Selenium and maternal blood pressure during childbirth

ArticleinJournal of Exposure Science and Environmental Epidemiology 22(2):191-7 · November 2011with30 Reads
Impact Factor: 3.19 · DOI: 10.1038/jes.2011.42 · Source: PubMed
Abstract

Evidence suggests selenium concentrations outside the nutritional range may worsen cardiovascular health. This paper examines the relationship between selenium and maternal blood pressure (BP) among 270 deliveries using umbilical cord serum as a proxy for maternal exposure levels. Multivariable models used linear splines for selenium and controlled for gestational age, maternal age, race, median household income, parity, smoking, and prepregnancy body mass index. Non-parametric analysis of this dataset was used to select spline knots for selenium at 70 and 90 μg/l. When selenium was <70 μg/l, increasing selenium levels were related to a non-statistically significant decrease in BP. For selenium 70-90 μg/l, a 1 μg/l increase was related to a 0.37 mm Hg (95% confidence interval (CI): 0.005, 0.73) change in systolic and a 0.35 mm Hg (0.07, 0.64) change in diastolic BP. There were very few selenium values >90 μg/l. Other studies indicate that the maternal/cord selenium ratio is 1.46 (95% CI: 1.28, 1.65). This u-shaped relationship between selenium and BP is consistent with a dual role of selenium as an essential micronutrient that is nonetheless a toxicant at higher concentrations; however, this needs to be studied further.

Figures

Full-text

Available from: Lynn R Goldman
S elenium and maternal blood pressure during childbirth
ELLEN M. WELLS
a,b
,LYNNR.GOLDMAN
a,c
, JEFFERY M. JARRETT
d
, BENJAMIN J. APELBE RG
e
,
JULIE B. HERBSTMAN
f
, KATHLEEN L. CALDWELL
d
, ROLF U. HALDEN
a,g
AND FRANK R. WITTER
h
a
Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
b
Department of Environmental Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
c
George Washington University School of Public Health and Health Services, Washington, DC, USA
d
Inorganic and Radiation Analytical Toxicology Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
e
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
f
The Columbia Center for Childrens Environmental Health, Columbia University Mailman School of Public Health, New York, New York, USA
g
Swette Center for Environmental Biotechnology, Biodesign Institute, Arizona State University, Tempe, Arizona, USA
h
Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Evidence suggests selenium concentrations outside the nutritional range may worsen cardiovascular health. This paper examines the relationship between
selenium and maternal blood pressure (BP) among 270 deliveries using umbilical cord serum as a proxy for maternal exposure levels. Multivariable
models used linear splines for selenium and controlled for gestational age, maternal age, race, median household income, parity, smoking, and
prepregnancy body mass index. Non-parametric analysis of this dataset was used to select spline knots for selenium at 70 and 90 mg/l. When selenium was
o70 mg/l, increasing selenium levels were related to a non-statistically significant decrease in BP. For selenium 70–90 mg/l, a 1 mg/l increase was related to
a 0.37 mm Hg (95% confidence interval (CI): 0.005, 0.73) change in systolic and a 0.35 mm Hg (0.07, 0.64) change in diastolic BP. There were very few
selenium values 490 mg/l. Other studies indicate that the maternal/cord selenium ratio is 1.46 (95% CI: 1.28, 1.65). This u-shaped relationship between
selenium and BP is consistent with a dual role of selenium as an essential micronutrient that is nonetheless a toxicant at higher concentrations; however,
this needs to be studied further.
Journal of Exposure Science and Environmental Epidemiology (2012) 22, 191–197; doi:10.1038/jes.2011.42; published online 23 November 2011
Keywords: blood pressure, pregnancy, selenium, umbilical cord.
Introduction
Selenium is an antioxidant and promotes thyroid and
immune system function (Brown and Arthur, 2001). The
recommended daily allowance for selenium, currently
55 mg/day (60 mg/day during pregnancy), is needed to maxi-
mize glutathione peroxidase synthesis (Institute of Medicine,
2000). Either selenium deciency or excess may lead to
adverse health effects (Institute of Medicine, 2000);
globally, defi ciency is a larger concern than excess (Combs,
2001).
In North America, daily requirements for selenium are
generally met or exceeded (Institute of Medicine, 2000;
Combs, 2001). It has been questioned whether selenium
intake in excess of recommended levels m ight contribute to
development of cardiovascular disease (Navas-Acien et al.,
2008). Additionally, increased selenium intake may
contribute to diabetes and cardiovascular outcomes (Stranges
et al., 2010).
