Subclinical Thyroid Disease and the

Incidence of Hypertension in Pregnancy

Karen L. Wilson, MD, Brian M. Casey,
and F. Gary Cunningham, MD

MD,

Donald D. McIntire,

OBJECTIVE: To estimate the possibility of long-term effects of subclinical thyroid dysfunction on hypertension and
other cardiovascular-related conditions during pregnancy.
METHODS: This is a secondary analysis of a prospective
prenatal population-based study in which serum thyroidfunction analytes were measured from November 2000
through April 2003. Women with evidence of overt
thyroid disease were excluded. The remaining women
were classified as being euthyroid, having subclinical
hyperthyroid, or having subclinical hypothyroid, and the
frequency of pregnancy-associated hypertensive disorders was compared between these groups.
RESULTS: Pregnancy outcomes in 24,883 women were
analyzed for pregnancy hypertension, classified as gestational hypertension, mild preeclampsia, or severe preeclampsia. The incidence of hypertensive disorders were
compared between the three cohorts. The overall incidences
of hypertension in pregnancy were 6.2%, 8.5%, and 10.9% in
the subclinical hyperthyroid, euthyroid, and subclinical hypothyroid groups, respectively, and were found to be significant
when unadjusted (P.016). After adjusting for confounding
factors, there was a significant association between subclinical
hypothyroidism and severe preeclampsia (adjusted odds ratio
1.6, 95% confidence interval 1.12.4; P.03).
CONCLUSION: Women with subclinical hypothyroidism
identified during pregnancy have an increased risk for severe
preeclampsia when compared with euthyroid women.
(Obstet Gynecol 2012;119:31520)
DOI: 10.1097/AOG.0b013e318240de6a

LEVEL OF EVIDENCE: II
From the University of Texas Southwestern Medical Center, Department of
Obstetrics and Gynecology, Dallas, Texas.
Corresponding author: Karen L. Wilson, MD, The University of Texas
Southwestern Medical Center, Department of Obstetrics & Gynecology, 5323
Harry Hines Blvd, Dallas, TX 75390-9032; e-mail: KarenL.Wilson@
utsouthwestern.edu.
Financial Disclosure
The authors did not report any potential conflicts of interest.
2012 by The American College of Obstetricians and Gynecologists. Published
by Lippincott Williams & Wilkins.
ISSN: 0029-7844/12

VOL. 119, NO. 2, PART 1, FEBRUARY 2012

PhD,

Lisa M. Halvorson,

MD,

hyroid hormones have a number of actions on

cardiovascular physiology and blood pressure regulation, which are mediated by genomic mechanisms that
cause ventricular remodeling or by direct effects. In
most cases, cardiovascular aberrations follow long-term
exposure to excessive or decreased hormone levels.13
The effects of long-standing subclinical thyroid
disorders are less well-studied, and there has been
vigorous debate for many decades whether either
contributes significantly to long-term cardiovascular
morbidity.4 11 Also, it has been shown that individuals
with subclinical hypothyroidism have impaired endothelium-derived vasodilatation from diminished nitric
oxide secretion that is restored after thyroxine (T4)
replacement.12
Possible adverse effects on pregnancy outcomes
related to these subclinical thyroid disorders had
renewed interest after publication of two landmark
studies in 1999.13,14 Both of these investigations were
of limited size and were specifically concerned with
the effects of thyroid hormone deficiency on early
fetal brain development. Subsequently, a number of
large population-based studies that were designed to
investigate any adverse effects on subclinical thyroid
hormone disorders.1523 In a study that included a
smaller cohort of women, including only women
screened before 20 weeks of gestation, we did not find
a relationship between subclinical hypothyroidism
and pregnancy-associated hypertension.16 In another
study from our group, although we found a possible
protective relationship between subclinical hyperthyroidism and pregnancy-associated hypertension, we
did not control for the important confounder of
maternal weight.17
In addition to these studies suggesting a possible
link with subclinical thyroid dysfunction and pregnancy-associated hypertension, there is further evidence of vascular-related sequelae. Specifically, autoimmune thyroid disorders have been associated with
an increased risk for placental abruption.15,16,19,24

OBSTETRICS & GYNECOLOGY

315

These observations, when coupled with the pathologic cardiovascular effects of overtly abnormal increased or decreased thyroid hormone production,
prompted the current study to further investigate the
relationship between hypertensive disorders and subclinical thyroid dysfunction in a larger cohort, including women who presented for prenatal care after 20
weeks of gestation.

