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Identifying the causes of stillbirth: a comparison

of four classification systemsPatrizia Vergani, MD; Sabrina Cozzolino, MD; Elisa Pozzi, MD; Maria Serena Cuttin, MD;

Massimiliano Greco, MD; Sara Ornaghi, MD; Valeria Lucchini, MD

OBJECTIVE: To identify the classification protocol for stillbirth thatminimizes the rate of unexplained causes.

STUDY DESIGN: All stillbirths at 22 weeks from 1995-2007 under-went a workup inclusive of fetal ultrasonography, amniocentesis forkaryotype and cultures, placental histology, fetal autopsy, skin biopsy,total body X-ray, maternal testing for thrombophilias, TORCH,  Parvo- virus  spp, thyroid function, indirect Coombs, Kleiheuer-Betke test, andgenital cultures. To such a cohort, we applied the 4 most commonlyused classification protocols.

RESULTS: The stillbirth rate during the study period was 0.4% (154/ 

37,958). The RoDeCo classification provided the lowest rate of unex-

plained stillbirth (14.3%) compared with Wigglesworth (47.4%), de Ga-

lan-Roosen (18.2%), and Tulip (16.2%) classifications. Mean gestational

age at stillbirth in unexplained vs explained stillbirth was similar in the 4

protocols.

CONCLUSION: Adoption of a consistent and appropriate workup proto-

col can reduce the rate of unexplained stillbirth to 14%.

Key words: Cause of death, classification systems, stillbirth

Cite this article as: Vergani P, Cozzolino S, Pozzi E, et al. Identifying the causes of stillbirth: a comparison of 4 classification systems. Am J Obstet Gynecol 2008;

199:319.e1-319.e4.

S tillbirths are one of the most com-

mon adverse pregnancy outcomes,

with estimated rates of 5.3 per 1000 de-

liveries in developed countries and 25.5

per 1000 in developing countries.1

Despite the intensification of obstet-

ric surveillance, the stillbirth rate at

22 weeks has remained constant for thepast 3 decades. Detection of causes of 

stillbirths is important to identify defi-

ciencies in the provision of care, to fo-

cus attention on areas in which im-

provements are possible, and to

indicate areas in which new develop-

ments or knowledge may be expected

to lead to preventive measures to lower

perinatal mortality.2 However, classifi-

cation of causes of stillbirth is oftenambiguous because of the complicatedpathophysiologic processes encoun-tered in the mother, fetus, and pla-centa, and the fact that stillbirths oftenresult from interaction of differentprocesses. The classification systems

proposed differ in approaches, defini-tions, and levels of complexity.3-8

However, no single system is univer-sally accepted and the comparisonamong systems is difficult.

The aim of this study is to comparedifferent classifications systems on a co-hort of stillbirths undergoing a consis-tent and comprehensive workup to es-tablish which classification minimizesrates of unexplained stillbirth, that is“unknown” cases of fetal death.

MATERIALS AND METHODS

We conducted a retrospective study on acohort of stillbirths diagnosed at the De-partment of Obstetrics and Gynecology of the San Gerardo Hospital. Monza, It-aly, between January 1995 and Decem-ber 2007. The diagnosis of stillbirth wasbased on the World Health Organiza-tion (WHO) recommendations andwas definedas fetal death at22 weeks of 

gestation or greater, or birthweight

500 g if the gestational age was un-

known.9,10 Patient information re-

corded included date of delivery, ges-

tational age, maternal demographic

characteristics, including body mass

index, neonatal sex and birthweight,

and pregnancy details.

During the study period, all stillbirths

underwent evaluation according to auniform and comprehensive protocol

that included fetal ultrasonography, am-

niocentesis for karyotype and cultures,

placentalhistology,autopsy, skin biopsy,

total body X ray, maternal testing for in-

herited and acquired thrombophilias,

TORCH,  Parvovirus  spp, thyroid func-

tion, indirect Coombs, Kleiheuer-Betke

test, and genital cultures. Growth restric-

tion was definedas fetal weight below the

10th customized percentile, using the

gestation-related optimal weight soft-

ware (GROW), version 7.4.2 (www.

gestation.net), which calculates the fetal

growth potential by adjusting for the fe-

tal sex and parental constitutional char-

acteristic known at the beginning of the

pregnancy.

To our cohort, we applied 4 classifica-

tion systems published in the obstetric

and pathology literature during the past

20 years for theidentification of causesof 

stillbirth.

3-8

A panel of 2 obstetricians re-viewed all stillbirth cases and classified

From the Departments of Obstetrics andGynecology (Drs Vergani, Cozzolino, Pozzi,

Greco, and Ornaghi) and Pathology (Drs

Cuttin and Lucchini), University of Milano-

Bicocca, Monza, Italy.

Presented at the 28th Annual Meeting of theSociety for Maternal-Fetal Medicine, Dallas, TX,Jan. 28-Feb. 2, 2008.

Received Feb. 28, 2008; revised May 1, 2008;accepted June 30, 2008.

Reprints not available from the author.

0002-9378/$34.00© 2008 Mosby, Inc. All rights reserved.

doi: 10.1016/j.ajog.2008.06.098

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the causes according to the 4 selectedclassification systems.