Elevations in blood pressure (BP) during pregnancy are
of concern due to possible chronic sequelae (Kaaja and
Greer, 2005; Lykke et al., 2009). However, few studies
have explored selenium and BP during pregnancy. Research
in the United Kingdom suggested preeclamptic mothers
have less selenium compared with healthy mothers (Rayman
et al., 2003; Mistry et al., 2008); in contrast, a study among
African mothers suggested the opposite (Mahomed et al.,
2000). Other work implicated selenium supplementation with
decreased risk of gestational hypertension among Chinese
mothers (Han and Zhou, 1994) and supplementation in a
clinical trial was related to a decrease in preeclampsia among
Iranian mothers (Tara et al., 2010).
The relationship of selenium and BP may depend on
whether nutritional needs for selenium have been met. This
study evaluates the relationship between selenium exposure as
measured in umbilical cord serum and maternal BP in a
cross-sectional study of mothers giving birth in Baltimore,
Maryland. Additionally, previous studies were used to create
a maternal/cord selenium ratio in order to estimate maternal
selenium in the current study.
Received 29 March 2011; accepted 14 June 2011; published online 23
November 2011
1. Address all correspondence to: Dr. Lynn R. Goldman, Department of
Environmental Health Sciences, Case Western Reserve University School
of Medicine, 2300 Eye St., NW, Suite 106, Washington, DC 20037, USA.
Tel.: þ 1 202 994 5179. Fax: þ 1 202 994 3773.
E-mail: lynn.goldman@gwumc.edu
Journal of Exposure Science and Environmental Epidemiology (2012) 22, 191–197
r
2012 Nature America, Inc. All rights reserved 1559-0631/12
www.nature.com/jes
Page 1
Materials and methods
The Baltimore THREE (Tracking Health Related to
Environmental Exposures) Study is a cross-sectional
study of mothers and infants conducted with approval of
the Maternal and Fetal Research Committee, Department
of Gynecology and Obstetrics, and the Johns Hopkins
School of Medicine Institutional Review Board (Apelberg
et al., 2007). Informed consent was not required for this
study because collected biological samples would otherwise
have been discarded and sample collection constituted no
more than minimal risk. Strict procedures were developed to
protect subject confidential ity. Owing to this design, maternal
serum was not availa ble.
Mothers giving birth between November 2004 and
March 2005 in the Johns Hopkins Hospital were eligible
for inclusion (n ¼ 603 deliveries). Deliveries with multiple
births (n ¼ 12) and births where cord blood was unavail-
able or of insufficient quantity (n ¼ 291) were excluded.
These analyses also excluded mothers with missing data on
selenium (n ¼ 13), BP (n ¼ 2), prepregnancy body mass
index (BMI) (n ¼ 11), and median household income (n ¼ 3).
One mother with admission systolic BP o20 mm Hg
was also excluded. Data were collected from analyses of
umbilical cord blood and maternal electronic medical
records. T wo study personnel extracted data from medical
records; a random 10% sample was reviewed by study
clinicians.
Hospital staff took maternal BP measurements as part of
routine medical care at admission and continuously while
hospitalized for labor and delivery. BP at hospital admission
and maximum BP (based on systolic) were abstracted.
Reliability of these measurements was assessed using other
variables within the dataset (Supplementary Information).
Measurements with systolic BP Z140 mm Hg or diastolic BP
Z90 mm Hg were considered ‘‘elevated’’, but not tanta-
mount to a diagnosis of hypertension. Hypertension was
classied as (1) all hypertension cases (pregnancy-related,
chronic, or medication use) and (2) the subset of women with
pregnancy-related hypertension diagnoses (Supplementary
Information).
Trained clinical staff collected umbilical cord blood using
standard procedures (Witter et al., 2001). Serum samples
were analyzed at the United States Centers for Disease
Control and Prevention (CDC). Selenium was determined
using National Institute of Standards and Technology-
traceable, matrix-matched calibrators on inductively coupled
plasma dynamic reaction cell mass spectrometry methodo-
logy adhering to Clinical Laboratory Improvement Amend-
ments
0
88 standards (Xiao, 2006). Limit of detection (LOD)
was 5 mg/l. Cotinine was measured using liquid chromato-
graphy i n conjunction with atmospheric pressure ionization
tandem mass spectrometry; LOD ¼ 0.015 ng/ml (Bernert
et al., 1997). A mother was classified as a smoker if serum
cotinine was Z10 ng/ml (CDC, 2005) or if smoking during
pregnancy was noted in the medical record.
BMI was calculated as prepregnan c y wei g h t (kg)/he i g h t (m
2
).
Median household income was obtained from the United
States 2000 Census. The median income was based on
a small census area called a block group, which includes
600–3000 individuals (Supplementary Information).
Statistical analyses were performed using Stata 11 (College
Station, TX, USA). Our hypothesis was that selenium’s
effect may be concentration-dependent; however, there are
no guidelines for umbilical cord selenium concentrations.
