Fetal Growth and Risk of Stillbirth: A Population-Based Case-Control Study

Radek Bukowski, Nellie I. Hansen, Marian Willinger, Marian Willinger, Uma M. Reddy, Corette B. Parker, Halit Pinar, Robert M. Silver, Donald J. Dudley, Barbara J. Stoll, George Saade, Matthew A. Koch, Carol J. Rowland Hogue, Michael W. Varner, Deborah L. Conway, Donald Coustan, Robert L. Goldenberg, Reverend Phillip Cato, James W. Collins, Terry DwyerWilliam P. Fifer, John Ilekis, Marc Incerpi, George Macones, M. Richard, Raymond W. Redline, Elizabeth Thom Thom

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Background:Stillbirth is strongly related to impaired fetal growth. However, the relationship between fetal growth and stillbirth is difficult to determine because of uncertainty in the timing of death and confounding characteristics affecting normal fetal growth.Methods and Findings:We conducted a population-based case-control study of all stillbirths and a representative sample of live births in 59 hospitals in five geographic areas in the US. Fetal growth abnormalities were categorized as small for gestational age (SGA) (<10th percentile) or large for gestational age (LGA) (>90th percentile) at death (stillbirth) or delivery (live birth) using population, ultrasound, and individualized norms. Gestational age at death was determined using an algorithm that considered the time-of-death interval, postmortem examination, and reliability of the gestational age estimate. Data were weighted to account for the sampling design and differential participation rates in various subgroups. Among 527 singleton stillbirths and 1,821 singleton live births studied, stillbirth was associated with SGA based on population, ultrasound, and individualized norms (odds ratio [OR] [95% CI]: 3.0 [2.2 to 4.0]; 4.7 [3.7 to 5.9]; 4.6 [3.6 to 5.9], respectively). LGA was also associated with increased risk of stillbirth using ultrasound and individualized norms (OR [95% CI]: 3.5 [2.4 to 5.0]; 2.3 [1.7 to 3.1], respectively), but not population norms (OR [95% CI]: 0.6 [0.4 to 1.0]). The associations were stronger with more severe SGA and LGA (<5th and >95th percentile). Analyses adjusted for stillbirth risk factors, subset analyses excluding potential confounders, and analyses in preterm and term pregnancies showed similar patterns of association. In this study 70% of cases and 63% of controls agreed to participate. Analysis weights accounted for differences between consenting and non-consenting women. Some of the characteristics used for individualized fetal growth estimates were missing and were replaced with reference values. However, a sensitivity analysis using individualized norms based on the subset of stillbirths and live births with non-missing variables showed similar findings.Conclusions:Stillbirth is associated with both growth restriction and excessive fetal growth. These findings suggest that, contrary to current practices and recommendations, stillbirth prevention strategies should focus on both severe SGA and severe LGA pregnancies.Please see later in the article for the Editors' Summary.

Original languageEnglish (US)
Article numbere1001633
JournalPLoS Medicine
Volume11
Issue number4
DOIs
StatePublished - 2014

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Stillbirth
Fetal Development
Case-Control Studies
Gestational Age
Population
Live Birth
Odds Ratio
Pregnancy
Statistical Factor Analysis
Uncertainty
Autopsy
Reference Values
Weights and Measures

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Bukowski, R., Hansen, N. I., Willinger, M., Willinger, M., Reddy, U. M., Parker, C. B., ... Thom, E. T. (2014). Fetal Growth and Risk of Stillbirth: A Population-Based Case-Control Study. PLoS Medicine, 11(4), [e1001633]. https://doi.org/10.1371/journal.pmed.1001633

Fetal Growth and Risk of Stillbirth : A Population-Based Case-Control Study. / Bukowski, Radek; Hansen, Nellie I.; Willinger, Marian; Willinger, Marian; Reddy, Uma M.; Parker, Corette B.; Pinar, Halit; Silver, Robert M.; Dudley, Donald J.; Stoll, Barbara J.; Saade, George; Koch, Matthew A.; Rowland Hogue, Carol J.; Varner, Michael W.; Conway, Deborah L.; Coustan, Donald; Goldenberg, Robert L.; Cato, Reverend Phillip; Collins, James W.; Dwyer, Terry; Fifer, William P.; Ilekis, John; Incerpi, Marc; Macones, George; Richard, M.; Redline, Raymond W.; Thom, Elizabeth Thom.

In: PLoS Medicine, Vol. 11, No. 4, e1001633, 2014.

