AGOS Papers www. AJOG.

org

The Hyperglycemia and Adverse Pregnancy Outcome

(HAPO) study: paving the way for new diagnostic
criteria for gestational diabetes mellitus
Donald R. Coustan, MD; Lynn P. Lowe, PhD; Boyd E. Metzger, MD; Alan R. Dyer, PhD

A t present, there is a lack of interna-

tional consistency with regard to
the diagnosis of gestational diabetes mel-
The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study was performed in
response to the need for internationally agreed upon diagnostic criteria for gestational
litus (GDM). While a glucose tolerance diabetes, based upon their predictive value for adverse pregnancy outcome. Increases in
test (GTT) is commonly employed, glu- each of the 3 values on the 75-g, 2-hour oral glucose tolerance test are associated with
cose challenge dosages vary and diagnos- graded increases in the likelihood of pregnancy outcomes such as large for gestational
tic thresholds are myriad. The 75-g glu- age, cesarean section, fetal insulin levels, and neonatal fat content. Based upon an
cose challenge is widely used throughout iterative process of decision making, a task force of the International Association of
the world for diagnostic testing in the Diabetes and Pregnancy Study Groups recommends that the diagnosis of gestational
nonpregnant state. At the Third Interna- diabetes be made when any of the following 3 75-g, 2-hour oral glucose tolerance test
tional Workshop-Conference on GDM thresholds are met or exceeded: fasting 92 mg/dL, 1-hour 180 mg/dL, or 2 hours 153
in 19901 a series of recommendations mg/dL. Various authoritative bodies around the world are expected to deliberate the
were made that included universal em- adoption of these criteria.
ployment of the 75-g glucose challenge
Key words: diagnostic oral glucose tolerance test criteria, gestational diabetes,
during pregnancy. Some sets of diagnos-
Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study
tic criteria, such as those proposed by the
World Health Organization (WHO), Cite this article as: Coustan DR, Lowe LP, Metzger BE, et al. The Hyperglycemia and Adverse
Pregnancy Outcome (HAPO) study: paving the way for new diagnostic criteria for gestational diabetes
were simply based on criteria used in
mellitus. Am J Obstet Gynecol 2010;202:654.e1-6.
nonpregnant individuals, and did not
take into account changes in carbohy-
drate metabolism brought about by the for international agreement on all as- ternal glucose and adverse neonatal out-
pregnant state. Others, such as the pects of diagnostic testing, and for the comes. A 1992 workshop sponsored by
O’Sullivan criteria2 in use in North development of criteria based on preg- the National Institute of Child Health
America, were based on data from nancy outcomes. and Human Development (NICHD)
pregnant women, but were derived Subsequently a group of investigators and the National Institute of Diabetes
mathematically as being 2 SD above from the disciplines of obstetrics and gy- and Digestive and Kidney Diseases3 sup-
the mean, and were validated for their necology, diabetology, and neonatology, ported the rationale behind this effort,
predictive value for future diabetes in based in North America, Europe, Asia, concluding that carefully designed stud-
the mother, rather than on pregnancy and the Middle East, met to plan a study ies were critical to answer outstanding
outcomes. The organizers advocated to examine the relationship between ma- questions about the sensitivity, specific-
ity, and cost-effectiveness of efforts to di-
agnose and treat GDM to prevent ad-
From the Division of Maternal-Fetal Medicine (Dr Coustan), Department of Obstetrics and verse perinatal effects.
Gynecology, Warren Alpert Medical School of Brown University and Women & Infants
The Fourth International Workshop-
Hospital of Rhode Island, Providence, RI, and Departments of Preventive Medicine (Drs
Conference on GDM4 in 1997 noted that
Lowe and Dyer) and Medicine (Dr Metzger), Northwestern University Feinberg School of
Medicine, Chicago, IL. the prevalence of GDM was increasing
Presented at the 28th Annual Meeting of the American Gynecological and Obstetrical Society,
around the world, and that “. . .al-
Chicago, IL, Sept. 12, 2009. though. . .some progress has been made
Received Dec. 1, 2009; revised Feb. 27, 2010; accepted April 8, 2010. toward building consensus there re-
Reprints: Donald R. Coustan, MD, Division of Maternal-Fetal Medicine, Department of Obstetrics mains a compelling need to develop di-
and Gynecology, Warren Alpert Medical School of Brown University, Women & Infants Hospital of agnostic criteria for GDM that are based
Rhode Island, 101 Dudley St., Providence, RI 02905-2401. dcoustan@wihri.org. on the specific relationships between
The HAPO study was supported by grants from the Eunice Kennedy Shriver National Institute of hyperglycemia and risk of adverse
Child Health and Human Development and the National Institute of Diabetes and Digestive and
outcome.”
Kidney Diseases (R01-HD34242 and R01-HD34243), the National Center for Research
Resources (M01-RR00048 and M01-RR00080), and the American Diabetes Association. Another area of controversy sur-
0002-9378/$36.00 • © 2010 Mosby, Inc. All rights reserved. • doi: 10.1016/j.ajog.2010.04.006 rounded the potential benefit, or lack of
benefit, of screening a population for