Therefore, we used our data to identify cutoff points for
spline models. Inflection points (where the dose–response
changes direction) were identifi ed visually using lowess curves
of selenium with each BP measurement (Supplementary
Information). The exact inection point differed slightly for
each BP measurement; for consistency, knots were chosen
to approximate inflection points across all BP measures.
Potential covariates were considered for inclusion based
on previous publications (Rayman et al., 2003; Schulpis
et al., 2004; Mistry et al., 2008) and bivariate comparisons
of variables within this dataset (criteria of Po0.30 for
one-way analysis of variances or t-tests). In addition to
covariates included in our final models, we considered
alcohol use, parity, medical insurance, anemia, cord blood
lead levels, and cord serum fatty acids; these were eliminated
based on likelihood ratio tests and observation of whether the
selenium coefficient changed 410% following their inclu-
sion. A series of final models (including gestational age,
maternal age, maternal race, primiparity, income, BM I, and
smoking) are presented with increasing levels of adjustment
for confounders. We also ran models with selenium as a
linear term. Models were evaluated using Akaikes informa-
tion criterion, likelihood ratio tests, normal quantile plots,
and residual vs fitted value plots. Similar procedures were
used for logistic models to evaluate hypertension and
‘‘elevated’’ BP.
In order to put our findings into perspective with other
studies that measured maternal serum selenium levels and
not cord serum levels, previous reports were used to calcu-
late maternal/umbilical cord serum selenium ratios. These
were used to estima te maternal serum selenium levels in this
population. Relevant articles were identifi ed using PubMed.
Summary data on maternal selenium and umbilical cord
selenium wer e extracted and used to calculate study specifi c
as well as an overall mean ratios weighted by study sample
size.
Results
Population characteristics are shown in Table 1. Mean
admission BP was 122.7 mm Hg (systolic) and 72.0 mm Hg
(diastolic). Corresponding values for maximum BP were
Selenium and blood pressure in childbirthWells et al.
192 Journal of Exposure Science and Environment al Epidemiolog y (2012) 22(2)
Page 2
144.3 mm Hg and 77.1 mm Hg. Mean selenium was 69.9 mg/l
(95% confidence interval (CI): 68.5, 71.4). Knots for
selenium splines were chosen at 70 and 90 mg/l. Roughly
half had selenium concentrations r70 mg/l, and very few
(n ¼ 12) had concentrations 490 mg/l (Table 1).
There was a consistent pattern in the relationship between
selenium concentrati ons and maternal BP (Table 2). When
selenium concentrations were o70 mg/l, increasing selenium
levels were related to decreasing BP. However, when
selenium concentrations were 70–90 mg/l, increasing selenium
levels were related to increasing BP; these were stati stically
significant (Po0.05) or of borderline significance (Po0.10)
for all measures except maximum diastolic BP. For selenium
concentrations 490 mg/l there was a decrease in BP with
increased selenium; however, there was a large uncertainty in
this range as this group only has 12 individuals. There was
no association between selenium and BP in models where
selenium was a linear term (Table 2).
Results from multivariable logistic regression models
for ‘‘elevated BP were similar to admission and maximum
BP. We did not observe any relationship of selenium with
hypertension outcomes (Supplementary Information).
A total of 11 studies with data on both maternal and
umbilical cord selenium were identified (Wasowicz et al., 1993;
Micetic-Turk et al., 2000; Osman et al., 2000; Kantola et al.,
2004; Makhoul et al., 2004; Schulpis et al., 2004; Lorenzo
Alonso et al., 2005; Butler Walker et al., 2006; Mistry et al.,
2008; Rudge et al., 2009; Sakamoto et al., 2010). Study-
specific and overall maternal/cord selenium ratios are pre-
sented (Table 3, Figure 1). Individual maternal/cord selenium
ratios ranged from 0.85 to 1.84, with a weighted average of
1.46 (95% CI: 1.28, 1.65). Applying this ratio to selenium
concentrations in our study suggests that there is decreasing
maternal BP with increasing selenium when maternal selenium
is o102 mg/l and increasing maternal BP with increasing
selenium when maternal selenium is 102131 mg/l.
Ta bl e 1 . Population characteristics, Baltimore THREE Study, 2004–2005.