MATERIALS AND METHODS

This is another secondary analysis of a prospectively
collected database initially designed to estimate normative values for thyroid hormone analytes in a large
population of pregnant women.16,17 The protocol was
approved by the Institutional Review Boards of the
University of Texas Southwestern Medical Center
and Parkland Hospital. The details of this process and
the thyroid-analyze assays have been previously described.16 18 Briefly, excess serum obtained for prenatal serologic screening from November 1, 2000 to
April 14, 2003, was delivered to our immunochemistry research laboratory for thyroid analyte studies.
Using a chemiluminescent assay (Immulite 2000 Analyzer), serum concentrations were determined for
thyrotropin (TSH) and free T4. Women identified to
have abnormal TSH levels had serum free T4 reflexively determined, and if it was either abnormally high
or low, then they were contacted and referred to an
obstetrical complications clinic for further evaluation
and possible treatment of overt thyroid dysfunction.
These women were excluded from study, whereas all
other women were enrolled in the prospective cohort.
For the purposes of the current study, normal
values were considered to be those that comprised the
range from the 2.5th to 97.5th percentiles for the entire
cohort. For TSH, these values were 0.03 to 4.13
milliunits/L and for free T4 these values ranged from
0.9 to 2.0 ng/dL. All women screened and delivered
at Parkland Hospital and without evidence of overt
thyroid dysfunction were included. Other inclusion
criteria were subsequent delivery of a singleton neonate weighing 500 g or more. Women with serum
TSH values within the normal range were considered
to be euthyroid. Those with an abnormally low TSH
but normal free T4 levels were classified as having
subclinical hyperthyroidism. Conversely, women
with abnormally high TSH but normal free T4 levels
were classified as having subclinical hypothyroidism.
Pregnancy outcomes were retrieved from the
computerized perinatal database that has been previously described.16 18 These data are routinely entered
for all women at the time of their delivery at Parkland
Hospital. For this study, the incidence of pregnancy-

316

Wilson et al

associated hypertensive disorders were compared for

the three cohorts described. Hypertensive disorders
were defined and classified according to a previously
described protocol.25 Briefly, gestational hypertension
was defined as persistent blood pressures of 140/90
mm Hg or more, occurring after 20 weeks of gestation, without evidence of proteinuria. Mild preeclampsia was diagnosed in hypertensive women who
also had 1 proteinuria determined by urine dipstick
analysis from a catheterized sample as per the protocol of our institution. Severe preeclampsia was diagnosed in hypertensive women with any of the following: 2 or more proteinuria by dipstick from a
catheterized urine sample, blood pressure higher than
160/110 mm Hg, persistent headache, visual disturbances, right upper quadrant or epigastric pain, serum
creatinine 1.2 mg/mL or more, serum aspartate
transaminase levels more than twice the upper limit of
normal, or thrombocytopenia less than 100,000/mL.
Statistical analyses included Pearson 2, CochranArmitage 2 for trend, analysis of variance, and
logistic regression. When the three-group omnibus
tests were statistically significant, contrast analyses
were used to examine two-group comparisons and
isolate significance of difference. Multivariable analyses were included to adjust for the effect modifiers of
maternal age and weight as continuous measures, and
categorical effects of race (as African American,
white, Hispanic, other) and parity (as 0, 1, 2, more
than 2). Statistical computations were performed with
SAS 9.2 and two-sided P.05 was considered statistically significant.

RESULTS
During the 30-month study, a total of 24,883 women
who delivered singleton neonates weighing more than
500 g were included in this study. Of these, 23,771
(95.5%) had TSH values within the normal range and
were considered to be euthyroid; 528 (2.1%) had TSH
levels more than 4.13 milliunits/L along with normal
free T4 levels, therefore meeting criteria for subclinical hypothyroidism. The remaining 584 (2.3%) had
TSH levels less than 0.03 milliunits/L along with
normal free T4 levels, therefore meeting criteria for
subclinical hyperthyroidism. Maternal demographics
of the three cohorts are shown in Table 1, in which
women within either the subclinical hyperthyroid
cohort or the hypothyroid cohort were compared
with those in the euthyroid cohort.
The incidences of pregnancy-associated hypertensive disorders as well as mild and severe preeclampsia were compared between the three study
cohorts. In general, as the serum TSH level increased

Subclinical Thyroid Disease and Hypertension

OBSTETRICS & GYNECOLOGY

Table 1. Maternal Demographics in Women With Subclinical Thyroid Dysfunction Compared With
Euthyroid Women
Subclinical Hyperthyroid
(n584)

