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The Journal of Clinical Endocrinology & Metabolism 89(8):4031– 4036
Copyright © 2004 by The Endocrine Society
doi: 10.1210/jc.2004-0018
Cord Plasma Adiponectin: A 20-Fold Rise between 24
Weeks Gestation and Term
EERO KAJANTIE, TIMO HYTINANTTI, PETTERI HOVI,
AND
STURE ANDERSSON
Hospital for Children and Adolescents (E.K., T.H., P.H., S.A.) and Department of Obstetrics and Gynecology (S.A.), Helsinki
University Central Hospital, 00029 HUS Helsinki, Finland; and National Public Health Institute (E.K.), 00300 Helsinki,
Finland
Adiponectin is an adipocyte-derived hormone with profound
insulin-sensitizing, antiinflammatory, and antiatherogenic
effects. Apart from its obvious potential as a mediator of adult
metabolic syndrome, adiponectin could have a significant role
in regulating fetal growth.
We measured plasma adiponectin concentrations by ELISA
in cord vein of 197 infants. Of them, 122 were born preterm
(gestational age, 22–32 wk), and 75 at term (49 from a healthy
and 26 from a diabetic pregnancy, with similar findings, and
thus all data from term infants pooled).
Mean adiponectin concentrations increased from less than
1 ␮g/ml at 24 wk gestation to approximately 20 ␮g/ml at term.
One week increase in gestational age corresponded in preterm infants to 43% increase (95% confidence interval 34 –53%;
P < 0.0001) in adiponectin and term infants to 21% increase
A
DIPONECTIN IS AN adipocyte-derived hormone with
profound metabolic effects that include increased insulin sensitivity (1–3) and antiinflammatory (3) and antiatherogenetic actions (3, 4). These effects make it an important therapeutic target in the prevention and treatment of the
metabolic syndrome and its cardiovascular complications.
Adiponectin is present in abundant concentrations in cord
blood of term infants (5, 6), but little is known about its role
earlier during the fetal period. It has, however, several features that make its role during the fetal period an intriguing
object to study. A body of evidence from experimental and
epidemiological studies have shown that the metabolic syndrome and its components are associated with small size at
birth, a proxy of intrauterine conditions that result in slow
fetal growth (7–10). Fetal growth is to a great extent controlled by actions of insulin (11). Adiponectin as a key regulator of insulin sensitivity could thus be expected to have
significant effects on fetal growth and development. If so, it
would constitute an important candidate to explain the link
between small size at birth and adult metabolic syndrome. A
further intriguing feature of adiponectin is that, although it
is the product of the most abundant gene transcript in adipocytes (12), in children (13) and adults (14 –16) its concentrations show paradoxically an inverse correlation with body
fat percentage, suggesting that the amount of fat may exert
negative feedback on adiponectin synthesis (3). Because the
Abbreviations: CI, Confidence interval; SDS, sd score.
JCEM is published monthly by The Endocrine Society (http://www.
endo-society.org), the foremost professional society serving the endocrine community.
(12–31%; P < 0.0001). In preterm infants, one unit increase in
birth weight SD score corresponded to 42% increase (22– 66%;
P ⴝ 0.0001) in adiponectin, and females had 57% higher adiponectin concentrations (0 –146%; P ⴝ 0.05) than males. These
differences were not seen in term infants. Adiponectin levels
were lower in preterm infants with recent (<12 h) exposure to
maternal betamethasone but were unrelated to mode of delivery, preeclampsia, or impaired umbilical artery flow.
In conclusion, adiponectin concentrations in fetal circulation show a 20-fold rise between 24 wk gestation and term and,
in preterm infants are associated with birth weight SD score,
sex, and glucocorticoid exposure. Adiponectin may play an
important role in regulating fetal growth and explaining its
links to the metabolic syndrome and its consequences during
adult life. (J Clin Endocrinol Metab 89: 4031– 4036, 2004)
proportion of body fat rises throughout mid- to late gestation, preterm infants across a wide range of gestational ages
constitute a useful model to test this hypothesis. With this
background, we set out to study how gestational age and
clinical conditions in preterm and term pregnancies affect
plasma adiponectin concentrations in a cohort of infants with
a wide range of gestational ages and prematurity-associated
morbidity.