Category Characteristic N %
All 270 100.0
Maternal age o20 years 55 20.4
20–29 years 128 47.4
Z30 years 87 32.2
Maternal race Caucasian 57 21.1
African American 190 70.4
Asian 23 8.5
Smoking Smoked during pregnancy 49 18.2
Did not smoke 221 81.9
Prepregnancy BMI o18.5 kg/m
2
14 5.2
18.5–24.9 kg/m
2
126 46.7
25.0–29.9 kg/m
2
61 22.6
Z30.0 kg/m
2
69 25.6
Median household income (neighborhood) o$25,000 82 30.4
$25,000–50,000 144 53.3
4$50,000 44 16.3
Parity First childbirth 117 43.3
Second or higher 153 56.7
Gestation Preterm delivery (o37 weeks) 34 12.6
Not preterm delivery 236 87.4
‘‘Elevated’’ admission BP Yes 36 13.3
No 234 86.7
‘‘Elevated’’ maximum BP Yes 115 42.6
No 155 57.4
GH or preeclampsia Yes 16 5.9
No 254 94.1
Any hypertension Yes 26 9.6
No 244 90.4
Selenium categories o70 mg/l 150 55.6
71–90 mg/l 108 40.0
490 mg/l 12 4.4
Abbreviations: BMI, body mass index; BP, blood pressure; GH, gestational hypertension; THREE, Tracking Health Related to Environmental Exposures.
Percentages may not sum to 100 due to rounding. ‘‘Elevated’’ BP is systolic blood pressure Z140 mm Hg or diastolic BPZ90 mm Hg. Any hypertension
includes gestational hypertension, preeclampsia, and chronic hypertension. Median household income is based on roughly 1500 persons in close geographic
proximity, in the same census block group.
Selenium and blood pressure in childbirth Wells et al.
Journal of Exposure Science and Environmental Epidemiology (2012) 22(2) 193
Page 3
Discussion
We did not find any evidence of a linear relationship of
selenium with BP across the entire range of blood
concentrations. However, when modeling selenium as a
spline, we saw both positive and negative relationships
that were dependent upon the selenium concentration
range. While these relationships were not all statistically
significant at the Po0.05 level, they were consistent among
different BP measurements. Maternal/cord selenium ratios
calculated from previous work have a weighted average
of 1.46. Variability between individual ratios could arise
from differen ces in selenium intake, health status, selection
criteria, or other genetic or environmental factors. Based
on application of this ratio, this study reports a trend of
lower maternal BP with increasing selenium when cord
serum selenium is o70 mg/l (and maternal serum selenium
Bo105 mg/l) and higher maternal BP with increasing
selenium when cord serum selenium is between 70 and
90 mg/l (and maternal serum selenium B102–131 mg/l).
There are too few observations over 90 mg/l to draw firm
conclusions about effects in that range.
The Institute of Medicine notes that adult nutritional
requirements of selenium are met where serum selenium is
70–90 mg/l (Institute of Medicine, 2000). Based on estimated
maternal selenium values in our study, roughly 75% of the
current population would meet the lower level of this
requirement. This is noticeably lo wer than other reports of
serum selenium among US adults (Laclaustra et al., 2009)
yet higher than many other reports (Table 3).
Our results are consistent with previous observations of a
similar biphasic relationship between selenium and cardio-
vascular mortality (Bleys et al., 2008) or hypertension
(Laclaustra et al., 2009). Overall, however, studies that have
directly assessed selenium and BP-related health outcomes
have had inconsistent results; it is possible that this variety
may reflect variability in basel ine selenium levels in different
populations. For example, several studies reporting that
increased selenium is protective of cardiovascular disease
have been performed in regions where selenium d eficiencies
are more prevalent (Broadley et al., 2006; Rayman, 2008).
This study and Laclaustra et al. (2009) both identified
biphasic relationships of selenium and cardiovascular out-
comes; however, unlike the Laclaustra study, we do not
Ta bl e 2 . Change and 95% CI for maternal blood pressure (in mm Hg) during childbirth related to a 1 mg/l increase in umbilical cord serum selenium,
Baltimore THREE Study, 2004–2005, n ¼ 270.
Outcome Linear model Spline model
Selenium Selenium o70 mg/l Selenium 71–90 mg/l Selenium Z91 mg/l
Change 95% CI Change 95% CI Change 95% CI Change 95% CI
Admission SBP
Model 1 0.07 0.08, 0.23 0.19 0.51, 0.13 0.41** 0.04, 0.77 0.25 1.03, 0.13
Model 2 0.05 0.10, 0.20 0.21 0.53, 0.11 0.36* 0.01, 0.73 0.16 0.95, 0.63
Model 3 0.08 0.07, 0.23 0.17 0.48, 0.14 0.37** 0.004, 0.73 0.09 0.86, 0.68
Admission DBP
Model 1 0.02 0.11, 0.14 0.15 0.40, 0.11 0.26* 0.03, 0.55 0.33 0.96, 0.26
Model 2 0.02 0.10, 0.14 0.13 0.38, 0.13 0.27* 0.02, 0.56 0.38 1.01, 0.25
Model 3 0.05 0.07, 0.17 0.11 0.36, 0.14 0.30** 0.01, 0.60 0.36 0.98, 0.26
Maximum SBP
Model 1 0.07 0.11, 0.25 0.29 0.67, 0.09 0.52** 0.09, 0.97 0.34 1.26, 0.58
Model 2 0.04
0.14, 0.22 0.33 0.71, 0.05 0.46** 0.02, 0.90 0.23 1.16, 0.71
Model 3 0.07 0.11, 0.25 0.24 0.61, 0.12 0.43** 0.003, 0.85 0.13 1.04, 0.77
Maximum DBP
Model 1 0.18 0.38, 0.02 0.59** 1.01, 0.17 0.17 0.31, 0.65 0.02 1.05, 1.02
Model 2 0.16 0.37, 0.04 0.56** 0.99, 0.13 0.18 0.31, 0.67 0.03 1.08, 1.01
Model 3 0.14 0.35, 0.07 0.52** 0.95, 0.10 0.19 0.31, 0.68 0.02 1.03, 1.08
Abbreviations: CI, confidence interval; DBP, diastolic blood pressure; SBP, systolic blood pressure; THREE, Tracking Health Related to Environmental
Exposures.
