The characteristics of the study population according to gestational age at birth are presented in Table 1. Overall, 2 838 (4 %) of all pregnancies ended preterm; 2 460 (3.5%) pregnancies ended between 32 and 37 weeks of gestation while 0.5% ended before 32 weeks of gestation. More specifically, 40.6% of overall preterm deliveries were initiated by clinicians (medically induced) and 59.4% started spontaneously. Mothers delivering preterm were more often pregnant through IVF, born outside the Nordic countries, were multiparous, overweight or obese, of short height or were treated for chronic hypertension.
Table 1. Baseline characteristics of mothers according to gestational age at birth. (N= 69 617 births).
Characteristics
|
Very preterm births a
(n=378)
|
Moderate preterm births b
(n=2 460)
|
Term birthsc
(n= 62 971)
|
Postterm births d
(n=3 808)
|
P- value
|
Maternal age older than 35 y
|
197 (52.1)
|
1 121 (45.6)
|
28 470 (45.2)
|
1 789 (46.9)
|
0.009
|
Short maternal height (< 155 cm)
|
17 (4.5)
|
98 (3.9)
|
1 508 (2.4)
|
57 (1.5)
|
<0.0001
|
Obesity (BMI ≥ 30 kg/m2)
|
40 (10.9)
|
219 (9.4)
|
4 055 (6.7)
|
271 (7.5)
|
<0.0001
|
Non- Nordic origin
|
88 (25.8)
|
413 (19.6)
|
10 312 (18.4)
|
525 (15.9)
|
<0.0001
|
Primiparity
|
182 (48.1)
|
1 187 (48.2)
|
36 197 (57.5)
|
1 629 (42.8)
|
<0.0001
|
Smoking
|
15 (4.1)
|
82 (3.4)
|
1 575 (2.5)
|
82 (2.2)
|
0.007
|
In vitro fertilization (IVF)
|
45 (11.9)
|
228 (9.3)
|
3 993 (6.3)
|
168 (4.4)
|
<0.0001
|
Chronic hypertension
|
11 (2.9)
|
51 (2.1)
|
556 (0.9)
|
27 (0.7)
|
<0.0001
|
Pre-gestational diabetes mellitus
|
1 (0.2)
|
28 (1.1)
|
116 (0.2)
|
0
|
<0.0001
|
Male fetal gender
|
208 (55.0)
|
1 334 (54.2)
|
31 959 (50.7)
|
2 028 (53.3)
|
<0.0001
|
a Very preterm birth: gestational age less than 32 weeks.
b Moderate preterm birth: gestational age between 32+0 and 36+6.
c Term birth: gestational age between 37+0 and 41+6.
d Postterm birth: gestational age 42 weeks or more.
Based on the information on biometric measurements, 7 091 (10.1 %) of fetuses had BPD growth more than the 90th percentile at the second trimester ultrasonic scans. In 55 571 (79.8 %) of fetuses, the growth was between 10th and 90th percentile, while 10.1 % of fetuses had a BPD growth smaller than expected (< 10th percentile). Mothers whose fetus had exhibited accelerated fetal growth at second trimester were more often younger and multiparous compared to those whose fetus had appropriate fetal growth. Male fetuses at second trimester were more often larger in size than female fetuses (Table 2).
Table 2. Baseline characteristics according to fetal growth in early pregnancy. (N=69 617 births)
Characteristics
|
Accelerated fetal growth a
(n= 6 955)
|
Appropriate fetal growth b
(n= 55 571)
|
Delayed fetal growth c
(n=7 091)
|
P- value
|
Maternal age older than 35 y
|
3 117 (43.9)
|
25 108 (45.2)
|
3 352 (47.2)
|
<.0001
|
Short maternal height
(< 155cm)
|
143 (2.0)
|
1 367 (2.4)
|
170 (2.4)
|
0.13
|
Obesity (BMI ≥30 kg/m2)
|
440 (6.5)
|
3 658 (6.9)
|
487 (6.8)
|
0.28
|
Non- Nordic origin
|
1 092 (17.7)
|
9 043 (18.4)
|
1 203 (16.9)
|
0.64
|
Primiparity
|
3 409 (48.1)
|
31 269 (56.3)
|
4 517 (63.7)
|
<0.0001
|
Smoking
|
177 (2.5)
|
1 538 (2.5)
|
210 (2.9)
|
0.03
|
In vitro fertilization (IVF)
|
443 (6.2)
|
3 649 (6.5)
|
342 (4.8)
|
<0.0001
|
Chronic hypertension
|
62 (0.8)
|
523 (0.9)
|
60 (0.8)
|
0.45
|
Pre-gestational diabetes mellitus
|
12 (0.2)
|
116 (0.2)
|
17 (0.2)
|
0.75
|
Male fetal gender
|
4 988 (70.4)
|
28 179 (50.7)
|
2 362 (33.9)
|
<0.0001
|
Difference in growth
mean (dispersion index)
|
5.14 (0.45)
|
-0.63(-7.29)
|
-6.56 (-0.34)
|
<0.0001
|
a Accelerated fetal growth at second trimester scan was defined as BPD measurement at the 90th percentile, or more of the expected for gestational age.
b Appropriate fetal growth at second trimester scan was defined as BPD measurement between 10th – 90th percentile of the expected for gestational age.
c Delayed fetal growth at second trimester scan was defined as BPD measurement at the 10th percentile, or less of the expected for gestational age
d Difference between observed and expected gestational age at second trimester scan.
