Journal of Obstetrics and Gynaecology, November 2014; 34: 662–665 © 2014 Informa UK, Ltd. ISSN 0144-3615 print/ISSN 1364-6893 online DOI: 10.3109/01443615.2014.920787
OBSTETRICS
Pregnancy outcome of overweight and obese Chinese women with gestational diabetes Y. Zhang, Z.-L. Wang, B. Liu & J. Cai
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Department of Obstetrics and Gynecology, The first Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
We investigated the pregnancy outcome of overweight and obese Chinese women with gestational diabetes mellitus (GDM). Patients diagnosed as GDM from January 2010 to December 2011 were categorised into three groups, as normal weight, overweight and obese, according to the maternal pre-pregnancy body mass index (BMI) (kg/m2), 18.5–24.9, 25–29.9 and ⱖ 30, respectively. Of the 604 GDM cases, 241 (39.9%), 211 (34.9%) and 152 (25.2%) subjects were normal weight, overweight and obese, respectively. Compared with subjects of normal weight, the incidence of assisted reproductive technology (ART) pregnancy, advanced maternal age, fetal macrosomia and emergency caesarean delivery were significantly higher in overweight and obese groups (p ⬍ 0.05). Obese women were at increased risk of premature rupture of membranes, pre-eclampsia and caesarean section compared with the other two groups (p ⬍ 0.05). Overweight and obese women with GDM have an increased risk of adverse pregnancy outcomes, even with good glycaemic control. Keywords: Gestational diabetes mellitus, obesity, overweight, pregnancy outcome
Introduction Gestational diabetes mellitus (GDM) is one of the most common metabolic complications during pregnancy, occurring in approximately 3–7% of pregnancies (Dabelea et al. 2005; Getahun et al. 2008; Yang et al. 2009). Several risk factors, such as maternal age, race/ethnicity, pre-pregnancy body mass index (BMI) and family history of diabetes have been identified for GDM (Berkowitz et al. 1992; Solomon et al. 1997; American Diabetes Association 2004; Ben-Haroush et al. 2004; Metzger et al. 2007). Consequently, it poses an increased risk for maternal and fetal complications, including emergency caesarean delivery, neonatal hypoglycaemia, fetal macrosomia and stillbirth (Langer et al. 2005). Considering the increasing incidence of GDM worldwide, as well as the reported ethnic differences with higher prevalence in south and central Asia (Berkowitz et al. 1992; Anna et al. 2008; Chu et al. 2009), there is an unmet need to identify and modify the risk factors complicating GDM in Chinese women. In this retrospective cohort study, the relationship between the pre-pregnancy BMI and perinatal outcome was evaluated.
Materials and methods From January 2010 to December 2011, all pregnant women who were diagnosed as GDM, received antenatal care, and were all primiparas with singleton pregnancy, attending The First Affiliated Hospital of Sun Yat-sen University in China, were eligible for this retrospective cohort study. Exclusion criteria were any pre-pregnancy chronic disease, including chronic hypertension and a history of diabetes. All GDM patients were managed for glycaemic control according to institutional practice and were monitored for blood glucose level according to institutional practice. All patients were checked for fasting blood glucose at first visit and the glucose level of all patients was ⬍ 5.8 mmol/l. The 75 g oral glucose tolerance test (OGTT) was performed at 28 weeks’ gestation to test for GDM. An initial blood sample was taken after 8–14 h of fasting and the patient was asked to drink 75 g glucose dissolved in 200–400 ml water, within 5 min. Blood samples were taken at fasting, 1 h and 2 h post-glucose load. The IADPSG criteria were used to diagnose GDM if any of the following levels were reported: a fasting plasma glucose level ⱖ 5.1 mmol/l; a 1-h level of ⱖ 10 mmol/l or a 2-h level of ⱖ 8.5 mmol/l (Metzger et al. 2010). Once diagnosed, all patients were given glycaemic control to maintain the fasting blood glucose level ⱕ 5.6 mmol/l, blood glucose level of 2 h after meal ⱕ 6.76 mmol/l and HbA1c ⬍ 6.0%. Once patients were diagnosed with GDM, they were given dietary consultation and intervention to achieve glycaemic control with blood glucose level ⱕ 5.6 mmol/l (fasting) and ⱕ 6.7 mmol/l (2 h after meal), as measured by the glucose oxidase method. The calculation of BMI (kg/m2) was based on the formula: BMI ⫽ body weight (kg)/[body height (m) ⫻ body height (m)]. The pre-pregnancy body weight and height were reported by subjects at the first visit attending the hospital and were measured again before delivery. Patients were categorised into three groups: normal weight, overweight and obese, according to the maternal pre-pregnancy BMI (kg/m2), 18.5–24.9, 25–29.9 and ⱖ 30, respectively. All patients were followed-up for the pregnancy outcomes. The statistical analysis was performed using SPSS 13.0 (SPSS Inc., Chicago, IL). The Student’s t-test was used to compare the mean. The χ2-test was used to compare categorical variables. All statistical tests were two-sided and a p value of ⬍ 0.05 was considered statistically significant.
