The n e w e ng l a n d j o u r na l of m e dic i n e

acute bipolar depression for short periods with trials, STEP-BD enrolled a large number of patients
antidepressants alone could result in higher re-
sponse rates than the use of antidepressants in
combination with mood stabilizers. However, a
blinded maintenance study1 reported lower re-
sponse rates when patients with bipolar disorder
who were receiving placebo under double-blind
conditions became depressed and received adjunc-
tive antidepressants, as compared with the re-
sponse rates observed when the antidepressants
were added to mood stabilizers in a blinded fash-
ion. To our knowledge, no published study has
had design features that directly address Dr. El-
Mallakh’s supposition, which requires that pa-
tients be randomly assigned to receive antidepres-
sants in combination with a mood stabilizer or
as monotherapy. Since evidence-based treatment
guidelines consistently recommend the concurrent
use of a mood stabilizer, it is likely that ethical
concerns, as well as concerns about practical com-
plexities and study costs, account for the lack of
such initiatives.
Dr. Belmaker’s concern about limited gener-
alizability and low recruitment rates in our study
requires some clarification. Unlike most clinical
with bipolar disorder who were seeking treatment.
However, the relatively low percentage of de-
pressed patients who underwent randomization
reflected the large number of patients who were
ineligible owing to previous treatment with both
bupropion and paroxetine, an unwillingness to
accept treatment with approved mood stabilizers,
or an unwillingness to taper the dose of a current
antidepressant medication. However, we acknowl-
edge that results from our study may not apply to
all antidepressants, since our study examined only
bupropion and paroxetine.
Gary S. Sachs, M.D.
Harvard Medical School
Boston, MA 02115
Charles Bowden, M.D.
University of Texas Health Science Center
San Antonio, TX 78229-3900
Michael E. Thase, M.D.
University of Pennsylvania
Philadelphia, PA 19104
1. Gyulai L, Bowden CL, McElroy SL, et al. Maintenance effi-
cacy of divalproex in the prevention of bipolar depression. Neu-
ropsychopharmacology 2003;28:1374-82.

Glucose Regulation in Young Adults with Very Low Birth Weight

To the Editor: Hovi et al. (May 17 issue)1 report
that young adults who had a very low birth weight
have higher indexes of glucose intolerance and
higher blood pressure than do those who were
born at term. Although the authors report that
maternal preeclampsia occurred significantly more
frequently in the very-low-birth-weight group (35
of 166) than in the term group (13 of 172,
P<0.001), they did not adjust their comparisons
for this variable.
In our tertiary neonatal intensive care unit in
an urban area in northern Italy, from 2000 to
2006, glucose intolerance (fasting glucose level,
>215 mg per deciliter)2 was recorded in 74 of 469
responses, possibly involving blood pressure and
glucose regulation. Since circumstances during
the fetal period may have lifelong programming
effects on various body functions and suscepti-
bility to disease, our data suggest that preeclamp-
sia — rather than very low birth weight itself
— might account for early disturbances in glu-
cose regulation.
Paolo Manzoni, M.D.
Maria Grazia Baù, M.D.
Daniele Farina, M.D.
Sant’Anna Obstetrics and Neonatology Hospital
10126 Turin, Italy
paolomanzoni@hotmail.com

neonates with a very low birth weight. Hypergly-

cemia occurred in 22 of 92 (23.9%) of those with
a history of maternal preeclampsia,3 as compared
with 52 of 377 (13.8%) without maternal pre-
eclampsia (95% confidence interval [CI], 1.12 to
3.44; P = 0.02).
Preeclampsia and insulin resistance may be
associated in pregnant women,4 putting stress on
the fetus and causing the onset of fetal hormonal
1. Hovi P, Andersson S, Eriksson JG, et al. Glucose regulation
in young adults with very low birth weight. N Engl J Med 2007;
356:2053-63.
2. Cowett RM, Farrag HM. Selected principles of perinatal-
neonatal glucose metabolism. Semin Neonatol 2004;9:37-47.
3. Report of the National High Blood Pressure Education Pro-
gram Working Group on High Blood Pressure in Pregnancy. Am
J Obstet Gynecol 2000;183:S1-S22.
4. Montoro MN, Kjos SL, Chandler M, Peters RK, Xiang AH,
Buchanan TA. Insulin resistance and preeclampsia in gestation-
al diabetes mellitus. Diabetes Care 2005;28:1995-2000.

