Cos Son 2015

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Available online at
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Diabetes & Metabolism xxx (2015) xxxxxx
Original article
Pregnancy adverse outcomes related to pregravid body mass index and

gestational weight gain, according to the presence or not of gestational
diabetes mellitus: A retrospective observational study
E. Cosson a,b, , C. Cussac-Pillegand a , A. Benbara c , I. Pharisien c , M.T. Nguyen a , S. Chiheb a ,
P. Valensi a , L. Carbillon c
a
Department of Endocrinology-Diabetology-Nutrition, CRNH-IdF, CINFO, Paris 13 University, Sorbonne Paris Cit, Jean-Verdier Hospital, APHP, Bondy,
France
b Sorbonne Paris Cit, UMR U1153 Inserm, U1125 Inra, Cnam, Universit Paris 13, Bobigny, France
c Department of Obstetrics and Gynecology, Paris 13 University, Sorbonne Paris Cit, Jean-Verdier Hospital, APHP, Bondy, France
Received 6 February 2015; received in revised form 1st June 2015; accepted 2 June 2015
Abstract
Aim. This study retrospectively evaluated the complications associated with prepregnancy overweight (OW) or obesity (OB) and gestational
weight gain (GWG) in women with or without universally screened and treated gestational diabetes mellitus (GDM).
Methods. A total of 15,551 non-Asian women without pregravid diabetes or hypertension who delivered singleton babies (20022010)
were classified according to GDM (13.5%), pregestational body mass index (BMI; normal range: 18.524.9 kg/m2 ), OW (26.2%), OB (13.9%;
BMI 30 kg/m2 ) and GWG (< 7 kg: 32%; 711.5 kg: 37%; 11.616 kg: 23%; > 16 kg: 8%). Main outcome measures were large/small for gestational
age (LGA/SGA), caesarean section, preeclampsia, preterm delivery and shoulder dystocia.
Results. GDM was associated with more LGA babies [Odds Ratio (OR): 2.12, 95% confidence interval (CI): 1.852.43], caesarean section
(OR: 1.49, 95% CI: 1.341.65) and preeclampsia (OR: 1.59, 95% CI: 1.212.09). OW/OB and GWG were associated with LGA infants whatever
the GDM status, and with SGA babies only in women without GDM. LGA status was independently associated with GWG in women with GDM
(11.616 kg: OR: 1.74, 95% CI: 1.492.03 and > 16 kg OR: 3.42, 95% CI: 2.834.13 vs 711.5 kg) and in women without GDM (OR: 2.14, 95%
CI: 1.542.97 or OR: 2.65, 95% CI: 1.684.17, respectively), and with BMI only in women without GDM (OR: 1.12, 95% CI: 1.001.24, per
10 kg/m2 ). SGA status was independently associated with OW (OR: 0.86, 95% CI: 0.770.98), OB (OR: 0.84, 95% CI: 0.720.98) and GWG < 7 kg
(1.14, 95% CI: 1.011.29) only in women without GDM.
Conclusion. In our European cohort and considering the triumvirate of GDM, BMI and GWG, GDM was the main contributor to caesarean
section and preeclampsia. OW/OB and GWG contributed to LGA and SGA infants mainly in women without GDM.
2015 Elsevier Masson SAS. All rights reserved.
Keywords: Gestational diabetes mellitus; Gestational weight gain; Obesity; Pregnancy; Prognosis
1. Introduction
Abbreviations: GWG, Gestational weight gain; IOM, Institute of Medicine;
HAPO, Hyperglycaemia and Adverse Pregnancy Outcomes; IADPSG, International Association of Diabetes and Pregnancy Study Groups; LGA, large for
gestational age; SGA, small for gestational age.
Corresponding author at: Department of Endocrinology-DiabetologyNutrition, hpital Jean-Verdier, avenue du 14-juillet, 93143 Bondy cedex,
France. Tel.: +33 148 02 65 80; fax: +33 148 02 65 79.
E-mail address: emmanuel.cosson@jvr.aphp.fr (E. Cosson).
Gestational diabetes mellitus (GDM) is defined as any degree

of glucose intolerance with onset or first recognition during
pregnancy, and is associated with adverse outcomes during
pregnancy [1]. Obesity has a growing prevalence in women
of childbearing age [2] and is a confounding factor. First, it is
a risk factor for GDM [2,3]. Second, it shares complications
with GDM, such as large-for-gestational-age (LGA) infants
http://dx.doi.org/10.1016/j.diabet.2015.06.001
1262-3636/ 2015 Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Cosson E, et al. Pregnancy adverse outcomes related to pregravid body mass index and gestational
weight gain, according to the presence or not of gestational diabetes mellitus: A retrospective observational study. Diabetes Metab (2015),
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E. Cosson et al. / Diabetes & Metabolism xxx (2015) xxxxxx
[411], caesarean section [4,5,7,8,11,12], hypertensive disorders [4,5,7,8] and, in certain studies, shoulder dystocia [5].
Also, gestational weight gain (GWG) appears to be crucial
[5,810,13,14].
To date, only five recent studies, four from the United States
[5,10,15,16] and only one from Europe [9], have explored the
impact of GDM, obesity and GWG together. Some limitations
may affect these observational studies. First, the prevalence
of GDM is sometimes very low [9,16] with screening which
might not have been universal [5,10,15,16]. Second, women
with pregravid diabetes and hypertension were not excluded
[5,9,10,15,16], whereas these conditions are often associated
with overweight and obesity. Therefore, considering women
with isolated obesity might better evaluate the role of obesity
per se [12]. Regarding body mass index (BMI), underweight
women are not always considered separately [5,16] nor is the
lower BMI cutoff point in Asian women [17] taken into account
to define overweight and obesity [5,9]. Finally, excessive GWG
[9,10], determined according to pregravid BMI status as proposed by the Institute of Medicine (IOM) [18] rather than GWG
per se, has often been considered and is an additional confounding factor.
Dietary advice and drugs are generally provided only to
women with GDM, as GWG [5,810,13,14], treatment modalities and glycaemic levels achieved can modify the outcomes
[19]. Only the Hyperglycaemia and Adverse Pregnancy Outcomes (HAPO) study reported obesity-related adverse events
independently of glycaemic status and its treatment [4,7]. However, in that study, BMI was measured at the time of oral glucose
tolerance tests at between 24 and 32 weeks of gestation, and not
before pregnancy. Therefore, GWG could not be assessed.
Given this context, a large multiethnic European cohort of
non-Asian women who delivered singleton babies and were
without pregravid diabetes or hypertension was selected for
our present retrospective observational study. In this cohort, the
adverse outcomes related to isolated overweight, obesity and
GWG were investigated in women with and without universally
screened and treated GDM.
2. Methods
2.1. Participants, GDM screening and care
A total of 20,653 women delivered at our hospital between
January 2002 and December 2010. Data are routinely entered at
birth for all women (no exceptions) giving birth at our university
hospital by the midwife assisting at the delivery, then checked
and collected during the maternity stay by a midwife qualified in data management and storage (I.P.), with no interactions
with the women themselves. The authors did not have access to
identification of patients information prior to anonymization.
The purposes of the database are to assess the overall quality
of obstetric care and to regularly update medical management
protocols. The data are retrospective and observational, with
no need for either approval by an ethics committee/institutional
review board or patients written informed consent. The patients
records/information are anonymous, and the database is declared
to the French data protection authority (Commission nationale

