Diabetes and Macrosomia

Pennington Biomedical
Research Center
Division of Education
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Gestational Diabetes Mellitus (GDM)
Overview
Affects 2 to 9 percent of all pregnancies.
Associated with maternal and perinatal complications.

Long-term adverse health outcomes among infants born to mothers
with GDM:

Sustained impairment of glucose tolerance
Subsequent obesity
Impaired intellectual achievement

The risk of macrosomia is increased.
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Gestational Diabetes (GDM)
Development
Related to increased maternal body mass index (BMI).
Pre-pregnancy BMI of 30 kg/m
2
or higher is a strong risk factor for the
development of GDM.
Maternal obesity combined with an excessive weight gain during pregnancy
are major risk factors for:
pre-eclampsia
Cesarean section
preterm delivery
fetal macrosomia
fetal death.
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Macrosomia
An oversized fetus.

Occurs frequently in women with diabetes.

Can lead to trauma during birth and a greater
chance of a cesarean delivery.
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Large for Gestational
Age babies
Birth weight above the
90th percentile, is
considered as LGA (large
for gestational age).
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Around the World
Increasing proportion of infants born with a high birth weight (HBW).
In Sweden, HBW infants has risen to more than 20%.
A similar pattern occurs in North America and Europe.
Researchers have found that
increasing maternal weight
gestational weight gain
gestational diabetes
reduced smoking prevalence
among pregnant women may likely explain the increase in proportion of LGA
births between 1976 and 1996 in Canada.

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Factors relating to LGA babies

Related to the level of glycemic control that
the mother achieves.

Other factors that contribute to the
development of LGA neonates are:
Obesity of the mother
Excessive weight gain in pregnancy

Research
Maternal diabetes
control on infant
health at birth and
in later life.
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Fetal Growth Spurt and Pregestational
Diabetic Pregnancy

Researchers assessed the timing of the fetal growth spurt among
pre-existing diabetic pregnancies (types 1 and 2) and its
relationship with diabetic control.

They hoped to find correlations between fetal growth
acceleration and factors influencing this occurrence.
Wong S, Oats J, Chan F, McIntyre D. Diabetes Care. 2002; 25: 1681-1684
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Fetal Growth Spurt and Pregestational
Diabetic Pregnancy

In this study of 101 diabetic pregnancies, glucose control was
found not to have a direct effect on the incidence of LGA
babies.

Instead, maternal BMI was shown to have the more direct
and greater effect.

Pregnancies were separated into two groups:

Diabetic mothers with normal weight babies
Diabetic mothers with LGA babies


Wong S, Oats J, Chan F, McIntyre D. Diabetes Care. 2002; 25: 1681-1684
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Fetal Growth Spurt and Pregestational
Diabetic Pregnancy

The women of the group with LGA babies were
shown to have significantly higher pre-pregnancy
body weights and BMIs.

There were no differences between the two
groups with glucose control in either the first,
second, or third trimester.

Wong S, Oats J, Chan F, McIntyre D. Diabetes Care. 2002; 25: 1681-1684
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Conclusions
Fetal growth acceleration in LGA fetuses of diabetic mothers was shown to
begin in the second trimester, from as early as 18 weeks.

In this particular study, glucose control did not appear to have any direct
effect on the incidence of LGA babies, and such observation might result
from the effects of other not yet identified contributing factors.
Wong S, Oats J, Chan F, McIntyre D. Diabetes Care. 2002; 25: 1681-1684
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Determinants of Fetal Growth at Different Periods of
Pregnancies Complicated by GDM or Impaired Glucose
Tolerance (IGT)

The aim of this study was to determine what maternal
factors had the strongest influence on fetal growth at
different periods of pregnancies complicated by an
abnormal glucose tolerance test (GTT).

The fetal abdominal circumference (AC) is used to describe
fetal growth in this study because accelerated growth in
the fetal AC in the early 3
rd
trimester has been shown to be
a good predictor of macrosomia at birth.