*Po0.10.
**Po0.05.
Model 1: Blood pressureBselenium+gestational age.
Model 2: Model 1+maternal age+maternal race.
Model 3: Model 2+primiparity+median household income+smoking+prepregnancy body mass index.
Selenium and blood pressure in childbirthWells et al.
194 Journal of Exposure Science and Environment al Epidemiolog y (2012) 22(2)
Page 4
observe a relationship with hypertension. There are several
potential explanations for this, including that this study had
lower selenium concentrations than Laclaustra (accounting
for imputation to maternal values), smaller sample size and
therefore less statistical power, and a younger population
(with a small number of cases of diagnosed hypertension)
compared with the Laclaustra et al study.
There are some potential limitations to this study.
We assayed total selenium and did not quantify the forms
of selenium that are found in serum, selenium–cysteine,
and selenium–methionine. Selenium–cysteine is immediately
available to be incorporated into proteins, whereas selenium–
methionine is a form of stored selenium that nonethel ess can
be made biologically available (Flores-Mateo et al., 2006).
These different forms of selenium may have differential
effects on BP. Also, selenium storage as selenium–methionine
occurs in tissues; the factors involved with selenium stor age
and release of selenium–methionine into blood are not well
understood. It is possible that such factors co uld confound
the relationship between selenium and BP.
BPwasmeasuredwithanautomateddeviceduringlabor
and delivery, and abstracted from electronic medical records.
Potential limitations of this approach are that we did not use
an average o f repeated measurements but instead abstracted
the BP at admission and the highest and lowest measurements.
Ta bl e 3 . Maternal and umbilical cord selenium concentrations reported in previous studies.
Study information Selenium Maternal (M) Cord (C) M/C
Study Location Media Method N Mean N Mean Ratio
Wasowicz et al. (1993) Poland Plasma FM 64 35 64 28.1 1.25
Micetic-Turk et al. (2000) Slovenia Serum FIHG-AAS 20 62 20 34 1.82
Osman et al. (2000) Sweden Serum GFAAS 74 71.89 74 52.93 1.36
Makhoul et al. (2004) Israel (preec.) Serum AAS 32 86.64 38 52.9 1.64
Makhoul et al. (2004) Israel (controls) Serum AAS 119 84.1 130 57.48 1.46
Schulpis et al. (2004) Greece Serum GFAAS 1118 68.3 1118 37.02 1.84
Schulpis et al. (2004) Albania Serum GFAAS 820 37.4 820 34.33 1.09
Kantola et al. (2004) Finland (non-smokers) Serum AAS 63 110 67 111 0.93
Kantola et al. (2004) Finland (smokers) Serum AAS 15 111 15 124 0.90
Lorenzo Alonso et al. (2005) Spain Serum AAS 48 90 48 76.3 1.18
Butler Walker et al. (2006) Canada (Caucasians) Plasma GFAAS 132 124 125 87 1.43
Butler Walker et al. (2006) Canada (Dene/Metis) Plasma GFAAS 92 119 81 75 1.59
Butler Walker et al. (2006) Canada (Inuit) Plasma GFAAS 144 119 161 74 1.61
Mistry et al. (2008) United Kingdom (preec.) Serum GFAAS 25 39.7 25 29 1.37
Mistry et al. (2008) United Kingdom (controls) Serum GFAAS 27 58.4 27 42.1 1.39
Rudge et al. (2009) South Africa WB ICP-MS 62 104 62 111 0.94
Sakamoto et al. (2010) Japan RBC ICP-MS 81 192 81 227 0.85
Abbreviations: AAS, atomic absorption spectroscopy; FIHG-AAS, flow injection hydride generation atomic absorption spectrometry; FM, LS-5
spectrofl ouromet er; GFAAS, graphite furnace atomic absorp tion spectroscopy; ICP-MS, inductively coupled plasma mass spectrometry; M/C, maternal/
cord; preec., preeclampsia; RBC, red blood cells; WB, whole blood. All maternal samples were collected around the time of delivery except for Osman et al.
