Fetal Growth and Body Proportion in Preeclampsia

Svein Rasmussen, MD, PhD, and Lorentz M. Irgens, MD, PhD

OBJECTIVE: To evaluate the effects of early- and late-onset
preeclampsia on fetal growth and body proportion.
METHODS: This was a population-based study based on
records of 672,130 pregnancies from the Medical Birth
Registry of Norway during 19671998. Women with a
prior birth, multiple births, those without valid data on the
last menstrual period or newborns crown heel length,
and chronic maternal disease were excluded.
RESULTS: In newborns of women with preeclampsia, mean
birth weight, crown heel length, and ponderal index were
4.4%, 0.8%, and 2.6% lower than in births without preeclampsia, respectively. In preterm births, mean differences in birth weight ranged from 11% to 23% against
near-equal birth weights in term births. Mean differences
in crown heel length and ponderal index ranged from
1% to 5% and from 5% to 10% before term, respectively. In late preeclampsia, rates of birth weight and
crown heel length above the 90th and 97.5th percentiles
and ponderal index above the 97.5th percentile were
slightly but significantly higher than in term births without
preeclampsia (odds ratios 1.11.5). However, infants
born to mothers with preterm preeclampsia were less
likely to be heavy, long, or with high ponderal index for
gestational age (odds ratios 0.4 0.6).
CONCLUSION: Our results support the hypothesis that preeclampsia is an etiologically heterogeneous disorder that
occurs in at least two subsets, one with normal or enhanced
placental function, and another involving placental dysfunction and fetal growth restriction, often with asymmetric fetal body proportion, reduced fetal length, and preterm
delivery. In future studies, distinguishing between the two
subtypes may be important. (Obstet Gynecol 2003;101:
575 83. 2003 by The American College of Obstetricians and Gynecologists.)

Fetal growth restriction (FGR) is closely related to perinatal morbidity and mortality.1 Numerous risk factors
for FGR have been established. Still, in many cases no
underlying pathology can be identified. Previous studies
have suggested that fetal leanness or asymmetry carries a
high risk for perinatal complications,2 4 whereas FGR
From the Medical Birth Registry of Norway, Locus of Registry Based Epidemiology, and Department of Obstetrics and Gynecology, University of Bergen, Bergen,
Norway.

with normal body proportions would be more prone to

long-term neurodevelopmental handicaps.5
Although it is well known that preeclampsia is associated with reduced fetal size, information on fetal proportion in preeclampsia is scarce. Early-onset preeclampsia
(gestational age less than 37 weeks) is associated with
placental vascular lesions or reduced uteroplacental
blood supply6 leading to reduced birth weight,7,8 suggesting that preeclampsia and FGR in general might
share pathophysiologic mechanisms. Shallow invasion
by fetal trophoblasts in maternal spiral arteries in early
pregnancy, which may cause occlusion of the vessels, has
been observed both in preeclampsia and in FGR.9,10
Clinical studies have suggested that in early-onset preeclampsia, FGR often precedes the development of preeclampsia.7 However, recent findings of excess rates
both of small (SGA) and large for gestational age (LGA)
in preeclampsia11 and of normal birth weight in most
cases of term preeclampsia11,12 challenge the hypothesis
that placental dysfunction is essential in the development
of preeclampsia.
The objective of the present population-based study
was to evaluate the effects of early- and late-onset preeclampsia on fetal growth and body proportion.

MATERIALS AND METHODS

Since 1967, medical data on all births in Norway with
gestational age at least 16 weeks have, by compulsory
notification, been forwarded to the Medical Birth Registry of Norway.13 The population of pregnant women in
Norway is relatively homogeneous. More than 99% of
them receive standardized antenatal care (Backe B. Studies on antenatal care [doctoral thesis]. Trondheim, Norway: Tapir, 1994). At each antenatal visit, blood pressure (BP) is measured, and urine is examined for protein
with a reagent strip. Medical data are collected in the
pregnancy record brought by the women to the delivery
unit, and selected items of data are transferred to the
Registry notification form. Immediately after birth, birth
weight is measured by the midwife to the nearest 10 g
and crown heel length to the nearest 1 cm. By the ninth
day postpartum, the form is sent to the Registry. The

VOL. 101, NO. 3, MARCH 2003

2003 by The American College of Obstetricians and Gynecologists. Published by Elsevier.