Subjects and Methods
Study population
The study population comprised 197 newborn infants born at the
Department of Obstetrics and Gynecology, Helsinki University Central
Hospital, Helsinki, Finland. To elucidate the role of circulating adiponectin during normal and pathologic development of the mid- and
late pregnancy fetus, we chose a study population consisting of three
separate groups. The preterm group encompassed 122 infants born
between 22 and 32 wk gestation. The 49 healthy term infants born after
36 wk gestation from an uncomplicated pregnancy served as a reference
group. The possible effects of maternal diabetes were studied in 26
infants from a full-term diabetic pregnancy. Table 1 shows the clinical
data.
Gestational age was confirmed by ultrasound before 20 wk gestation.
The infants were weighed immediately after birth. To describe size at
birth in units adjusted for gestational age, relative birth weight, expressed in sd units, was determined separately for both sexes with
reference to current Finnish standards (17). Ponderal index at birth was
calculated as weight (kilograms)/[length (meters)3]. Maternal hypertension during pregnancy was defined as systolic blood pressure 140
mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or a
30 mm Hg or greater increase in systolic or 15 mm Hg or greater increase
in diastolic blood pressure. For the fetal blood gas analysis, a heparinized
syringe was used to aspirate blood from a single artery of a doubleclamped cord immediately after birth. Preeclampsia was diagnosed
when proteinuria of 0.3 g/d or greater was present together with hy-
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J Clin Endocrinol Metab, August 2004, 89(8):4031– 4036
Kajantie et al. • Cord Plasma Adiponectin
TABLE 1. Clinical data
Preterm
N
Male/female
Cesarean section
Preeclampsia
Impaired umbilical artery flow
Gestational diabetes
Type 1 diabetes
Gestational age (wk)
Birth weight (g)
Birth weight (SDS)
Length at birth (cm)
Ponderal index at birth (kg/m3)
Mother’s length (cm)
Mother’s BMI before pregnancy (kg/m2)
Adiponectin concentration (␮g/ml)a
122
65/57
65
22
24
10
3
28.7 (2.5) [22.4 –32.0]
1195 (410) [455–2010]
⫺0.93 (1.38) [⫺4.9 –⫹3.0]
37.6 (4.0) [27.0 – 45.0]
22.3 (2.5) [16.2–29.6]
164.9 (6.2) [145–178]
23.8 (4.7) [17.0 – 44.1]
3.7 [0.080 –31.4]
Term healthy
Term diabetic
49
24/25
7
0
0
0
0
40.1 (1.2) [36.0 – 42.1]
3478 (475) [2140 – 4400]
⫺0.3 (1.0) [⫺2.0 –⫹2.0]
50.2 (1.9) [45.0 –54.0]
27.4 (2.1) [23.2–33.5]
166.5 (6.2) [155–181]
23.1 (3.2) [18.9 –31.6]
23.7 [5.5–54.8]
26
13/13
8
0
0
21
5
39.4 (1.6) [36.6 – 41.7]
3707 (543) [2430 – 4630]
0.3 (1.0) [⫺1.9 –⫹2.1]
50.5 (2.0) [45.5–54.0]
28.6 (2.3) [23.7–32.8]
165.0 (6.2) [153–174]
25.0 (4.6) [17.8 –34.7]
18.7 [4.4 – 42.4]
Data represent number of patients or mean (SD) [range]. BMI, Body mass index.
Geometric mean.
a
pertension. Increased umbilical artery resistance was defined as Doppler
flow velocitometry showing an umbilical artery resistance index of 2 sd
or greater above mean for gestational age (18). The diagnosis of gestational diabetes was based on oral glucose tolerance test, with venous
plasma glucose exceeding one of the values of 4.8 mmol/liter (baseline),
10.0 mmol/liter (1 h), or 8.7 mmol/liter (2 h), which represent the 97.5
percentile values of pregnant Finnish women (19).