Correspondence: Y. Zhang, Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, 58# Zhongshan Road 2, Guangzhou 510080, China. E-mail: [email protected]
Pregnancy outcome of overweight and obese Chinese women with gestational diabetes
663
Table I. Demographic characteristics of pregnant women with GDM (mean ⫾ SD). Characteristics
Normal weight group (n ⫽ 241)
Overweight group (n ⫽ 211)
Obese group (n ⫽ 152)
29.8 ⫾ 2.7 3.0 ⫾ 0.1 1.2 ⫾ 0.5 22.3 ⫾ 2.1 11.6 ⫾ 5.6 39.4 ⫾ 1.4 26.4 ⫾ 1.8
31.7 ⫾ 3.1 2.3 ⫾ 0.2 1.0 ⫾ 0.7 27.1 ⫾ 1.9 10.0 ⫾ 6.2 39.1 ⫾ 2.3 24.9 ⫾ 2.0
32.3 ⫾ 2.4 2.0 ⫾ 0.4 1.1 ⫾ 0.4 31.8 ⫾ 3.4 8.8 ⫾ 6.0 38 ⫾ 1.7 23.4 ⫾ 1.7
Age (years) Number of pregnancies Number of previous delivery Average prenatal BMI (kg/m2) Weight gain during pregnancy (kg) Gestational age (weeks) Gestational weeks for OGTT
BMI, body mass index; GDM, gestational diabetes mellitus; OGTT, oral glucose tolerance test.
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Results Characteristics of the study population are shown in Table I. A total of 604 eligible GDM cases included 241 (39.9%), 211 (34.9%) and 152 (25.2%) subjects, who were normal weight, overweight and obese, respectively. Compared with the normal weight group, a significantly higher percentage of pregnant women were at advanced maternal age, here defined as ⱖ 35 years, in the overweight group (14.1% vs 28.0%, p ⫽ 0.0001) and in the obese group (14.1% vs 32.2%, p ⬍ 0.0001). Significantly more cases requiring assisted reproductive technology (ART) for conception were observed in the overweight group (10.4% vs 5.8%, p ⫽ 0.0275) and the obese group (19.1% vs 5.8%, p ⬍ 0.0001) when compared with that in the normal weight group (Table II). An increased risk of complications during pregnancy was observed in the overweight and obese groups when compared with the normal weight group (Table III). The odds ratio (OR) of pre-eclampsia was about 3.00 (95% CI ⫽ 1.42–6.31) and 2.15 (95% CI ⫽ 1.06–4.38) in the obese group when compared with the normal weight and overweight groups, respectively. A significantly increased risk of premature rupture of membranes (PROM) was observed with ORs of 1.4 (95% CI ⫽ 1.05–1.86) and 1.63(95% ⫽ CI 1.20–2.22) in the obese group when compared with the normal weight and overweight groups, respectively. The increased risk of preterm premature rupture of membranes (PPROM) was observed with ORs of 2.86 (95% CI ⫽ 1.02–8.00) in the obese group and 1.86 (95% CI ⫽ 0.60–5.78) in the overweight group respectively compared with the normal weight group. However, no difference in risk of preterm birth was observed between the groups. The pregnancy outcomes were different between the groups (Table IV). The rate of vaginal delivery in the normal weight group was significantly higher than that in the obese group (46.5% vs 32.9%, χ2 ⫽ 18.696, p ⫽ 0.005). Compared with the normal weight group, the overweight group and obese group were at significantly increased risk of emergency caesarean delivery, with ORs of 1.56 (95% CI ⫽ 1.08–2.25 and 1.67 (95% CI ⫽ 1.23–2.27), respectively. The difference in primary caesarean delivery rate was not observed between the overweight and normal weight groups. But
the obese group was at significantly increased risk of caesarean delivery with ORs of 1.28 (95% CI ⫽ 1.05–1.56) and 1.36 (95% CI ⫽ 1.11–1.66) when compared with the overweight and normal groups, respectively. No significant difference was observed in the rate of forceps delivery. At delivery, an increased risk for the large-for-gestational age term neonates was observed in the obese group with ORs of 2.04 (95% CI 1.03–4.03) and 2.5 (95% CI 1.22–5.12) when compared with the normal and overweight groups, respectively, but no significant difference was observed between the normal weight and overweight groups. The risk of fetal macrosomia was significantly increased in both the overweight and obese groups, with ORs of 2.63 (95% CI 1.26–5.46) and 5.09 (95% CI 2.11–12.26), respectively, when compared with the control group (Table V). There were no significant differences between the groups regarding neonatal complications, including hypoglycaemia, jaundice and respiratory distress syndrome (not presented here). Also, no stillbirth was observed in this study.