0029-7844/03/$30.00
doi:10.1016/S0029-7844(02)03071-5

575

Table 1. Maternal and Reproductive Characteristics in Early and Late Preeclampsia and Non-preeclamptic Pregnancies,
Norway, 196798
Preeclampsia
Early preeclampsia (37 weeks)
Characteristic

Maternal age (y)

20
2024
2529
3034
35
Maternal education (y)
10
1012
13
Unknown
Year of birth
196776
197786
198798
Gender*
Boy
Girl
Gestational age (wk)
Birth weight (g)
Ponderal index (100 g/cm3)
Crownheel length (cm)

Mean

Late preeclampsia (37 weeks)

95% CI

320
1340
1191
522
212

8.9
37.4
33.2
14.6
5.9

8.0, 9.9
35.8, 39.0
31.7, 34.8
13.4, 15.8
5.2, 6.7

2341
9140
7130
2387
891

384
2102
952
147

10.7
58.6
26.6
4.1

9.7, 11.8
57.0, 60.2
25.1, 28.0
3.5, 4.8

2808
12,917
5451
713

855
1015
1715

23.8
28.3
47.8

22.5, 25.3
26.9, 29.8
46.2, 49.5

6302
7165
8422

1957
1627

54.6
45.4

53.0, 56.2
43.8, 47.0
33.88, 34.0
2041, 2078
2.35, 2.37
43.6, 43.8

33.95
2060
2.36
43.7

11,672
10,216

Mean

39.71
3366
2.68
49.93

CI confidence interval.
* 133 (0.2%) without known gender.

form has been unchanged since the start of registration,

except for the addition, in 1978, of Apgar scores.
The study was based on records of all births in Norway from 1967 through 1998 and comprised 1,869,388
births, more than one third of Norways total population.
This file has been linked to population census files containing socioeconomic data from the Central Bureau of
Statistics and the National Education Register. We excluded women with a prior birth (n 1,088,443), multiple births (n 16,474), and those without data or invalid
data on first day of the last menstrual period (n 58,595)
or newborns crown heel length (n 19,156). The
invalid data were detected by methods described previously.14,15 We also excluded women with chronic maternal disease (essential hypertension, connective tissue
diseases, hyperthyroidism, hypothyroidism, chronic glomerulonephritis, renal failure, and diabetes mellitus) or
gestational diabetes (n 14,590), leaving 672,130 birth
order one pregnancies for study. Variables used in the
present study were pregnancy outcome, obstetric complications, and sociodemographic characteristics. Data
on education were collected from census files and the
education register. Gestational age was based on the first
day of the last menstrual period.
Preeclampsia is usually notified to the Registry as a
specific diagnosis. The notification form also contains

576

Rasmussen and Irgens

Fetal Size in Preeclampsia

information on separate symptoms of preeclampsia,

such as hypertension, proteinuria, and edema. In Norway, the diagnosis is in accordance with the 1972 recommendations of the American College of Obstetricians
and Gynecologists,16 which defined preeclampsia as increased BP after 20 weeks gestation with proteinuria,
edema, or both. According to clinical practice in Norway, pregnancies with edema but without proteinuria
are not included in the definition.17 Hypertension is
defined as persistent and consistent increased BP on at
least two occasions or BP of 140/90 mm Hg or greater, or
increase in diastolic BP of at least 15 mm Hg or systolic
BP of at least 30 mm Hg from the womans average
levels before 20 weeks gestation. Proteinuria is defined
as excretion of 0.3 g or more per day, usually equivalent
to at least 1 on a urine reagent strip. In the present
study, preeclampsia included all pregnancies with a notified diagnosis of preeclampsia or pregnancies recorded
with hypertension and proteinuria in combination.
Severe preeclampsia is likely to result in a preterm
birth. Therefore, we compared infants size in preterm
(less than 37 weeks gestation) and term or postterm
births (37 weeks or more) to mothers with and without
preeclampsia.
Birth weight was adjusted for gestational age and
gender, using birth weight ratios (ie, 100 [the actual

