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Subclinical chorioamnionitis as a causal factor in unexplained stillbirths
International Journal of Gynecology & Obstetrics 74 Ž2001. 195᎐197
Brief communication
Subclinical chorioamnionitis as a causal factor in unexplained stillbirths J.E. Mathews a , M. Mathai a,U , A. Peedicayil a , K.P. Mathews b, J. Ponnaiyac , M.P. Jasper a a
Department of Obstetrics & Gynecology, Christian Medical College & Hospital, Vellore, India b Department of Medicine, Christian Medical College & Hospital, Vellore, India c Department of Pathology, Christian Medical College & Hospital, Vellore, India
Received 27 October 2000; received in revised form 13 March 2001; accepted 14 March 2001
Keywords: Stillbirths; Unexplained; Chorioamnionitis; Perinatal death
Subclinical chorioamnionitis has been implicated as a cause for stillbirths w1᎐3x. However, it is unclear if chorioamnionitis is an independent risk factor for unexplained stillbirth. We used a prospective case᎐control design to determine the role of subclinical chorioamnionitis in unexplained stillbirths in India. Women with unexplained stillbirths at or beyond 26 weeks gestation were the cases. Two controls were selected for each case, matched for gestation and sex of infant. The first group comprised women who had stillbirths with identifiable causes; the second included women who had delivered live babies. For each case, the next eligible women were selected as controls. Assuming a
U
Corresponding author. Department of Obstetrics & Gynecology, Christian Medical College & Hospital, Vellore 632 004, India. Fax: q91-416-232035r232103. E-mail address: [email protected] ŽM. Mathai..
30% occurrence of histological chorioamnionitis in unexplained stillbirths, a type I error of 5% and a type II error of 20%, the sample size required to demonstrate an odds ratio of 5 was 30 in each group. Placentas from cases and controls preserved in 10% formalin were examined by a pathologist ŽJ.P.., unaware of clinical details. Blocks were prepared from roll mop preparation of membranes, full thickness slices of the central area of the placenta, grossly abnormal areas and from the cord. Stained 4-m sections were assessed for histological chorioamnionitis Žpresence of leukocytes in the chorionic plate andror subchorionic space., villitis, vasculitis, villous edema, and inflammation in the decidua and extraplacental membranes using the grading of Naeye w4x. Data were analyzed by univariate and conditional logistic regression analyses. During the study period, there were 7062 births
0020-7292r01r$20.00 䊚 2001 International Federation of Gynecology and Obstetrics. All rights reserved PII: S 0 0 2 0 - 7 2 9 2 Ž 0 1 . 0 0 3 8 6 - 1
J.E. Mathews et al. r International Journal of Gynecology & Obstetrics 74 (2001) 195᎐197
196
Table 1 Some maternal and perinatal characteristics ŽS.D. in brackets.
Mean maternal age Žyears. Mean maternal height Žcm. Mean maternal weight Žkg. Consanguineous marriage History of previous stillbirth Mean hemoglobin Žgrdl. Spontaneous onset of labor Mean gestation at delivery Žweeks. Mean placental weight Žg.
Unexplained stillbirth Ž n s 33.
Explained stillbirth Ž n s 33.
Live birth Ž n s 33.
25.1 Ž4.5. 150 Ž10.3. 54 Ž11.7. 7 4 11.3 Ž1.7. 25 34.6 Ž4. 295 Ž129.
25.2 Ž3.5. 152 Ž4.9. 53 Ž7.8. 5 5 11.4 Ž2. 18 34.4 Ž4. 302 Ž131.
24.2 Ž4. 154 Ž6. 56 Ž9.5. 8 3 11 Ž1.3. 29 34.8 Ž4. 350 Ž87.
and 216 stillbirths. All 33 women with unexplained stillbirths were included as cases. There were 33 women in each control group. Most maternal and perinatal characteristics were comparable among the groups ŽTables 1 and 3., but fewer women with unexplained stillbirths had antenatal care. Chorioamnionitis was more common Ž P- 0.05. and more severe among unexplained stillbirths ŽTable 2.. Women with chorioamnionitis were
significantly more likely to have unexplained stillbirths than explained stillbirths ŽOR 6.5; 95% CI 1.4, 28.8. or live births ŽOR 17; 95% CI 2.6, 127. ŽTable 3.. Chorioamnionitis was the only independent risk factor for unexplained stillbirth Žadjusted OR 3.48 compared to live births. ŽTable 4.. Fetal vasculitis was associated with a trend towards increased risk of unexplained stillbirth ŽTable 3.. Villous edema hindering oxygen diffusion may be an underlying cause of death in
Table 2 Types of inflammation in cases and controls Unexplained stillbirth Ž n s 33.