Discussion There is increasing evidence to show that obesity is becoming an important public health issue in fast-developing countries, such as China. According to the data from the Pregnancy Risk Assessment Monitoring System, the incidence of pre-pregnancy obesity increased 69.3% between 1993 and 2003 (Kim et al. 2007). Pre-pregnancy obesity is one of the major risk factors for GDM, which subsequently results in adverse pregnancy and neonatal outcomes. In different countries and regions, GDM patients with different BMIs seem to experience different pregnancy outcomes. Nevertheless, there are not many reports demonstrating the relationship between BMI and the pregnancy outcomes of this group of patients in China. In this study, significantly more overweight or obese pregnant women with GDM were older at time of pregnancy and required ART. According to Wang’s study of 3,586 women receiving ART, Table III. Different pregnancy outcomes between the three groups.
Table II. Different pre-pregnancy conditions between three groups. Normal weight group (n ⫽ 241)
Overweight group (n ⫽ 211)
Overweight group (n ⫽ 211)
Normal weight group (n ⫽ 241)
Obese group (n ⫽ 152)
Incidence
n
(%)
n
(%)
n
(%)
Advanced maternal age ART pregnancy
34 14
14.1∗ 5.8∗
59 22
28.0 10.4
49 29
32.2 19.1
ART, assisted reproductive technology. ∗Statistically significant compared with the overweight and obese groups (p ⬍ 0.05).
Incidence Pre-eclampsia PROM PPROM Preterm birth
Obese group (n ⫽ 152)
n
(%)
n
(%)
n
(%)
9 68 5 14
3.7 28.2 2.1 5.8
11 51 8 13
5.2 24.2 3.8 6.2
17 60 9 12
11.2∗ 39.5∗ 5.9† 7.9
PROM, premature rupture of membranes; PPROM, preterm premature rupture of membranes. ∗Statistically significant compared with the normal and overweight groups (p ⬍ 0.05). †Statistically significant compared with the normal weight group (p ⬍ 0.05).
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Table IV. Different ways of delivery between the three groups.
Incidence VD PCD ECD FD
Normal weight group (n ⫽ 241)
Overweight group (n ⫽ 211)
Obese group (n ⫽ 152)
n
(%)
n
(%)
n
(%)
112 102 38 27
46.5 42.3 15.8‡ 11.2
85 95 52 31
40.3 45.0 24.7 14.7
50 88 45 14
32.9∗ 57.9† 26.3 9.2
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VD, vaginal delivery; PCD, primary caesarean delivery; ECD, emergency caesarean delivery; FD, forceps delivery. ∗Statistically significant compared with the normal weight group (p ⬍ 0.01). †Statistically significant compared with the overweight and normal weight groups (p ⬍ 0.05). ‡Statistically significant compared with the overweight and obese groups (p ⬍ 0.01).