654.e1 American Journal of Obstetrics & Gynecology JUNE 2010

www.AJOG.org
GDM and treating when the diagnosis
was made. As recently as 2008 the US
Preventive Services Task Force (USP-
STF) Guide To Clinical Preventive Ser-
vice5 recommended as follows: “The
USPSTF concludes that the current evi-
dence is insufficient to assess the benefits
and harms of screening for GDM either
before or after 24 weeks gestation.” The
opposing view to this assertion is based
upon studies showing increased perina-
tal morbidity even when only 1 GTT
value is elevated.6
The Hyperglycemia and Adverse Preg-
nancy Outcome (HAPO) study was de-
signed to answer some of the questions
posed above. While there was little or no
argument that type 1 and type 2 diabetes
increase the risk of any number of ad-
verse pregnancy outcomes, the HAPO
study sought to determine the level of
glucose intolerance during pregnancy,
short of overt diabetes, that is associated
with adverse outcomes. The study design
has been described in detail elsewhere.7
More than 25,000 nondiabetic gravidas
were enrolled in 15 field centers located
in 9 different countries. Each subject un-
derwent a 75-g, 2-hour oral GTT
(OGTT) at between 24-32 weeks’ gesta-
tion (mean gestational age, 27.8 weeks);
subjects and caregivers were blinded to
the GTT results unless the fasting plasma
glucose was ⬎105 mg/dL or the 2-hour
value was ⬎200 mg/dL, in which case the
caregiver was informed of the results and
the subject was excluded from participa-
tion so that she could be treated as deter-
mined by the caregiver. As a safety pre-
caution, a sample for random plasma
glucose was collected at 34-37 weeks and
unblinded if the value was ⱖ160 mg/dL.
Participants were also unblinded for any
glucose value ⬍45 mg/dL.
At the time of delivery, cord blood
samples were obtained and analyzed at
the central laboratory for glucose and for
C-peptide. C-peptide was chosen as a
marker for fetal insulin levels because, in
the presence of hemolysis, it is much
more stable than insulin in stored speci-
mens. Neonatal anthropometric mea-
surements were collected within 72
hours of delivery. These consisted of
weight, length, head circumference, and
skinfold thickness measured at the flank,
subscapular, and triceps areas. Addi-
tional data were abstracted from mater-
nal and neonatal medical records.
The 4 primary outcomes for which the
study was powered included macroso-
mia (birthweight ⬎90th centile for ges-
tational age, gender, parity, ethnicity,
and field center), primary cesarean deliv-
ery, clinical neonatal hypoglycemia (as
noted in the medical record), and hyper-
insulinemia (cord serum C-peptide
⬎90th centile for the study group as a
whole). A number of secondary out-
comes were also considered. These in-
cluded preterm birth (defined as ⬍37
weeks’ gestation), shoulder dystocia
and/or birth injury, sum of skinfold
thicknesses ⬎90th centile for gestational
age, gender, ethnicity, parity and field
center, percent body fat ⬎90th centile
for gestational age (calculated from
birthweight, length, and flank skinfold8),
admission for neonatal intensive care,
hyperbilirubinemia, and preeclampsia.
Participants were enrolled between
July 2000 and April 2006. Data were an-
alyzed, blinded to test results, for 23,316
mother-newborn pairs. The mean fast-
ing plasma glucose value across all par-
