Association between adiposity and inflammatory markers in maternal and fetal blood in a group of Mexican pregnant women.
ABSTRACT In the present pilot study, we evaluated the effect of maternal adiposity on the plasma concentration of adipocytokines in pregnant women and their newborns. Twenty patients with term gestations without labour were initially selected by pregestational BMI and then classified into two study groups (n 10 each), according to their median value of adiposity (total body fat). Concentrations of TNF-α, IL-1β, IL-6, leptin and adiponectin in plasma of maternal peripheral blood and fetal cord blood were measured and correlated to maternal adiposity. Maternal adiposity showed a significant negative correlation with fetal adiponectin (r - 0·587, P = 0·01) and IL-6 (r - 0·466, P = 0·05), a significant positive correlation with maternal leptin (r 0·527, P = 0·02) and no correlation with TNF-α or IL-1β. Adiponectin was higher in fetal plasma than in maternal plasma (P = 0·043), but significantly lower in newborns from women with high adiposity than in newborns from women with low adiposity (P = 0·040). Our results suggest that fetuses from obese women may be less able to control inflammation, due to lower circulating anti-inflammatory adipocytokines, which could limit their optimal development or even increase the risk of abortion or preterm labour.
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ABSTRACT: In the nonpregnant population, there is extensive evidence of a systemic low-grade inflammatory status in relation to excess adipose tissue. Less is known about the relation during pregnancy. Our main objective was therefore to explore the effect of pregnancy on adiposity-related systemic inflammation. This study is a longitudinal cohort study of 240 pregnant women of Scandinavian heritage at Oslo University hospital-Rikshospitalet, Norway from 2002 to 2005. The inflammatory markers (C-reactive protein [CRP], Interleukin-6 [IL-6], monocyte chemoattractant protein 1 [MCP-1], IL1-Ra, tumor necrosis factor receptor II, and IL-10) were measured at four timepoints during pregnancy and analyzed by enzyme immuno-assay. The women were categorized based on BMI at inclusion (BMI <25, 25-30, and >30 kg/m(2) ). Data were analyzed by Friedman-test, Wilcoxon signed rank test, or Kruskal-Wallis test as appropriate. Maternal adiposity was associated with significantly higher circulatory levels of several inflammatory markers (CRP, MCP-1, IL-6, and IL-1Ra). However, this proinflammatory upregulation was not evident toward the end of pregnancy, as levels of CRP, MCP-1, and IL-6 were not any longer significantly different between the BMI categories. Although normal pregnancy exhibits proinflammatory features, this does not seem to have additive or synergistic effects on the inflammation associated with adiposity. On the contrary, we found that the BMI-dependent increase in proinflammatory markers was not evident at the end of pregnancy.Obesity 01/2013; 21(1):E124-30. · 3.92 Impact Factor
Association between adiposity and inflammatory markers in maternal and
fetal blood in a group of Mexican pregnant women
Rodrigo Vega-Sanchez1*, Hector A. Barajas-Vega1, Guadalupe Rozada1, Aurora Espejel-Nun ˜ez2,
Jorge Beltran-Montoya3and Felipe Vadillo-Ortega4
1Department of Nutrition Research, Instituto Nacional de Perinatologia Isidro Espinosa de los Reyes, Montes Urales 800,
Lomas Virreyes, CP 11000 Mexico D.F., Mexico City, Mexico
2Department of Biochemistry and Molecular Biology, Instituto Nacional de Perinatologia Isidro Espinosa de los Reyes,
Montes Urales 800, Lomas Virreyes, CP 11000 Mexico D.F., Mexico City, Mexico
3Toco-surgical Unit, Instituto Nacional de Perinatologia Isidro Espinosa de los Reyes, Montes Urales 800,
Lomas Virreyes, CP 11000 Mexico D.F., Mexico City, Mexico
4Department of Experimental Medicine, School of Medicine, UNAM, Mexico City, Mexico
(Received 22 September 2009 – Revised 6 March 2010 – Accepted 14 June 2010 – First published online 23 July 2010)
In the present pilot study, we evaluated the effect of maternal adiposity on the plasma concentration of adipocytokines in pregnant women and their
newborns. Twenty patients with term gestations without labour were initially selected by pregestational BMI and then classified into two study
groups (n 10 each), according to their median value of adiposity (total body fat). Concentrations of TNF-a, IL-1b, IL-6, leptin and adiponectin
in plasma of maternal peripheral blood and fetal cord blood were measured and correlated to maternal adiposity. Maternal adiposity showed a
significant negative correlation with fetal adiponectin (r 20·587, P¼0·01) and IL-6 (r 20·466, P¼0·05), a significant positive correlation with
maternal leptin (r 0·527, P¼0·02) and no correlation with TNF-a or IL-1b. Adiponectin was higher in fetal plasma than in maternal plasma
(P¼0·043), but significantly lower in newborns from women with high adiposity than in newborns from women with low adiposity
(P¼0·040). Our results suggest that fetuses from obese women may be less able to control inflammation, due to lower circulating anti-inflamma-
tory adipocytokines, which could limit their optimal development or even increase the risk of abortion or preterm labour.