BMI was significantly associated with reduced fecundity in a linear reduction in fecundity for individuals from moderate (20.0 mg/m2–24.9 mg/m2) to very obese (ⱖ 35 mg/m2) groups (p ⬍ 0.0001) (Wang et al. 2000). It seems pre-pregnancy obesity is not only a risk factor for GDM, but also an independent risk factor for sub fertility. The relationship between pre-pregnancy BMI and the complications of pregnancy remains to be explored in GDM patients. Nevertheless, obesity is a risk factor of adverse pregnancy outcome. Bhattacharya et al. (2007) found that the risk of pre-eclampsia was three-fold (OR: 3.1, 95% CI 2.8–3.5) greater in pregnant women with pre-pregnancy obesity than those with normal body weight. Considering that diabetes mellitus is a significant risk factor of hypertension during pregnancy (Reece et al. 1998), the maternal complication in obese women with GDM is of concern. In our study, the incidence of pre-eclampsia in obese GDM women was three-fold and two-fold higher than normal weight and overweight GDM women, respectively. The relationship between pre-pregnancy body weight and PPROM was not clear, with inconsistent results from different studies (Rudra et al. 2008; Chen et al. 2010; Zhong et al. 2010). The risk of PPROM in the obese group was 1.4-fold and 1.6-fold greater than that in the normal weight and overweight groups, respectively, in our study. The risk of PPROM was 2.9-fold higher in the obese group than that in the normal weight group. The mechanism of this adverse impact is unclear, but it may be possible that women with different body fat content may have different hormonal levels in the body, which subsequently affect uterine contractility. On the other hand, disequilibrium in vaginal microflora happens more frequently in obese pregnant women and in turn, reduces the strength of the fetal membrane, which ruptures more easily. As a result, pre-pregnancy body weight control is important, especially for those with GDM in order to reduce the incidence of pregnancy complications. Intrapartum outcome is also a concern for obese pregnant women. Delivery in obese women is more likely to be complicated by fetal distress, cephalopelvic disproportion and hyperTable V. Different neonatal weights between the three groups. Normal weight group (n ⫽ 241)
Overweight group (n ⫽ 211)
Obese group (n ⫽ 152)
Incidence
n
(%)
n
(%)
n
(%)
LGA term neonates Fetal macrosomia
14 5
5.8 2.1∗
10 15
4.7 7.1
18 16
11.8† 10.5
LGA, large-for-gestational age. ∗Statistically significant compared with the overweight and obese groups (p ⬍ 0.01). †Statistically significant compared with the overweight and normal weight groups (p ⬍ 0.05).
tonic uterine inertia during pregnancy. The risk of uterine atony might further increase the chance for caesarean section. According to a retrospective cohort study of 5,162 pregnant women by Lynch et al. (2008), the rate of vaginal delivery was progressively reduced with increasing BMI, with significant reductions by 33.5% and 23.6% observed for morbidly obese primigravida and multigravida, respectively. In our study, vaginal delivery rate in the normal weight group was higher than that in the obese group, with statistical significance. The caesarean delivery rate was 1.28-fold and 1.36-fold higher in the obese group than the overweight and normal weight group, respectively; the emergency caesarean delivery rate was 1.56-fold and 1.67-fold higher in the obese group and overweight group when compared with the normal weight group, respectively. The increased incidence of caesarean delivery for GDM pregnant women, which at the same time would increase the risk for abnormal fetal heart rate and other labour abnormalities, was very likely attributed to the obesity-associated pregnancy complications. Large-for-gestational-age (LGA) newborns and fetal macrosomia are serious obstetric complications of GDM (SchaeferGraf et al. 2002; Leipold et al. 2005; Olmos et al. 2012). In our study of women with GDM, the risk of LGA newborns was 2.04fold and 2.5-fold greater in the obese group than the normal weight and overweight groups, respectively. The risk of fetal macrosomia in the obese and overweight groups was 5.09-fold and 2.63-fold greater than that in the normal weight group, respectively. GDM could lead to fetal overgrowth, which in turn results in LGA newborns and macrosomia. It is reported that GDM might be transmittable to the next generation, even with good glycaemic control in the diabetic mother (McLean et al. 2006). Obese women with GDM more likely than normal weight pregnant women with insulin resistance, to have fetal hyperinsulinaemia, which subsequently influences fetal lipid metabolism. The increased chance of fetal growth disorders would increase the likelihood of LGA newborns and fetal macrosomia. As reported in other studies we found that, obesity is still a risk factor for adverse outcomes of pregnancy in patients with good glycaemic control (Joy et al. 2012). To our knowledge, there is increased risk of infertility and other pregnancy outcomes in obese women of childbearing age. Unfortunately, there is increasing evidence to support the intergenerational transmission of obesity. In recent years, the incidence of GDM in China has increased significantly and the pre-pregnancy BMI of GDM pregnant women is strongly associated with adverse pregnancy outcomes. Therefore, it is possible to reduce the maternal risk by controlling the body weight. Clinicians should provide more comprehensive prenatal counselling and offer adequate health education for obese women of childbearing age, in order to reduce the risk of complications during pregnancy. