111/ppe.12563

The association of stillbirth with placental abnormalities in growth-restricted and normally grown fetuses. / Freedman, Alexa A.; Silver, Robert M.; Gibbins, Karen; Hogue, Carol J.; Goldenberg, Robert L.; Dudley, Donald J.; Pinar, Halit; Drews-Botsch, Carolyn.

In: Paediatric and Perinatal Epidemiology, Vol. 33, No. 4, 01.07.2019, p. 274-383.

Research output: Contribution to journalArticle

Freedman, AA, Silver, RM, Gibbins, K, Hogue, CJ, Goldenberg, RL, Dudley, DJ, Pinar, H & Drews-Botsch, C 2019, 'The association of stillbirth with placental abnormalities in growth-restricted and normally grown fetuses', Paediatric and Perinatal Epidemiology, vol. 33, no. 4, pp. 274-383. https://doi.org/10.1111/ppe.12563
Freedman, Alexa A. ; Silver, Robert M. ; Gibbins, Karen ; Hogue, Carol J. ; Goldenberg, Robert L. ; Dudley, Donald J. ; Pinar, Halit ; Drews-Botsch, Carolyn. / The association of stillbirth with placental abnormalities in growth-restricted and normally grown fetuses. In: Paediatric and Perinatal Epidemiology. 2019 ; Vol. 33, No. 4. pp. 274-383.
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abstract = "Background: Stillbirth, defined as foetal death ≥20 weeks’ gestation, is associated with poor foetal growth and is often attributed to placental abnormalities, which are also associated with poor foetal growth. Evaluating inter-relationships between placental abnormalities, poor foetal growth, and stillbirth may improve our understanding of the underlying mechanisms for some causes of stillbirth. Objective: Our primary objective was to determine whether poor foetal growth, operationalised as small for gestational age (SGA), mediates the relationship between placental abnormalities and stillbirth. Methods: We used data from the Stillbirth Collaborative Research Network study, a population-based case-control study conducted from 2006-2008. Our analysis included 266 stillbirths and 1135 livebirths. We evaluated associations of stillbirth with five types of placental characteristics (developmental disorders, maternal and foetal inflammatory responses, and maternal and foetal circulatory disorders) and examined mediation of these relationships by SGA. We also assessed exposure-mediator interaction. Models were adjusted for maternal age, race/ethnicity, education, body mass index, parity, and smoking status. Results: All five placental abnormalities were more prevalent in cases than controls. After adjustment for potential confounders, maternal inflammatory response (odds ratio [OR] 2.58, 95{\%} confidence interval [CI] 1.77, 3.75), maternal circulatory disorders OR 4.14, 95{\%} CI 2.93, 5.84, and foetal circulatory disorders OR 4.58, 95{\%} CI 3.11, 6.74 were strongly associated with stillbirth, and the relationships did not appear to be mediated by SGA status. Associations for developmental disorders and foetal inflammatory response diverged for SGA and non-SGA births, and strong associations were only observed when SGA was not present. Conclusions: Foetal growth did not mediate the relationships between placental abnormalities and stillbirth. The relationships of stillbirth with maternal and foetal circulatory disorders and maternal inflammatory response appear to be independent of poor foetal growth, while developmental disorders and foetal inflammatory response likely interact with foetal growth to affect stillbirth risk.",
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AU - Silver, Robert M.

AU - Gibbins, Karen

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AU - Goldenberg, Robert L.

AU - Dudley, Donald J.

AU - Pinar, Halit

AU - Drews-Botsch, Carolyn

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N2 - Background: Stillbirth, defined as foetal death ≥20 weeks’ gestation, is associated with poor foetal growth and is often attributed to placental abnormalities, which are also associated with poor foetal growth. Evaluating inter-relationships between placental abnormalities, poor foetal growth, and stillbirth may improve our understanding of the underlying mechanisms for some causes of stillbirth. Objective: Our primary objective was to determine whether poor foetal growth, operationalised as small for gestational age (SGA), mediates the relationship between placental abnormalities and stillbirth. Methods: We used data from the Stillbirth Collaborative Research Network study, a population-based case-control study conducted from 2006-2008. Our analysis included 266 stillbirths and 1135 livebirths. We evaluated associations of stillbirth with five types of placental characteristics (developmental disorders, maternal and foetal inflammatory responses, and maternal and foetal circulatory disorders) and examined mediation of these relationships by SGA. We also assessed exposure-mediator interaction. Models were adjusted for maternal age, race/ethnicity, education, body mass index, parity, and smoking status. Results: All five placental abnormalities were more prevalent in cases than controls. After adjustment for potential confounders, maternal inflammatory response (odds ratio [OR] 2.58, 95% confidence interval [CI] 1.77, 3.75), maternal circulatory disorders OR 4.14, 95% CI 2.93, 5.84, and foetal circulatory disorders OR 4.58, 95% CI 3.11, 6.74 were strongly associated with stillbirth, and the relationships did not appear to be mediated by SGA status. Associations for developmental disorders and foetal inflammatory response diverged for SGA and non-SGA births, and strong associations were only observed when SGA was not present. Conclusions: Foetal growth did not mediate the relationships between placental abnormalities and stillbirth. The relationships of stillbirth with maternal and foetal circulatory disorders and maternal inflammatory response appear to be independent of poor foetal growth, while developmental disorders and foetal inflammatory response likely interact with foetal growth to affect stillbirth risk.

AB - Background: Stillbirth, defined as foetal death ≥20 weeks’ gestation, is associated with poor foetal growth and is often attributed to placental abnormalities, which are also associated with poor foetal growth. Evaluating inter-relationships between placental abnormalities, poor foetal growth, and stillbirth may improve our understanding of the underlying mechanisms for some causes of stillbirth. Objective: Our primary objective was to determine whether poor foetal growth, operationalised as small for gestational age (SGA), mediates the relationship between placental abnormalities and stillbirth. Methods: We used data from the Stillbirth Collaborative Research Network study, a population-based case-control study conducted from 2006-2008. Our analysis included 266 stillbirths and 1135 livebirths. We evaluated associations of stillbirth with five types of placental characteristics (developmental disorders, maternal and foetal inflammatory responses, and maternal and foetal circulatory disorders) and examined mediation of these relationships by SGA. We also assessed exposure-mediator interaction. Models were adjusted for maternal age, race/ethnicity, education, body mass index, parity, and smoking status. Results: All five placental abnormalities were more prevalent in cases than controls. After adjustment for potential confounders, maternal inflammatory response (odds ratio [OR] 2.58, 95% confidence interval [CI] 1.77, 3.75), maternal circulatory disorders OR 4.14, 95% CI 2.93, 5.84, and foetal circulatory disorders OR 4.58, 95% CI 3.11, 6.74 were strongly associated with stillbirth, and the relationships did not appear to be mediated by SGA status. Associations for developmental disorders and foetal inflammatory response diverged for SGA and non-SGA births, and strong associations were only observed when SGA was not present. Conclusions: Foetal growth did not mediate the relationships between placental abnormalities and stillbirth. The relationships of stillbirth with maternal and foetal circulatory disorders and maternal inflammatory response appear to be independent of poor foetal growth, while developmental disorders and foetal inflammatory response likely interact with foetal growth to affect stillbirth risk.

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