ticipants was 80.9 mg/dL. At 1 and 2
hours after the 75-g oral glucose chal-
lenge the means were 134.1 and 111 mg/
dL, respectively. The average gestational
age at delivery was 39.4 weeks; 6.9% of
deliveries were preterm. Participants
were ethnically diverse, with 48% white
non-Hispanic, 12% black non-Hispanic,
29% Asian/Oriental, 8% Hispanic, and
3% other or unknown.9
For categorical analyses, fasting
plasma glucose values were divided a pri-
ori into 7 categories in 5-mg/dL incre-
ments, with the lowest category being
⬍75 mg/dL and the highest being ⱖ100
mg/dL. The 1- and 2-hour value catego-
ries were chosen to yield proportions of
the population that were similar to those
of the fasting plasma glucose categories.
The lowest 2 categories contained ap-
proximately 50% of subjects. The high-
est 2 categories contained only 1% and
3% of subjects, to determine whether
there was a threshold for any effects
present. As shown in the Figure, the 4
primary outcomes were all related to
each of the 3 glucose determinations in a
JUNE 2010 American Journal of Obstetrics & Gynecology
AGOS Papers
continuous and graded manner. Clinical
neonatal hypoglycemia, which occurred
in only 2.1% of the total population in
the study, showed the least robust asso-
ciation with fasting and other OGTT val-
ues, whereas the other 3 outcomes were
more strongly related. For example, the
prevalence of cord C-peptide ⬎90th
centile increased from 3.7% when fasting
plasma glucose was ⬍75 mg/dL to 32.4%
when it was ⱖ100 mg/dL. When logistic
models were constructed to account for
potential confounders of location (ie,
field center), age, body mass index, and a
number of other variables, the relation-
ships described above held although they
were somewhat attenuated.9
The relationship between OGTT val-
ues and each of the 4 primary outcomes
was also evaluated using glucose as a
continuous variable, and correcting for
the potential confounders described
above. As shown in Table 1 these rela-
tionships were expressed as the odds ra-
tio (OR) for a given outcome for each SD
increase in glucose. The association be-
tween each of the OGTT values and each
of the primary outcomes remained sig-
nificant with the exception of that be-
tween both fasting plasma glucose and
2-hour plasma glucose with clinical neo-
natal hypoglycemia. A number of sec-
ondary outcomes were also evaluated.
Both preeclampsia and shoulder dysto-
cia/birth injury were significantly asso-
ciated with each of the glucose values.
Preterm delivery was associated with the
1- and 2-hour glucose values, but not
with fasting plasma glucose.
One of the most critical observations
of the HAPO study was that the associa-
tions of various adverse outcomes with
OGTT results were continuous, and no
clear inflection points could be identi-
fied. The relationships held even down to
the most “normal” maternal glucose lev-
els. This led to 2 conclusions: (1) the re-
lationship between maternal glucose lev-
els and fetal growth and fetal outcome
appears to be a basic biological phenom-
enon, and not a clearly demarcated dis-
ease state; and (2) the construction of di-
agnostic criteria for a condition called
“gestational diabetes” was not going to
be easily accomplished directly from the
configuration of significant associations
654.e2
AGOS Papers www.AJOG.org