OBSTETRICS & GYNECOLOGY

Preeclampsia
Late preeclampsia (37 weeks)
%

95% CI

No preeclampsia
n

Mean

95% CI

10.7
41.8
32.6
10.9
4.1

10.3, 11.1
41.1, 42.4
32.0, 33.2
10.5, 11.3
3.8, 4.3

73,716
27,889
20,900
66,288
18,749

11.4
43.1
32.3
10.3
2.9

11.3, 11.5
43.0, 43.3
32.2, 32.4
10.2, 10.33
2.86, 2.94

12.8
59.0
24.9
3.3

12.4, 13.3
58.4, 59.7
24.3, 25.5
3.0, 3.5

83,624
36,365
17,162
27,750

12.9
56.2
26.5
4.3

12.85, 13.0
56.1, 56.4
26.4, 26.7
4.2, 4.34

28.8
32.7
38.5

28.2, 29.4
32.1, 33.4
37.8, 39.1

22,778
20,208
21,678

35.2
31.3
33.5

35.1, 35.3
31.1, 31.4
33.4, 33.6

53.3
46.7

52.7, 54.0
46.0, 47.3
39.68, 39.74
3358, 3373
2.677, 2.684
49.90, 49.97

33,295
31,357

51.5
48.5

51.4, 51.6
48.4, 48.6
39.81, 39.82
3440, 3442
2.722, 2.723
50.3, 50.5

birth weight]/[the mean birth weight for that gestational

age (completed weeks) and gender among the 672,130
births]). The two other main outcomes, crown heel
length and ponderal index (100 g/cm3)18 were, in a
similar way, adjusted for gestational age and gender.
Births were categorized according to birth weight,
crown heel length, and ponderal index into four groups
with cutoff points equivalent to the 2.5th, 10th, 90th, and
97.5th gestational age and gender-specific percentiles
among the 672,130 births. Small for gestational age was
divided into asymmetric and symmetric SGA, according
to the definition of Walther and Ramaekers, who classified SGA as symmetric or asymmetric according to the
ponderal index.3 Symmetric and asymmetric SGA infants below the 10th birth weight percentile were defined
as those who had ponderal index at or above and below
the 10th percentile, respectively. The cutoff point for
asymmetric and symmetric SGA below the 2.5th birth
weight percentile was at the 2.5th ponderal index percentile.
The association of preeclampsia with low birth
weight-, short crown heel length-, and low ponderal
index percentiles were estimated by relative risks (RR) in
terms of odds ratios (OR) obtained from logistic regression analyses (Statistical Package for the Social Sciences;
SPSS Inc., Chicago, IL), in which we adjusted for educa-

VOL. 101, NO. 3, MARCH 2003

39.813
3441
2.721
50.4

P
.001

.001

.001

.001
.001
.001
.001
.001

tion in years (fewer than 10, 10 12, more than 12, and
unknown), maternal age in years (19 or less, 20 29,
30 34, and 35 or more), and year of birth (196776,
1977 86, and 198798). The effects of preeclampsia on
mean birth weight, crown heel length, and ponderal
index were assessed by analysis of variance (SPSS), in
which we adjusted for potential confounders.
RESULTS
In the study population of 672,130 pregnancies, 3585
(0.5%) cases of early preeclampsia and 21,889 (3.3%)
cases of late (gestational age 37 weeks or more) preeclampsia occurred.
The proportion of women aged 35 years or more was
5.9% in women with early preeclampsia, compared with
women with late preeclapsia (4.1%) and without preeclampsia (2.9%) (Table 1). Educational level was significantly associated with preeclamspia. However, the differences were small. There was a secular trend with
more women being diagnosed with early and late preeclampsia in the late registry period.
Women with preeclampsia delivered on average significantly lighter, shorter, and leaner infants than those
without preeclampsia; mean birth weight, crown heel
length, and ponderal index were 4.4% (Table 2), 0.8%

Rasmussen and Irgens

Fetal Size in Preeclampsia

577

Table 2. Mean and Adjusted* Mean Difference of Birth Weight Ratio (95% CI) in Infants of Mothers With and Without
Preeclampsia by Gestational Age, Norway, 196798
Birth weight ratio (mean)
Gestational age
(wk)

Preeclampsia

Nonpreeclampsia

Mean difference
(95% CI)

27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
Total

86.4
91.8
87.3
84.9
84.7
79.5
81.6
81.9
84.4
88.2
92.2
94.2
97.3
99.0
99.6
99.7
98.7
100.1
95.8

100.6
102.3
102.4
102.6
102.8
102.9
102.9
102.3
101.5
101.0
100.4
100.2
100.1
100.0
100.0
100.0
100.1
100.3
100.1

14.3 (8.8, 19.8)