de linformatique et des liberts [CNIL]).
In the present study, women with known diabetes (n = 204),
previous hypertensive disorders (n = 448) and multiple pregnancies (n = 378) were not included. Furthermore, women whose
prepregnancy BMI (n = 1669) and GWG (n = 2) were unknown
were also not included. Finally, those also excluded were women
from Asia (n = 628) or India/Pakistan/Sri Lanka (n = 1076), and
those with a BMI < 18.5 kg/m2 (n = 687).
Thus, 15,551 pregnancies were analyzed. Definitions of our
parameters did not change over the 9 years of the study. BMI was
calculated from self-reported pregravid weight and measured
height during pregnancy, using the following formula: weight
(in kg) divided by the height (in m) squared. Women were classified as normal weight, overweight and obese when their BMI
was 18.524.9 kg/m2 , 25.029.9 kg/m2 and 30 kg/m2 , respectively [17]. GWG categories (< 7 kg, 7.011.5 kg, 11.616 kg
and > 16 kg) were defined according to the usual thresholds
proposed by IOM guidelines for overweight women (optimal
GWG: 711.5 kg) and normal-weight women (optimal GWG:
11.616 kg) [18].
GDM was assessed using a one-step screening and diagnostic test, which always comprised a 75-g oral glucose tolerance
test [2,20,21]. GDM was defined as a fasting plasma glucose
value 5.3 mmol/L (the same fasting plasma glucose target as
in previous French recommendations) and/or a 2-h blood glucose value 7.8 mmol/L (World Health Organization criteria)
[2,20,21]. One-step screening was chosen to limit the number
of participants lost to follow-up, as our study population was characterized by widespread geographical origins [21]. Screening
was specifically prescribed during the hospital routine follow-up
visit and then performed out of hospital. As is usual for epidemiological studies, the women without screening were considered
to be without GDM [2,9,10,15].
Women who were overweight or obese had no specific
follow-up unless they were diagnosed with GDM. All women
with such a diagnosis were referred to a multidisciplinary
team, which included a diabetologist, obstetrician, midwife,
dietitian and nurse educator. These women received individualized dietary advice, were instructed on how to perform
self-monitoring of blood glucose levels six times a day, and
visited the diabetologist every two to four weeks. Insulin therapy was started if fasting and 2-h postprandial glucose levels
were > 5.3 mmol/L and > 6.8 mmol/L, respectively. Antenatal
visits were scheduled for every two to four weeks up to 34 weeks,
and weekly thereafter, with cardiotocography and assessment of
amniotic fluid volume [2,21].
2.2. Prognosis
The following outcomes were considered: LGA or SGA
(birth weight > 90th percentile or < 10th percentile, respectively,
of the general French population) [22]; caesarean section;
preeclampsia (blood pressure 140/90 mmHg on two measurements taken 4 h apart and proteinuria 300 mg/24 h or 3+ or
more on dipstick testing of a random urine sample); preterm
delivery (before 37 full weeks); and shoulder dystocia, defined
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Table 1
Maternal characteristics and complications by gestational diabetes mellitus (GDM) status and pregravid body mass index (BMI).
Characteristics
Pregravid BMI (kg/m2 )
BMI classification
Normal weight (%)
Overweight (%)
Obesity (%)
Age (years)
Parity (n)
Multiparity (%)
Maternal smoking
Before pregnancy (%)
During pregnancy (%)
Ethnicity
Caucasian (%)
Sub-Saharan African (%)
Caribbean (%)
Other (%)
Family history of diabetes (%)
Previous pregnancy with macrosomia (%)
Previous pregnancy with GDM (%)
Events
GDM (%)
Gestational weight gain (kg)
Gestational weight gain classification
< 7 kg (%)
711.5 kg (%)
11.616 kg (%)
> 16 kg (%)
Large-for-gestational-age babies (%)
Small-for-gestational-age babies (%)
Caesarean section (%)
Preeclampsia (%)
Preterm delivery (%)
Shoulder dystocia (%)
Total cohort
(n = 15,551)
No GDM
(n = 13,436)
GDM
(n = 2097)
ANOVA, Normal
P
weight
(n = 9317)
Overweight
(n = 4075)
Obesity
(n = 2159)
ANOVA,
P
24.6 4.7
24.6 4.7
24.9 4.8
< 0.001
< 0.01
21.6 1.6
26.6 1.4a
33.6 4.0a,b
< 0.001
9317 (59.9)
4075 (26.2)
2159 (13.9)
29.7 5.8
2.1 1.3
9045 (58.2)
8127 (60.4)
3489 (25.9)
1838 (13.7)
29.6 5.8
2.0 1.3
7728 (57.4)
1190 (56.7)
586 (27.9)
321 (15.3)
30.6 5.8
2.2 1.4
1317 (62.8)
29.7 5.9
2.0 1.2
5315 (57.0)
29.9 5.8
2.1 1.3a
2426 (59.5)a
29.7 5.9
2.2 1.4a
1304 (60.4)a
2243 (14.4)
1503 (9.7)
1994 (14.8)
1352 (10.0)
249 (11.9)
151 (7.2)
1421 (15.3)
946 (10.2)
526 (12.9)a
344 (8.4)a
296 (13.7)
213 (9.9)
9881 (63.5)
3566 (22.9)
1365 (8.8)
739 (4.8)
3227 (20.8)
457 (2.9)
498 (3.2)
8434 (62.7)
3181 (23.6)
1196 (8.9)
643 (4.8)
2718 (20.2)
366 (2.7)
268 (2.0)
1447 (69.0)
385 (18.4)
169 (8.1)
96 (4.6)
509 (24.3)
91 (4.3)
230 (11.0)
5998 (64.4)
2058 (22.1)
817 (8.8)
444 (4.8)
1950 (20.9)
266 (2.9)
276 (3.0)
2530 (62.1)
1020 (25.0)
324 (8.0)
201 (4.9)
833 (20.4)
124 (3.0)
136 (3.3)
1353 (62.7)
488 (22.6)
224 (10.4)
94 (4.4)
444 (20.6)
27 (3.1)
86 (4.0)a
2097 (13.5)
8.9 5.7
9.0 5.7
8.5 5.5
1190 (12.8)
9.1 5.6
586 (14.4)a
8.8 5.6
321 (14.9)a
8.5 5.8a
5041 (32.4)
5695 (36.6)
3586 (23.1)
1229 (7.9)
1341 (8.6)
2114 (13.6)
3265 (21.0)
335 (2.2)
1207 (7.8)
231 (1.5)
4272 (31.8)
4945 (36.8)
3149 (23.4)
1088 (8.1)
1028 (7.6)
1837 (13.7)
2696 (20.0)
269 (2.0)
1032 (7.7)
193 (1.4)
769 (36.7)
750 (35.8)
437 (20.8)
141 (6.7)
313 (14.9)
277 (13.1)
569 (27.1)
66 (3.1)
175 (8.3)
38 (1.8)
2902 (31.1)
3481 (37.4)
2180 (23.4)
754 (8.1)
778 (8.4)
1332 (14.3)
1944 (20.9)
185 (2.0)
733 (7.9)
137 (1.5)
1362 (33.4)
1471 (36.1)
929 (22.8)
313 (7.7)
361 (8.9)
517 (12.7)a
863 (21.2)
88 (2.2)
296 (7.3)
59 (1.4)
777 (32.4)
743 (29.6)
477 (22.1)
162 (7.5)
202 (9.4)
123 (13.9)a
458 (21.2)
62 (2.9)a
178 (8.2)
35 (1.6)
< 000.1
< 000.1
< 000.1
< 000.1
< 000.1
< 000.1
< 000.1
< 000.1
< 000.1
< 000.1
< 0.01
< 000.1
NS
< 000.1
< 000.1
NS
NS
NS
< 0.001
< 0.01
< 0.001
< 0.01
< 0.01
NS
NS
< 0.05
< 0.01
< 0.001
< 0.001
NS
< 0.01
NS
< 0.05
NS
NS
Data are presented as means SD or as n (%); NS: not significant.