FIGURE
Frequency of primary outcomes across glucose categories

Fasting: category 1 ⫽ ⬍75, 2 ⫽ 75-79, 3 ⫽ 80-84, 4 ⫽ 85-89, 5 ⫽ 90-94, 6 ⫽ 95-99, 7 ⫽ ⱖ100 mg/dL. One-hour oral glucose tolerance test
(OGTT): category 1 ⫽ ⱕ105, 2 ⫽ 106-132, 3 ⫽ 133-155, 4 ⫽ 156-171, 5 ⫽ 172-193, 6 ⫽ 194-211, 7 ⫽ ⱖ212 mg/dL. Two-hour OGTT: category
1 ⫽ ⱕ90, 2 ⫽ 91-108, 3 ⫽ 109-125, 4 ⫽ 126-139, 5 ⫽ 140-157, 6 ⫽ 158-177, 7 ⫽ ⱖ178 mg/dL.
C, cesarean.
Reprinted, with permission, from HAPO Study Cooperative Research Group.9
Coustan. The HAPO study: paving the way. Am J Obstet Gynecol 2010.

between maternal glycemia and out-
comes. It was clear that the results of the
HAPO study were applicable to all the
involved field centers since the associa-
tions did not vary significantly across
field centers, even though the prevalence
of adverse outcomes differed among
them. Thus the HAPO study results
should be applicable globally to develop
outcome-based criteria for classifying
glucose metabolism in pregnancy.
The HAPO study investigators did not
make specific recommendations for di-
agnostic criteria. Because there were not
obvious inflection points in the associa-
tions, and because it was important that
any recommended diagnostic criteria be
accepted internationally, a committee of
experts was convened to develop a con-
sensus regarding appropriate diagnostic
criteria. This task was undertaken by the
International Association of Diabetes
and Pregnancy Study Groups (IADPSG,
www.iadpsg.org), an umbrella organiza-
tion that was formed to encourage and
facilitate research and advance educa-
tion in the field of diabetes in pregnancy,
and that aims to facilitate an interna-
tional approach to enhancing the quality
of care for women with diabetes in preg-
nancy. IADPSG’s affiliated organiza-
tions include the Diabetic Pregnancy
Study Group of the European Associa-
tion for the Study of Diabetes, the Japa-
nese Association of Diabetes and Preg-
nancy, the Australasian Diabetes in
Pregnancy Society, the West Coast USA
Diabetic Pregnancy Study Group of
North America, the Diabetes in Preg-
nancy Society of India, and the Canadian
Special Interest Group for Diabetes and
Pregnancy. Associated organizations in-
clude the European Association of Peri-
natal Medicine, the Society for Maternal
Fetal Medicine of the USA, the Preg-
nancy and Reproductive Health Interest
Group of the American Diabetes Associ-
ation (ADA), and the Saredia Interna-
tional Association.
The IADPSG convened a workshop/
conference in June 2008. There were pre-
sentations of data from the HAPO study
and other studies, and discussion of
these data by the 220 delegates from ap-

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www.AJOG.org AGOS Papers

TABLE 1
Adjusteda odds ratios and 95% confidence intervals for associations between
maternal glucose as continuous variable and perinatal outcomes
FPG 1-h PG 2-h PG
b
Outcome OR 95% CI OR 95% CI OR 95% CI
Birthweight ⬎90th centile 1.38 (1.32–1.44) 1.46 (1.39–1.53) 1.38 (1.32–1.44)
................................................................................................................................................................................................................................................................................................................................................................................
c
Primary cesarean delivery 1.11 (1.06–1.15) 1.10 (1.06–1.15) 1.08 (1.03–1.12)
................................................................................................................................................................................................................................................................................................................................................................................
Clinical neonatal hypoglycemia 1.08 (0.98–1.19) 1.13 (1.03–1.26) 1.10 (1.00–1.12)
................................................................................................................................................................................................................................................................................................................................................................................
Cord C-peptide ⬎90th centile 1.55 (1.47–1.64) 1.46 (1.38–1.54) 1.37 (1.30–1.44)
................................................................................................................................................................................................................................................................................................................................................................................
Preterm delivery, ⬍37 wk 1.05 (0.99–1.11) 1.18 (1.12–1.25) 1.16 (1.10–1.23)
................................................................................................................................................................................................................................................................................................................................................................................
Shoulder dystocia and/or birth injury 1.18 (1.04–1.33) 1.23 (1.09–1.38) 1.22 (1.09–1.37)
................................................................................................................................................................................................................................................................................................................................................................................
Sum of skinfolds ⬎90th centile 1.39 (1.33–1.47) 1.42 (1.35–1.49) 1.36 (1.30–1.43)
................................................................................................................................................................................................................................................................................................................................................................................
Intensive neonatal care 0.99 (0.94–1.05) 1.07 (1.02–1.13) 1.09 (1.03–1.14)
................................................................................................................................................................................................................................................................................................................................................................................
Hyperbilirubinemia 1.00 (0.95–1.05) 1.11 (1.05–1.17) 1.08 (1.02–1.13)
................................................................................................................................................................................................................................................................................................................................................................................
Preeclampsia 1.21 (1.13–1.29) 1.28 (1.20–1.37) 1.28 (1.20–1.37)
................................................................................................................................................................................................................................................................................................................................................................................
CI, confidence interval; FPG, fasting plasma glucose; OR, odds ratio; PG, plasma glucose.
a
Associations were adjusted for field center, age, body mass index, height, smoking status, alcohol use, family history of diabetes, gestational age at oral glucose tolerance test, infant’s gender,
hospitalization prior to delivery, mean arterial pressure, parity (not included in model for primary cesarean delivery), and cord PG (included in model for cord serum C-peptide ⬎90th centile
only)–preeclampsia did not include adjustment for hospitalization or mean arterial pressure, and family history of hypertension and prenatal urinary tract infection were included only in model for
preeclampsia; b ORs for glucose higher by 1 SD (6.9 mg/dL for FPG, 30.9 mg/dL for 1-h PG, 23.5 mg/dL for 2-h PG) (mmol/L ⫽ mg/dL/18); c Excluding those with prior cesarean section.
Reprinted, with permission, from New England Journal of Medicine.9
Coustan. The HAPO study: paving the way. Am J Obstet Gynecol 2010.