10.5 (3.8, 17.3)
15.0 (8.7, 21.4)
17.7 (12.3, 23.1)
18.1 (13.5, 22.6)
23.4 (19.6, 27.2)
21.3 (18.1, 24.4)
20.4 (17.9, 22.8)
17.1 (15.1, 19.2)
12.8 (11.2, 14.4)
8.2 (6.9, 9.5)
6.0 (5.0, 7.0)
2.8 (2.0, 3.6)
1.0 (0.3, 1.8)
0.4 (0.4, 1.3)
0.3 (1.0, 1.5)
1.4 (0.8, 3.7)
0.2 (3.6, 3.9)
4.4 (4.5, 4.2)

CI confidence interval.
* Adjusted for education in years (fewer than 10, 10 12, more than 12, and unknown), maternal age in years (19 or less, 20 29, 30 34, and 35
or more), and year of birth (196776, 1977 86, and 198798).

(Table 3), and 2.6% (Table 4) lower than in births

without preeclampsia, respectively. In preterm births
(gestational age less than 37 weeks), mean differences in
birth weight ratio ranged from 11% to 23% against
near equal ratios in term and postterm births (Table 2).
Likewise, mean differences in crown heel length- and
ponderal index ratios ranged from 1% to 5% and
from 5% to 10% before term, against near equal
ratios from 37 weeks gestation (Tables 3 and 4).
Increased occurrences of weight-, crown heel length-,
and ponderal index percentiles below the 2.5th and 10th
percentiles were found in preterm (Table 5) as well as
term and postterm preeclampsia (Table 6). Both in preterm and late preeclampsia, excess risks were particularly observed for asymmetric rather than symmetric
SGA. Newborns born to mothers with preterm preeclampsia were two to five times more likely than those
who were delivered preterm without preeclampsia to be
below the 2.5th or 10th birth weight-, crown heel
length-, and ponderal index percentiles (OR 2.2 4.7)
(Table 5). Newborns whose mothers had preterm preeclampsia were five and two times more likely to be
asymmetric and symmetric SGA below the 2.5th birth
weight percentile than newborns of mothers without
preeclampsia (OR 4.6 and 2.2, respectively) (Table 5).
For asymmetric and symmetric SGA less than the 10th
percentile, ORs were 5.5 and 3.2, respectively (Table 5).

578

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Fetal Size in Preeclampsia

Infants born to mothers with preterm preeclampsia were

less likely to be heavy, long, or to have high ponderal
index for gestational age (ORs 0.4 0.6) (Table 5).
In late preeclampsia (gestational age 37 weeks or
more), newborns were two to three times more likely
than newborns of mothers without preeclampsia to be
below the 2.5th or 10th birth weight-, crown heel
length-, and ponderal index percentiles (OR 1.6 3.4)
(Table 6). Newborns whose mothers had preeclampsia
were about five and two times more likely to be asymmetric and symmetric SGA below the 2.5th birth weight
percentile than newborns of mothers without preeclampsia (OR 4.8 and 2.3, respectively) (Table 6). For
asymmetric and symmetric SGA less than the 10th percentile, ORs were 3.0 and 1.5, respectively (Table 6). In
late preeclampsia, rates of birth weight and crown heel
length above the 90th and 97.5th percentiles and ponderal index above the 97.5th percentile were slightly but
significantly higher than in term births without preeclampsia (ORs 1.11.5) (Table 6).
DISCUSSION
In the present study, preterm preeclampsia was associated with lighter, shorter, and leaner newborns, whereas
late preeclampsia had increased rates of both larger and
smaller newborns.

OBSTETRICS & GYNECOLOGY

Table 3. Mean and Adjusted* Mean Difference of CrownHeel Length Ratio (95% CI) in Infants of Mothers With and
Without Preeclampsia by Gestational Age, Norway, 196798
Birth crownheel length ratio (mean)

Gestational age
(wk)

Preeclampsia

Nonpreeclampsia

Mean difference (95% CI)

27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
Total

97.0
99.0
97.6
96.5
97.2
95.6
95.7
96.1
96.4
97.5
98.4
98.9
99.7
100.0
100.2
100.2
100.0
100.4
99.3

100.2
100.4
100.4
100.5
100.4
100.6
100.6
100.5
100.4
100.3
100.1
100.1
100.0
100.0
100.0
100.0
100.0
100.0
100.0