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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Metzger BE, Buchanan TA, Coustan DR, de Leiva A, Dunger DB, Hadden DR et al. 2007. Summary and recommendations of the Fifth International Workshop-Conference on Gestational Diabetes Mellitus. Diabetes Care 30: s251–s260. Metzger BE, Gabbe SG, Persson B, Buchanan TA, Catalano PA; International Association of Diabetes and Pregnancy Study Groups Consensus Panel. 2010. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 33:676–682. Olmos PR, Borzone GR, Olmos RI, Valencia CN, Bravo FA, Hodgson MI et al. 2012. Gestational diabetes and pre-pregnancy overweight: possible factors involved in newborn macrosomia. Journal of Obstetrics and Gynaecology Research 38:208–214. Reece EA, Sivan E, Francis G, Homko CJ. 1998. Pregnancy outcomes among women with and without diabetic microvascular disease (White’s classes B to FR) versus non-diabetic controls. American Journal of Perinatology 15:549–555. Rudra CB, Frederick IO, Williams MA. 2008. Pre-pregnancy body mass index and weight gain during pregnancy in relation to preterm delivery subtypes. Acta Obstetricia et Gynecologica Scandinavica 87:510–517. Schaefer-Graf UM, Heuer R, Kilavuz O, Pandura A, Henrich W, Vetter K. 2002. Maternal obesity not maternal glucose values correlates best with high rates of fetal macrosomia in pregnancies complicated by gestational diabetes. Journal of Perinatal Medicine 30:313–321. Solomon CG, Willett WC, Carey VJ, Rich-Edwards J, Hunter DJ, Colditz GA et al. 1997. A prospective study of pregravid determinants of gestational diabetes mellitus. Journal of the American Medical Association 278:1078–1083. Wang JX, Davies M, Norman RJ. 2000. Body mass and probability of pregnancy during assisted reproduction treatment: retrospective study. British Medical Journal 321:1320–1321. Yang H, Wei Y, Gao X, Xu X, Fan L, He J et al. 2009. Risk factors for gestational diabetes mellitus in Chinese women: a prospective study of 16,286 pregnant women in China. Diabetic Medicine 26: 1099–1104. Zhong Y, Cahill AG, Macones GA, Zhu F, Odibo AO. 2010. The association between prepregnancy maternal body mass index and preterm delivery. American Journal of Perinatology 27:293–298.
OBSTETRICS
Pregnancy outcome of overweight and obese Chinese women with gestational diabetes Y. Zhang, Z.-L. Wang, B. Liu & J. Cai
J Obstet Gynaecol Downloaded from informahealthcare.com by Universite De Sherbrooke on 11/19/14 For personal use only.
Department of Obstetrics and Gynecology, The first Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
We investigated the pregnancy outcome of overweight and obese Chinese women with gestational diabetes mellitus (GDM). Patients diagnosed as GDM from January 2010 to December 2011 were categorised into three groups, as normal weight, overweight and obese, according to the maternal pre-pregnancy body mass index (BMI) (kg/m2), 18.5–24.9, 25–29.9 and ⱖ 30, respectively. Of the 604 GDM cases, 241 (39.9%), 211 (34.9%) and 152 (25.2%) subjects were normal weight, overweight and obese, respectively. Compared with subjects of normal weight, the incidence of assisted reproductive technology (ART) pregnancy, advanced maternal age, fetal macrosomia and emergency caesarean delivery were significantly higher in overweight and obese groups (p ⬍ 0.05). Obese women were at increased risk of premature rupture of membranes, pre-eclampsia and caesarean section compared with the other two groups (p ⬍ 0.05). Overweight and obese women with GDM have an increased risk of adverse pregnancy outcomes, even with good glycaemic control. Keywords: Gestational diabetes mellitus, obesity, overweight, pregnancy outcome
Introduction Gestational diabetes mellitus (GDM) is one of the most common metabolic complications during pregnancy, occurring in approximately 3–7% of pregnancies (Dabelea et al. 2005; Getahun et al. 2008; Yang et al. 2009). Several risk factors, such as maternal age, race/ethnicity, pre-pregnancy body mass index (BMI) and family history of diabetes have been identified for GDM (Berkowitz et al. 1992; Solomon et al. 1997; American Diabetes Association 2004; Ben-Haroush et al. 2004; Metzger et al. 2007). Consequently, it poses an increased risk for maternal and fetal complications, including emergency caesarean delivery, neonatal hypoglycaemia, fetal macrosomia and stillbirth (Langer et al. 2005). Considering the increasing incidence of GDM worldwide, as well as the reported ethnic differences with higher prevalence in south and central Asia (Berkowitz et al. 1992; Anna et al. 2008; Chu et al. 2009), there is an unmet need to identify and modify the risk factors complicating GDM in Chinese women. In this retrospective cohort study, the relationship between the pre-pregnancy BMI and perinatal outcome was evaluated.