Euthyroid
(n23,771)

P*
.001

Race
African American
White
Hispanic
Other
Parity
0
1
2
More than 2
Age (y)
Weight

P
.001

100 (17)
10 (2)
449 (77)
25 (4)

2,690 (11)
558 (2)
20,002 (84)
521 (2)
.415

195 (33)
179 (31)
117 (20)
93 (16)
25.85.5
16230

Subclinical Hypothyroid
(n528)
31 (6)
20 (4)
455 (86)
22 (4)

.845
8,232 (35)
7,561 (32)
4,757 (20)
3,221 (14)
25.25.6
17034

.009
.001

.001
.057

184 (35)
163 (31)
113 (21)
68 (13)
26.75.7
17638

Data are n (%) or meanstandard deviation unless otherwise specified.

* Compares hypothesis of equality of subclinical hyperthyroid and euthyroid.

Compares hypothesis of equality of subclinical hypothyroid and euthyroid.

in the entire population, the incidence of hypertensive

disorders increased concomitantly (P for trend,
P.004). This relationship is shown in Figure 1, in
which subclinical hyperthyroid women who had the
lowest TSH levels had an incidence of hypertensive
disorders of 6.2% compared with 8.5% of euthyroid
women and 10.9% of subclinical hypothyroid women.
These differences when unadjusted were significant
(P.016). These were then adjusted for maternal age,
race, parity, and weight using logistic regression.
Shown in Figure 2 are the adjusted odds ratios when

Women delivered (%; upper 95% CI)

16
14
12
10
8
6
4
2
0
Any hypertension
P=.004

Mild hypertension Severe hypertension

P=.018
P=.003

Hypertension classification

Fig. 1. Incidence of hypertension during pregnancy and

mild or severe preeclampsia according to classification of
subclinical hyperthyroidism (dark gray bars), euthyroid
(light gray bars), and subclinical hypothyroidism (black
bars) in 24,883 pregnant women who were screened during
the first prenatal visit.
Wilson. Subclinical Thyroid Disease and Hypertension. Obstet
Gynecol 2011.

VOL. 119, NO. 2, PART 1, FEBRUARY 2012

the risks for hypertensive disorders were compared

between the three cohorts. After adjustments, the only
remaining significant association was in the cohort of
women with subclinical hypothyroidism who were at
increased risk for severe preeclampsia (adjusted odds
ratio 1.6, 95% confidence interval 1.12.4; P .031).

DISCUSSION
The one salient finding of this study that included
nearly 25,000 pregnant women was that those identified to have subclinical hypothyroidism had a significantly increased risk for development of severe preeclampsia when compared with euthyroid women.
This association is particularly strong because its
significance persisted after adjustment for factors
known to increase preeclampsia risks, such as age,
parity, race, and weight.26,27 There are a number of
observations that support the biological plausibility of
this association. These include the cardiovascular
effects of abnormal concentrations of thyroid hormones, the adverse pregnancy outcomes reported for
women with overt hypothyroidism, other vascularrelated pregnancy complications that have been
linked to subclinical hypothyroidism, and, finally,
endothelial cell activation from abnormal amounts of
thyroid hormones.
Regarding the first observation, there are welldocumented widespread cardiovascular effects in
nonpregnant women who secrete abnormal amounts
of thyroid hormones. Those that are genomically
mediated include transcription of structural and regulatory proteins within myocytes that stimulate cell
growth.1 Nongenomic direct T4 actions include increased cardiac contractility and decreased systemic

Wilson et al

Subclinical Thyroid Disease and Hypertension

317

Any hypertension
Subclinical hyperthyroidism

0.78 (0.551.10)

Subclinical hypothyroidism

1.25 (0.941.66)

Mild hypertension
Subclinical hyperthyroidism

0.83 (0.531.31)

Subclinical hypothyroidism

1.35 (0.951.94)

Severe hypertension
Subclinical hyperthyroidism

0.71 (0.401.26)

Subclinical hypothyroidism

1.60 (1.082.37)

0.0

0.5

1.0

1.5

2.0

2.5

Wilson. Subclinical Thyroid Disease and Hypertension.

Obstet Gynecol 2011.