a P < 0.05 vs women with BMI 18.524.9 kg/m2 .
b P < 0.05 vs women with BMI 2529.9 kg/m2 .
as the use of obstetric manoeuvres (such as a McRoberts episiotomy after delivery of the fetal head, suprapubic pressure,
posterior arm rotation to an oblique angle, rotation of the infant
by 180 degrees and delivery of the posterior arm) [23].
SPSS software (SPSS, Chicago, IL, USA). The 0.05 probability

level was considered statistically significant.
3. Results
2.3. Statistical analyses
3.1. Characteristics of the study population
Continuous variables were expressed as means SD, and

compared by one-way analysis of variance (ANOVA) or the
MannWhitney U test as adequate. The significance of differences in proportions was tested with the Chi2 test. Logistic
regression was used for analyses of BMI and GWG effects on
LGA and SGA infants, caesarean section and preeclampsia in
women with and without GDM. Logistic regression was also
used for multivariate analyses based on a model including factors
associated with LGA and then SGA, with a P value < 0.10 on univariate analyses. All statistical analyses were carried out using
Maternal characteristics are shown in Table 1. In summary,

the women were 29.7 5.8 years old, and their mean parity
was 2.1 1.3. GDM was diagnosed in 13.5%. The mean pregravid BMI was 24.6 4.7 kg/m2 , with overweight and obesity
observed in 26.2% and 13.9%, respectively. Mean GWG was
8.9 5.7 kg. Of note, the cohort was multiethnic, with most of
the subjects being Caucasian (from Europe or North Africa;
63.5%) or from sub-Saharan Africa (22.9%).
Pregravid parameters associated with GDM were BMI, age,
parity, maternal smoking, ethnicity, family history of diabetes
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and previous pregnancy with macrosomia or GDM (Table 1).