Betamethasone (12 mg im twice at 24-h intervals) served as an antenatal glucocorticoid treatment when a preterm delivery was imminent.
The treatment was repeated in 7–10 d, if necessary. Of the 122 preterm
infants, nine received no betamethasone, 89 infants one course, 21 infants
two courses, and three infants three courses. The time between the last
betamethasone dose and birth and the number of betamethasone treatments were both considered variables in the data analysis.
Adiponectin measurements
Immediately after birth, umbilical vein samples were drawn into
EDTA-containing tubes with plasma frozen without delay and stored at
⫺20 C until analysis. Adiponectin concentrations were measured by
ELISA (R&D Systems Inc., Minneapolis, MN).
The study protocol was approved by the Ethics Committee of the
Department of Obstetrics and Gynecology, Helsinki University Central
Hospital.
Data analysis
Adiponectin concentrations were right skewed and thus log transformed into normality. Simple and multiple linear regressions were used
to assess correlation between variables. Unless otherwise stated, regression equations are adjusted for gestational age, relative birth weight, and
infant sex. Because of the logarithmic transformation of the independent
variables, each regression coefficient indicates percent change in plasma
adiponectin concentration associated with one unit change in the dependent variable. To allow for possible nonlinear effects, a reference cell
dummy coding was employed to account for the time between the last
betamethasone dose and birth. Subjects were divided into four groups:
1) less than 12 h (n ⫽ 26); 2) 12–72 h (n ⫽ 33); 3) 72 h to 7 d (n ⫽ 28);
and 4) the reference group with more than 7 d or no betamethasone (n ⫽
35), who are no longer expected to show any effect of administered
betamethasone (20). As a consequence of the reference cell dummy
coding, the regression coefficient of each dummy variable in groups 1,
2, and 3 denotes difference to the reference group (21).
Results
Mean adiponectin concentrations together with clinical
data are shown in Table 1. Term infants from pregnancies
with maternal diabetes had similar adiponectin concentrations as healthy term infants (18.7 vs. 23.7 ␮g/ml, P ⫽ 0.2),
with no difference between infants of mothers with gesta-
FIG. 1. Cord plasma adiponectin concentrations according to gestational age at birth. Dashed lines represent linear regression slopes
separately for preterm and term infants. One-week increase in gestational age is associated in preterm infants with 43% increase (95%
CI 34 –53%; P ⬍ 0.0001) in plasma adiponectin and term infants with
a 21% increase (12–31%; P ⬍ 0.0001) (P for difference between
slopes ⫽ 0.03). The solid line stands for quadratic regression in all
infants combined (adjusted r2 ⫽ 0.68; P ⬍ 0.0001).
tional and type 1 diabetes (P ⫽ 0.8). Therefore, we present a
pooled analysis for infants from healthy and diabetic term
pregnancies.
Gestational age
Plasma adiponectin concentrations were closely correlated
with gestational age (Fig. 1 and Table 2). In preterm infants,
1 wk of increase in gestational age was associated with 43%
[95% confidence interval (CI) 34 –53%; P ⬍ 0.0001] increase
in plasma adiponectin, whereas the relationship was less
steep in term infants, 21% (12–31%; P ⬍ 0.0001; P for interaction preterm vs. term infants ⫽ 0.03) (Table 2). With preterm and term infants combined, the relationship between
gestational age and plasma adiponectin gave a good fit to a
quadratic model [log (adiponectin) ⫽ ⫺19.56 ⫹ 1.14 ⴱ gestational age ⫺ 0.0143 ⴱ gestational age2; adjusted r2 ⫽ 0.68;
P ⬍ 0.0001] (Fig. 1).
