Comparison between cases and control pregnancies of the variables analyzed is shown in Table 1. The mean age for women who experienced a perinatal loss was 1.4 years older than those who did not (p = 0.02), but there was no significant difference in the proportion of who were at or above 35 years old (controls 8.4% vs cases 11.7%, p = 0.23). The following factors were associated with increased odds of perinatal death: prematurity, low birth weight, multiple gestation, breech presentation, antepartum hemorrhage, cesarean delivery and cord prolapse. Factors associated with decreased odds of perinatal death included grand multiparity and presenting in spontaneous labor. There were no significant associations between perinatal death and nulliparity, HIV infection, preeclampsia, or prior uterine scar. Multiple logistic regression controlling for maternal age, nulliparity, twin pregnancy, and prematurity demonstrated that the adjusted OR for all of the proceeding associations remained statistically significant with the sole exception of antepartum hemorrhage.
Table 1 Maternal, pregnancy, fetal and neonatal characteristics of case and control pregnancies
|
Control pregnancies
N = 3541
n (% ) or Mean (SD)
|
Case pregnancies
N= 1851
n (% ) or Mean (SD)
|
Unadjusted Odds Ratio
(Confidence Interval)
|
Adjusted Odds Ratio2
(Confidence Interval)
|
P value for Multiple Regression
|
MATERNAL FACTORS
|
Maternal Age (years)
|
24.4 (6.3)
|
25.8 (6.6)
|
--
|
--
|
--
|
Advanced Maternal Age >= 35 years
|
29/345 (8.4%)
|
21/180 (11.7%)
|
1.4
(0.8 – 2.7)
|
1.2
(0.6 -2.3)
|
0.63
|
Nulliparity
|
132/344 (38.4%)
|
62/179 (34.6%)
|
0.9
(0.6 – 1.3)
|
1.1
(0.7 – 1.1)
|
0.65
|
Grand multiparity
|
277/344 (80.5%)
|
116/179 (64.8%)
|
0.4
(0.3 – 0.7)
|
0.3
(0.2 – 0.7)
|
0.001
|
Prior Scar
|
8/348 (2.3%)
|
4 (2.2%)
|
0.9
(0.2 – 3.6)
|
1.3
(0.4 – 4.7)
|
0.67
|
HIV
|
26/342 (7.6%)
|
9/176 (5.1%)
|
0.7
(0.3 – 1.5)
|
0.5
(0.2 – 1.2)
|
0.13
|
PREGNANCY FACTORS
|
Twin pregnancy
|
5 (1.4%)
|
19 (10.3%)
|
7.9
(2.8 -- 27.7)
|
4.0
(1.1 – 13.9)
|
0.03
|
Preeclampsia
|
2/343 (0.6%)
|
0/179 (0%)
|
--
|
--
|
--
|
Antepartum hemorrhage
|
4/343 (1.2%)
|
8/179 (4.5%)
|
4.0
(1.0 – 18.2)
|
3.2
0.9 – 12.2
|
0.09
|
Infection
|
7/343 (2.0%)
|
7/179 (3.9%)
|
2.0
(0.6 – 6.6)
|
2.5
(0.8 – 7.7)
|
0.11
|
Breech
|
2/348 (0.6%)
|
8 (4.3%)
|
7.8
(1.5 – 76.0)
|
7.0
(1.4 – 35.5)
|
0.02
|
Cord prolapse
|
0/343 (0%)
|
7/179 (3.9%)
|
--
|
--
|
--
|
Normal labor
|
317/343 (92.4%)
|
97/179 (54.2%)
|
0.1
(0.1 – 0.2)
|
0.1
(0.1—0.2)
|
<0.001
|
Cesarean delivery
|
35/347 (10.0%)
|
46/182 (25.3%)
|
3.0
(1.8 – 5.0)
|
3.8
(2.3 – 6.4)
|
<0.001
|
FETAL/NEONATAL FACTORS
|
Prematurity
|
5/348 (1.4%)
|
40/179 (22.2%)
|
19.7
(7.5 – 65.1)
|
18.9
(7.2 -49.2)
|
<0.001
|
Birthweight (mean in grams)3
|
3046.9 (463.8)
|
2496.2 (941.1)
|
--
|
--
|
--
|
Low birth weight (<2500g)3
|
21/338 (3.7%)
|
56 (37.3%)
|
9.0
(5.0 – 16.4)
|
2.5
(1.1 – 5.3)
|
0.02
|
1 Denominators noted when distinct from these secondary to missing data
2 Adjusted for maternal age (except for adjusted odds for the dichotomous variable of advanced maternal age), nulliparity, twin pregnancy, and prematurity
3 Data was analyzed on the level of the fetus/neonate rather than pregnancy
To assess for factors more likely associated with perinatal death during or after labor, cases with fresh stillbirths and neonatal deaths were compared to macerated stillbirths as shown in Table 2. Only singleton pregnancies were included in this subgroup analysis given that some twin dyads had different types of perinatal death (e.g. twin A was a stillbirth, twin B was a neonatal demise). The mean age for women who experienced a macerated stillbirth was 1.9 years older than those who did not (p value 0.04), but there was no significant difference in the proportion of who were at or above 35 years old. Pregnancies with fresh stillbirths or neonatal deaths occurred more frequently among nulliparous women (41.2% vs 24.6%, p = 0.03), grand multiparous women (71.6% vs 52.5%, p = 0.01) and those delivered by cesarean section (38.6% vs 7.9%, p <0.0001). Pregnancies with macerated stillbirths were more likely to be associated with low birthweight (46.8% vs 25.8%, p = 0.01). There were no significant associations between macerated stillbirths as compared to fresh stillbirths and neonatal deaths for antepartum hemorrhage, cord prolapse, HIV infection, prior scar, preeclampsia, presenting in spontaneous labor, or prematurity.
