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Significant thresholds for the 75-g oral glucose tolerance test in pregnancy Charles Savona-Ventura 4 , Marcel Chircop Diabetic Pregnancy Joint Clinic, Department of Obstetrics–Gynecology, St. Luke’s Teaching Hospital, Gwardamangia, Malta Received 15 August 2006; accepted 3 October 2006 Abstract The significant threshold values for the 75-g oral glucose tolerance test (oGTT) during pregnancy have yet to be conclusively determined. This study aimed to identify the risk significance of various set thresholds for the oGTT result. Women undergoing a 75-g oGTT during the third trimester of pregnancy were classified into three groups: mild gestational impaired glucose tolerance (GIGT; 2-h postload glucose, 8.0– 8.5 mmol/l; n =75), moderate-severe GIGT (8.6–10.9 mmol/l; n =167), and GDM (z11.0 mmol/l; n =76). Outcome indicators of these three groups of women were compared to the parameters of the women with a presumed normal carbohydrate metabolism (n =12,185). The results show that with increasing oGTT thresholds, there was an increasing risk of maternal morbidity in the form of hypertensive disorders complicating pregnancy, as well as obstetric intervention such as induction of labor, cesarean delivery, and preterm delivery. The infant was also at increasing risk with increasing oGTT thresholds from respiratory distress, macrosomia, and associated shoulder dystocia. It would appear, therefore, that abnormal glucose tolerance in pregnancy, even as defined by the World Health Organization criteria, has proportionate risks to both mother and child. D 2008 Elsevier Inc. All rights reserved. Keywords: Diabetes mellitus; Pregnancy; Diagnosis; Complications 1. Introduction The World Health Organization (WHO) criteria for the diagnosis of abnormal carbohydrate metabolism during pregnancy have been set to levels similar to the nonpregnant state (WHO, 1994). These diagnostic criteria, therefore, ignore the physiological changes of pregnancy and, thus, include a significant proportion of pregnant women whose carbohydrate metabolism is normal for their pregnant state. We have previously shown that the short-term indicator outcomes in women with very mild forms of gestational impaired glucose tolerance (mild GIGT) were not signifi- cantly different from those in presumed normal women. However, there did appear to be a slight rise in certain outcome indicators, suggesting that there may be a possible relationship between post-glucose-load blood sugar levels and outcome (Savona-Ventura & Chircop, 2003). The present study attempts to investigate the short-term risk significance of various blood glucose value thresholds. 2. Materials and methods This study reviewed the medical records of 315 Maltese women who had undergone a 75-g oral glucose tolerance test (oGTT) during the third trimester of pregnancy and who were found to have abnormal glucose tolerance as defined by the WHO criteria (WHO, 1994). These were subdivided into three groups: (a) mild GIGT, when the 2-h postload glucose value was 8.0–8.5 mmol/l (n =75); (b) moderate-severe GIGT, with a 2-h value of 8.6–10.9 mmol/l (n =167); and (c) GDM, with a 2-h value of 11.0 mmol/l or more (n =76). The maternal and neonatal outcome indicators of the various groups were compared with those of women with presumed or confirmed normal carbohydrate metabolism 1056-8727/08/$ – see front matter D 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.jdiacomp.2006.10.001 4 Corresponding author. bNorthWyndsQ 7 Antonio Zammit Street, Gharghur Nxr08, Malta. E-mail address: [email protected] (C. Savona-Ventura). Journal of Diabetes and Its Complications 22 (2008) 178 – 180

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Page 1: Significant thresholds for the 75-g oral glucose tolerance test in pregnancy

Journal of Diabetes and Its C

Significant thresholds for the 75-g oral glucose tolerance test in pregnancy

Charles Savona-Ventura4, Marcel Chircop

Diabetic Pregnancy Joint Clinic, Department of Obstetrics–Gynecology, St. Luke’s Teaching Hospital, Gwardamangia, Malta

Received 15 August 2006; accepted 3 October 2006

Abstract

The significant threshold values for the 75-g oral glucose tolerance test (oGTT) during pregnancy have yet to be conclusively determined.