Explained stillbirth Ž n s 33.
Live birth Ž n s 33.
No.
%
No.
%
No.
%
Chorionic plate Mild Severe
13 4
39 13
6 2
18 7
2 1
6 3
Subchorionic plate Mild Severe
13 9
39 28
9 4
27 13
3 4
9 13
Chorioamnionitisa Mild Severe
14 10
42 30
8 5
24 15
4 4
13 13
Vasculitis Villitis Deciduitis Inflammation of membrane Villous edema
12 13 30 24 7
36 39 90 72 21
5 8 30 21 6
15 24 90 73 18
5 2 19 14 3
15 6 57 42 6
a
Chorioamnionitis, inflammation in the subchorionic andror chorionic plates.
J.E. Mathews et al. r International Journal of Gynecology & Obstetrics 74 (2001) 195᎐197
197
Table 3 Potential risk factors for unexplained stillbirths ᎏ univariate analysis Variables
Booked for antenatal care Heavy work Parity Fuel-wood vs. kerosene q gas Vaginal examination more than 2 Duration of RM Žh. Mean birth weight Žkg. Chorioamnionitis Vasculitis Villitis Villous edema a
USB
ESB
9 20 13 12r16 1 4.1 2.1 24 12 13 7
8 26 16 9r22 2 5.4 1.8 13 5 8 6
LB
21 30 20 9r24 1 5.7 2.3 8 5 2 3
USB vs. ESBa
USB vs. LB
OR
95% CI
OR
95% CI
1.2 0.33 1.4 0.42 0.3 0.98 3.14 6.5 2.5 0.6 1.2
0.37, 3.93 0.09, 1.23 0.54, 3.8 0.11, 1.65 0.09, 1.2 0.93, 1.04 1.08, 9.08 1.4, 28.8 0.84, 6.81 0.14, 2.5 0.36, 3.9
0.2 0.09 2.0 0.375 0.3 0.97 0.4 17 3.3 2.14 2.33
0.6, 0.7 0.01, 0.7 0.81, 4.96 0.08, 1.41 0.11, 1.03 0.91, 1.04 0.13, 1.32 2.3, 127 0.9, 12.1 0 0.6, 9.02
Abbre¨ iations: USB, unexplained stillbirth; ESB, explained stillbirth; LB, live birth; RM, rupture of membrane.
Table 4 Conditional logistic regression Variable
Heavy work Fuel wood vs. kerosene and gas Booking Chorioamnionitis Parity a
USB vs. ESBa
USB vs. LB
OR
Ž95% CI.
OR
Ž95% CI.
0.61 0.44 0.99 3.48 1.83
Ž0.2᎐1.7. Ž0.2᎐1.0. Ž0.2᎐5.3. Ž1.2᎐9.9. Ž0.9᎐3.9.
0.03 0.03 0 2.62 2.57
Ž0᎐1.4. Ž0᎐0.8. Ž0᎐0.6. Ž0.4᎐15.8. Ž0.7᎐10.1.
Abbre¨ iations: USB, unexplained stillbirth; ESB, explained stillbirth; LB, live birth.
chorioamnionitis w4x. Fetal vasculitis also suggests a temporal relationship between infection and death, i.e. chorioamnionitis precedes fetal demise. These findings when considered with other reports w1᎐3x suggest that there is a biological plausibility and coherence to support a causative role for chorioamnionitis in unexplained stillbirths. References w1x Moyo SR, Tswana SA, Mahomed K, Nystrom ¨ L, ˚ An incidence case referent Bergstrom ¨ S, Ljungh A.
study at Harare Maternity Hospital. Socioeconomic and obstetric risk factors. Gynecol Obstet Invest 1993;37: 34᎐39. w2x Osman NB, Folgosa E, Gonzales C, Bergstrom ¨ S. Genital infections in the aetiology of late fetal death: an incidence case-referent study. J Trop Pediatr 1995;41: 267᎐272. w3x Moyo SR, Hagerstrand L, Nystrom ¨ ¨ L, Tswana SA, Blomberg J, Bergstrom ¨ S et al. Stillbirths and intrauterine infection, histologic chorioamnionitis and microbiological findings. Int J Gynecol Obstet 1996;54:115᎐123. w4x Naeye RL. Acute bacterial chorioamnionitis. Transplacental effects on fetal health. New York: Liss, 1988: 73᎐86.