Odds ratios (95% confidence interval)

vascular resistance. Also, with prolonged exposure to

either abnormally excessive or decreased amounts of
hormone, ventricular hypertrophy can lead to heart
failure.1,2,28 Up to one fourth of overtly hypothyroid
individuals are hypertensive, with a decreased pulse
pressure, slowed diastolic filling, decreased ventricular filling and contractility, and increased systemic
vascular resistance.1,2 Although less well-studied,
there is evidence that subclinical hypothyroidism in
some, usually older, patients can cause hypertension,
heart failure, and atherosclerotic vascular disease.1,6,8,29 Finally, subclinical hypothyroidism has
been shown to cause endothelial cell dysfunction
characterized by diminished nitric oxide production
with impaired vasorelaxation.12
A second observation that strengthens the biological plausibility of a link between subclinical hypothyroidism and preeclampsia is that adverse outcomes are increased in pregnant women with overt
thyroid disorders. A number of investigators have
reported that pregnancies in women with untreated
or poorly controlled thyrotoxicosis have increased
incidences of cardiovascular and related complications such as preeclampsia, placental abruption,
and heart failure.3,30 34 Similarly, reports of pregnant women with untreated overt hypothyroidism
describe inordinately high rates of preeclampsia,
placental abruption, and heart failure.30,33,34
The third link is derived from large prenatal
screening studies designed to ascertain normal serum
levels of thyroid-related analytes, as well as to study
adverse pregnancy outcomes caused by thyroid disorders.19,21,35 Although in none of these was an association found between subclinical hypothyroidism or
hyperthyroidism and preeclampsia, in one study
pregnant women with subclinical hypothyroidism
had a significant association with placental abruption,
which is another vascular-related complication. In
this study, such women were observed to have a
significant threefold increased risk for placental abruption compared with euthyroid pregnant women.16

318

Wilson et al

Fig. 2. Risk (adjusted odds ratio) of hypertension

during pregnancy and mild or severe preeclampsia
according to classification of subclinical thyroid
dysfunction in 24,883 pregnant women who were
screened during the first prenatal visit. Odds ratios
are adjusted for maternal age, race, parity, and
weight. Euthyroid women (n23,771) served as the
referent population.

Additionally, in two of these large population-based

studies, a significantly increased twofold to threefold
risk for placental abruption was reported in women
who had abnormally elevated serum antithyroid antibody levels.15,16
The unifying theme of these cited studies is that
abnormal levels of thyroid hormones can lead to
long-term cardiovascular sequelae that are mediated
in part by chronic endothelial cell damage. In this
regard, preeclampsia is thought to be a syndrome
characterized by multiorgan involvement that results
from endothelial cell activation.36 Thus, it seems
reasonable to posit that abnormal levels of thyroid
hormones are additive or synergistic toward the development of preeclampsia in women genetically
predisposed.37 As such, the effects of subclinical hypothyroidism are similar to those observed in other
maternal conditions characterized by chronic endothelial activation with an increased risk for preeclampsia. Some of these underlying conditions include obesity and the metabolic syndrome, chronic
hypertension, diabetes, and renal disease.27,3739
The strengths of this study are principally related
to the number of women enrolled. Specifically, even
after adjusting for maternal age, race, parity, and
weight, the association of subclinical hypothyroidism
and severe preeclampsia remains significant. Conversely, there are three weaknesses that are apparent.
One is that the majority of women are of Hispanic
heritage, and thus our observations may not be applicable in other ethnic populations. A second is that our
database precluded identification of women with
chronic hypertension or other such risk factors that
are known to increase the risk for preeclampsia.
Finally, because height was not recorded for all
women enrolled in the first part of the study, we
adjusted using weight as a continuous variable instead
of body mass index, which many consider to be a
more accurate indicator of obesity.
What are the implications of this persistent association between subclinical hypothyroidism and se-