Classes of increasing BMI (normal weight, overweight and obesity) were associated with higher parity, less smoking before and
during pregnancy, ethnicity and a more frequent personal history
of GDM. Mean GWG was lower in obese women (Table 1).
3.2. Pregnancy-related events associated with GDM and
overweight/obesity
Table 1 also shows that GDM was associated with less GWG,
and more LGA infants (OR: 2.12, 95% CI: 1.852.43), caesarean section (OR: 1.49, 95% CI: 1.341.65) and preeclampsia
(OR: 1.59, 95% CI: 1.212.09). An increased BMI classification
was associated with lower GWG, more GDM, preeclampsia and
fewer SGA infants (Table 1).
3.3. Complications associated with BMI and GWG
according to GDM status
11.516 kg and > 16 kg, but with none of the other parameters,
including BMI (Table 2).
The probability of delivering an SGA infant was associated
with BMI classification, multiparity (60.0% in women without an SGA infant vs 57.7% in those with; P < 0.05), smoking
before and during pregnancy (9.3% vs 10.7%, respectively;
P < 0.05), family history of diabetes (21.2% vs 17.8%, respectively; P < 0.0001), previous pregnancy with macrosomia (3.1%
vs 1.9%, respectively; P < 0.01), preeclampsia (1.9% vs 3.5%,
respectively; P < 0.001) and GWG class (P < 0.01). On multivariate analyses, all of these parameters, except multiparity,
were associated with SGA infants, including BMI (negative
association) and GWG < 7 kg (positive association; Table 3).
On multivariate analyses performed according to GDM status,
overweight/obese and GWG classes remained independently
associated with SGA infants in women without GDM, but no
longer for women with GDM (Table 3).
4. Discussion
On analyzing the contribution of overweight/obesity and

GWG classification to the incidence of LGA infants (Fig. 1A),
SGA infants (Fig. 1B), caesarean sections (Fig. 1C) and
preeclampsia (Fig. 1D) by GDM status, the GWG and BMI class
were associated with LGA infants regardless of GDM status
(Fig. 1A, P < 0.0001) and with SGA infants only in women without GDM (Fig. 1B, P < 0.01). Of note, the mean rate of SGA was
13.7% in women without GDM whereas, when GWG was < 7 kg
with normal weight, overweight and obesity, the rates were
16.3%, 12.8% and 13.6%, respectively. There were no associations between GWG, BMI class, caesarean section (Fig. 1C)
and preeclampsia (Fig. 1D) in women with and without GDM.
3.4. Factors independently associated with LGA and SGA
infants
The probability of delivering an LGA infant was associated with the following maternal and pregnancy characteristics:
positive association with increasing age (29.7 5.9 years in
women without an LGA infant vs 30.2 5.7 years in those
with an LGA infant; P < 0.01), BMI (24.6 4.7 kg/m2 vs
24.9 4.8 kg/m2 , respectively; P < 0.05), multiparity (58.4%
vs 73.2%, respectively; P < 0.0001), family history of diabetes
(20.4% vs 24.4%, respectively; P < 0.05), previous pregnancy
with macrosomia (2.1% vs 11.3%, respectively; P < 0.0001),
GDM (12.6% vs 23.3%, respectively; P < 0.0001) and GWG
classification (P < 0.001); negative association with smoking
before and during pregnancy (9.9% vs 5.6%, respectively;
P < 0.0001), sub-Saharan African (24.0% vs 19.8%, respectively; P < 0.0001) and Caribbean (9.1% vs 6.6%, respectively;
P < 0.0001) origins, and preeclampsia (2.3% vs 11.0%, respectively; P < 0.01). Multivariate analyses taking into account these
parameters to explain LGA infants showed that all of these
factors, except age, were independently associated with LGA
infants, including BMI and GWG (Table 2); this was also true
when only women without GDM were considered. Factors independently associated with LGA in women with GDM were age,
multiparity, previous pregnancy with macrosomia, and GWG
Our present findings confirm and extend previous reports

linking GDM, high maternal BMI and GWG with pregnancy
outcomes. In our large European, non-Asian cohort of women
without pregestational diabetes or hypertension, both pregravid
BMI and GWG were associated with LGA and SGA infants in
women without GDM. In contrast, in women with treated GDM,
overweight/obesity was not independently associated with LGA
and SGA infants, and GWG was only associated with LGA
infants. Considered altogether, these results suggest that both
overweight/obesity and GWG are crucial for fetal growth in
women without GDM, whereas GWG is the main additional
contributor in GDM to fetal overgrowth, with the role of BMI
blunted in women treated for GDM.
4.1. GDM prevalence, BMI excess and GWG in our
European cohort
As previously reported, GDM prevalence was high in our
followed-up women [2]. This was due to our diagnostic criteria,
which used low thresholds even before our adoption of International Association of Diabetes and Pregnancy Study Groups
(IADPSG) criteria for defining GDM in 2011. In addition, many
of our patients have risk factors for GDM: 20% of our women are
from North Africa [21] and are particularly vulnerable. Indeed, it
was recently reported that more than half the women with GDM
in the four largest maternity units in our area had psychosocial
insecurity [24,25]. A large proportion of women in our cohort
began their pregnancies while overweight (26.2%) or obese
(13.9%); these are among the highest rates in France and most
likely due to the large proportion of deprived populations living
in our area. In addition, the proportion of women of childbearing
age with obesity is increasing in France [26,27]; it was recently
reported that the proportion of pregnant women with overweight
or obesity had increased from 30.8% in 2002 to 37.6% in 2010
at our centre [2]. The prevalence of obesity was higher than that
of FriuliVenezia Giulia, a region in northeastern Italy [9], and
almost the same as that reported by the international HAPO study
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Fig. 1. Crude prevalences in women with and without gestational diabetes mellitus (GDM) of (A) large-for-gestational-age (LGA) and (B) small-for-gestational-age
(SGA) infants, (C) caesarean section and (D) preeclampsia, according to body mass index (obesity, overweight and normal weight) and gestational weight gain.
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6
Table 2
Parameters associated with large-for-gestational-age (LGA) infants in the total cohort and in women without and with gestational diabetes mellitus (GDM).
Total cohort
Women without GDM
Women with GDM
Multivariate analysis
OR [95 CI]
Age (10 years)