3.1 (4.8, 1.4)

1.3 (3.3, 0.7)
2.8 (4.7, 0.9)
4.0 (5.6, 2.3)
3.2 (4.6, 1.9)
5.0 (6.1, 3.9)
5.0 (5.9, 4.0)
4.4 (5.2, 3.7)
4.0 (4.6, 3.4)
2.8 (3.3, 2.3)
1.7 (2.1, 1.4)
1.1 (1.4, 0.8)
0.3 (0.6, 0.1)
0.0 (0.2, 0.2)
0.2 (0.1, 0.4)
0.2 (0.2, 0.6)
0.0 (0.7, 0.6)
0.4 (0.8, 1.5)
0.8 (0.81, 0.7)

CI confidence interval.
* Adjusted for education in years (fewer than 10, 10 12, more than 12, and unknown), maternal age in years (19 or less, 20 29, 30 34, and 35
or more), and year of birth (196776, 1977 86, and 198798).

A strength of this study is its large size. Furthermore,

based on the total Norwegian birth population, the study
was most likely not affected by selection bias. Some of
the effect of preeclampsia on infants size might be ex-

plained by shared risk factors for preeclampsia and small

infants size that were not adjusted for in the present
analysis, such as thrombophilia, which have been associated with both conditions,19 but not consistently.20

Table 4. Mean and Adjusted* Mean Difference of Ponderal Index Ratio (95% CI) in Infants of Mothers With and Without
Preeclampsia by Gestational Age, Norway, 196798
Birth ponderal index ratio (mean)

Gestational age
(wk)

Preeclampsia

Nonpreeclampsia

Mean difference (95% CI)

27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
Total

94.1
95.4
95.7
95.3
93.2
91.4
93.4
92.0
93.8
94.7
96.2
96.8
97.9
98.7
98.9
98.9
98.2
98.9
97.5

100.3
101.2
101.0
100.5
101.5
101.5
101.1
101.0
100.5
100.3
100.1
100.0
100.0
100.0
100.0
100.0
100.1
100.3
100.1

6.2 (9.9, 2.5)

5.9 (10.4, 1.3)
5.4 (9.7, 1.0)
5.2 (8.8, 1.5)
8.3 (11.4, 5.3)
10.1 (12.6, 7.5)
7.8 (9.9, 5.6)
9.0 (10.6, 7.3)
6.7 (8.1, 5.3)
5.6 (6.7, 4.5)
3.8 (4.7, 3.0)
3.2 (3.9, 2.5)
2.2 (2.7, 1.6)
1.4 (1.9, 0.9)
1.1 (1.7, 0.5)
1.1 (2.0, 0.3)
1.9 (3.4, 0.4)
1.5 (4.0, 1.1)
2.6 (2.7, 2.5)

CI confidence interval.
* Adjusted for education in years (fewer than 10, 10 12, more than 12, and unknown), maternal age in years (19 or less, 20 29, 30 34, and 35
or more), and year of birth (196776, 1977 86, and 198798).

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Fetal Size in Preeclampsia

579

Table 5. Numbers and Percentages With Adjusted* Odds Ratios, Beyond Specified Percentiles for Infants Size of Preterm
Births With and Without Preeclampsia, Norway, 196798
Percentile cut-off points
Preeclampsia
Preclampsia
No preeclampsia
Preclampsia
No preeclampsia
Preclampsia
No preeclampsia
Preclampsia
No preeclampsia
Preclampsia
No preeclampsia

2.5

Type of
percentile
Birth weight percentile
Asymmetric SGA
Symmetric SGA
Crownheel length percentile
Ponderal index percentile

10

OR (95% CI)

213
658
95
225
56
260
130
595
253
662

5.9
2.0
2.6
0.7
1.6
0.8
3.6
1.8
7.1
2.0

3.4 (2.9, 4.0)

1 (referent)
4.6 (3.6, 5.9)
1 (referent)
2.2 (1.6, 2.9)
1 (referent)
2.2 (1.8, 2.7)
1 (referent)
4.2 (3.6, 4.9)
1 (referent)

1001
2633
530
1099
471
1534
623
2126
837
2877

27.9
7.8
14.8
3.3
13.1
4.6
17.4
6.3
23.3
8.5

OR odds ratio; CI confidence interval; SGA small for gestational age.