616 n engl j med 357;6  www.nejm.org  august 9, 2007

The New England Journal of Medicine

Downloaded from www.nejm.org by haga respect on October 19, 2010. For personal use only. No other uses without permission.
Copyright © 2007 Massachusetts Medical Society. All rights reserved.
 correspondence

The authors reply: Manzoni et al. raise the im-
portant issue of maternal preeclampsia, which is
a frequent reason for prematurity. Previous reports
suggest that offspring of mothers with preeclamp-
sia have higher-than-normal blood pressure in
childhood1 and impaired glucose regulation in
adulthood.2 In our study, we decided not to pre­
sent results adjusted for preeclampsia because
such an adjustment would not have altered the
results. We here present numerical data to sup-
port this decision.
Young adults born to mothers with preeclamp-
sia had glucose and insulin concentrations simi-
lar to those of the rest of the subjects. However,
their systolic blood pressure was increased by
3.8 mm Hg (95% CI, 0.2 to 7.4). After adjustment
for preeclampsia, very low birth weight was associ-
ated with an increase in the fasting insulin level
of 16.7% (95% CI, 4.2 to 30.6), an increase in the
2-hour glucose level of 6.4% (95% CI, 0.3 to 12.7),
and an increase in systolic blood pressure of 4.4
mm Hg (95% CI, 1.7 to 7.1). These estimates are
similar to those we reported without adjustment
for preeclampsia. Also, when we excluded subjects
with a history of maternal preeclampsia, the ef-
fects of very low birth weight remained similar
and statistically significant. Therefore, we con-
clude that maternal preeclampsia did not explain
the association of very low birth weight with
impaired glucose regulation and higher blood
pressure.
Petteri Hovi, M.D.
National Public Health Institute
FI-00300 Helsinki, Finland
Sture Andersson, M.D., Ph.D.
Hospital for Children and Adolescents
FI-00029 HUS Helsinki, Finland
Eero Kajantie, M.D., Ph.D.
National Public Health Institute
FI-00300 Helsinki, Finland
1. Tenhola S, Rahiala E, Martikainen A, Halonen P, Voutilainen
R. Blood pressure, serum lipids, fasting insulin, and adrenal
hormones in 12-year-old children born with maternal pre-
eclampsia. J Clin Endocrinol Metab 2003;88:1217-22.
2. Thomas C, Hyppönen E, Power C. Prenatal exposures and
glucose metabolism in adulthood: are effects mediated through
birth weight and adiposity? Diabetes Care 2007;30:918-24.

Use of Physicians’ Services for Medicare Beneficiaries

To the Editor: The Specialty Society Relative
Value Update Committee of the American Medi-
cal Association (AMA) has two primary concerns
regarding the article by Maxwell et al. (May 3 is-
sue).1 First, we are unable to reconcile the data in
Table 1 of the article with our recommendations
in this time period. For example, our recommen-
dations for “tests” represent a 2% increase, not a
68% increase, as asserted in the article. Second,
the authors did not consider major changes from
the most recent 5-year review of the resource-
based relative-value scale. A comparison of 1992
and 2007 work relative-value units (RVUs), with
the 2005 utilization data used as a common mul-
tiplier, reveals that evaluation and management
work valuation has increased 45%, while imaging
work valuation has decreased 6% since 1992.
We question the appropriateness of excluding
the most significant change and subsequent re-
distribution since the inception of the resource-
based relative-value scale — the revaluation of
evaluation and management services in 2007. We
agree that the scale’s improvements should be
ongoing, and we have submitted to the Centers
for Medicare and Medicaid Services (CMS) a num-
ber of significant recommendations related to the
practice-expense payments for consideration in
the 2008 Medicare resource-based relative-value
scale.
William L. Rich, III, M.D.
American Medical Association
Chicago, IL 60610
1. Maxwell S, Zuckerman S, Berenson RA. Use of physicians’
services under Medicare’s resource-based payments. N Engl J
Med 2007;356:1853-61.
To the Editor: Maxwell et al. analyzed the effect
of the resource-based relative-value scale, report-
ing that the share of Medicare total RVUs for eval-
uation and management services did not change
between 1992 and 2002. In an accompanying edi-
torial, Newhouse describes concerns about po-
tential underpayment for these services.1
My colleagues and I believe the Berenson–
Eggers Type of Service (BETOS) classification used
by Maxwell et al. does not provide sufficiently
accurate clinical-service-group delineation. For ex-
ample, the BETOS evaluation and management

n engl j med 357;6  www.nejm.org  august 9, 2007 617

The New England Journal of Medicine
Downloaded from www.nejm.org by haga respect on October 19, 2010. For personal use only. No other uses without permission.
Copyright © 2007 Massachusetts Medical Society. All rights reserved.