(2000), where they were collected at gestational week 36. Selenium is measured in mg/l except for Sakamoto et al. (2010), which was measured in ng/g.
Arithmetic means are presented except for Rudge et al. (2009), where the median was used. Maternal/cord ratio is calculated for this paper using the
individual authors summary data.
0
100
200
300
Maternal selenium, µg/L
0 100 200 300
Umbilical cord selenium, µg/L
Figure 1. Average maternal and umbilical cord selenium concentra-
tions as reported previously (Table 3). Circles are scaled by the average
of maternal and cord sample size of the individual studies; this ranges
from n ¼ 15 to n ¼ 1118. The solid line indicates a maternal/cord
ratio of 1; the dashed line represents the weighted average among
maternal/cord ratios, 1.46.
Selenium and blood pressure in childbirth Wells et al.
Journal of Exposure Science and Environmental Epidemiology (2012) 22(2) 195
Page 5
Also, measurements were taken during a potentially stressful
time and may not refl ect BP levels at other times. However,
BP measurements were consistent for all participants, and
there is no reason to assume that the process of labor and
delivery would modify the relationship between selenium
and BP. BP was recorded automatically rather than being
charted by hand, eliminating one potential source of bias and
error. Also, in comparing BP with diagnosed h ypertension
and other variables such as delivery mode (Supplementary
Information), it seems that the measures produce consis tent
results. Therefore, it is reasonable to expect these measure-
ments serve to describe relative BP within this population.
Previous studies that assumed a linear relationship between
selenium and BP produced results that are consistent with
our findings, in that they reported small positive or no
associations between selenium and BP (Jossa et al., 1991;
Suadicani et al., 1992; Taittonen et al., 1997; Nawrot et al.,
2007). A spline model is more appropriate given the nature of
the statistical relationship and biological plausibility of that
relationship because of the dual role of selenium as a nutrient
atlowlevelsandatoxicantathigherlevels.
We were able to obtain high-quality selenium measure-
ments. Umbilical cord serum was used as a proxy for
maternal serum selenium levels; these levels are highly
correlated (Micetic-Turk et al., 2000; Rudge et al., 2009;
Sakamoto et al., 2010). However, use of umbilical cord
measures probably results in some misclassification of
maternal exposure, which, if random, would attenuate the
relationship between selenium and BP.
Our exposure and outcome measurements reflect roughly
the same time period, to the extent that BP is responding
immediately to selen ium levels this could be advantageous.
However, it also is possible that selenium levels over time
have chronic effects on BP. Previous work suggests that
increasing maternal blood volume and fetal nutritional
needs may affect selenium concentrations over the course of
pregnancy (Kantola et al., 2004). It is currently unclear
whether maternal selenium generally increases (Dawson
et al., 2000), decreases (Kantola et al., 2004), or remains
constant (Navarro et al., 1996) over the course of pregnancy.
As we do not have information about maternal selenium
levels over the course of pregnancy, we cannot evaluate
whether these changes are important in this population.
However, we are not aware of any evidence that changes in
selenium over the course of pregnancy are differentially
related to BP; therefore, we would expect any m isclassifi ca-
tion to either not affect or attenuate the relationships
presented here.
Another consideration is whether mothers deficient in
selenium might transfer selenium at a higher rate to the fetus,
as these elements are critical for the process of growth and
development. This is supported by Schulpis et al. (2004),
who reported much lower selenium levels in maternal serum
among Albanians compared with Greeks, but only small
differences in cord serum selenium concentra tions from the
two populations. However, concentratio ns of umbilical cord
serum selenium in this study are roughly twice as high as
those reported by Schulpis. This suggests that umbilical cord
serum selenium concentrations in our population would not
be affected by maternal selenium deficiency.
In this study, we employed flexible models to evaluate
the relationship be tween se lenium in umbilical cord serum,
maternal BP during labor and delivery. Consistent with
previous studies, our results show that there may be different
effects of selenium exposure depending on the overall concen-
trations. This suggests that for some populati ons, selenium
may be a factor in increased BP. Moreover, we stress the
importance of applying fl exible models when evaluating
associations that are likely to have different relationships
within different exposure ranges. These results should be
verifi ed in larger populations, ideally through the study of
additional exposure and outcome biomarkers.
Conflict of interest
The auth ors declare no conflict of interest.
Acknowledgements
WethankDrs.JohnBernert,JochenHeidler,Joseph
Hibbeln, Robert Jones, and Norman Salem, Jr. for
contributing to data collection; Drs. Ana Navas-Acien and
Ellen Silbergeld for advice; and Ruth Quinn and Tonya
Shephard for pr oject support. This work was supported in
part by the Maryland Cigarette Restitution Program
Research Grant, National Institute of Environmental Health
Sciences grant 1R01ES015445 (RUH), and a United States
Environmental Protection Agency Science to Achieve
Results (STAR) Fellowship (EMW). The content and views
presented in this work are solely the responsibility of the
authors and do not necessarily represent those of US EPA,
CDC, or NIH.