proximately 40 different countries. This mendations. A smaller steering commit- primary basis for the recommended di-
was followed by caucuses of the various tee and writing group was appointed. agnostic criteria. It would have simpli-
groups that were present. Then a consen- The delegates agreed that the choice of fied matters if a single glucose determi-
sus development session was held, in thresholds would have to be somewhat nation, such as fasting plasma glucose,
which approximately 50 delegates repre- arbitrary since inflection points in these would be sufficient for the diagnosis, so
senting the IADPSG organizations such continuous and graded relationships as to preclude the need for a full OGTT.
as American College of Obstetricians were not apparent. The group decided Therefore, the relative independent con-
and Gynecologists, WHO, ADA, Euro- that the various adverse outcomes were tributions of the fasting, 1-hour, and
pean Association for the Study of Diabe- not equally important in devising diag- 2-hour glucose values were considered.
tes, International Diabetes Federation, nostic thresholds, and that some out- As described below, each of the 3 samples
and Centers for Disease Control and Pre- comes such as macrosomia and cesarean contributed at least partially indepen-
vention as well as a number of “at-large” section were interrelated. The outcomes dently as a predictor of adverse preg-
delegates took the first steps to reach of large for gestational age (LGA) and fat nancy outcome, and the group decided
consensus around international recom- or hyperinsulinemic babies comprise the to recommend the full 2-hour, 75-g
OGTT, leaving open the possibility that a
particular professional organization
TABLE 2 might opt to eliminate ⱖ1 of the 3 tests,
Plasma glucose concentrations at specified odds ratios thereby reducing the sensitivity of the
Sample time process but also decreasing the cost and
OR 1.5 1.75 2.0 inconvenience.
..............................................................................................................................................................................................................................................
PG, mg/dL The mean glucose value at each of the
.....................................................................................................................................................................................................................................
3 time points was chosen as the reference
FPG 90 92 95
..................................................................................................................................................................................................................................... value, against which proposed thresh-
1-h PG 167 180 191 olds would be compared. Thresholds
.....................................................................................................................................................................................................................................
2-h PG 142 153 162 that yielded ORs of 1.5, 1.75, and 2.0
..............................................................................................................................................................................................................................................
PG values represent mean of threshold values for OR for increased neonatal body fat, large for gestational age, and cord serum times the likelihood of adverse outcomes
C-peptide ⬎90th centile. at mean glucose levels were considered
FPG, fasting plasma glucose; OR, odds ratio; PG, plasma glucose.
Coustan. The HAPO study: paving the way. Am J Obstet Gynecol 2010.
(Table 2). Setting thresholds at an OR of
1.5 identifies ⬎20% of the cohort with