This study aimed to identify the risk significance of various set thresholds for the oGTT result. Women undergoing a 75-g oGTT during the

third trimester of pregnancy were classified into three groups: mild gestational impaired glucose tolerance (GIGT; 2-h postload glucose, 8.0–

8.5 mmol/l; n=75), moderate-severe GIGT (8.6–10.9 mmol/l; n=167), and GDM (z11.0 mmol/l; n=76). Outcome indicators of these three

groups of women were compared to the parameters of the women with a presumed normal carbohydrate metabolism (n=12,185). The results

show that with increasing oGTT thresholds, there was an increasing risk of maternal morbidity in the form of hypertensive disorders

complicating pregnancy, as well as obstetric intervention such as induction of labor, cesarean delivery, and preterm delivery. The infant was

also at increasing risk with increasing oGTT thresholds from respiratory distress, macrosomia, and associated shoulder dystocia. It would

appear, therefore, that abnormal glucose tolerance in pregnancy, even as defined by the World Health Organization criteria, has proportionate

risks to both mother and child.

D 2008 Elsevier Inc. All rights reserved.

Keywords: Diabetes mellitus; Pregnancy; Diagnosis; Complications

1. Introduction

The World Health Organization (WHO) criteria for the

diagnosis of abnormal carbohydrate metabolism during

pregnancy have been set to levels similar to the nonpregnant

state (WHO, 1994). These diagnostic criteria, therefore,

ignore the physiological changes of pregnancy and, thus,

include a significant proportion of pregnant women whose

carbohydrate metabolism is normal for their pregnant state.

We have previously shown that the short-term indicator

outcomes in women with very mild forms of gestational

impaired glucose tolerance (mild GIGT) were not signifi-

cantly different from those in presumed normal women.

However, there did appear to be a slight rise in certain

outcome indicators, suggesting that there may be a possible

4 Corresponding author. bNorthWyndsQ 7 Antonio Zammit Street,

harghur Nxr08, Malta.

E-mail address: [email protected]

G

1056-8727/08/$ – see front matter D 2008 Elsevier Inc. All rights reserved.

doi:10.1016/j.jdiacomp.2006.10.001

(C. Savona-Ventura).

relationship between post-glucose-load blood sugar levels

and outcome (Savona-Ventura & Chircop, 2003). The

present study attempts to investigate the short-term risk

significance of various blood glucose value thresholds.

2. Materials and methods

This study reviewed the medical records of 315 Maltese

women who had undergone a 75-g oral glucose tolerance

test (oGTT) during the third trimester of pregnancy and

who were found to have abnormal glucose tolerance as

defined by the WHO criteria (WHO, 1994). These were

subdivided into three groups: (a) mild GIGT, when the 2-h

postload glucose value was 8.0–8.5 mmol/l (n=75); (b)

moderate-severe GIGT, with a 2-h value of 8.6–10.9 mmol/l

(n=167); and (c) GDM, with a 2-h value of 11.0 mmol/l or

more (n=76).

The maternal and neonatal outcome indicators of the

various groups were compared with those of women with

presumed or confirmed normal carbohydrate metabolism

omplications 22 (2008) 178–180

Page 2: Significant thresholds for the 75-g oral glucose tolerance test in pregnancy

Table 1

Maternal complications

Parameter

Normal

metabolisma

Mild GIGT

(2-h value=8.0–8.5 mmol/l)

Moderate-severe GIGT

(2-h value=8.6–10.9 mmol/l)

GDM

(2-h valuez11.0 mmol/l)

n % n % n % n %

Multiple births ( P=.958) 159 1.3 1 1.3 ( P=.63) 3 1.8 ( P=.48) 1 1.3 ( P=1.0)

Maternal PIH/PET ( Pb.00014) 801 6.6 8 10.7 ( P=.24) 22 13.2 ( P=.0014) 17 22.4 ( Pb.00014)

Induction of labor ( Pb.00014) 4398 36.1 22 29.3 ( P=.28) 89 53.3 ( Pb.00014) 33 43.4 ( P=.23)

Cesarean section ( Pb.00014) 2866 23.5 21 28.0 ( P=.44) 56 33.5 ( P=.0034) 35 46.1 ( Pb.00014)

Operative vaginal delivery ( P=.616) 438 3.9 1 1.3 ( P=.46) 9 5.4 ( P=.31) 2 2.6 ( P=.48)

Preterm delivery ( P=.00024) 759 6.2 6 7.9 ( P=.70) 12 7.2 ( P=.73) 14 18.4 ( P=.00024)

Total number of maternity cases 12,185 75 167 76

a Based on 1999–2001 data.