References
Apelberg B.J., Goldman L.R., Calafat A.M., Herbstman J.B., Kuklenyik Z., and
Heidler J., et al. Determinants of fetal exposure to polyfluoroalkyl compounds
in Baltimore, Maryland. Environ Sci Technol 2007: 41(11): 3891–3897.
Bernert Jr J.T., Turner W.E., Pirkle J.L., Sosnoff C.S., Akins J.R., and Waldrep
M.K., et al. Development and validation of sensitive method for determination
of serum cotinine in smokers and nonsmokers by liquid chromatography/
atmospheric pressure ionization tandem mass spectrometry. Clin Chem 1997:
43(12): 2281–2291.
Bleys J., Navas-Acien A., and Guallar E. Serum selenium levels and all-cause,
cancer, and cardiovascular mortality among US adults. Arch Intern Med 2008:
168(4): 404–410.
Broadley M.R., White P.J., Bryson R.J., Meacham M.C., Bowen H.C.,
and Johnson S.E., et al. Biofortication of UK food crops with selenium.
Proc Nutr Soc 2006: 65(2): 169–181.
Selenium and blood pressure in childbirthWells et al.
196 Journal of Exposure Science and Environment al Epidemiolog y (2012) 22(2)
Page 6
Brown K.M., and Arthur J.R. Selenium, selenoproteins and human health: a
review. Public Health Nutr 2001: 4(2B): 593–599.
Butler Walker J., Houseman J., Seddon L., McMullen E., Tofflemire K., and
Mills C., et al. Maternal and umbilical cord blood levels of mercury, lead,
cadmium, and essential trace elements in Arctic Canada. Environ Res 2006:
100(3): 295–318.
Combs Jr G.F. Selenium in global food systems. Br J Nutr 2001: 85(5): 517–547.
Dawson E.B., Albers J.H., and McGanity W.J. The apparent effect of iron
supplementation on serum selenium levels in teenage pregnancy. Biol Trace
Elem Res 2000: 77(3): 209–217.
Flores-Mateo G., Navas-Acien A., Pastor-Barriuso R., and Guallar E. Selenium
and coronary heart disease: a meta-analysis. Am J Clin Nutr 2006: 84(4):
762–773.
Han L., and Zhou S.M. Selenium supplement in the prevention of pregnancy
induced hypertension. Chin Med J (Engl) 1994: 107(11): 870–871.
Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E,
Selenium, and Carotenoids. National Academy Press, Washington, DC, 2000.
Jossa F., Trevisan M., Krogh V., Farinaro E., Giumetti D., and Fusco G., et al.
Serum selenium and coronary heart disease risk factors in southern Italian
men. Atherosclerosis 1991: 87(2–3): 129–134.
Kaaja R.J., and Greer I.A. Manifestations of chronic disease during pregnancy.
JAMA 2005: 294(21): 2751–2757.
Kantola M., Purkunen R., Kroger P., Tooming A., Juravskaja J., and Pasanen
M., et al. Selenium in pregnancy: is selenium an active defective ion against
environmental chemical stress? Environ Res 2004: 96(1): 51–61.
Laclaustra M., Navas-Acien A., Stranges S., Ordovas J.M., and Guallar E. Serum
selenium concentrations and hypertension in the US population. Circ
Cardiovasc Qual Outcomes 2009: 2(4): 369–376.
Lorenzo Alonso M.J., Bermejo Barrera A., Cocho de Juan J.A., Fraga Bermudez
J.M., and Bermejo Barrera P. Selenium levels in related biological samples:
human placenta, maternal and umbilical cord blood, hair and nails. JTrace
Elem Med Biol 2005: 19(1): 49–54.
Lykke J.A., Langhoff-Roos J., Sibai B.M., Funai E.F., Triche E.W., and Paidas
M.J. Hypertensive pregnancy disorders and subsequent cardiovascular
morbidity and type 2 diabetes mellitus in the mother. Hypertension 2009:
53(6): 944–951.
Mahomed K., Williams M.A., Woelk G.B., Mudzamiri S., Madzime S., and King
I.B., et al. Leukocyte selenium, zinc, and copper concentrations in
preeclamptic and normotensive pregnant women. Biol T race Elem Res 2000:
75(1–3): 107–118.
Makhoul I.R., Sammour R.N., Diamond E., Shohat I., Tamir A., and Shamir R.
Selenium concentrations in maternal and umbilical cord blood at 24–42 weeks
of gestation: basis for optimization of selenium supplementation to premature
infants. Clin Nutr 2004: 23(3): 373–381.