Pregnancy: Adiposity: Cytokines: Inflammation: Obesity
Obesity represents one of the major public health problems
worldwide. In Mexico alone, it affects almost 70% of
people between 30 and 60 years old(1).
Obesity directly contributes to an increase in proinflamma-
tory adipocytokines, such as leptin, TNF-a, IL-6 and IL-1b,
and a decrease in adiponectin. Alterations in the concen-
trations of these cytokines are known to result from greater
fat mass (adiposity), causing the chronic inflammation
associated with type 2 diabetes and CVD, among other com-
In pregnant women, obesity may exacerbate the chronic
inflammation associated with gestation, particularly at term,
increasing the mother’s risk of presenting several compli-
cations such as gestational diabetes, pre-eclampsia, infection
and preterm labour, among others(5–7).
cytokines can also affect fetal development by causing
major alterations in bronchopulmonar and neurological
development and predisposing to a number of childhood and
adult obesity-related conditions(4,8,9).
However, the impact that greater maternal adiposity might
have on the concentration of pro-inflammatory cytokines in
fetal circulation is still uncertain. Therefore, the purpose of
the present pilot study was to identify the possible associations
between maternal adiposity and the concentration of various
pro-inflammatory markers at term gestation both in maternal
and fetal circulations.
The present study was conducted according to the guidelines
laid down in the Declaration of Helsinki and all procedures
*Corresponding author: Dr R. Vega-Sanchez, fax þ52 55 55200034, email email@example.com
British Journal of Nutrition (2010), 104, 1735–1739
q The Authors 2010
British Journal of Nutrition
involving patients were approved by the Internal Research and
Ethics Committees of the National Institute of Perinatology
in Mexico City. A written informed consent was obtained
from all patients.
Twenty women with term pregnancies (.37 weeks of
gestation) who delivered by elective caesarean section at the
National Institute of Perinatology in Mexico City were
included in the present study, together with their newborns.
Patients were carefully selected to discard labour, infection,
metabolic or autoimmune pathologies.
Patients were programmed for elective caesarean section
because of a personal or familial history of pregnancy-related
or other complications, according to institutional policies.
Most of the patients had a history of pre-eclampsia, abortions
and preterm deliveries; however, these were all conditions of
previous pregnancies and patients presented no complications
during the current gestation.
For the present pilot study, women were initially selected
using their pregestational BMI to include ten patients diag-
nosed as ‘normal’ and ten diagnosed as ‘overweight/obese’
according to the BMI classification of the World Health
The main characteristics of participant women and their
newborns are presented in Table 1. No differences were
found in maternal age, parity or gestational age. Maternal
(as expected). No differences were found in newborn charac-
teristics between groups.