Schaefer-Graf U et al. Diabetes Care. 2003; 26: 193-198.
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Determinants of Fetal Growth at Different
Periods of Pregnancies Complicated by GDM
or Impaired Glucose Tolerance (IGT)
Normalizing the macrosomia rate is the primary goal in treating women with
pregnancies complicated by GDM.

Macrosomia is not only associated with a higher rate of birth injury for the
mother and newborn, but it is also associated with higher weight and
accumulation of fat in childhood, with a higher rate of obesity in adulthood.

Although normalizing maternal glucose levels has reduced neonatal
morbidity in GDM, it has not been as effective in regards to macrosomia.

Macrosomia rates in mothers with GDM when compared to mothers without
GDM still remain elevated even with maternal glucose normalization.

Schaefer-Graf U et al. Diabetes Care. 2003; 26: 193-198.
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Because maternal weight, glycemia after therapy, rates of fetal
macrosomia, and LGA were not significantly different between GDM
and IGT groups, they were analyzed together.

Results indicated that in the late 2
nd
and early 3
rd
trimester,
maternal BMI and LGA in a previous pregnancy appear to have the
strongest influence on fetal growth.

Later in the 3
rd
trimester, coincident with the period of maximal growth
described in diabetic pregnancies, maternal glycemia predominates.
Determinants of Fetal Growth at Different
Periods of Pregnancies Complicated by GDM
or Impaired Glucose Tolerance (IGT)
Schaefer-Graf U et al. Diabetes Care. 2003; 26: 193-198.
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Conclusions
Conclusions of this second study were in agreement with the first, stating
that maternal BMI has a great effect on the development of LGA babies.

However, this study went a step further in finding that both maternal BMI
and LGA in a previous pregnancy had the largest influence on fetal growth,
and identified the time frame when this effect was predominant.

This study also found that maternal glycemia does effect fetal growth, and
found the particular time frame when its effects occurred.
Schaefer-Graf U et al. Diabetes Care. 2003; 26: 193-198.
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What Degree of Maternal Metabolic Control in
Women With Type 1 DM is Associated with
Normal Size & Proportions in Full-Term Infants?

The aim of this study was to assess the degree of maternal metabolic
control in women with Type 1 DM necessary to allow for normal fetal
growth and normal neonatal body proportions.

In this study, the anthropometric characteristics of 98 full-term singleton
infants born to 98 Caucasian women with Type 1 DM were measured.

All women were enrolled within 12 weeks of gestation and were later placed
in one of three mother-infant pair groups based on the level of glycemic
control they were able to maintain over the 2
nd
and 3
rd
trimesters of
pregnancy.
Mello G et al. Diabetes Care. 2000; 23: 1494-1498.
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What Degree of Maternal Metabolic Control in
Women With Type 1 DM is Associated with
Normal Size & Proportions in Full-Term Infants?
The three groups were:











There was a control group of 1,415 Caucasian mother-infant pairs with
full-term singleton pregnancies. Members of the control group had normal
glucose challenge test when screened for gestational diabetes.


Number of mother-infant pairs Criteria required to be a member
Group 1 37 An average daily glucose level during
the 2
nd
and 3
rd
trimester of 95 mg/dl
Group 2 37 An average daily glucose level during
the 2
nd
trimester of > 95 mg/dl and
during the 3
rd
trimester of 95 mg/dl
Group 3 24 An average daily glucose level during
the 2
nd
and 3
rd
trimester of > 95 mg/dl
Mello G et al. Diabetes Care. 2000; 23: 1494-1498.
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What Degree of Maternal Metabolic Control in
Women With Type 1 DM is Associated with
Normal Size & Proportions in Full-Term Infants?
Infants of diabetic mothers in group 1 of this study were found to be
similar to those of the control group in birth weight and in other
anthropometric parameters.