* Statistically significant.

C. Savona-Ventura, M. Chircop / Journal of Diabetes and Its Complications 22 (2008) 178–180 179

who delivered in the same hospital during 1999–2001

(n=12,185). Glucose tolerance testing is not routinely

carried out on all maternity cases at the hospital but only

in those women who are considered at particular risk of

GDM. It has been estimated that about 6.8% (or about

730 individuals) of this group have various forms of mild-

severe GIGT (Savona-Ventura and Chircop, 2003).

Statistical significance that compares the outcome

indicators and risks of the various subgroups was tested

via the chi-square test and Yates and Fisher exact

analysis, as appropriate, using the WHO-StatCalc statis-

tical package. Further analyses were performed for each

morbidity outcome, comparing each of the subgroups

with the group having normal carbohydrate metabolism.

A probability value of b.05 was taken to represent a

significant correlation.

3. Results

There appeared to be an increasing risk of maternal

morbidity with increasing oGTT thresholds (Table 1).

Thus, a statistically significant rise was noted for hyper-

tensive disorders complicating pregnancy, increasing from

6.6% in normal tolerance women to 22.4% in GDM. There

was also a statistically significant increase in maternal

morbidity from a greater predisposition to obstetric

intervention from induction of labor (36.1% to 43.4%),

Table 2

Infant outcome

Parameter

Normal

metabolisma

Mild GIGT

(2-h value=8.0–8.5 m

n % n %

Fetal and neonatal loss ( P=.238) 118 1.0 1 1.3 ( P=.

Birth weight b2.5 kg ( P=.739) 768 6.3 3 3.9 ( P=.

Infant with RDS ( Pb.00014) 268 2.2 1 1.3 ( P=.

Macrosomia [N4.0 kg] ( P=.0034) 732 6.0 6 7.9 ( P=.

Shoulder dystocia ( Pb.00014) 51 0.4 0 – ( P=.

Apgar score V6 at 5 min ( P=.573) 140 1.1 1 1.3 ( P=.

Total number of infants born 12,274 76

a Based on 1999–2001 data.

4 Statistically significant.

cesarean delivery (23.5% to 46.1%), and preterm delivery

(6.2% to 18.4%). The statistically significant increases in

morbidity were only noticeable in the moderate-severe

GIGT and GDM subgroups.

The increased obstetric intervention rate contributed

toward a statistically significant increasing incidence of

respiratory distress (2.2% to 9.1%). There appeared to be

also a non-statistically significant rise in low-birth-weight

infants (6.3% to 9.1%) and in those with low Apgar score

at 5 min of life (6.3% to 9.1%). There was also a

statistically significant increase in the incidence of macro-

somia (6.0% to 14.3%) and associated shoulder dystocia

(0.4% to 6.5%). There appeared to be little difference in

fetal and neonatal loss (Table 2). The statistically signifi-

cant increases in morbidity were only markedly noticeable

in the GDM subgroup.

4. Conclusions

In 1980, the WHO suggested that the criteria used to

diagnose diabetes and IGT in the general population could

be applied to pregnant women. This view was endorsed

in 1985 and 1994 (WHO, 1994). The 1994 WHO criteria

for gestational diabetes still required a plasma glucose of

z7.0 mmol/l (fasting) or z7.8 mmol/l (2 h). These criteria

do not take into account the diabetogenic effects of preg-

nancy, and it has been argued that these criteria include a

mol/l)

Moderate-severe GIGT

(2-h value=8.6–10.9 mmol/l)

GDM

(2-h valuez11.0 mmol/l)

n % n %

79) 3 1.8 ( P=.23) 0 – ( P=.48)

56) 12 7.1 ( P=.79) 7 9.1 ( P=.21)

90) 8 4.7 ( P=.0364) 7 9.1 ( P=.0024)

65) 16 9.4 ( P=.09) 11 14.3 ( P=.0064)

73) 2 1.2 ( P=.16) 5 6.5 ( Pb.00014)