Maternal measurements were made at the time of their
admission, 12h before surgery. The present weight of the
participants was measured using a Tanita scale model 1631
(Tanita, Arlington Heights, IL, USA). Height was measured
with a Seca 206 instrument (Seca Corporation, Hanover,
were measured using a Harpender skinfold caliper (Baty
International, West Sussex, UK). Resistance was measured
Township, MI, USA) according to the manufacturer’s
instructions. All measurements were made by the same stan-
Newborn characteristics, including weight, length, cephalic,
thoracic and abdominal perimeters, were obtained from the
Pregestational BMI was calculated using pregestational
weight referred by the patients.
Estimation of maternal adiposity
Although pregestational BMI was used to initially select the
patients, we believe that maternal adiposity (measured at
the time of cytokine quantification) would be a much better
parameter to relate with the inflammatory environment of
Maternal adiposity, defined as total body fat, was estimated
for each patient using the equation developed by Villar
et al.(11), which considers present weight, body surface,
subscapular skinfold, leg skinfold and resistance.
Maternal blood (5–10ml) was drained from the patient’s fore-
arm 12h before surgery and fetal blood was taken from the
umbilical cord vein immediately after the placenta was
removed. Samples were collected in 10ml plastic tubes with
heparin, and plasma was separated by centrifuging at room
temperature for 15min at 3000 rpm and stored at 2708C
Hb concentrations were determined to ensure equal blood
volumes (Table 1).
Table 1. Characteristics of participant women and their newborns
(Median values and ranges)
Low adiposity (n 10)High adiposity (n 10)
Maternal age (years)
Gestational age (weeks)
Total body fat (kg)†
Birth weight (g)
Birth length (cm)
Cephalic perimeter (cm)
Thoracic perimeter (cm)
Abdominal perimeter (cm)
PreBMI, pregestational BMI.
* Values were statistically different using Mann–Whitney’s test.
† Total body fat calculated with the equation from Villar et al.(11).
R. Vega-Sanchez et al.1736
British Journal of Nutrition
Leptin, adiponectin, TNF-a, IL-6 and IL-1b were chosen
because of their known implication in the onset of inflamma-
tory processes, which may affect fetal development and
gestational outcome(4). These cytokines were quantified
Profiling kit (R&D Systems, Minneapolis, MN, USA) with
molecule-specific antibodies in a Bio-Plex system (Bio-Rad,
Hercules, CA, USA) following the manufacturer’s protocol.
Samples were diluted fourfold as recommended by the manu-
facturer, and the results were multiplied by the dilution factor.
Detection ranges of the assays were 53·8–43668·9
pg/ml for leptin, 347·4–255722·9pg/ml for adiponectin,
3·8–2793·5pg/ml for TNF-a, 4·7–3487·5pg/ml for IL-6 and
2·2–1596·1pg/ml for IL-1b. Intra-assay coefficients of
variance were ,5% for all cytokines.
Maternal adiposity was arbitrarily categorised in to two groups
according to the median value of total body fat (group 1 ‘low
adiposity’ ¼ total body fat ,50 percentile; group 2 ‘high
adiposity’ ¼ total body fat .50 percentile).
Correlations between maternal adiposity (uncategorised)
and cytokine concentrations were evaluated with Spearman’s
test. Only strong, significant correlations are reported.
Differences in cytokine concentrations were analysed
with Mann–Whitney’s test. Differences with P#0·05 were
Differences in sex frequencies of newborns between
adiposity groups were analysed with a x2test, since fetal sex
has been correlated with higher amounts of cytokines(12,13).
All statistical analyseswere
Package for Social Sciences version 12.0 software (Chicago,
No differences were found in maternal age, gestational age,
newborn birth weight and length, and newborn cephalic,
thoracic or abdominal perimeters between low-adiposity and
P = 0·043
P = 0·001
P = 0·0001
P = 0·001
P = 0·040
P = 0·043
P < 0·0001
Fig. 1. Plasma concentration of cytokines in maternal and fetal blood. (a) TNF-a, (b) IL-6, (c) leptin and (d) adiponectin. Samples were categorised in to
‘low-adiposity’ group (,50 percentile (A) of total body fat) and ‘high-adiposity’ group (.50 percentile ( ) of total body fat), according to the median value
of maternal adiposity. The values represent median concentrations with interquartile ranges. Outlier values are represented by X. Differences tested with
Mann–Whitney’s test. NS (P.0·05).