Micetic-Turk D., Rossipal E., Krachler M., and Li F. Maternal selenium status in
Slovenia and its impact on the selenium concentration of umbilical cord serum
and colostrum. Eur J Clin Nutr 2000: 54(6): 522–524.
Mistry H.D., Wilson V., Ramsay M.M., Symonds M.E., and Broughton Pipkin
F. Reduced selenium concentrations and glutathione peroxidase activity in
preeclamptic pregnancies. Hypertension 2008: 52(5): 881–888.
Navarro M., Lopez H., Perez V., and Lopez M.C. Serum selenium levels during
normal pregnancy in healthy Spanish women. Sci Total Environ 1996: 186(3):
237–242.
Navas-Acien A., Bleys J., and Guallar E. Selenium intake and cardiovascular risk:
what is new? Curr Opin Lipidol 2008: 19(1): 43–49.
Nawrot T.S., Staessen J.A., Roels H.A., Den Hond E., Thijs L., and Fagard
R.H., et al. Blood pressure and blood selenium: a cross-sectional and
longitudinal population study. Eur Heart J 2007: 28(5): 628–633.
Osman K., Akesson A., Berglund M., Bremme K., Schutz A., and Ask K., et al.
Toxic and essential elements in placentas of Swedish women. Clin Biochem
2000: 33(2): 131–138.
Rayman M.P. Food-chain selenium and human health: emphasis on intake.
Br J Nutr 2008: 100(2): 254–268.
Rayman M.P., Bode P., and Redman C.W. Low selenium status is associated with
the occurrence of the pregnancy disease preeclampsia in women from the
United Kingdom. Am J Obstet Gynecol 2003: 189(5): 1343–1349.
Rudge C.V., Rollin H.B., Nogueira C.M., Thomassen Y., Rudge M.C., and
Odland J.O. The placenta as a barrier for toxic and essential elements in paired
maternal and cord blood samples of South African delivering women.
J Environ Monit 2009: 11(7): 1322–1330.
Sakamoto M., Murata K., Kubota M., Nakai K., and Satoh H. Mercury and
heavy metal profiles of maternal and umbilical cord RBCs in Japanese
population. Ecotoxicol Environ Saf 2010: 73(1): 1–6.
Schulpis K.H., Karakonstantakis T., Gavrili S., Chronopoulou G., Karikas G.A.,
and Vlachos G., et al. Maternal F neonatal serum selenium and copper levels
in Greeks and Albanians. Eur J Clin Nutr 2004: 58(9): 1314–1318.
Stranges S., Navas-Acien A., Rayman M.P., and Guallar E. Selenium status and
cardiometabolic health: state of the evidence. Nutr Metab Cardiovasc Dis 2010:
20(10): 754–760.
Suadicani P., Hein H.O., and Gyntelberg F. Serum selenium concentration and
risk of ischaemic heart disease in a prospective cohort study of 3000 males.
Atherosclerosis 1992: 96(1): 33–42.
Taittonen L., Nuutinen M., Rasanen L., Mussalo-Rauhamaa H., Turtinen J., and
Uhari M. Lack of association between copper, zinc, selenium and blood
pressure among healthy children. JHumHypertens1997: 11(7): 429–433.
Tara F., Maamouri G., Rayman M.P., Ghayour-Mobarhan M., Sahebkar A.,
and Yazarlu O., et al. Selenium supplementation and the incidence of
preeclampsia in pregnant Iranian women: a randomized, double-blind,
placebo-controlled pilot trial. Taiwan J Obstet Gynecol 2010: 49(2): 181–187.
US Centers for Disease Control and Prevention (CDC). Third National
Report on Human Exposure to Environmental Chemicals. CDC, Atlanta,
(GA), 2005.
Wasowicz W., Wolkanin P., Bednarski M., Gromadzinska J., Sklodowska M., and
Grzybowska K. Plasma trace element (Se, Zn, Cu) concentrations in maternal
and umbilical cord blood in Poland. Relation with birth weight, gestational
age, and parity. Biol Trace Elem Res 1993: 38(2): 205–215.
Witter F.R., Ten Broeck J., and Fox H.E. A new device for safer collection of
postpartum cord blood. Int J Gynaecol Obstet 2001: 72(3): 259–260.
Xiao G. Zinc, Copper and Selenium in Serum by ICP-DRC-MS (ICPDRCMS-
3006.1). Centers for Disease Control and Prevention, Atlanta, GA, 2006.
Supplementary Information accompanies the paper on the Journal of Exposure Science and Environmental Epidemiology
website (http://www.nature.com/jes)
Selenium and blood pressure in childbirth Wells et al.
Journal of Exposure Science and Environmental Epidemiology (2012) 22(2) 197
Page 7