Kajantie et al. • Cord Plasma Adiponectin
J Clin Endocrinol Metab, August 2004, 89(8):4031– 4036 4033
TABLE 2. Regression equations showing percentage change in plasma adiponectin concentration produced by one unit change in each
independent variable (95% CI in parentheses)
Adjusted R2
Gestational age
(wk)
Preterm infants
0.48
43% (34 to 53%)
P ⬍ 0.0001
0.15
Relative birth weight
(SD)
0.70
Term infants
0.28
41% (33 to 49%)
P ⬍ 0.0001
40% (32 to 47%)
P ⬍ 0.0001
12–72 h
72 h–7 d
40% (27 to 55%)
P ⬍ 0.0001
45% (32 to 60%)
P ⬍ 0.0001
57% (0 to 146%)
P ⫽ 0.05
47% (11 to 95%)
P ⫽ 0.008
35% (2 to 79%)
P ⫽ 0.04
⫺34% (⫺49 to ⫺14%) 0% (⫺20 to 25%) 60% (26 to 104%)
P ⫽ 0.002
P ⫽ 1.0
P ⫽ 0.0002
21% (12 to 31%)
P ⬍ 0.0001
0.03
8% (⫺4 to 22%)
P ⫽ 0.2
0.01
0.30
0 –12 h
42% (22 to 66%)
P ⫽ 0.0001
0.03
0.62
Time after last betamethasonea
Sex
(1 ⫽ male; 2 ⫽ female)
20% (11 to 30%)
P ⫽ 0.0001
5% (⫺6 to 16%)
P ⫽ 0.4
⫺10% (⫺29 to 15%)
P ⫽ 0.4
⫺10% (⫺27 to 11%)
P ⫽ 0.3
Each row represents one regression model, adjusted R2 of the model shown in the left column.
a
Compared with infants with at least 7 d after last betamethasone or unexposed to betamethasone, adjusted for the number of betamethasone
courses.
similar when adjusted for gestational age and sex. No relationship with birth weight SDS was, however, seen in term
infants (P ⫽ 0.2; P for interaction preterm vs. term ⫽ 0.05)
(Table 2). Moreover, in both preterm and term infants, no
association was seen between ponderal index and plasma
adiponectin, whether adjusted for gestational age, birth
weight SDS, and sex. Adiponectin concentrations were as
well unaffected by maternal height (P ⫽ 0.4 for preterm and
0.2 for term infants) or prepregnancy body mass index (P ⫽
0.2 for preterm and 0.3 for term infants).
Infant sex
FIG. 2. Cord plasma adiponectin concentrations according to birth
weight SDS in preterm infants (born ⬍ 32 wk gestation). One SDS
increase in birth weight SDS is associated with 42% increase (95% CI
22– 66%; P ⫽ 0.0001) in adiponectin concentration.
Size at birth
In an unadjusted regression analysis, birth weight was
associated with cord plasma adiponectin in preterm infants,
in whom a 100-g increase in birth weight corresponded to
26% increase (95% CI 22–31%, P ⬍ 0.0001) in adiponectin and
also in term infants, a corresponding increase being 3.5%
(95% CI 1.1–5.9%, P ⫽ 0.005). Table 2 shows that the relationship between size at birth and plasma adiponectin was
independent of gestational age in preterm but not term infants. In preterms, one sd score (SDS) increase in birth weight
SDS was associated with 42% increase (95% CI 22– 66%; P ⫽
0.0001) in adiponectin (Fig. 2). This relationship remained
Preterm girls had 57% higher plasma adiponectin concentrations (95% CI 0 –146%; P ⫽ 0.05) than preterm boys. Adjusted for gestational age and relative birth weight, the difference was 47% (11–95%; P ⫽ 0.008). There was no sex
difference in all term infants combined (P ⫽ 0.4; P for interaction preterm vs. term ⫽ 0.09) (Table 2) or in infants from
healthy or diabetic pregnancies.
Mode of delivery
Plasma adiponectin concentrations were similar in infants
born with cesarean section, compared with vaginal delivery
(P ⫽ 0.7 for preterm and 0.6 for term infants).