Materials and methods From January 2010 to December 2011, all pregnant women who were diagnosed as GDM, received antenatal care, and were all primiparas with singleton pregnancy, attending The First Affiliated Hospital of Sun Yat-sen University in China, were eligible for this retrospective cohort study. Exclusion criteria were any pre-pregnancy chronic disease, including chronic hypertension and a history of diabetes. All GDM patients were managed for glycaemic control according to institutional practice and were monitored for blood glucose level according to institutional practice. All patients were checked for fasting blood glucose at first visit and the glucose level of all patients was ⬍ 5.8 mmol/l. The 75 g oral glucose tolerance test (OGTT) was performed at 28 weeks’ gestation to test for GDM. An initial blood sample was taken after 8–14 h of fasting and the patient was asked to drink 75 g glucose dissolved in 200–400 ml water, within 5 min. Blood samples were taken at fasting, 1 h and 2 h post-glucose load. The IADPSG criteria were used to diagnose GDM if any of the following levels were reported: a fasting plasma glucose level ⱖ 5.1 mmol/l; a 1-h level of ⱖ 10 mmol/l or a 2-h level of ⱖ 8.5 mmol/l (Metzger et al. 2010). Once diagnosed, all patients were given glycaemic control to maintain the fasting blood glucose level ⱕ 5.6 mmol/l, blood glucose level of 2 h after meal ⱕ 6.76 mmol/l and HbA1c ⬍ 6.0%. Once patients were diagnosed with GDM, they were given dietary consultation and intervention to achieve glycaemic control with blood glucose level ⱕ 5.6 mmol/l (fasting) and ⱕ 6.7 mmol/l (2 h after meal), as measured by the glucose oxidase method. The calculation of BMI (kg/m2) was based on the formula: BMI ⫽ body weight (kg)/[body height (m) ⫻ body height (m)]. The pre-pregnancy body weight and height were reported by subjects at the first visit attending the hospital and were measured again before delivery. Patients were categorised into three groups: normal weight, overweight and obese, according to the maternal pre-pregnancy BMI (kg/m2), 18.5–24.9, 25–29.9 and ⱖ 30, respectively. All patients were followed-up for the pregnancy outcomes. The statistical analysis was performed using SPSS 13.0 (SPSS Inc., Chicago, IL). The Student’s t-test was used to compare the mean. The χ2-test was used to compare categorical variables. All statistical tests were two-sided and a p value of ⬍ 0.05 was considered statistically significant.
Correspondence: Y. Zhang, Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, 58# Zhongshan Road 2, Guangzhou 510080, China. E-mail: [email protected]
Pregnancy outcome of overweight and obese Chinese women with gestational diabetes
663
Table I. Demographic characteristics of pregnant women with GDM (mean ⫾ SD). Characteristics
Normal weight group (n ⫽ 241)
Overweight group (n ⫽ 211)
Obese group (n ⫽ 152)
29.8 ⫾ 2.7 3.0 ⫾ 0.1 1.2 ⫾ 0.5 22.3 ⫾ 2.1 11.6 ⫾ 5.6 39.4 ⫾ 1.4 26.4 ⫾ 1.8
31.7 ⫾ 3.1 2.3 ⫾ 0.2 1.0 ⫾ 0.7 27.1 ⫾ 1.9 10.0 ⫾ 6.2 39.1 ⫾ 2.3 24.9 ⫾ 2.0
32.3 ⫾ 2.4 2.0 ⫾ 0.4 1.1 ⫾ 0.4 31.8 ⫾ 3.4 8.8 ⫾ 6.0 38 ⫾ 1.7 23.4 ⫾ 1.7
Age (years) Number of pregnancies Number of previous delivery Average prenatal BMI (kg/m2) Weight gain during pregnancy (kg) Gestational age (weeks) Gestational weeks for OGTT
BMI, body mass index; GDM, gestational diabetes mellitus; OGTT, oral glucose tolerance test.
