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. 2025 Jun 9;16:1561798. doi: 10.3389/fimmu.2025.1561798

Table 1.

Characteristics of the Discovery Cohort, Replication Cohort I, and Replication Cohort II.

Characteristic Discovery Cohort
(n= 8,082)
Replication Cohort I
(n=2,535)
Replication Cohort II
(n=587)
Maternal age in years, mean (SD) 30.3 (7.5) 32.9 (5.3) 31.3 (3.6)
National background, n (%)
  Non-Dutch
  Dutch
 
4,135 (51.2)
3,947 (48.8)
 
Non-White: 1,493 (59.6)
White: 1,042 (40.4)
 
Non-Dutch: 80 (13)
Dutch: 507 (82.3)
Education level, n (%)
  No education
  Primary education
  Secondary education
  Missing
 
25 (0.3)
4,748 (58.7)
3,309 (41)
-
 
N/A*
 
-
155 (26.4)
421 (71.7)
11 (1.9)
Monthly household income, n (%)**
  <€2,220/month
  >€2200/month
  Missing
 
4,127 (51.1)
3,952 (48.9)
-
 
648 (25.6)
1,881 (74.2)
6 (0.2)
 
33 (5.6)
542 (92.3)
12 (2.0)
Pre-pregnancy BMI (kg/m2), median (IQR) 22.7 (4.7) 25.4 (7.9) 23.2 (4.4)
Parity, n (%)
   Nulliparity
   Multiparity
   Missing
 
4,497 (55.6)
3,585 (44.4)
-
 
1,357 (53.5)
1,178 (46.5)
-
 
326 (55.5)
250 (42.6)
11 (1.9)
Maternal Psychopathology, median (IQR) 0.17 (0.29) N/A* N/A*
Fetal sex, n (%)
   Male
   Female
   Missing
 
4,092 (50.6)
3,988 (49.4)
-
 
1,130 (44.6)
1,142 (45.0)
263 (10.4)
 
254 (43.3)
270 (46.0)
63 (10.7)
Birthweight in grams (median, IQR) 3,430 (685) 3,232 (629) 3,450 (630)
Gestational age at birth in weeks, median (IQR) 40.1 (1.9) 39.1 (1.7) 39.7 (1.7)
Maternal tobacco use, n (%)
 Never smoked during pregnancy
 Smoked until pregnancy was known
 Continued smoking in pregnancy
 Missing
 
5,845 (72.3)
702 (8.7)
1,535 (19)
-
 
N/A*
 
562 (95.7)
-
12 (2.0)
13 (2.2)
Maternal alcohol use, n (%)
 Drank no alcohol during pregnancy
 Drank alcohol until pregnancy was known
 Drank occasionally during pregnancy
 Drank frequently during pregnancy (>1 glass/week
 in early pregnancy)
 Missing
 
3,879 (48)
1,049 (13)
2,568 (31.8)
586 (7.2)
 
-
 
N/A*
 
573 (97.6)
-
1 (0.2)
-
 
13 (2.2)
Maternal substance use, n (%) 600 (7.4) 19 (0.7) N/A*
Season of 1st blood sample***, n (%)
   Winter
   Spring
   Summer
   Fall
 
1,713 (28.2)
1,665 (27.4)
1,327 (21.9)
1,367 (22.5)
 
578 (20.4)
1,036 (36.7)
599 (21.2)
608 (21.6)
 
160 (35.4)
120 (26.5)
126 (27.9)
46 (10.2)
Season of 2nd blood sample***, n (%)
   Winter
   Spring
   Summer
   Fall
 
1,798 (24.3)
2,142 (29)
1,754 (17.9)
1,702 (18.5)
 
186 (23.8)
182 (23.3)
229 (29.3)
184 (23.6)
 
131(34.2)
68 (17.8)
82 (21.4)
102 (26.6)
Infection score prior to first blood draw, n (%)
    0
    1
    2
    3
    4
    5 or higher
 
2,151 (26.6)
2,306 (28.5)
1,252 (15.6)
592 (7.3)
175 (2.1)
32 (0.4)
 
N/A*
 
N/A*
Infection score prior to second blood draw, n (%)
    0
    1
    2
    3
    4
    5 or higher
 
2,292 (28.4)
2,331 (28.8)
1,118 (13.8)
458 (5.7)
118 (1.5)
18 (0.2)
 
N/A*
 
N/A*
Twin pregnancy, n (%) 88 (1.1) 42 (1.7) N/A*
Immune-related disease, n (%)**** 650 (8.2) N/A** 41 (7.0)
Gestational age at sampling (weeks), median (min-max) 19.2 (4.5-26.9) 27.7 (3.7-42.1) 20.2 (9.4-42.0)

A total of 11,204 participants were included in the current study.

*N/A indicates that data was specific to the Discovery Cohort and was not measured or incomplete (>75% missing) in the replication cohorts.

**Monthly household income: For Replication Cohort I, numbers indicate insurance status: public (n=648) and private (n=1,881). For Replication Cohort II, numbers indicate employment status: unemployed (n=33) and paid job (n=552).

***Season: For the Discovery Cohort, season of first blood sample indicates the season of the sample collected at timepoint 1 in 6,062 participants. For Replication Cohort I, it indicates the season of the first blood sample that was collected (n=2,535). For Replication Cohort II, it indicates the season of the blood sample collected in trimester 1 (n=452). For the Discovery Cohort, season of second blood sample indicates the season of the sample collected at timepoint 2 (n=7,395). In Replication Cohort I, it indicates the season of the second blood sample that was collected (n=781). In Replication Cohort II, it indicates the season of the blood sample collected in trimester 2 (n=383).

****Immune-related disease include HIV, eczema, systemic lupus erythematosus (SLE), intestinal disorder, pre-gestation diabetes, multiple sclerosis, rheumatism.