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AGOS Papers www.AJOG.org

comes for both mother and offspring

TABLE 3 and we have reported those findings as
Pregnancies meeting glucose thresholds and positive well.
predictive values for outcomes The proposed thresholds identify
Glucose gravidas having an increased risk, com-
thresholds, % subjects PPV for BW PPV for C-peptide PPV for % body pared to the general population, of ad-
mg/dL > threshold >90th centilea >90th centileb fat >90th centilec
verse outcomes such as large, fat, and hy-
92/180/153 16.1 16.2 17.5 16.6 perinsulinemic babies, and cesarean
..............................................................................................................................................................................................................................................
95/191/162 8.8 17.6 19.7 18.8 section. Secondary outcomes such as
..............................................................................................................................................................................................................................................
BW, birthweight; PPV, positive predictive value. shoulder dystocia or birth injury, pre-
a
9.6% of total population had birthweight ⬎90th centile; b 8.4% of total population had C-peptide ⬎90th centile; c 9.8% of total term delivery, and preeclampsia were
population had neonatal % body fat ⬎90th centile. also increased in these individuals.9
Coustan. The HAPO study: paving the way. Am J Obstet Gynecol 2010.
However, it would be important to be
able to demonstrate that identification of
GDM by these criteria and intervention
ⱖ1 glucose values that met or exceeded bies decreased with the addition of pa- can prevent such adverse outcomes. The
the threshold. Using an OR of 1.75 rather tients identified by only the 1-hour Australian Carbohydrate Intolerance
than 2.0 increased the yield of cases with and/or 2-hour thresholds because the Study in Pregnant Women Trial investi-
similar risks of adverse outcome by 83%, positive predictive value of these thresh- gators10 demonstrated improvement in
and identified 16.1% of the population olds was slightly lower than that of the outcomes when subjects with a 2-hour
as having GDM (Table 3). The thresh- fasting, which did not preclude values for value on the 75-g OGTT between 140-
olds recommended represent ORs of 1-hour and/or 2-hour also above 200 mg/dL were treated for GDM with
1.75, and are fasting plasma glucose 92 threshold. diet and insulin as needed, compared to
mg/dL (5.1 mmol/L), 1 hour after the It may be stated that the IADPSG rec- control subjects who were not screened
75-g challenge 180 mg/dL (10 mmol/L), ommendations are based on pregnancy for GDM. A recent randomized trial of
and 2 hours after the 75-g challenge 153 outcomes, but do not take into account screening and treatment of mild GDM
mg/dL (8.5 mmol/L). the predictive values for maternal well- (fasting ⬍95 mg/dL, 2 of the other 3
As shown in Table 4, at the proposed being or long-term neonatal outcomes. 100-g, 3-hour OGTT values meeting or
threshold of 92 mg/dL for fasting plasma The original O’Sullivan criteria were exceeding 180, 155, and/or 140 mg/dL,
glucose, 8.3% of the HAPO study popu- based on the likelihood of subsequent di- respectively) by the NICHD-sponsored
lation was identified and 19.5% of the abetes in the mother. The HAPO study Maternal-Fetal Medicine Units Net-
babies were LGA. Adding the 1-hour does not include follow-up data on ei- work11 demonstrated a significant re-
threshold of 180 mg/dL identified an ad- ther mothers or offspring. However, we duction in macrosomia, neonatal fat
ditional 5.7% of the population who did have examined and to date reported mass, shoulder dystocia, preeclampsia,
not have an elevated fasting value and a some of our data on maternal outcomes. and cesarean section. These data strongly
total of 16.5% of identified pregnancies In the New England Journal of Medicine suggest that intervention in mild forms
delivered babies with LGA. Adding the article9 we report 2 maternal deaths, of GDM will be beneficial. Importantly,
2-hour threshold of 153 mg/dL identi- both of which would not have had GDM only 20% of treated Australian Carbohy-
fied an additional 2.1% of the popula- by the recommended thresholds, among drate Intolerance Study in Pregnant
tion, and a cumulative total of 16.2% ⬎23,000 pregnancies. Outcomes like ce- Women Trial subjects and 8% of Mater-
with LGA. The proportion with LGA ba- sarean section and preeclampsia are out- nal-Fetal Medicine Units Network sub-
jects required insulin, implying that di-
etary intervention will be effective in the
TABLE 4 great majority of mild GDM.
Contributions of each sample interval to diagnosis Table 5 compares the current ADA
and large-for-gestational-age frequencies recommendations for the 75-g OGTT12
Glucose, Subjects, LGA babies, with the proposed thresholds. It is im-
Sample time mg/dL cumulative % cumulative %a portant to note that the proposed thresh-
Fasting 92 8.3 19.5 olds require only a single elevated value,
..............................................................................................................................................................................................................................................
1-h 180 14.0 16.5 while the current ADA recommendation
..............................................................................................................................................................................................................................................
is for 2 abnormal values to be present. It
2-h 153 16.1 16.2
.............................................................................................................................................................................................................................................. is of significant concern that the recom-
LGA, large for gestational age. mended thresholds will result in 16.1%
a
Cumulative percentage of LGA babies reflects both numerator increases and denominator increases when additional subjects are
identified.
of the population being identified as hav-
Coustan. The HAPO study: paving the way. Am J Obstet Gynecol 2010. ing GDM. In fact, an additional 1.7% of
the HAPO study participants were un-