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Results Characteristics of the study population are shown in Table I. A total of 604 eligible GDM cases included 241 (39.9%), 211 (34.9%) and 152 (25.2%) subjects, who were normal weight, overweight and obese, respectively. Compared with the normal weight group, a significantly higher percentage of pregnant women were at advanced maternal age, here defined as ⱖ 35 years, in the overweight group (14.1% vs 28.0%, p ⫽ 0.0001) and in the obese group (14.1% vs 32.2%, p ⬍ 0.0001). Significantly more cases requiring assisted reproductive technology (ART) for conception were observed in the overweight group (10.4% vs 5.8%, p ⫽ 0.0275) and the obese group (19.1% vs 5.8%, p ⬍ 0.0001) when compared with that in the normal weight group (Table II). An increased risk of complications during pregnancy was observed in the overweight and obese groups when compared with the normal weight group (Table III). The odds ratio (OR) of pre-eclampsia was about 3.00 (95% CI ⫽ 1.42–6.31) and 2.15 (95% CI ⫽ 1.06–4.38) in the obese group when compared with the normal weight and overweight groups, respectively. A significantly increased risk of premature rupture of membranes (PROM) was observed with ORs of 1.4 (95% CI ⫽ 1.05–1.86) and 1.63(95% ⫽ CI 1.20–2.22) in the obese group when compared with the normal weight and overweight groups, respectively. The increased risk of preterm premature rupture of membranes (PPROM) was observed with ORs of 2.86 (95% CI ⫽ 1.02–8.00) in the obese group and 1.86 (95% CI ⫽ 0.60–5.78) in the overweight group respectively compared with the normal weight group. However, no difference in risk of preterm birth was observed between the groups. The pregnancy outcomes were different between the groups (Table IV). The rate of vaginal delivery in the normal weight group was significantly higher than that in the obese group (46.5% vs 32.9%, χ2 ⫽ 18.696, p ⫽ 0.005). Compared with the normal weight group, the overweight group and obese group were at significantly increased risk of emergency caesarean delivery, with ORs of 1.56 (95% CI ⫽ 1.08–2.25 and 1.67 (95% CI ⫽ 1.23–2.27), respectively. The difference in primary caesarean delivery rate was not observed between the overweight and normal weight groups. But
the obese group was at significantly increased risk of caesarean delivery with ORs of 1.28 (95% CI ⫽ 1.05–1.56) and 1.36 (95% CI ⫽ 1.11–1.66) when compared with the overweight and normal groups, respectively. No significant difference was observed in the rate of forceps delivery. At delivery, an increased risk for the large-for-gestational age term neonates was observed in the obese group with ORs of 2.04 (95% CI 1.03–4.03) and 2.5 (95% CI 1.22–5.12) when compared with the normal and overweight groups, respectively, but no significant difference was observed between the normal weight and overweight groups. The risk of fetal macrosomia was significantly increased in both the overweight and obese groups, with ORs of 2.63 (95% CI 1.26–5.46) and 5.09 (95% CI 2.11–12.26), respectively, when compared with the control group (Table V). There were no significant differences between the groups regarding neonatal complications, including hypoglycaemia, jaundice and respiratory distress syndrome (not presented here). Also, no stillbirth was observed in this study.
Discussion There is increasing evidence to show that obesity is becoming an important public health issue in fast-developing countries, such as China. According to the data from the Pregnancy Risk Assessment Monitoring System, the incidence of pre-pregnancy obesity increased 69.3% between 1993 and 2003 (Kim et al. 2007). Pre-pregnancy obesity is one of the major risk factors for GDM, which subsequently results in adverse pregnancy and neonatal outcomes. In different countries and regions, GDM patients with different BMIs seem to experience different pregnancy outcomes. Nevertheless, there are not many reports demonstrating the relationship between BMI and the pregnancy outcomes of this group of patients in China. In this study, significantly more overweight or obese pregnant women with GDM were older at time of pregnancy and required ART. According to Wang’s study of 3,586 women receiving ART, Table III. Different pregnancy outcomes between the three groups.