Compared to fetuses with appropriate growth at early second trimester ultrasound, fetuses with accelerated growth had a 40 % increased risk for prematurity, both what regards moderate as well as very preterm birth. The association between fetal growth and overall and moderate preterm birth remained unchanged despite adjusting for maternal characteristics, pre-pregnancy diabetes, chronic hypertension and fetal gender (Table 3). However, the risk for very preterm birth did not reach statistical significance after adjustment.
Table 3. Growth in early pregnancy and risk of overall preterm birth, very preterm and moderate preterm birth. (N=2 838 births).
Growth at second trim scan
|
All preterm births
(n=2 838)
|
Very preterm births
(n=378)
|
Moderate preterm births
(n=2 460)
|
No. of women
|
Odds ratio (95% CI)
|
No. of women
|
Odds ratio (95% CI)
|
No. of women
|
Odds ratio (95% CI)
|
|
Crude
|
Adjusted d
|
Crude
|
Adjusted d
|
|
Crude
|
Adjusted d
|
Accelerated fetal growtha
|
389
|
1.39
(1.25-1.56)*
|
1.36
(1.20-1.54)*
|
52
|
1.38
(1.01-1.86)**
|
1.33
(0.96-1.83)**
|
337
|
1.39
(1.24-1.57)*
|
1.36
(1.18-1.55)*
|
Appropriate fetal growthb
|
2 215
|
Ref
|
Ref
|
295
|
Ref
|
Ref
|
1 920
|
Ref
|
Ref
|
Delayed fetal growthc
|
234
|
0.85
(0.73-0.96)*
|
0.84
(0.71-0.97)*
|
31
|
0.84
(0.58-1.21)***
|
0.73
(0.47-1.12)***
|
203
|
0.84
(0.72-0.97)*
|
0.85
(0.73-1.00)*
|
a Accelerated fetal growth at second trimester scan was defined as BPD measurement at the 90th percentile, or more of the expected for gestational age.
b Appropriate fetal growth at second trimester scan was defined as BPD measurement between 10th -90th percentile of the expected for gestational age.
c Delayed fetal growth at second trimester scan was defined as BPD measurement at the 10th percentile, or less of the expected for gestational age
dAdjusted OR for maternal age older than 35 yrs., short maternal height < 155 cm, BMI ≥ 30 kg/m2, non-Nordic origin, primiparity, smoking, IVF, pre-gestational diabetes mellitus, chronic hypertension and male fetal gender.
*p<0.0001
**p<0.05
***p>0.05
Medically induced labor was observed in 40.6 % of preterm births with the odds of prematurity being increased among fetuses with accelerated growth compared to fetuses with appropriate growth at second trimester scan. Even after adjustment for relevant confounders, the odds remained elevated (Table 4).
Table 4. Growth in early pregnancy and risk of preterm birth either spontaneous or medically induced. (N= 2 838 births)
Growth at second trim scan
|
Spontaneous preterm birth
(n=1 687)
|
Medically induced preterm birth
(n=1 151)
|
No. of women
|
Odds ratio (95% CI)
|
No. of women
|
Odds ratio (95 % CI)
|
Crude
|
Adjusted d
|
|
Crude
|
Adjustedd
|
Accelerated fetal growtha
|
234
|
1.39
(1.21-1.61)*
|
1.35
(1.15-1.58)*
|
155
|
1.37
(1.15-1.63)*
|
1.34
(1.11-1.63)**
|
Appropriate fetal growthb
|
1 325
|
Ref
|
Ref
|
890
|
Ref
|
Ref
|
Delayed fetal growthc
|
128
|
0.78
(0.64-0.92)*
|
0.78
(0.63-0.96)*
|
106
|
0.95
(0.77-1.16)***
|
0.91
(0.72-1.15)***
|
a Accelerated fetal growth at second trimester scan was defined as BPD measurement at the 90th percentile, or more of the expected for gestational age.
b Appropriate fetal growth at second trimester scan was defined as BPD measurement between 10th - 90th percentile of the expected for gestational age.
c Delayed fetal growth at second trimester scan was defined as BPD measurement at the 10th percentile, or less of the expected for gestational age.
dAdjusted OR for maternal age older than 35 yrs., short maternal height < 155 cm, BMI ≥ 30 kg/m2, non-Nordic origin, primiparity, smoking, IVF, chronic hypertension, pre-gestational diabetes mellitus and male fetal gender.
*p<0.0001
**p<0.01
***p=0.05
On the other hand, 6 955 fetuses were smaller than expected at second trimester scan (growth less than 10th percentile). Among them, 234 fetuses were born preterm (31 were born very preterm and 203 moderate preterm). Fetuses that experienced delayed growth in early pregnancy, had a decreased risk for preterm birth (aOR 0.84; 95% CI 0.71-0.97), an effect seen mostly among spontaneously preterm born infants (Table 3 and 4).