In contrast, offspring of diabetic mothers of groups 2 and 3 had an
increased incidence of LGA, significantly greater means of ponderal index
and thoracic circumferences, and significantly smaller cranial/thoracic
circumference ratios with respect to the control group.
Mello G et al. Diabetes Care. 2000; 23: 1494-1498.
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Conclusions

The results of the study indicate that, in diabetic pregnancies, only overall
daily glucose values of 95 mg/dl throughout the second and third
trimesters can avoid alterations in fetal growth.
Mello G et al. Diabetes Care. 2000; 23: 1494-1498.
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Evaluation of Body Composition of LGA Infants
of Women with GDM compared with Women
with Normal Glucose Tolerance Levels
The purpose of this study was to determine whether or not there is a
difference in body composition in the LGA infants of women with GDM
compared with the LGA infants of women with normal glucose tolerance
levels.

The researchers also wanted to identify factors associated with the
different levels of fat mass in these infants if a difference in body
composition was found.
Durnwald C, Huston-Presley L, Amini S, Catalano P. Am J Obstet Gynecol 2004; 191: 804-8
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Evaluation of Body Composition of LGA Infants
of Women with GDM compared with Women
with Normal Glucose Tolerance Levels
Fifty cases of women with gestational diabetes and 52 cases of women
with normal glucose tolerance levels were evaluated in the study.

Researchers found that infants born in the two groups did have similar
birth weights.

Infants born to mothers with gestational diabetes did, in fact, have
increased fat mass and percent body fat, with decreased lean body mass,
when compared to infants of mothers with normal glucose tolerance levels.


Durnwald C, Huston-Presley L, Amini S, Catalano P. Am J Obstet Gynecol 2004; 191: 804-8
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Conclusions
Results of the study indicated that LGA infants of mothers with
gestational diabetes mellitus have increased fat mass and decreased lean
body mass when compared with infants of mothers with normal glucose
tolerance levels.

Factors were also identified which are believed to affect the level of
fat mass an infant has.

Researchers indicated that in gestational diabetes, gestational age, and
fasting value of the oral glucose tolerance test was shown to correlate
best with the fat mass observed.
Durnwald C, Huston-Presley L, Amini S, Catalano P. Am J Obstet Gynecol 2004; 191: 804-8
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Growth and Fatness at Three to Six Years of
Age of Children Born Small- or Large-for
Gestational Age

The objective of this study was to determine whether or not there are
differences in growth and fatness in early childhood as associated with
birth weight status.

Children 3 to 6 years of age who were born small-for-gestational age (SGA)
or large-for-gestational age (LGA) were compared with those who were
born appropriate-for-gestational age.
Hediger M et al. Pediatrics. 1999; 104(3).
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Growth and Fatness at Three to Six Years of
Age of Children Born Small- or Large-for
Gestational Age
From the third National Health and Nutrition Examination survey, 3,192
US-born non-Hispanic white, non-Hispanic black, and Mexican-American
children were included in the study.

The children were categorized, and growth outcome was assessed by birth
weight-for-gestational age status.

The growth outcomes considered in these analyses were body weight (kg),
height (cm), head circumference (cm), mid-upper arm circumference
(MUAC; cm), and triceps and subscapular skinfold thicknesses (mm).
Hediger M et al. Pediatrics. 1999; 104(3).
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Growth and Fatness at Three to Six Years of
Age of Children Born Small- or Large-for
Gestational Age
The study found that SGA children remain significantly shorter and
lighter throughout early childhood.

The children do not seem to catch up from 36 to 83 months of age.

On the other hand, LGA infants remain longer and heavier throughout
83 months of age, but, unlike children born SGA, LGA children have a
tendency to accumulate fat in early childhood.

This indicates that early childhood may be a particularly sensitive period in
which there are increases in variation in levels of fatness associated with
size at birth. If this is so, then one could conclude that intrauterine
growth is associated with size in early childhood.

Hediger M et al. Pediatrics. 1999; 104(3).
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Conclusions
Further research is needed to confirm that LGA children may be at risk
for accumulating excess fat at an early age.