* Adjusted for education in years (fewer than 10, 10 12, more than 12, and unknown), maternal age in years (19 or less, 20 29, 30 34, and 35
or more), and year of birth (196776, 1977 86, and 198798).

Asymmetric SGA below the 2.5th percentile: birth weight- and ponderal index-percentiles 2.5; asymmetric SGA below the 10th percentile:
birth weight- and ponderal index-percentiles 10.

Symmetric SGA below the 2.5th percentile: birth weight percentile 10 and ponderal index percentile 2.5; symmetric SGA below the 10th
percentile: birth weight percentile 10 and ponderal index percentile 10.

However, most established risk factors, such as maternal

short stature and overt renal disease, are weak or uncommon and would not influence the associations essentially. Owing to lack of data, we were not able to include
in the study excessive weight gain and prepregnancy
weight, which are both strong and common risk factors
for preeclampsia and tend to increase fetal weight.21
However, it is likely that adjusting for maternal weight
or weight gain would increase the effect of preterm
preeclampsia on infants size. Nor did our database
include smoking status. It is well known that smoking is

a strong and common risk factor for low birth weight.

Smoking seems to be negatively associated with preeclampsia.22,23 Thus, adjusting for smoking would increase rather than decrease the effect of preeclampsia on
infants size. On the other hand, adjusting for obesity or
smoking should reduce the association of late preeclampsia with large infant size in late pregnancy, but probably
not to the extent that would significantly reverse the
effect. Besides, although obesity becomes more prevalent in Norway, the Norwegian pregnancy population is
still relatively lean.24

Table 6. Numbers and Percentages With Adjusted* Odds Ratios, Beyond Specified Percentiles for Infants Size of Births
From 37 Weeks Gestation With and Without Preeclampsia, Norway, 196798
Percentile cut-off points
2.5
Preeclampsia
Preclampsia
No preeclampsia
Preclampsia
No preeclampsia
Preclampsia
No preeclampsia
Preclampsia
No preeclampsia
Preclampsia
No preeclampsia

Type of percentile
Birth weight percentile
Asymmetric SGA
Symmetric SGA
Crown-heel length percentile
Ponderal index percentile

10

OR (95% CI)

1584
13,922
640
4001
496
6097
790
9668
1327
14,523

7.2
2.3
2.9
0.7
2.3
1.0
3.6
1.6
6.1
2.4

3.4 (3.3, 3.6)

1 (referent)
4.8 (4.4, 5.2)
1 (referent)
2.3 (2.1, 2.5)
1 (referent)
2.3 (2.1, 2.5)
1 (referent)
2.8 (2.7, 3.0)
1 (referent)

4046
58,173
2111
21,729
1935
36,444
2311
41,236
3756
59,808

18.5
9.5
9.6
3.5
8.8
5.9
10.6
6.7
17.2
9.8

Abbreviations as in Table 5.
* Adjusted for education in years (fewer than 10, 10 12, more than 12, and unknown), maternal age in years (19 or less, 20 29, 30 34, and 35
or more), and year of birth (196776, 1977 86, and 198798).

Asymmetric SGA below the 2.5th percentile: birth weight- and ponderal index percentiles 2.5; asymmetric SGA below the 10th percentile:
birth weight- and ponderal index percentiles 10.

Symmetric SGA below the 2.5th percentile: birth weight percentile 10 and ponderal index percentile 2.5; symmetric SGA below the 10th
percentile: birth weight percentile 10 and ponderal index percentile 10.

580

Rasmussen and Irgens

Fetal Size in Preeclampsia

OBSTETRICS & GYNECOLOGY

Percentile cut-off points

10

90

97.5

OR (95% CI)

OR (95% CI)

OR (95% CI)

4.7 (4.3, 5.1)

1 (referent)
5.5 (4.9, 6.1)
1 (referent)
3.2 (2.8, 3.4)
1 (referent)
3.1 (2.8, 3.4)
1 (referent)
3.4 (3.2, 3.8)
1 (referent)

141
3415

3.9
10.1

0.4 (0.3, 0.5)

1 (referent)

36
808

1.0
2.4

0.4 (0.3, 0.6)

1 (referent)

117
2753
211
3438

3.3
8.2
5.9
10.2

0.4 (0.3, 0.5)

1 (referent)
0.5 (0.4, 0.6)
1 (referent)

20
518
53
841

0.6
1.5
1.5
2.5

0.4 (0.3, 0.6)