Maternal adiposity and inflammatory markers1737
British Journal of Nutrition
Maternal adiposity showed a significant negative correlation
with fetal plasma adiponectin (r 20·587, P¼0·01) not
observed in maternal plasma. Adiponectin concentration was
significantly higher in fetal blood than in maternal blood in
both groups. Interestingly, this cytokine was significantly
lower in fetal blood of newborns from women in the high-
adiposity group compared with newborns in the low-adiposity
group, a difference not observed in maternal blood (Fig. 1).
IL-6 also showed a significant negative correlation with
maternal adiposity (r 20·466, P¼0·05). However, its concen-
tration showed no difference between blood (maternal/fetal) or
adiposity (low/high) groups (Fig. 1).
As expected, there was a significant positive correlation
between maternal adiposity and leptin plasma concentration
in maternal peripheral blood (r 0·527, P¼0·02). This was
not observed in fetal blood. Leptin concentrations were not
different between the low-adiposity
groups, although they clearly tended to increase in the high-
adiposity group. Its concentrations were significantly higher
in maternal blood compared with fetal blood (Fig. 1).
Plasma concentration of TNF-a did not correlate with
maternal adiposity and was not different between low-
adiposity and high-adiposity groups. However, it was signifi-
cantly higher in fetal blood than in maternal blood (Fig. 1).
IL-1b could not be quantified in any sample, since all of
the measurements were below the assay sensitivity limit
In the present study, we provide evidence that maternal adi-
posity has an effect on the concentration of adipocytokines
in fetal and maternal circulations. The relevance of these
findings lies in the fact that a chronic inflammatory environ-
ment, such as that characteristic of obesity, may have several
adverse effects on pregnancy outcomes and fetal development
and predisposition to obesity-related complications(4).
We found a significant inverse correlation between maternal
adiposity and fetal blood concentrations of adiponectin and
IL-6. Adiponectin is known to be anti-inflammatory in various
cell types, while IL-6 plays a regulatory role in inflammation
processes(14,15). The present study results also show higher
amounts of adiponectin in fetal circulation, agreeing with a
previous report(16). Since the major source of this hormone
is the fetus, this could suggest that there may be some
maternal-originated factors that could pass through the
placenta and affect adiponectin secretion by fetal tissues.
The fact that newborns from patients with high adiposity
inflammatory cytokines might suggest that their capacity to
control inflammation could be diminished, and therefore be
at more risk of complications resulting from an exacerbated
inflammation (e.g. abortion and preterm labour)(17).
Maternal adiposity correlated with leptin concentrations in
maternal but not fetal blood, suggesting that its transport to
fetal circulation is carefully controlled by the placenta.
Plasma concentrations of TNF-a and IL-1b were not altered
by maternal adiposity since the effects of these adipose-
derived cytokines are limited to the local environment and
not extended systemically(18,19).
Even with the small sample size of the present pilot study,
some interesting associations between adipocytokines and
maternal adiposity could be observed. A larger study, with
sample size and power calculated from the results of the pre-
sent pilot study, would allow us to divide the patients in more
groups and further strengthen the associations.
In summary, the present results suggest that, due to lower
circulating anti-inflammatory cytokines, fetuses from obese
women may be less able to control the inflammatory process
(e.g. during intra-uterine infections or even during normal
labour), which could limit optimal fetal development or
even increase the risk of abortion or preterm labour.
We thank Otilia Perichart-Perera for valuable technical
and methodological assistance throughout the study. The
authors declare no conflict of interests. Funding was obtained
through internal funds of the National Institute of Perinatology
in Mexico City. R. V.-S. designed the study, analysed the data
and wrote the manuscript; H. A. B.-V. recruited the patients,
collected and processed the samples and analysed the data;
G. R. also analysed the data and wrote the manuscript;
A. E.-N. processed the samples; J. B.-M. recruited the
patients; F. V.-O. designed the study.
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