Table 2 Maternal, pregnancy, fetal and neonatal characteristics compared with macerated stillbirths versus fresh stillbirths and neonatal death cases in singleton pregnancies
|
Cases with a Macerated Stillbirth
n = 64
n (%) or
Mean (SD)
|
Cases with a Fresh Stillbirth or Neonatal Death
n = 102
n (%) or
Mean (SD)
|
P value
|
MATERNAL FACTORS
|
Maternal Age (years)
|
26.8 (6.3)
|
24.9 (6.4)
|
0.04
|
Advanced maternal age
(>= 35 years)
|
7 (10.9%)
|
10 (10.2%)
|
0.88
|
Nulliparity
|
15/61 (24.6%)
|
42 (41.2%)
|
0.03
|
Grand multiparity
|
32/61 (52.5%)
|
73 (71.6%)
|
0.01
|
Prior scar
|
0 (0%)
|
3 (2.9%)
|
0.29
|
HIV
|
3/59 (5.1%)
|
3 (3.1%)
|
0.67
|
PREGNANCY FACTORS
|
Preeclampsia
|
0 (0.0%)
|
0 (0.0%)
|
--
|
Antepartum hemorrhage
|
2/62 (3.2%)
|
5/100 (5.0%)
|
0.71
|
Infection
|
1/62 (1.6%)
|
5/100 (5%)
|
0.41
|
Breech
|
2 (3.1%)
|
6 (5.9%)
|
0.71
|
Cord prolapse
|
2 (3.2%)
|
5 (5.0%)
|
0.71
|
Spontaneous Labor
|
36/62 (58.1%)
|
82 (80.3)
|
0.05
|
Cesarean section
|
5/63 (7.9%)
|
39/101 (38.6%)
|
<0.001
|
FETAL/NEONATAL FACTORS
|
Prematurity
|
15 (23.4%)
|
20 (19.6%)
|
0.56
|
Birthweight (grams)1
|
2431.9 (937.2)
|
2722.7 (864.9)
|
0.07
|
Low birth weight (<2500g)1
|
22/47 (46.8%)
|
23/89 (25.8%)
|
0.01
|
1 Analyzed on the level of fetus/neonate
Given the significantly increased risk of perinatal death noted with twin pregnancies, subgroup comparison of singleton and twin cases pregnancies was undertaken to see if there were any additional risk factors that were distinct to multiple gestation (Table 3). Notably, twin perinatal deaths were more likely to be fresh stillbirths than singleton perinatal deaths (68.4% vs 36.8%, p = 0.01). The only factor analyzed that was associated with increased risk of perinatal death in twin cases over singleton was birthweight both as a mean (singleton mean 2622.2 grams vs twin mean 1594.7 grams) and as a proportion of low birth weight (singleton 33.1% vs twin 82.4%, p <0.001).
Table 3 Maternal, pregnancy, fetal and neonatal characteristics among singleton and multiple pregnancies with perinatal deaths
|
Singleton Cases
n = 166
n (%) or Mean (SD)
|
Twin Cases
n = 19
n (%) or Mean (SD)
|
P value
|
TYPE OF PERINATAL DEATH1
|
Stillbirth, macerated
|
64 (38.6%)
|
3 (15.8%)
|
0.08
|
Stillbirth, fresh
|
61 (36.8%)
|
13 (68.4%)
|
0.01
|
Neonatal death
|
41 (24.7%)
|
4 (21.1%)
|
0.49
|
MATERNAL FACTORS
|
Maternal Age (years)
|
25.7 (6.5)
|
26.9/18
|
0.64
|
Advanced Maternal Age
(>= 35 years)
|
17 (10.5%)
|
4 (22.2%)
|
0.14
|
Nulliparity
|
57/163 (35.0%)
|
5/16 (31.3%)
|
1.0
|
Grand multiparity
|
105/163 (64.4%)
|
11/16 (68.8%)
|
0.79
|
Prior scar
|
3 (1.8%)
|
1 (5.3%)
|
0.35
|
HIV
|
6/156 (3.9%)
|
1/18 (5.6%)
|
0.54
|
PREGNANCY FACTORS
|
Preeclampsia
|
0 (0%)
|
0 (0%)
|
|
Antepartum hemorrhage
|
7/162 (4.3%)
|
1/17 (5.8%)
|
0.56
|
Infection
|
6/162 (3.7%)
|
1/17 (5.9%)
|
0.51
|
Breech
|
8 (4.8%)
|
0 (0%)
|
1.0
|
Cord prolapse
|
7/162 (4.3%)
|
0 (0%)
|
1.00
|
Spontaneous labor
|
84/162 (51.9%)
|
13 (76.5%)
|
0.07
|
Cesarean delivery
|
44/164 (26.8)
|
2/18 (11.1%)
|
0.25
|
FETAL/NEONATAL FACTORS2
|
Prematurity
|
35 (21.1%)
|
6/16 (37.5%)
|
0.44
|
Birthweight (grams)
|
2622.2 (897.9)
|
1594.7 (744.2)
|
<0.001
|
Low birth weight (<2500g)
|
45/136 (33.1%)
|
14/17 (82.4%)
|
<0.001
|
1 Outcome present in one or both twins
2 Analyzed on the level of fetus/neonate