Maternal BMI
OR [95 CI]
NS
(10 kg/m2 )
Multiparity (%)
Maternal smoking
No (%)
Before (%)
Before and during (%)
Ethnicity
Caucasian (%)
Sub-Saharan African (%)
Caribbean (%)
Other (%)
OR [95 CI]
NS
1.29 [1.071.51]
< 0.01
1.12 [1.001.24]
< 0.05
1.17 [1.031.31]
< 0.001
1.87 [1.642.14]
< 0.001
1.90 [1.642.21]
< 0.001
NS
0.48 [0.370.61]
REF
NS
< 0.001
0.42 [0.320.56]
REF
NS
< 0.001
REF
NS
NS
1.74 [1.302.35]
< 0.001
0.74 [0.640.89]
0.63 [0.500.80]
REF
< 0.001
< 0.001
NS
0.70 [0.590.83]
0.64 [0.490.83]
REF
< 0.001
< 0.001
NS
REF
NS
NS
NS
1.16 [1.011.33]
< 0.05
1.18 [1.011.38]
< 0.05
NS
Previous pregnancy with macrosomia (%)
4.52 [3.656.00]
< 0.001
4.86 [3.826.19]
< 0.001
3.78 [2.395.96]
< 0.001
GDM (%)
2.01 [1.752.32]
< 0.001
Preeclampsia (%)
0.49 [0.290.83]
< 0.01
0.42 [0.210.84]
< 0.05
NS
1.74 [1.492.03]
3.42 [2.834.13]
NS
REF
< 0.001
< 0.001
1.64 [1.381.95]
3.58 [2.914.40]
NS
REF
< 0.001
< 0.001
NS
REF
< 0.001
< 0.001
GWG classication
< 7 kg (%)
711.5 kg (%)
11.616 kg (%)
> 16 kg (%)
2.14 [1.542.97]
2.65 [1.684.17]
Mutivariate analyses used a logistic-regression model including the above factors associated with LGA infants and P < 0.10 on univariate analyses; NS: not significant;
REF: reference group.
Table 3
Parameters associated with small-for-gestational-age (SMA) infants in the total cohort, and in women without and with gestational diabetes mellitus (GDM).
BMI classication
Normal weight (%)
Overweight (%)
Obesity (%)
Multiparity (%)
Maternal smoking
No (%)
Before (%)
Before and during (%)
Total cohort
Women without GDM
Women with GDM
OR [95 CI]
0.87 [0.780.97]
0.83 [0.720.96]
REF
< 0.05
< 0.05
NS
OR [95 CI]
OR [95 CI]
0.86 [0.770.98]
0.84 [0.720.98]
0.90 [0.821.00]
REF
< 0.05
< 0.05
0.05
REF
NS
NS
NS
REF
NS
NS
1.2 [1.031.4]
REF
NS
< 0.05
1.2 [1.031.4]
REF
NS
< 0.05
0.81 [0.720.91]
< 0.001
0.84 [0.740.95]
< 0.01
0.65 [0.470.91]
< 0.05
Preeclampsia (%)
1.87 [1.442.44]
< 0.001
1.90 [1.422.54]
< 0.001
1.85 [1.013.40]
0.05
1.13 [1.011.26]
< 0.05
REF
NS
NS
1.14 [1.011.29]
< 0.05
REF
NS
NS
GWG classication
< 7 kg (%)
711.5 kg (%)
11.616 kg (%)
> 16 kg (%)
NS
REF
NS
NS
Multivariate analyses used a logistic-regression model including the above factors, which were associated with SGA and P < 0.10 on univariate analyses, plus previous
pregnancy with macrosomia; REF: reference group; NS: not significant.
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ARTICLE IN PRESS
[7], in which 13.7% had a BMI 33 kg/m2 at inclusion. However, obesity is still far less than reported in recent US reports,
which ranged from 20.0% [28] to 31.9% [29]. Indeed, as in the
US [15], our study shows that race/ethnicity is a determinant of
overweight/obesity.
As previously reported, women with overweight and obesity had less GWG than those with a normal BMI [5,8,13,14].
As women diagnosed with GDM are followed-up with dietary
counselling, this probably explains why this is so [30]. For this
reason, our study analyzed the incidence of pregnancy events
according to mutually exclusive BMI/GWG groups in women
without GDM and then in those treated for GDM.
4.2. Roles of BMI and GWG on fetal growth in women with
and without GDM
As in the five studies looking at the triumvirate of GDM, BMI
and GWG, multivariate analyses of our total cohort showed that
these three factors were independently associated with LGA
infants. Interestingly, Black et al. [5] recently reported on the
contributions of BMI, mild untreated GDM and GWG to fetal
overgrowth: 21.6% of LGA infants were attributable to maternal
overweight or obesity and 23.3% to overweight or obesity with
GDM, with an increasing GWG associated with a greater prevalence of LGA in all groups. Similarly, Kim et al. [10] showed,
in another US cohort, that for all racial or ethnic groups, GDM
contributed the least, whereas GWG contributed the most, to
LGA. This result was partly due to a notably high prevalence
of overweight/obesity in that cohort. Indeed, their calculation of
the partial population attributable fraction took into account both
the prevalence and OR of a given risk factor, and was interpreted
as the proportion of cases that would be prevented if it were possible to eliminate that risk factor from the population [10]. As
the partial population attributable fraction of GDM, BMI and
GWG was < 50%, other factors may be important contributors
to LGA infants. Similar to the findings of others, our data indicate that, while ethnicity [15,16], a familial history of diabetes
and personal history of a child with macrosomia [15,29] suggest
genetic causes of macrosomia, smoking habits [6], multiparity
and preeclampsia [31] are also possible, non-genetic causes of
macrosomia. All these factors may play a role through epigenetic
mechanisms, with fetal epigenetic programming of adipokines
involved when considering BMI and GWG [32].
The effects of BMI and GWG may vary according to GDM
status. Our present study found that the effects of BMI and
GWG were greatest in patients without GDM, who received
no specific care in our maternity unit at the time. This has been
consistently reported in women without GDM [5,15,16,28]. For
example, Di Benedetto et al. [8] showed, in an Italian cohort,
that the effect of overweight and obesity was present only in
glucose-tolerant women who had excess weight gain during
pregnancy. This suggests that the risk of macrosomia associated
with overweight/obesity might be limited by well-controlled
GWG. The counterpart of a low GWG would be a higher incidence of SGA infants [14,18]. In our cohort, however, this effect
was blunted in overweight/obese women, who were unlikely to
deliver SGA infants. The increase in SGA infants associated