Brief communication
Subclinical chorioamnionitis as a causal factor in unexplained stillbirths J.E. Mathews a , M. Mathai a,U , A. Peedicayil a , K.P. Mathews b, J. Ponnaiyac , M.P. Jasper a a
Department of Obstetrics & Gynecology, Christian Medical College & Hospital, Vellore, India b Department of Medicine, Christian Medical College & Hospital, Vellore, India c Department of Pathology, Christian Medical College & Hospital, Vellore, India
Received 27 October 2000; received in revised form 13 March 2001; accepted 14 March 2001
Keywords: Stillbirths; Unexplained; Chorioamnionitis; Perinatal death
Subclinical chorioamnionitis has been implicated as a cause for stillbirths w1᎐3x. However, it is unclear if chorioamnionitis is an independent risk factor for unexplained stillbirth. We used a prospective case᎐control design to determine the role of subclinical chorioamnionitis in unexplained stillbirths in India. Women with unexplained stillbirths at or beyond 26 weeks gestation were the cases. Two controls were selected for each case, matched for gestation and sex of infant. The first group comprised women who had stillbirths with identifiable causes; the second included women who had delivered live babies. For each case, the next eligible women were selected as controls. Assuming a
U
Corresponding author. Department of Obstetrics & Gynecology, Christian Medical College & Hospital, Vellore 632 004, India. Fax: q91-416-232035r232103. E-mail address: [email protected] ŽM. Mathai..
30% occurrence of histological chorioamnionitis in unexplained stillbirths, a type I error of 5% and a type II error of 20%, the sample size required to demonstrate an odds ratio of 5 was 30 in each group. Placentas from cases and controls preserved in 10% formalin were examined by a pathologist ŽJ.P.., unaware of clinical details. Blocks were prepared from roll mop preparation of membranes, full thickness slices of the central area of the placenta, grossly abnormal areas and from the cord. Stained 4-m sections were assessed for histological chorioamnionitis Žpresence of leukocytes in the chorionic plate andror subchorionic space., villitis, vasculitis, villous edema, and inflammation in the decidua and extraplacental membranes using the grading of Naeye w4x. Data were analyzed by univariate and conditional logistic regression analyses. During the study period, there were 7062 births
0020-7292r01r$20.00 䊚 2001 International Federation of Gynecology and Obstetrics. All rights reserved PII: S 0 0 2 0 - 7 2 9 2 Ž 0 1 . 0 0 3 8 6 - 1
J.E. Mathews et al. r International Journal of Gynecology & Obstetrics 74 (2001) 195᎐197
196
Table 1 Some maternal and perinatal characteristics ŽS.D. in brackets.
Mean maternal age Žyears. Mean maternal height Žcm. Mean maternal weight Žkg. Consanguineous marriage History of previous stillbirth Mean hemoglobin Žgrdl. Spontaneous onset of labor Mean gestation at delivery Žweeks. Mean placental weight Žg.
Unexplained stillbirth Ž n s 33.
Explained stillbirth Ž n s 33.
Live birth Ž n s 33.
25.1 Ž4.5. 150 Ž10.3. 54 Ž11.7. 7 4 11.3 Ž1.7. 25 34.6 Ž4. 295 Ž129.
25.2 Ž3.5. 152 Ž4.9. 53 Ž7.8. 5 5 11.4 Ž2. 18 34.4 Ž4. 302 Ž131.
24.2 Ž4. 154 Ž6. 56 Ž9.5. 8 3 11 Ž1.3. 29 34.8 Ž4. 350 Ž87.
and 216 stillbirths. All 33 women with unexplained stillbirths were included as cases. There were 33 women in each control group. Most maternal and perinatal characteristics were comparable among the groups ŽTables 1 and 3., but fewer women with unexplained stillbirths had antenatal care. Chorioamnionitis was more common Ž P- 0.05. and more severe among unexplained stillbirths ŽTable 2.. Women with chorioamnionitis were
significantly more likely to have unexplained stillbirths than explained stillbirths ŽOR 6.5; 95% CI 1.4, 28.8. or live births ŽOR 17; 95% CI 2.6, 127. ŽTable 3.. Chorioamnionitis was the only independent risk factor for unexplained stillbirth Žadjusted OR 3.48 compared to live births. ŽTable 4.. Fetal vasculitis was associated with a trend towards increased risk of unexplained stillbirth ŽTable 3.. Villous edema hindering oxygen diffusion may be an underlying cause of death in
Table 2 Types of inflammation in cases and controls Unexplained stillbirth Ž n s 33.