This study suggests that birth weight status and gestational age may be
useful in assembling a prognostic risk profile for children, with LGA infants
being placed in a category of highest risk.
Hediger M et al. Pediatrics. 1999; 104(3).
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Maternal and Fetal Outcomes if Gestational
Impaired Glucose Tolerance is Not Treated
The purpose of this study was to evaluate whether there is increased
maternal or neonatal morbidity in connection with impaired glucose
tolerance (IGT) during pregnancy when the condition is not treated.

The 213 study participants were from a defined geographic area in
Sweden, and the study period was from 1997-2001.
Ostlund I et al. Diabetes Care. 2003; 26(7): 2107-2111.
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Maternal and Fetal Outcomes if Gestational
Impaired Glucose Tolerance is Not Treated
The diagnostic criteria for gestational diabetes in this area was
limited to the criteria used for diabetes.
Because of this, 213 women, who were identified with IGT during
pregnancy, were not diagnosed or treated.
Researchers collected the data on the maternal and fetal outcomes
for each subject.
For each research subject used in the study, four control subjects
were taken from the same delivery department.
Ostlund I et al. Diabetes Care. 2003; 26(7): 2107-2111.
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Maternal and Fetal Outcomes if Gestational
Impaired Glucose Tolerance is Not Treated
The researchers found that the proportion of women who underwent
cesarean section was significantly higher in the research subjects than in
the control subjects and was independently associated with IGT.

They also found that the proportion of infants who were LGA was
independently and significantly associated with untreated IGT
during pregnancy.

Admission to a neonatal intensive care unit for 2 days or longer was also
more common for infants of mothers with untreated IGT during pregnancy.

Overall, 71.3% of the children in the IGT group and 87.3% of the children
in the control group had no neonatal complications.
Ostlund I et al. Diabetes Care. 2003; 26(7): 2107-2111.
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Conclusions
The researchers concluded that there is an increased independent
association between cesarean section rate, prematurity, LGA, and
macrosomic infants born to mothers with untreated IGT.

Although most of the children were healthy in this study, there was
still increased morbidity in the group of children born to mothers with
untreated IGT.

Researchers call for further investigations on this topic.
Ostlund I et al. Diabetes Care. 2003; 26(7): 2107-2111.
Division of Education
Phillip Brantley, PhD,
Director
Pennington Biomedical
Research Center
Claude Bouchard, PhD,
Executive Director.
Heli J Roy, PhD, RD
Reviewed by:
Beth Kalicki
Edited : October 2009
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References
Wong S, Oats J, Chan F, McIntyre D. Fetal growth spurt and pre-gestational
diabetic pregnancy. Diabetes Care. 2002; 25: 1681-1684.

Crowther C, Hiller J, Moss J, McPhee A, Jeffries W, Robinson J. Effect of
treatment of gestational diabetes mellitus on pregnancy outcomes. NEJM.
2005; 352(24): 2477-2486.

Schaefer-Graf U et al. Determinants of fetal growth at different periods of
pregnancies complicated by gestational diabetes mellitus or impaired glucose
tolerance. Diabetes Care. 2003; 26: 193-198.

Mello G et al. What degree of maternal metabolic control in women with type 1
diabetes is associated with normal body size and proportions in full-term
infants? Diabetes Care. 2000; 23: 1494-1498.

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References
Durnwald C, Huston-Presley L, Amini S, Catalano P. Evaluation of body
composition of large-for-gestational age infants of women with gestational
diabetes mellitus compared with women with normal glucose tolerance
levels. American Journal of Obstetrics and Gynecology. 2004; 191: 804-8.

Hediger M et al. Growth and fatness at three to six years of age of
children born small- or large-for-gestational age. Pediatrics. 1999; 104(3).

Ostlund I et al. Maternal and fetal outcomes if gestational impaired
glucose tolerance is not treated. Diabetes Care. 2003; 26(7): 2107-2111.

http://www.umm.edu/ency/article/002248.htm

Copyright 2009
PBRC # PPT30