with GWG < 7 kg was balanced by a decreased incidence of
overweight/obese women. To illustrate this point, GWG < 7 kg
was associated with the highest prevalence of SGA infants only
in lean women whereas, in the overweight/obese women, SGA
rates were similar to the mean rate of the overall cohort. These
findings suggest that closer monitoring of GWG in women
with pregravid BMIs 25 kg/m2 may be warranted to prevent
LGA infants with no negative impact on SGA births, as recommended by the IOM [18]. Nevertheless, meta-analyses also
show that, although antenatal interventions for overweight or
obesity can limit GWG [33], the outcomes are often unchanged
[33,34].
Our present results differed in women with GDM, who were
followed-up to control both their diets and blood glucose levels.
In fact, as found by others [30], these women had less GWG
than women without GDM. Also, in these women, BMI no
longer had any effect on LGA births. Indeed, the effect of BMI
might be driven by GDM, which is more frequent when BMI
is increased [3,15]. Otherwise, GWG remained an important
contributor to fetal overgrowth in this subpopulation, with the
same result as found in an Italian cohort. When only women
with GDM were considered, GWG, but neither overweight nor
obesity, were associated with macrosomia [9]. However, an independent effect of GWG and obesity on LGA infants was found
in three American studies [16,28,29]. This was also the case of
the study by Black et al. [5] although, in that study, GDM was
treated by neither diet nor medication.
4.3. Other outcomes
As in previous reports, GDM [1,5,9,10,15] and obesity
[4,5,7,8] were associated in our cohort with more preeclampsia, and GDM with more caesarean section, after examining the
contributions of BMI and GWG to these outcomes according
to GDM status. Regarding preeclampsia, there was no influence
of overweight/obesity and GWG classification, thus stressing
the role of GDM per se. Also, no association was identified
between BMI and GWG classes for caesarean section regardless of GDM status, whereas such an association has often been
reported [4,5,7,8,12]. Several population-based studies found
that planned and especially emergency caesarean delivery was
significantly increased with increasing BMI [35]. However,
these studies did not stratify patients according to GDM status.
Caregivers were inclined to perform caesarean sections in obese
patients because of concerns about obesity-related macrosomia,
and perinatal complications such as shoulder dystocia [5] and
perinatal mortality [36].
4.4. Strengths and weaknesses of the study
Our study involved a large sample size, thereby giving power
to its significant differences, and allowing multivariate analyses
and strict selection criteria, including no known hypertensive
disorders or diabetes before pregnancy, no underweight women,
no women of Asian origin and no twin pregnancies. This
removed the major sources of potential confounders. The data
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ARTICLE IN PRESS
came from a single institution with a comprehensive and consistent perinatal care programme, and the multiethnic population
included a large proportion of women living with psychosocial vulnerability [24,25]. All information was collected at a
university hospital, precluding generalization of the results.
Regarding the parameters of interest, although GDM screening was universal, some women were not screened. Therefore,
our study considered the presence of GDM in the intentionto-screen population, as done in other studies [10,15]. The
proportion of unscreened women was 12.5% in 2011 at our
hospital and is likely to have remained stable over the past
decade. GDM was not defined according to IADPSG criteria.
However, the association between BMI and pregnancy outcomes is reportedly not influenced by the definition of GDM
[37,38], and our cohort had a GDM prevalence rate similar to
that of the IADPSG criteria. Our results were not adjusted for
glucose control, as these data were not available. BMI was calculated from measured height, but weight before pregnancy was
self-reported.
One strength of our study is that GWG was not considered
according to BMI, as that would have led to consideration of the
BMI effect twicefirst per se and then through excessive GWG,
defined according to normal weight, overweight and obesity status. However, GWG was not adjusted for gestational age at
delivery, which is difficult as GWG is not linear during pregnancy, but increases during the lattermost weeks of pregnancy.
Finally, LGA and SGA infants were defined by comparison
to the general French population [22] with similar thresholds
across ethnicities. However, their determinants were adjusted
for ethnicity.
5. Conclusion
In the context of the current escalation of obesity [26,27] and
GDM [39], our present study confirms that GDM, even when
treated, is associated with adverse pregnancy outcomes. In our
European cohort of women with GDM, GWG is additionally
and independently associated with more LGA infants, whereas
overweight/obesity is not. This suggests that, even after reinforcing GWG control in women treated for GDM, the most this
would achieve does not appear to include more SGA infants in