Preeclampsia and fetal distress
We assessed whether fetal distress per se is associated with
plasma adiponectin concentrations in preterm infants of
mothers with associated conditions. Compared with other
preterm infants, adjusted for gestational age and sex, infants
of mothers with maternal hypertension had 36% (95% CI
10 –54%, P ⫽ 0.01), with preeclampsia 28% (⫺10 to 54%, P ⫽
0.1) and impaired umbilical artery flow 50% lower (25– 67%,
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J Clin Endocrinol Metab, August 2004, 89(8):4031– 4036
P ⫽ 0.001) adiponectin concentration. However, this association was entirely attributable to the growth restriction associated with these conditions: further adjustment with birth
weight SDS resulted in no association with maternal hypertension (P ⫽ 0.7), preeclampsia (P ⫽ 0.8), or increased umbilical artery resistance (P ⫽ 0.4). Moreover, in both preterm
(P ⫽ 0.6) and term (P ⫽ 0.8) infants, cord vein adiponectin
was unrelated to cord artery pH.
Maternal betamethasone treatment
Most preterm infants had been exposed to maternal betamethasone treatment, administered to reduce neonatal
morbidity and mortality. We assessed its effects by comparing plasma adiponectin concentrations with those of preterm
infants unexposed to betamethasone with at least 7 d after
last betamethasone exposure, who are expected to have
no residual betamethasone activity (20). Compared with
this group, as shown in Fig. 3, adiponectin concentrations
were reduced in infants with less than 12 h after last betamethasone dose, similar in those with 12–72 h after last
betamethasone and increased in those with 72 h to 7 d after
last betamethasone. Plasma adiponectin concentrations were
unrelated to the number of betamethasone treatments given.
Multiple regression models
To demonstrate the combined effects of clinical variables
on cord plasma adiponectin concentrations, we calculated
multiple regression models shown in Table 2. In both preterm and term infants, adjustment of the effects of gestational
age, birth weight SDS, and infant sex on plasma adiponectin
FIG. 3. Boxplots (median, 25th, and 75th percentiles, range, and extreme values) showing plasma adiponectin concentrations in preterm
infants according to the time between last maternal betamethasone
dose and birth. The concentrations in each group are compared with
the reference group consisting of infants either unexposed to betamethasone or with at least 7 d after last betamethasone dose, who are
not expected to have any residual betamethasone in circulation (20).
One infant with a high adiponectin concentration of 34.2 ␮g/ml, unexposed to betamethasone, is not shown in the figure. Adiponectin concentrations and P values are adjusted for gestational age, birth weight
SDS, infant sex, and the number of betamethasone courses given.
Kajantie et al. • Cord Plasma Adiponectin
to each other produced only a moderate change in the associations. We further checked whether any two- or threeway interactions are present between the effects of these
variables on plasma adiponectin. No interaction was seen in
preterm infants, but in term infants the interaction between
the gestational age and birth weight SDS was statistically
significant (P ⫽ 0.007). To examine this interaction, we divided the term group into two groups according to gestational age. In term infants born before 40 wk gestation, one
unit in birth weight SDS corresponded to 14% increase (95%
CI ⫺5 to 36%, P ⫽ 0.1) in adiponectin concentration, whereas
in infants born after 40 wk gestation, the corresponding
change was ⫺7% (⫺17 to 4%, P ⫽ 0.2).
Discussion
The main finding of the present study was the striking
increase of plasma adiponectin concentrations with gestational age. Concentrations at term, 2- to 3-fold higher than
those reported in adults (4, 16, 22), were more than 20-fold
higher, compared with 24 wk gestation. In small preterm
infants, lower plasma adiponectin was in addition predicted
by low birth weight SDS, male sex, and recent exposure to
betamethasone.
In a term newborn, adipose tissue is a crucial element for
survival as an energy reserve, although little has so far been
known about its role as an endocrine organ. Adipose tissue
is present at least from 14 wk gestation, and its morphologic
differentiation mostly takes place during the second trimester, by the end of which adipose tissue is present at principal
body fat deposit areas (23, 24). Most of the increase in the
amount of adipose tissue occurs during the last trimester,
paralleling closely the gestational age increase we found in
adiponectin concentrations. This is in marked contrast with
adults (14 –16) and children (13), in whom adiponectin concentrations paradoxically show an inverse correlation with
body fat percentage. Together with the correlation with birth
weight SDS we observed in preterm infants, this finding
implies that the proposed inhibition of adiponectin synthesis
by the amount of fat mass, possibly through the production
of other adipocytokines (3), is not yet operative in the fetus
before 32 wk gestation.