654.e5 American Journal of Obstetrics & Gynecology JUNE 2010

www.AJOG.org AGOS Papers
3. Blank A, Grave GD, Metzger BE. Effects of
TABLE 5 gestational diabetes on perinatal morbidity re-
Comparison of proposed thresholds to current thresholds assessed. Diabetes Care 1995;18:127-9.
for 75 gram OGTT in pregnancy (ADA) 4. Metzger BE, Coustan DR; and the Organizing
Committee. Summary and recommendations of
Proposed glucose Current ADA the fourth international workshop-conference on
Sample time threshold, mg/dL recommendations gestational diabetes mellitus. Diabetes Care
Fasting 92 95 1998;21(Suppl):B161-7.
.............................................................................................................................................................................................................................................. 5. US Preventive Services Task Force. USPSTF
1-h 180 180 guide to clinical preventive service; May
..............................................................................................................................................................................................................................................
2-h 153 155 2008. Available at: http://www.ahrq.gov/clinic/
.............................................................................................................................................................................................................................................. uspstf08/gestdiab/gdrs.htm. Accessed May 4,
Proposed: gestational diabetes is diagnosed if ⱖ1 of the thresholds is met or exceeded. 16
Current ADA recommendations:
2010.
gestational diabetes is diagnosed if ⱖ 2 thresholds are met or exceeded.12
ADA, American Diabetes Association; OGTT, oral glucose tolerance test. 6. Langer O, Anyaegbunam A, Brustman L, Di-
Coustan. The HAPO study: paving the way. Am J Obstet Gynecol 2010. von M. Management of women with one abnor-
mal oral glucose tolerance test value reduces
adverse outcome in pregnancy. Am J Obstet
Gynecol 1989;161:593.
blinded because of glucose values ex- In summary, the HAPO study pro- 7. HAPO Study Cooperative Research Group.
The hyperglycemia and adverse pregnancy out-
ceeding predetermined limits, so that vides an opportunity to revise diagnostic
come (HAPO) study. Int J Gynaecol Obstet
17.8% of HAPO study participants criteria for GDM. The proposed criteria 2002;78:69-77.
would meet the new thresholds. How- for the 75-g, 2-hour OGTT are that any 8. Catalano PM, Thomas AJ, Avallone DA,
ever, current population trends in both ⱖ1 of the following thresholds be met or Amini SB. Anthropometric estimation of neona-
GDM and type 2 diabetes render the exceeded: tal body composition. Am J Obstet Gynecol
1995;173:1176-81.
above projections biologically plausible. ● Fasting plasma glucose 92 mg/dL (5.1
9. HAPO Study Cooperative Research Group.
Getahun et al13 demonstrated that the mmol/L). Hyperglycemia and adverse pregnancy out-
rate of diagnosed GDM more than dou- ● One-hour plasma glucose 180 mg/dL comes. N Engl J Med 2008;358:1991-2002.
bled in the United States between 1989 (10 mmol/L). 10. Crowther CA, Hiller JE, Moss JR, McPhee
and 2004, with the rate in gravidas age AJ, Jeffries WS, Robinson JSL. Effect of treat-
● Two-hour plasma glucose 153 mg/dL
ment of gestational diabetes mellitus on preg-
ⱖ35 years exceeding 8%. This is consis- (8.5 mmol/L). nancy outcomes. N Engl J Med 2005;352:
tent with the current epidemic of obesity These proposed diagnostic criteria are 2477-86.
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similarity to “prediabetes,” defined as made with a single elevated value. Treat- statement: diagnosis and classification of dia-
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whether to adopt it. f
14. National Health and Nutrition Examination
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JUNE 2010 American Journal of Obstetrics & Gynecology 654.e6