this pregnant population. However, weight loss subsequent to a
diagnosis of GDM has recently been reported to be associated
with a 1.69-fold increased rate of SGA infants [40].
In women without GDM, our data show that considering pregravid BMI and GWG is crucial for estimating the risk for LGA
infants. Our observational results suggest that dietary advice
could be offered to overweight/obese women before pregnancy
to reduce the risk of preeclampsia and LGA as well as the risk
of GDM. In women without GDM, controlling weight gain
during pregnancy might limit the incidence of LGA without
inducing fetal restriction in those who are overweight/obese. It
was recently shown that a low-intensity lifestyle intervention in
women at high risk for GDM optimalized healthy GWG, while
limiting weight gain was more effective in overweight women
[41].
Disclosure of interest
The authors declare that they have no conflicts of interest
concerning this article.
Acknowledgements
We thank Prof Eric Vicaut (APHP, Unit of Clinical
Research, Lariboisire Hospital, Paris 7 University, Paris,
France) for his help with the statistical analyses.
References
[1] World Health Organization. Diagnostic criteria and classification of
hyperglycaemia first detected in Pregnancy; 2013 http://apps.who.
int/iris/bitstream/10665/85975/1/WHO NMH MND 13.2 eng.pdf
[2] Cosson E, Benbara A, Pharisien I, Nguyen MT, Revaux A, Lormeau B, et al.
Diagnostic and prognostic performances over 9 years of a selective screening strategy for gestational diabetes mellitus in a cohort of 18,775 subjects.
Diabetes Care 2013;36:598603.
[3] Galtier F. Definition, epidemiology, risk factors. Diabetes Metab
2010;36:62851.
[4] Hyperglycaemia and adverse pregnancy outcome (HAPO) study: associations with neonatal anthropometrics. Diabetes 2009;58:4539.
[5] Black MH, Sacks DA, Xiang AH, Lawrence JM. The relative contribution of prepregnancy overweight and obesity, gestational weight gain, and
IADPSG-defined gestational diabetes mellitus to fetal overgrowth. Diabetes Care 2013;36:5662.
[6] Djelantik AA, Kunst AE, van der Wal MF, Smit HA, Vrijkotte TG. Contribution of overweight and obesity to the occurrence of adverse pregnancy
outcomes in a multi-ethnic cohort: population attributive fractions for Amsterdam. BJOG 2012;119:28390.
[7] Catalano PM, McIntyre HD, Cruickshank JK, McCance DR, Dyer AR,
Metzger BE, et al. The hyperglycaemia and adverse pregnancy outcome
study: associations of GDM and obesity with pregnancy outcomes. Diabetes Care 2012;35:7806.
[8] Di Benedetto A, DAnna R, Cannata ML, Giordano D, Interdonato ML,
Corrado F. Effects of prepregnancy body mass index and weight gain during pregnancy on perinatal outcome in glucose-tolerant women. Diabetes
Metab 2012;38:637.
[9] Alberico S, Montico M, Barresi V, Monasta L, Businelli C, Soini V, et al.
The role of gestational diabetes, pre-pregnancy body mass index and gestational weight gain on the risk of newborn macrosomia: results from a
prospective multicentre study. BMC Pregnancy Childbirth 2014;14:23.
[10] Kim SY, Sharma AJ, Sappenfield W, Wilson HG, Salihu HM. Association of maternal body mass index, excessive weight gain, and gestational
diabetes mellitus with large-for-gestational-age births. Obstet Gynecol
2014;123:73744.
[11] Oteng-Ntim E, Kopeika J, Seed P, Wandiembe S, Doyle P. Impact of obesity
on pregnancy outcome in different ethnic groups: calculating population
attributable fractions. PLoS One 2013;8:e53749.
[12] Gilead R, Yaniv Salem S, Sergienko R, Sheiner E. Maternal isolated obesity and obstetric complications. J Matern Fetal Neonatal Med
2012;25:257982.
[13] Blomberg M. Maternal and neonatal outcomes among obese women with
weight gain below the new Institute of Medicine recommendations. Obstet
Gynecol 2011;117:106570.
[14] Hinkle SN, Sharma AJ, Dietz PM. Gestational weight gain in obese mothers
and associations with fetal growth. Am J Clin Nutr 2010;92:64451.
[15] Bowers K, Laughon SK, Kiely M, Brite J, Chen Z, Zhang C. Gestational diabetes, pre-pregnancy obesity and pregnancy weight gain in
relation to excess fetal growth: variations by race/ethnicity. Diabetologia
2013;56:126371.
+Model
ARTICLE IN PRESS
[16] Ellerbe CN, Gebregziabher M, Korte JE, Mauldin J, Hunt KJ. Quantifying
the impact of gestational diabetes mellitus, maternal weight and race on
birthweight via quantile regression. PLoS One 2013;8:e65017.
[17] Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA,
et al. Harmonizing the metabolic syndrome: a joint interim statement of
the International Diabetes Federation Task Force on Epidemiology and
Prevention; National Heart, Lung, and Blood Institute; American Heart
Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation
2009;120:16405.
[18] Rasmussen KM, Catalano PM, Yaktine AL. New guidelines for weight
gain during pregnancy: what obstetrician/gynecologists should know. Curr
Opin Obstet Gynecol 2009;21:5216.
[19] Langer O, Yogev Y, Xenakis EM, Brustman L. Overweight and obese
in gestational diabetes: the impact on pregnancy outcome. Am J Obstet
Gynecol 2005;192:176876.
[20] Cosson E, Benchimol M, Carbillon L, Pharisien I, Paries J, Valensi P, et al.
Universal rather than selective screening for gestational diabetes mellitus
may improve fetal outcomes. Diabetes Metab 2006;32:1406.