At term, however, we found adiponectin concentrations to
be unrelated to relative birth weight, although there was a
significant interaction between the effects of gestational age
and birth weight SDS, suggesting a weak positive relationship that fades away with increasing gestational age. A modest positive relationship between birth weight and cord vein
adiponectin was also shown in a recent study of healthy term
infants, although it remains uncertain how much of this
relationship was attributable to increasing gestational age,
which was not accounted for in that study (6). Moreover, we
found no relationship between adiponectin and maternal
diabetes (gestational or type 1), and another study has shown
only a minor decrease in adiponectin in term infants of mothers with type 1 diabetes (5). The faintness of these relationships may be explained by the fact that none of these studies
included a sufficient number of term infants born small for
gestational age. Alternatively, they may suggest that the
phenomenon of reduced adiponectin concentration per amount
of adipose tissue is becoming apparent already at term.
Kajantie et al. • Cord Plasma Adiponectin
Apart from the energy-storing white adipose tissue, newborn infants possess an amount of brown adipose tissue
whose main function, nonshivering thermogenesis, makes it
crucial for body temperature homeostasis after birth. The
amount of brown adipose tissue increases significantly during late gestation, but during childhood this tissue tends to
become atrophied (25). Brown adipocytes exhibit abundant
expression of the adiponectin gene (26). Interestingly, its
regulation appears to differ from that in white adipocytes.
For example, the effect of insulin on adiponectin synthesis is
inhibitory in white (27) and stimulatory in brown adipocytes
(26). It is thus possible that these differences in regulation of
adiponectin synthesis may in part explain why the negative
association between corpulence and adiponectin concentration
in children (13) and adults (14 –16) is not seen in newborns.
An obvious reservation to these conclusions is that we do
not have a specific measure of the amount of adipose tissue.
However, particularly in ventilated small preterm infants,
specific measurements such as dual-energy x-ray absorptiometry are highly impractical, and there is no consensus on
how anthropometric variables such as skinfolds should be
interpreted. Yet in preterm and term neonates, body weight
has been shown to explain, together with infant sex, 85% of
variation in fat mass and 72% of variation in percent body fat
as assessed by dual-energy x-ray absorptiometry (28), and
thus it constitutes a satisfactory estimation of body fat content.
The reduced adiponectin concentrations we found in
growth-retarded preterm infants are intriguing in light of the
enhancing effect of adiponectin on insulin sensitivity. The
regulation of fetal growth differs considerably from that
during the postnatal period. The IGF system is mostly controlled by insulin, which allows rapid responses to nutritional fluctuations, in contrast to the more stable actions of
the GH system, which predominates during the postnatal
period (11). The sensitivity of fetal tissues to insulin action
has thus potentially profound effects on fetal growth. Rare
inherited disorders with impaired insulin sensitivity, such as
leprechaunism caused by homozygous mutations in the insulin receptor gene, are associated with marked intrauterine
growth retardation (29). A significant number of small preterm infants requires postnatal insulin infusions to maintain
glucose homeostasis (30). However, the role and mechanisms
of the regulation of insulin sensitivity during the fetal period
have been poorly understood. The present study suggests
that adiponectin is a key candidate for further studies on the
regulation of insulin sensitivity in the growing fetus.
In adults, adiponectin concentrations are consistently
lower in males than females. A similar difference has been
observed in a group of infants of mothers with type 1 diabetes, with mean gestational age of 37 wk 6 d (5) but not in
term infants from healthy pregnancies (5, 6). These findings,
together with our result of a comparable difference in preterm but not in term infants, suggest that the mechanism(s)
responsible for the sex difference in the fetus could be associated with gestational age. In adults, the suppression of
adiponectin synthesis by androgens has been suggested to
account for the sex difference (22). During midpregnancy
male fetuses exhibit 5-fold higher mean testosterone concentrations than females (31), a difference that is reduced to
less than 1.5-fold by term (32). It is therefore possible that a
J Clin Endocrinol Metab, August 2004, 89(8):4031– 4036 4035
similar regulation is operative in the growing fetus, but to
confirm that requires further study.