Research output: Contribution to journalArticle

Bukowski, R, Hansen, NI, Willinger, M, Willinger, M, Reddy, UM, Parker, CB, Pinar, H, Silver, RM, Dudley, DJ, Stoll, BJ, Saade, G, Koch, MA, Rowland Hogue, CJ, Varner, MW, Conway, DL, Coustan, D, Goldenberg, RL, Cato, RP, Collins, JW, Dwyer, T, Fifer, WP, Ilekis, J, Incerpi, M, Macones, G, Richard, M, Redline, RW & Thom, ET 2014, 'Fetal Growth and Risk of Stillbirth: A Population-Based Case-Control Study', PLoS Medicine, vol. 11, no. 4, e1001633. https://doi.org/10.1371/journal.pmed.1001633
Bukowski R, Hansen NI, Willinger M, Willinger M, Reddy UM, Parker CB et al. Fetal Growth and Risk of Stillbirth: A Population-Based Case-Control Study. PLoS Medicine. 2014;11(4). e1001633. https://doi.org/10.1371/journal.pmed.1001633
Bukowski, Radek ; Hansen, Nellie I. ; Willinger, Marian ; Willinger, Marian ; Reddy, Uma M. ; Parker, Corette B. ; Pinar, Halit ; Silver, Robert M. ; Dudley, Donald J. ; Stoll, Barbara J. ; Saade, George ; Koch, Matthew A. ; Rowland Hogue, Carol J. ; Varner, Michael W. ; Conway, Deborah L. ; Coustan, Donald ; Goldenberg, Robert L. ; Cato, Reverend Phillip ; Collins, James W. ; Dwyer, Terry ; Fifer, William P. ; Ilekis, John ; Incerpi, Marc ; Macones, George ; Richard, M. ; Redline, Raymond W. ; Thom, Elizabeth Thom. / Fetal Growth and Risk of Stillbirth : A Population-Based Case-Control Study. In: PLoS Medicine. 2014 ; Vol. 11, No. 4.
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abstract = "Background:Stillbirth is strongly related to impaired fetal growth. However, the relationship between fetal growth and stillbirth is difficult to determine because of uncertainty in the timing of death and confounding characteristics affecting normal fetal growth.Methods and Findings:We conducted a population-based case-control study of all stillbirths and a representative sample of live births in 59 hospitals in five geographic areas in the US. Fetal growth abnormalities were categorized as small for gestational age (SGA) (<10th percentile) or large for gestational age (LGA) (>90th percentile) at death (stillbirth) or delivery (live birth) using population, ultrasound, and individualized norms. Gestational age at death was determined using an algorithm that considered the time-of-death interval, postmortem examination, and reliability of the gestational age estimate. Data were weighted to account for the sampling design and differential participation rates in various subgroups. Among 527 singleton stillbirths and 1,821 singleton live births studied, stillbirth was associated with SGA based on population, ultrasound, and individualized norms (odds ratio [OR] [95{\%} CI]: 3.0 [2.2 to 4.0]; 4.7 [3.7 to 5.9]; 4.6 [3.6 to 5.9], respectively). LGA was also associated with increased risk of stillbirth using ultrasound and individualized norms (OR [95{\%} CI]: 3.5 [2.4 to 5.0]; 2.3 [1.7 to 3.1], respectively), but not population norms (OR [95{\%} CI]: 0.6 [0.4 to 1.0]). The associations were stronger with more severe SGA and LGA (<5th and >95th percentile). Analyses adjusted for stillbirth risk factors, subset analyses excluding potential confounders, and analyses in preterm and term pregnancies showed similar patterns of association. In this study 70{\%} of cases and 63{\%} of controls agreed to participate. Analysis weights accounted for differences between consenting and non-consenting women. Some of the characteristics used for individualized fetal growth estimates were missing and were replaced with reference values. However, a sensitivity analysis using individualized norms based on the subset of stillbirths and live births with non-missing variables showed similar findings.Conclusions:Stillbirth is associated with both growth restriction and excessive fetal growth. These findings suggest that, contrary to current practices and recommendations, stillbirth prevention strategies should focus on both severe SGA and severe LGA pregnancies.Please see later in the article for the Editors' Summary.",
author = "Radek Bukowski and Hansen, {Nellie I.} and Marian Willinger and Marian Willinger and Reddy, {Uma M.} and Parker, {Corette B.} and Halit Pinar and Silver, {Robert M.} and Dudley, {Donald J.} and Stoll, {Barbara J.} and George Saade and Koch, {Matthew A.} and {Rowland Hogue}, {Carol J.} and Varner, {Michael W.} and Conway, {Deborah L.} and Donald Coustan and Goldenberg, {Robert L.} and Cato, {Reverend Phillip} and Collins, {James W.} and Terry Dwyer and Fifer, {William P.} and John Ilekis and Marc Incerpi and George Macones and M. Richard and Redline, {Raymond W.} and Thom, {Elizabeth Thom}",
year = "2014",
doi = "10.1371/journal.pmed.1001633",
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TY - JOUR

T1 - Fetal Growth and Risk of Stillbirth

T2 - A Population-Based Case-Control Study

AU - Bukowski, Radek

AU - Hansen, Nellie I.

AU - Willinger, Marian

AU - Willinger, Marian

AU - Reddy, Uma M.

AU - Parker, Corette B.

AU - Pinar, Halit

AU - Silver, Robert M.

AU - Dudley, Donald J.