R ESULTS

During the 12 years of the study period,there were 154 stillbirths of a total of 37,958 births, yielding a stillbirth rate of 4 per 1000. Clinical records were avail-able for all deaths. Median gestationalage at delivery was 31 weeks and 2 days(range, 22-42 weeks). Median age of themothers was 31 years (range, 18-43

 years). Autopsy and placental examina-tion were performed in 152 (98.7%)cases.

The contribution of individual tests inthe detection of risk or causative factorsfor stillbirth is delineated in Table 1.

Tables 2-5 display the distribution of causes of death in our cohort accordingto the classifications of Wigglesworth,3

de   Galan-Roosen,6 ReCoDe,7 and Tu-lip.8 The extended Wigglesworth classi-fication, which is the classification

system most commonly used interna-tionally, found “unknown” causes (un-explained or unclassifiable) in 73 cases(47.4%) in our cohort. The 3 more re-cent classification systems allocated aproportion of these 73 cases to known

causes of stillbirth. The de Galan-Roosenclassification allocated 42 of 73 cases toplacental causes; the ReCoDe classifica-tion allocated 20 of 73 cases to fetalgrowth restriction; and the Tulip classi-fication identified placenta/umbilicalcord causes in 45 of 73 cases. The 3 morerecent classification systems had thusfewer unknown cases of stillbirth thanthe extended Wigglesworth classifica-tion, with percentages of 18.2% for deGalan-Roosen classification, 14.3% for

ReCoDe classification, and 16.2% forTulip classification.The median gestational ages were sim-

ilar in the group with “unknown” vsknown causes of stillbirth (31.4 [range,25.0-40.0] vs 31.2 [range, 22.3-42.2]);however, all cases of “unknown” still-births in all 4 classifications occurred af-ter 25 weeks.

COMMENT

We have found that the commonly usedWigglesworth classification3 of still-births results in a higher proportion of unexplained stillbirths compared withnewer classification systems that includefetal growth restriction and placentaldisease as causative processes of fetaldeath. Indeed, in our cohort, theWigglesworth classification3 failed toidentify a cause of stillbirth in nearly half of the cases, whereas such rate decreasedto 18%, 14%, and 16% using the classifi-

cations proposed by  de Galan Roosen,

6

ReCoDe,7 and Tulip,8 respectively.The reduction in rates of unexplained

stillbirthin the more recent classificationsystems results from the inclusion of ab-normalities in fetal growth and patho-logic changes of placenta as causal cate-gories. Indeed, both conditions are largecontributing factors to stillbirths, andthe newer classifications acknowledgethe vital role of the placenta in determin-ing optimal fetal development. The Tu-

lip classification

8

focused on placentalcauses of death, validating the impor-

TABLE 1

Contribution of individual tests in the identificationof causative or risk factors for stillbirths

Test n %

Placental histology 119 77.3.....................................................................................................................................................................................................................................

Severe lesionsa

75 48.7.....................................................................................................................................................................................................................................

Mild lesionsb 44 28.6..............................................................................................................................................................................................................................................

 Autopsy findings (with normal karyotype) 38 24.7..............................................................................................................................................................................................................................................

 Abnormal karyotype 18 11.7..............................................................................................................................................................................................................................................

Total body X- ray 0 0..............................................................................................................................................................................................................................................

Skin biopsy 0 0..............................................................................................................................................................................................................................................

TORCH, Parvovirus  spp, and genital cultures 29 18.8..............................................................................................................................................................................................................................................

Kleiheuer-Betke test 1 0.6..............................................................................................................................................................................................................................................

Maternal testing for inherited and acquired thrombophilias 44 28.6..............................................................................................................................................................................................................................................

Total 154

..............................................................................................................................................................................................................................................a Severe lesions: severe vascular or inflammatory lesions, placental abruptio, true knots of the umbilical cord, thrombosisof umbilical vessels.

b Mild lesions: mild vascular or inflammatory lesions.

Vergani. Identifying the causes of stillbirth. Am J Obstet Gynecol 2008.

TABLE 2

Extended Wigglesworth classification: application to current study

Code Classification n %

154..............................................................................................................................................................................................................................................

1 Congenital defect/malformation (lethal or severe) 55 35.7..............................................................................................................................................................................................................................................

2 Unexplained antepartum fetal death 70 45.5..............................................................................................................................................................................................................................................

3 Death from intrapartum asphyxia, anoxia, or trauma 1 0.6..............................................................................................................................................................................................................................................

4 Immaturity 2 1.3..............................................................................................................................................................................................................................................

5 Infection 10 6.5..............................................................................................................................................................................................................................................

6 Death caused by other specific causes 13 8.4..............................................................................................................................................................................................................................................

7 Death caused by accident or nonintrapartum causes 0 0..............................................................................................................................................................................................................................................

8 Sudden infant death, cause unknown 0 0..............................................................................................................................................................................................................................................

9 Unclassifiable 3 1.9..............................................................................................................................................................................................................................................

10 Problematic 0 0

Vergani. Identifying the causes of stillbirth. Am J Obstet Gynecol 2008.

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protocols aimed at evaluating the patho-genic processes at play in fetal death, andpossibly at preventative strategies.   f

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