Explained stillbirth Ž n s 33.
Live birth Ž n s 33.
No.
%
No.
%
No.
%
Chorionic plate Mild Severe
13 4
39 13
6 2
18 7
2 1
6 3
Subchorionic plate Mild Severe
13 9
39 28
9 4
27 13
3 4
9 13
Chorioamnionitisa Mild Severe
14 10
42 30
8 5
24 15
4 4
13 13
Vasculitis Villitis Deciduitis Inflammation of membrane Villous edema
12 13 30 24 7
36 39 90 72 21
5 8 30 21 6
15 24 90 73 18
5 2 19 14 3
15 6 57 42 6
a
Chorioamnionitis, inflammation in the subchorionic andror chorionic plates.
J.E. Mathews et al. r International Journal of Gynecology & Obstetrics 74 (2001) 195᎐197
197
Table 3 Potential risk factors for unexplained stillbirths ᎏ univariate analysis Variables
Booked for antenatal care Heavy work Parity Fuel-wood vs. kerosene q gas Vaginal examination more than 2 Duration of RM Žh. Mean birth weight Žkg. Chorioamnionitis Vasculitis Villitis Villous edema a
USB
ESB
9 20 13 12r16 1 4.1 2.1 24 12 13 7
8 26 16 9r22 2 5.4 1.8 13 5 8 6
LB
21 30 20 9r24 1 5.7 2.3 8 5 2 3
USB vs. ESBa
USB vs. LB
OR
95% CI
OR
95% CI
1.2 0.33 1.4 0.42 0.3 0.98 3.14 6.5 2.5 0.6 1.2
0.37, 3.93 0.09, 1.23 0.54, 3.8 0.11, 1.65 0.09, 1.2 0.93, 1.04 1.08, 9.08 1.4, 28.8 0.84, 6.81 0.14, 2.5 0.36, 3.9
0.2 0.09 2.0 0.375 0.3 0.97 0.4 17 3.3 2.14 2.33
0.6, 0.7 0.01, 0.7 0.81, 4.96 0.08, 1.41 0.11, 1.03 0.91, 1.04 0.13, 1.32 2.3, 127 0.9, 12.1 0 0.6, 9.02
Abbre¨ iations: USB, unexplained stillbirth; ESB, explained stillbirth; LB, live birth; RM, rupture of membrane.
Table 4 Conditional logistic regression Variable
Heavy work Fuel wood vs. kerosene and gas Booking Chorioamnionitis Parity a
USB vs. ESBa
USB vs. LB
OR
Ž95% CI.
OR
Ž95% CI.
0.61 0.44 0.99 3.48 1.83
Ž0.2᎐1.7. Ž0.2᎐1.0. Ž0.2᎐5.3. Ž1.2᎐9.9. Ž0.9᎐3.9.
0.03 0.03 0 2.62 2.57
Ž0᎐1.4. Ž0᎐0.8. Ž0᎐0.6. Ž0.4᎐15.8. Ž0.7᎐10.1.
Abbre¨ iations: USB, unexplained stillbirth; ESB, explained stillbirth; LB, live birth.
chorioamnionitis w4x. Fetal vasculitis also suggests a temporal relationship between infection and death, i.e. chorioamnionitis precedes fetal demise. These findings when considered with other reports w1᎐3x suggest that there is a biological plausibility and coherence to support a causative role for chorioamnionitis in unexplained stillbirths. References w1x Moyo SR, Tswana SA, Mahomed K, Nystrom ¨ L, ˚ An incidence case referent Bergstrom ¨ S, Ljungh A.
study at Harare Maternity Hospital. Socioeconomic and obstetric risk factors. Gynecol Obstet Invest 1993;37: 34᎐39. w2x Osman NB, Folgosa E, Gonzales C, Bergstrom ¨ S. Genital infections in the aetiology of late fetal death: an incidence case-referent study. J Trop Pediatr 1995;41: 267᎐272. w3x Moyo SR, Hagerstrand L, Nystrom ¨ ¨ L, Tswana SA, Blomberg J, Bergstrom ¨ S et al. Stillbirths and intrauterine infection, histologic chorioamnionitis and microbiological findings. Int J Gynecol Obstet 1996;54:115᎐123. w4x Naeye RL. Acute bacterial chorioamnionitis. Transplacental effects on fetal health. New York: Liss, 1988: 73᎐86.