We found no association between adiponectin concentrations and mode of delivery. This suggests that fetal stress
associated with vaginal delivery does not have a significant
effect on adiponectin concentrations, implying that concentrations measured from cord vein samples obtained after
birth are a reliable indicator of adiponectin concentrations
during similar conditions in utero. This relative stability is
consistent with findings of no changes in adiponectin concentrations between birth and 4 d of age in term infants (6)
or in adults after physical exercise (33) or a high-fat meal (34)
and only modest changes during a diurnal cycle (35).
Low adiponectin concentration was associated with preeclampsia, maternal hypertension, or impaired umbilical artery flow, which is an end-stage feature of these and other
conditions characterized by severe placental dysfunction.
However, all these associations became nonsignificant when
adjusted for birth weight SDS. Fetal growth impairment is a
key feature of these conditions, which in turn are most important causes of intrauterine growth restriction, particularly
in preterm infants. This makes it difficult to distinguish
whether the low adiponectin concentration is a consequence
of fetal growth restriction in general or a specific characteristic of these disorders. A specific mechanism is argued for
by the association of preeclampsia with impaired placental
11␤-hydroxysteroid dehydrogenase 2 function (36, 37). This
results in increased fetal exposure to maternal cortisol, which
would be expected to reduce adiponectin concentrations.
However, the role of adiponectin in the pathophysiology of
preeclampsia may be more complex. The reduction in 11␤hydroxysteroid dehydrogenase 2 function is less pronounced before 32 wk gestation (38), and despite the wellknown association of preeclampsia and maternal insulin
resistance (39), there is at least one report (40) showing increased adiponectin concentrations in maternal circulation
during preeclampsia, compared with normal pregnancies.
Glucocorticoids are known inhibitors of adiponectin synthesis (41). Consistent with that, we found reduced adiponectin concentrations in preterm infants exposed to betamethasone less than 12 h before birth. It is thus possible that the
adverse metabolic effects of perinatal glucocorticoid administration, such as decrease in insulin sensitivity and increase
in blood pressure, could in part be mediated through decreased adiponectin concentrations. The increased adiponectin concentrations we found in infants born between 3 and
7 d after last betamethasone are more difficult to explain.
Whether they are related to the overall favorable effects of
antenatal glucocorticoids in reducing neonatal morbidity remains to be studied.
In conclusion, adiponectin concentrations in fetal circulation show a 20-fold rise between 24 wk gestation and term.
They are unrelated to the mode of delivery implying that
cord plasma concentrations at birth represent circulating
concentrations in the growing fetus. In preterm infants, low
adiponectin concentrations are also associated with low-birthweight SDS, male sex, and recent exposure to maternal betamethasone. These findings suggest that the proposed inhibition
of adiponectin by the amount of body fat is not yet operative
before 32 wk gestation. Adiponectin may play a significant role
4036
J Clin Endocrinol Metab, August 2004, 89(8):4031– 4036
Kajantie et al. • Cord Plasma Adiponectin
in regulating fetal growth and explaining its links to the metabolic syndrome and its consequences during adult life.
17.
Acknowledgments
18.
We thank the midwives at Department of Obstetrics and Gynecology
(Helsinki University Central Hospital) for help in collecting the blood
samples and Marjatta Vallas for excellent technical assistance.
19.
20.
Received January 6, 2004. Accepted April 27, 2004.
Address all correspondence and requests for reprints to: Eero Kajantie, M.D., National Public Health Institute, Mannerheimintie 166,
00300 Helsinki, Finland. E-mail: [email protected].
This work was supported by grants from the Finnish Heart Foundation, Finnish Medical Society Duodecim, Finska Läkaresällskapet,
Foundation for Pediatric Research, Helsinki University Central Hospital
Research Fund, Jalmari and Rauha Ahokas Foundation, Sigrid Jusélius
Foundation, and Yrjö Jahnsson Foundation.
E.K. and T.H. contributed equally to this work.
24.
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