1 (referent)
0.6 (0.5, 0.8)
1 (referent)

Although average birth weight of newborns to mothers with late preeclampsia approached those of mothers
without preeclampsia (Table 2), the newborns were
more likely to be SGA (Table 6). However, newborns
whose mothers had preterm preeclampsia were both on
average smaller (Table 2) and more likely than expected
to be SGA (Table 6). Our results agree with earlier
studies reporting that neonates to mothers with preeclampsia, particularly preterm, are smaller7,11,12,2527
and support the prevailing hypothesis that placental
hypoperfusion caused by shallow invasion of fetal trophoblasts in early pregnancy may cause preeclampsia or
FGR, or both.9,10 Morphologic studies have reported

that in pregnancies with asymmetric FGR, placental

infarcts and other signs of reduced placental perfusion
are common.28 Thus, our finding that newborns to
mothers with early preeclampsia were significantly
shorter and leaner, further suggests the ischemic hypothesis involving reduced perfusion of the fetoplacental
unit.
Consistent with the present study, recent evidence
indicates that in most cases of late preeclampsia, the
newborn has normal weight,12 and more infants than
expected are LGA.11 Moreover, in the present study, the
subsets of newborns that were long or had high ponderal
index were more common in preeclamptic than in non-

Percentile cut-off points

10

90

97.5

OR (95% CI)

OR (95% CI)

OR (95% CI)

2.2 (2.1, 2.3)

1 (referent)
3.0 (2.9, 3.2)
1 (referent)
1.5 (1.5, 1.6)
1 (referent)
1.6 (1.5, 1.7)
1 (referent)
2.0 (1.96, 2.1)
1 (referent)

2508
58,998

11.5
9.6

1.2 (1.1, 1.24)

1 (referent)

811
14,492

3.7
2.4

1.5 (1.4, 1.7)

1 (referent)

1522
35,601
2082
60,974

7.0
5.8
9.5
9.9

1.2 (1.17, 1.29)

1 (referent)
0.9 (0.85, 0.94)
1 (referent)

525
11,193
618
15,040

2.4
1.8
2.8
2.5

1.3 (1.2, 1.5)

1 (referent)
1.1 (1.0, 1.2)
1 (referent)

VOL. 101, NO. 3, MARCH 2003

Rasmussen and Irgens

Fetal Size in Preeclampsia

581

preeclamptic term and postterm deliveries. Thus, our

results do not support the widely accepted hypothesis
that placental dysfunction is necessary in the development of preeclampsia. It is generally believed that preeclampsia is caused by products released by the ischemic
placenta, causing endothelial activation, which results in
hypertension and proteinuria.29 Decreased perfusion of
the fetoplacental unit would decrease fetal size, even
before the appearance of the defining criteria of preeclampsia (hypertension and proteinuria).7 Our finding
of excess of large newborns in late preeclampsia rather
suggests that placental dysfunction is absent or plays a
minor role in a subset of preeclamptic pregnancies.
Our finding of excess of large newborns in late preeclampsia could be explained by the earlier demonstrated increased cardiac output in late-onset preeclamptic pregnancies.30 Consistently with that finding, Gant et
al31 reported increased uteroplacental perfusion, as indicated by increased placental clearance of dehydroisoandrosterone sulfate, in term preeclampsia compared with
pregnancies without preeclampsia, whereas in severe
preeclampsia clearance was lower.
The present study supports the hypothesis that preeclampsia is an etiologically heterogeneous disorder32
that occurs in at least two separate subsets,11 one with
normal or enhanced placental function and another involving placental dysfunction. In the subset with placental dysfunction and FGR, newborns often have asymmetric fetal body proportion, reduced fetal length, or are
delivered preterm, which is consistent with the prevailing hypoperfusion model. Our results indicate that
most cases of preeclampsia do not follow this model. It is
unlikely that a single treatment or preventive measure
will be effective. In future studies, it may be important to
study the two subtypes separately to examine whether
the subsets differ in severity or have different risk determinants.

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Address reprint requests to: Svein Rasmussen, MD, PhD,

University of Bergen, Department of Obstetrics and Gynecology, Kvinneklinikken, N-5021 Bergen, Norway; E-mail:
svein.rasmussen@mfr.uib.no.
Received June 3, 2002. Received in revised form August 19, 2002.
Accepted September 26, 2002.

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583