Subclinical Thyroid Disease and Hypertension

OBSTETRICS & GYNECOLOGY

vere preeclampsia? We are of the opinion that our

findings are more biologically significant than clinically relevant. Our observations add to accruing data
that subclinical hypothyroidism, a relatively common
finding in women of childbearing age, may be associated with some adverse perinatal outcomes. Nonetheless, we remain convinced that routine prenatal
screening for thyroid disorders should not be implemented until clear benefit is established. The Eunice
Kennedy Shriver National Institute of Child Health and
Human Developmentsponsored randomized intervention trial of women identified to have subclinical
thyroid disorders currently being conducted by the
Maternal-Fetal Medicine Units Network may provide
such data.
REFERENCES
1. Danzi S, Klein I. Thyroid hormone and blood pressure regulation. Curr Hypertens Rep 2003;5:51320.
2. Klein I, Ojamaa K. Thyroid hormone and the cardiovascular
system. N Engl J Med 2001;344:5019.
3. Sheffield JS, Cunningham FG. Thyrotoxicosis and heart failure
that complicate pregnancy. Am J Obstet Gynecol 2004;190:
2117.
4. Cappola AR, Fried LP, Arnold AM, Danese MD, Kuller LH,
Burke GL, et al. Thyroid status, cardiovascular risk, and
mortality in older adults. JAMA 2006;295:1033 41.
5. Dorr M, Wolff B, Robinson DM, John U, Ludemann J, Meng
W, et al. The association of thyroid function with cardiac mass
and left ventricular hypertrophy. J Clin Endocrinol Metab
2005;90:6737.
6. Duan Y, Peng W, Wang X, Tang W, Liu X, Xu S, et al.
Community-based study of the association of subclinical thyroid dysfunction with blood pressure. Endocrinology 2009;35:
136 42.
7. Volzke H, Ittermann T, Schmidt CO, Dorr M, John U,
Wallaschofski H, et al. Subclinical hyperthyroidism and blood
pressure in a population-based prospective cohort study. Eur J
Endocrinol 2009;161:61521.
8. Liu D, Jiang F, Shan Z, Wang B, Wang J, Lai Y, et al. A
cross-sectional survey of relationship between serum TSH
level and blood pressure. J Hum Hypertension 2010;24:
134 8.
9. Imaizumi M, Akahoshi M, Ichimaru S, Nakashima E, Hida A,
Soda M, et al. Risk for ischemic heart disease and all-cause
mortality in subclinical hypothyroidism. J Clin Endocrinol
Metab 2004;89:336570.

and subsequent neuropsychological development of the child.

N Engl J Med 1999;341:549 55.
14. Pop VJ, Kuijpens JL, van Baar AL, Verkerk G, van Son MM,
de Vijlder JJ, et al. Low maternal free thyroxine concentrations
during early pregnancy are associated with impaired psychomotor development in infancy. Clin Endocrinol (Oxf)
1999;50:149 55.
15. Abbassi-Ghanavati M, Casey BM, Spong CY, McIntire DD,
Halvorson LM, Cunningham FG. Pregnancy outcomes in
women with thyroid peroxidase antibodies. Obstet Gynecol
2010;116:381 6.
16. Casey BM, Dashe JS, Wells CE, McIntire DD, Byrd W,
Leveno KJ, et al. Subclinical hypothyroidism and pregnancy
outcomes. Obstet Gynecol 2005;105:239 45.
17. Casey BM, Dashe JS, Wells CE, McIntire DD, Leveno KJ,
Cunningham FG. Subclinical hyperthyroidism and pregnancy
outcomes. Obstet Gynecol 2006;107:337 41.
18. Casey BM, Dashe JS, Spong CY, McIntire DD, Leveno KJ,
Cunningham GF. Perinatal significance of isolated maternal
hypothyroxinemia identified in the first half of pregnancy.
Obstet Gynecol 2007;109:1129 35.
19. Cleary-Goldman J, Malone FD, Lambert-Messerlian G, Sullivan L, Canick J, Porter TF, et al. Maternal thyroid hypofunction and pregnancy outcome. Obstet Gynecol 2008;112:8592.
20. Pop VJ, Brouwers EP, Vader HL, Vulsma T, van Baar AL, de
Vijlder JJ. Maternal hypothyroxinaemia during early pregnancy and subsequent child development: a 3-year follow-up
study. Clin Endocrinol (Oxf) 2003;59:282 8.
21. Mannisto T, Vaarasmaki M, Pouta A, Hartikainen AL, Ruokonen A, Surcel HM, et al. Perinatal outcome of children born
to mothers with thyroid dysfunction or antibodies: a prospective population-based cohort study. J Clin Endocrinol Metab
2009;94:7729.
22. Mannisto T, Vaarasmaki M, Pouta A, Hartikainen AL, Ruokonen A, Surcel HM, et al. Thyroid dysfunction and autoantibodies during pregnancy as predictive factors of pregnancy
complications and maternal morbidity in later life. J Clin
Endocriniol Metab 2010;95:1084 94.
23. Stagnaro-Green A, Chen X, Bogden JD, Davies TF, Scholl TO.
The thyroid and pregnancy: a novel risk factor for very
preterm delivery. Thyroid 2005;15:35157.24.
24. Haddow JE, McClain MR, Palomaki GE, Neveux LM, Lambert-Messerlian G, Canick JA, et al. Thyroperoxidase and
thyroglobulin antibodies in early pregnancy and placental
abruption. Obstet Gynecol 2011;117(2 Pt 1):28792.
25. Alexander JM, McIntire DD, Leveno KJ, Cunningham FG.
Selective magnesium sulfate prophylaxis for the prevention of
eclampsia in women with gestational hypertension. Obstet
Gynecol 2006;108:826 32.