[21] Cosson E, Cussac-Pillegand C, Benbara A, Pharisien I, Jaber Y, Banu I,
et al. The diagnostic and prognostic performance of a selective screening
strategy for gestational diabetes mellitus according to ethnicity in Europe.
J Clin Endocrinol Metab 2014;99:9961005.
[22] Leroy B, Lefort F. [The weight and size of newborn infants at birth]. Rev
Fr Gynecol Obstet 1971;66:3916.
[23] Spong CY, Beall M, Rodrigues D, Ross MG. An objective definition of
shoulder dystocia: prolonged head-to-body delivery intervals and/or the
use of ancillary obstetric maneuvers. Obstet Gynecol 1995;86:4336.
[24] Bihan H, Cosson E, Khiter C, Vittaz L, Faghfouri F, Leboeuf D, et al. Factors associated with screening for glucose abnormalities after gestational
diabetes mellitus: baseline cohort of the interventional IMPACT study.
Diabetes Metab 2014;40:1517.
[25] Cosson E, Bihan H, Vittaz L, Khiter C, Carbillon L, Faghfouri F, et al.
Improving postpartum glucose screening after gestational diabetes mellitus: a cohort study to evaluate the multicentre IMPACT initiative. Diabet
Med 2015;32:18997.
[26] Diouf I, Charles MA, Ducimetiere P, Basdevant A, Eschwege E, Heude B.
Evolution of obesity prevalence in France: an age-period-cohort analysis.
Epidemiology 2010;21:3605.
[27] Eschwege E, Basdevant A, Crine A, Moisan C, Charles MA. Type 2 diabetes
mellitus in France in 2012: results from the ObEpi survey. Diabetes Metab
2015;41:5561.
[28] Kim C. Maternal outcomes and follow-up after gestational diabetes mellitus. Diabet Med 2014;31:292301.
[29] Ouzounian JG, Hernandez GD, Korst LM, Montoro MM, Battista LR,
Walden CL, et al. Pre-pregnancy weight and excess weight gain are risk
factors for macrosomia in women with gestational diabetes. J Perinatol
2011;31:71721.
[30] Bo S, Menato G, Bardelli C, Lezo A, Signorile A, Repetti E, et al. Low
socioeconomic status as a risk factor for gestational diabetes. Diabetes
Metab 2002;28:13940.
[31] Eskild A, Romundstad PR, Vatten LJ. Placental weight and birthweight: does the association differ between pregnancies with and without
preeclampsia? Am J Obstet Gynecol 2009;201:595e15.
[32] Houde AA, Hivert MF, Bouchard L. Fetal epigenetic programming of
adipokines. Adipocyte 2013;2:416.
[33] Quinlivan JA, Julania S, Lam L. Antenatal dietary interventions in
obese pregnant women to restrict gestational weight gain to Institute of
Medicine recommendations: a meta-analysis. Obstet Gynecol 2011;118:
1395401.
[34] Dodd JM, Grivell RM, Crowther CA, Robinson JS. Antenatal interventions for overweight or obese pregnant women: a systematic review of
randomised trials. BJOG 2010;117:131626.
[35] Ovesen P, Rasmussen S, Kesmodel U. Effect of prepregnancy maternal overweight and obesity on pregnancy outcome. Obstet Gynecol
2011;118:30512.
[36] Cresswell JA, Campbell OM, De Silva MJ, Filippi V. Effect of maternal
obesity on neonatal death in sub-Saharan Africa: multivariable analysis of
27 national datasets. Lancet 2012;380:132530.
[37] Owens LA, OSullivan EP, Kirwan B, Avalos G, Gaffney G, Dunne F.
ATLANTIC DIP: the impact of obesity on pregnancy outcome in glucosetolerant women. Diabetes Care 2010;33:5779.
[38] Dennedy MC, Avalos G, OReilly MW, OSullivan EP, Gaffney G, Dunne F.
ATLANTIC-DIP: raised maternal body mass index (BMI) adversely affects
maternal and fetal outcomes in glucose-tolerant women according to International Association of Diabetes and Pregnancy Study Groups (IADPSG)
criteria. J Clin Endocrinol Metab 2012;97:E60812.
[39] Feig DS, Hwee J, Shah BR, Booth GL, Bierman AS, Lipscombe LL. Trends
in incidence of diabetes in pregnancy and serious perinatal outcomes: a
large, population-based study in Ontario, Canada, 19962010. Diabetes
Care 2014;20:17683.
[40] Yee LM, Cheng YW, Inturrisi M, Caughey AB. Gestational weight loss
and perinatal outcomes in overweight and obese women subsequent
to diagnosis of gestational diabetes mellitus. Obesity (Silver Spring)
2013;21:E7704.
[41] Harrison CL, Lombard CB, Strauss BJ, Teede HJ. Optimizing healthy
gestational weight gain in women at high risk of gestational diabetes: a
randomized controlled trial. Obesity (Silver Spring) 2013;21:9049.

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DIABET-702; No. of Pages 9

Pregnancy adverse outcomes related to pregravid body mass index and

Gestational diabetes mellitus (GDM) is defined as any degree

to the French data protection authority (Commission nationale

Data are presented as means SD or as n (%); NS: not significant.

SPSS software (SPSS, Chicago, IL, USA). The 0.05 probability

3.1. Characteristics of the study population

Continuous variables were expressed as means SD, and

Maternal characteristics are shown in Table 1. In summary,

and previous pregnancy with macrosomia or GDM (Table 1).

On analyzing the contribution of overweight/obesity and

Our present findings confirm and extend previous reports

DIABET-702; No. of Pages 9

E. Cosson et al. / Diabetes & Metabolism xxx (2015) xxxxxx

Women without GDM

Women with GDM

Age (10 years)

Family history of diabetes (%)

Previous pregnancy with macrosomia (%)

Women without GDM

Women with GDM

Family history of diabetes (%)

deliver SGA infants. The increase in SGA infants associated

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