96) 3 1.8 ( P=.31) 2 2.6 ( P=.22)

170 77

Page 3: Significant thresholds for the 75-g oral glucose tolerance test in pregnancy

C. Savona-Ventura, M. Chircop / Journal of Diabetes and Its Complications 22 (2008) 178–180180

significant proportion of normal women. The American

Diabetes Association (ADA) (2002) requires two plasma glu-

cose values of z5.3 mmol/l (fasting), z10.0 mmol/l (1 h),

and z8.6 mmol/l (2 h). The latter threshold recommenda-

tions appear to be slowly being universally accepted, having

been adopted by the European Association of Perinatal

Medicine (Hod & Carrapato, 2002). Our previous study

appeared to confirm the observation that cases defined as

mild GIGT by the WHO criteria and normal by the ADA

criteria, that is, a 2-h blood glucose value of 7.9–8.6 mmol/l,

were not associated with any apparent statistically signifi-

cant increase in maternal and infant short-term morbidity

(Savona-Ventura & Chircop, 2003). This observation has

been reconfirmed in the present study. These observations

contrasted with a previously published study that had shown

that there was a continuum of risk related to the 2-h

maternal post-75-g-load blood glucose level for the prob-

ability of having an assisted delivery and the likelihood of

the baby being admitted to a Special Care Unit, even when

the 2-h value was below 8.0 mmol/l (Moses & Calvert,

1995). The significance of the values obtained after a 75-g

glucose load is yet to be determined by large-scale clinical

studies. Those with a special interest in GDM await the

results of the Hyperglycemia and Adverse Pregnancy

Outcome (HAPO) Study that should determine clear-cut

points for the complications associated with GDM (HAPO

Study Cooperative Research Group, 2002). The present

study has, however, confirmed that significant risk to both

mother and child exhibits itself with 2-h values greater that

8.6 mmol/l and that the risk is related to the 2-h maternal

post-75-g-load blood glucose levels becoming more sig-

nificant with values greater than 11.0 mmol/l.

Women with mild GIGT showed no statistically

increased risk for short-term morbidity but appeared to

be transitional between normal women and women with

moderate-severe GIGT. These women have, however, been

shown to have long-term morbidities related to subsequent

onset of diabetes. Maltese women with a mild GIGT have

been shown to be 3.6 times more likely to develop an

abnormal glucose tolerance 8 years postpartum than

women with a normal glucose tolerance test as defined

by the WHO criteria (Schranz & Savona-Ventura, 2002). In

spite of the apparent absence of short-term effects of mild

GIGT, it may remain prudent to continue advising women

with a borderline glucose tolerance test to reduce their

refined sugar intake, thus reducing the day-to-day blood

glucose loads presented to the developing fetus. The long-

term risks to the woman need also be discussed during the

antenatal and postpartum visits in order that lifestyle

modifications may be made to reduce or delay the advent

of adult-onset diabetes.

References

American Diabetes Association. (2002). Gestational diabetes mellitus.

Diabetes Care, 25 (Suppl. 1), S94–S96.

HAPO Study Cooperative Research Group. (2002). The Hyperglycemia

and Adverse Pregnancy Outcome (HAPO) Study. International Journal

of Gynecology & Obstetrics, 78 (1), 69–77.

Hod, M., & Carrapato, M. (2002). Working group on diabetes and

pregnancy: Diabetes and pregnancy. Update and guidelines. European

Association of Perinatal Medicine, 1–37.

Moses, R. G., & Calvert, D. (1995). Pregnancy outcome in women without

gestational diabetes mellitus related to the maternal glucose level.

Diabetes Care, 18 (2), 1527–1533.

Savona-Ventura, C., & Chircop, M. (2003). The threshold criteria for the

75g oral glucose tolerance test in pregnancy and short-term adverse

pregnancy outcomes. International Journal of Diabetes & Metabolism,

11, 7–9.

Schranz, A. G., & Savona-Ventura, C. (2002). Long-term significance of

mild gestational diabetes mellitus—A longitudinal study. Experimental

and Clinical Endocrinology & Diabetes, 110, 219–222.

World Health Organization. (1994). Report of a WHO Study Group:

Prevention of diabetes mellitus. Geneva7World Health Org (Tech. Rep.

Ser. No.844).