10. Volzke H, Robinson DM, Schminke U, Ludemann J, Rettig R,

Felix SB, et al. Thyroid function and carotid wall thickness.
J Clin Endocrinol Metab 2004;89:21459.

26. Ness RB, Roberts JM. Epidemiology of pregnancy-related

hypertension. In: Lindheimer MD, Roberts JM, Cunningham
FG, editors. Chesleys hypertensive disorders in pregnancy.
San Diego (CA): Elsevier; 2009. p. 3750.

11. Walsh JP, Bremner AP, Bulsara MK, OLeary P, Leedman PJ,
Feddema P, et al. Subclinical thyroid dysfunction as a risk
factor for cardiovascular disease. Arch Intern Med 2005;165:
246772.

27. Hubel CA, Roberts JM. Metabolic syndrome and preeclampsia. In: Lindheimer MD, Roberts JM, Cunningham FG, editors. Chesleys hypertensive disorders in pregnancy. San Diego
(CA): Elsevier; 2009. p. 10528.

12. Taddei S, Caraccio N, Virdis A, Dardano A, Versari D,

Ghiadoni L, et al. Impaired endothelium-dependent vasodilation in subclinical hypothyroidism: Beneficial effect of levothyroxine therapy. J Clin Endocrinol Metab 2003;88:37317.

28. Fletcher AK, Weetman AP. Hypertension and hypothyroidism. J Hum Hypertension 1998;12:79 82.

13. Haddow JE, Palomaki GE, Allan WC, Williams JR, Knight GJ,
Gagnon J, et al. Maternal thyroid deficiency during pregnancy

VOL. 119, NO. 2, PART 1, FEBRUARY 2012

29. Rodondi N, Newman AB, Vittinghoff E, de Rekeneire N,

Satterfield S, Harris TB, et al. Subclinical hypothyroidism and
the risk of heart failure, other cardiovascular events, and death.
Arch Intern Med 2010;165:2460 6.

Wilson et al

Subclinical Thyroid Disease and Hypertension

319

30. Davis LE, Lucas MJ, Hankins GD, Roark ML, Cunningham
FG. Thyrotoxicosis complicating pregnancy. Am J Obstet
Gynecol 1989;160:6370.
31. Kriplani A, Buckshee K, Bhargava VL, Takkar D, Ammini
AC. Maternal and perinatal outcome in thyrotoxicosis complicating pregnancy. Eur J Obstet Gynecol Reprod Biol 1994;54:
159 63.
32. Mestman JH. Hyperthyroidism in pregnancy. Clin Obstet
Gynecol 1997;40:45 64.
33. Abalovich M, Gutierrez S, Alcaraz G, Maccallini G, Garcia A,
Levalle O. Overt and subclinical hypothyroidism complicating
pregnancy. Thyroid 2002;12:63 8.
34. Leung AS, Millar LK, Koonings PP, Montoro M, Mestman JH.
Perinatal outcome in hypothyroid pregnancies. Obstet Gynecol 1993;81:349 53.

320

Wilson et al

35. Dashe JS, Casey BM, Wells CE, McIntire DD, Byrd EW,
Leveno KJ, et al. Thyroid-stimulating hormone in singleton
and twin pregnancy: importance of gestational age-specific
reference ranges. Obstet Gynecol 2005;106:7537.
36. Taylor RN, Davidge ST, Roberts JM. Endothelial cell dysfunction and oxidative stress. In: Lindheimer MD, Roberts JM,
Cunningham FG, editors. Chesleys hypertensive disorders in
pregnancy. San Diego (CA): Elsevier; 2009. p. 143 68.
37. Maynard SE, Karumanchi SA. Angiogenic factors and preeclampsia. Semin Nephrol 2011;31:33 46.
38. Cornelis T, Odutayo A, Keunen J, Hladunewich M. The
kidney in normal pregnancy and preeclampsia. Semin Nephrol 2011;31:4 14.
39. Davison JM, Lindheimer MD. Pregnancy and chronic kidney
disease. Semin Nephrol 2011;31:86 99.

Subclinical Thyroid Disease and Hypertension

OBSTETRICS & GYNECOLOGY