AU - Stoll, Barbara J.

AU - Saade, George

AU - Koch, Matthew A.

AU - Rowland Hogue, Carol J.

AU - Varner, Michael W.

AU - Conway, Deborah L.

AU - Coustan, Donald

AU - Goldenberg, Robert L.

AU - Cato, Reverend Phillip

AU - Collins, James W.

AU - Dwyer, Terry

AU - Fifer, William P.

AU - Ilekis, John

AU - Incerpi, Marc

AU - Macones, George

AU - Richard, M.

AU - Redline, Raymond W.

AU - Thom, Elizabeth Thom

PY - 2014

Y1 - 2014

N2 - Background:Stillbirth is strongly related to impaired fetal growth. However, the relationship between fetal growth and stillbirth is difficult to determine because of uncertainty in the timing of death and confounding characteristics affecting normal fetal growth.Methods and Findings:We conducted a population-based case-control study of all stillbirths and a representative sample of live births in 59 hospitals in five geographic areas in the US. Fetal growth abnormalities were categorized as small for gestational age (SGA) (<10th percentile) or large for gestational age (LGA) (>90th percentile) at death (stillbirth) or delivery (live birth) using population, ultrasound, and individualized norms. Gestational age at death was determined using an algorithm that considered the time-of-death interval, postmortem examination, and reliability of the gestational age estimate. Data were weighted to account for the sampling design and differential participation rates in various subgroups. Among 527 singleton stillbirths and 1,821 singleton live births studied, stillbirth was associated with SGA based on population, ultrasound, and individualized norms (odds ratio [OR] [95% CI]: 3.0 [2.2 to 4.0]; 4.7 [3.7 to 5.9]; 4.6 [3.6 to 5.9], respectively). LGA was also associated with increased risk of stillbirth using ultrasound and individualized norms (OR [95% CI]: 3.5 [2.4 to 5.0]; 2.3 [1.7 to 3.1], respectively), but not population norms (OR [95% CI]: 0.6 [0.4 to 1.0]). The associations were stronger with more severe SGA and LGA (<5th and >95th percentile). Analyses adjusted for stillbirth risk factors, subset analyses excluding potential confounders, and analyses in preterm and term pregnancies showed similar patterns of association. In this study 70% of cases and 63% of controls agreed to participate. Analysis weights accounted for differences between consenting and non-consenting women. Some of the characteristics used for individualized fetal growth estimates were missing and were replaced with reference values. However, a sensitivity analysis using individualized norms based on the subset of stillbirths and live births with non-missing variables showed similar findings.Conclusions:Stillbirth is associated with both growth restriction and excessive fetal growth. These findings suggest that, contrary to current practices and recommendations, stillbirth prevention strategies should focus on both severe SGA and severe LGA pregnancies.Please see later in the article for the Editors' Summary.

AB - Background:Stillbirth is strongly related to impaired fetal growth. However, the relationship between fetal growth and stillbirth is difficult to determine because of uncertainty in the timing of death and confounding characteristics affecting normal fetal growth.Methods and Findings:We conducted a population-based case-control study of all stillbirths and a representative sample of live births in 59 hospitals in five geographic areas in the US. Fetal growth abnormalities were categorized as small for gestational age (SGA) (<10th percentile) or large for gestational age (LGA) (>90th percentile) at death (stillbirth) or delivery (live birth) using population, ultrasound, and individualized norms. Gestational age at death was determined using an algorithm that considered the time-of-death interval, postmortem examination, and reliability of the gestational age estimate. Data were weighted to account for the sampling design and differential participation rates in various subgroups. Among 527 singleton stillbirths and 1,821 singleton live births studied, stillbirth was associated with SGA based on population, ultrasound, and individualized norms (odds ratio [OR] [95% CI]: 3.0 [2.2 to 4.0]; 4.7 [3.7 to 5.9]; 4.6 [3.6 to 5.9], respectively). LGA was also associated with increased risk of stillbirth using ultrasound and individualized norms (OR [95% CI]: 3.5 [2.4 to 5.0]; 2.3 [1.7 to 3.1], respectively), but not population norms (OR [95% CI]: 0.6 [0.4 to 1.0]). The associations were stronger with more severe SGA and LGA (<5th and >95th percentile). Analyses adjusted for stillbirth risk factors, subset analyses excluding potential confounders, and analyses in preterm and term pregnancies showed similar patterns of association. In this study 70% of cases and 63% of controls agreed to participate. Analysis weights accounted for differences between consenting and non-consenting women. Some of the characteristics used for individualized fetal growth estimates were missing and were replaced with reference values. However, a sensitivity analysis using individualized norms based on the subset of stillbirths and live births with non-missing variables showed similar findings.Conclusions:Stillbirth is associated with both growth restriction and excessive fetal growth. These findings suggest that, contrary to current practices and recommendations, stillbirth prevention strategies should focus on both severe SGA and severe LGA pregnancies.Please see later in the article for the Editors' Summary.

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