Table II. Different pre-pregnancy conditions between three groups. Normal weight group (n ⫽ 241)
Overweight group (n ⫽ 211)
Overweight group (n ⫽ 211)
Normal weight group (n ⫽ 241)
Obese group (n ⫽ 152)
Incidence
n
(%)
n
(%)
n
(%)
Advanced maternal age ART pregnancy
34 14
14.1∗ 5.8∗
59 22
28.0 10.4
49 29
32.2 19.1
ART, assisted reproductive technology. ∗Statistically significant compared with the overweight and obese groups (p ⬍ 0.05).
Incidence Pre-eclampsia PROM PPROM Preterm birth
Obese group (n ⫽ 152)
n
(%)
n
(%)
n
(%)
9 68 5 14
3.7 28.2 2.1 5.8
11 51 8 13
5.2 24.2 3.8 6.2
17 60 9 12
11.2∗ 39.5∗ 5.9† 7.9
PROM, premature rupture of membranes; PPROM, preterm premature rupture of membranes. ∗Statistically significant compared with the normal and overweight groups (p ⬍ 0.05). †Statistically significant compared with the normal weight group (p ⬍ 0.05).
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Table IV. Different ways of delivery between the three groups.
Incidence VD PCD ECD FD
Normal weight group (n ⫽ 241)
Overweight group (n ⫽ 211)
Obese group (n ⫽ 152)
n
(%)
n
(%)
n
(%)
112 102 38 27
46.5 42.3 15.8‡ 11.2
85 95 52 31
40.3 45.0 24.7 14.7
50 88 45 14
32.9∗ 57.9† 26.3 9.2
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VD, vaginal delivery; PCD, primary caesarean delivery; ECD, emergency caesarean delivery; FD, forceps delivery. ∗Statistically significant compared with the normal weight group (p ⬍ 0.01). †Statistically significant compared with the overweight and normal weight groups (p ⬍ 0.05). ‡Statistically significant compared with the overweight and obese groups (p ⬍ 0.01).
BMI was significantly associated with reduced fecundity in a linear reduction in fecundity for individuals from moderate (20.0 mg/m2–24.9 mg/m2) to very obese (ⱖ 35 mg/m2) groups (p ⬍ 0.0001) (Wang et al. 2000). It seems pre-pregnancy obesity is not only a risk factor for GDM, but also an independent risk factor for sub fertility. The relationship between pre-pregnancy BMI and the complications of pregnancy remains to be explored in GDM patients. Nevertheless, obesity is a risk factor of adverse pregnancy outcome. Bhattacharya et al. (2007) found that the risk of pre-eclampsia was three-fold (OR: 3.1, 95% CI 2.8–3.5) greater in pregnant women with pre-pregnancy obesity than those with normal body weight. Considering that diabetes mellitus is a significant risk factor of hypertension during pregnancy (Reece et al. 1998), the maternal complication in obese women with GDM is of concern. In our study, the incidence of pre-eclampsia in obese GDM women was three-fold and two-fold higher than normal weight and overweight GDM women, respectively. The relationship between pre-pregnancy body weight and PPROM was not clear, with inconsistent results from different studies (Rudra et al. 2008; Chen et al. 2010; Zhong et al. 2010). The risk of PPROM in the obese group was 1.4-fold and 1.6-fold greater than that in the normal weight and overweight groups, respectively, in our study. The risk of PPROM was 2.9-fold higher in the obese group than that in the normal weight group. The mechanism of this adverse impact is unclear, but it may be possible that women with different body fat content may have different hormonal levels in the body, which subsequently affect uterine contractility. On the other hand, disequilibrium in vaginal microflora happens more frequently in obese pregnant women and in turn, reduces the strength of the fetal membrane, which ruptures more easily. As a result, pre-pregnancy body weight control is important, especially for those with GDM in order to reduce the incidence of pregnancy complications. Intrapartum outcome is also a concern for obese pregnant women. Delivery in obese women is more likely to be complicated by fetal distress, cephalopelvic disproportion and hyperTable V. Different neonatal weights between the three groups. Normal weight group (n ⫽ 241)
Overweight group (n ⫽ 211)
Obese group (n ⫽ 152)
Incidence
n
(%)
n
(%)
n
(%)
LGA term neonates Fetal macrosomia
14 5
5.8 2.1∗
10 15
4.7 7.1
18 16
11.8† 10.5
LGA, large-for-gestational age. ∗Statistically significant compared with the overweight and obese groups (p ⬍ 0.01). †Statistically significant compared with the overweight and normal weight groups (p ⬍ 0.05).
tonic uterine inertia during pregnancy. The risk of uterine atony might further increase the chance for caesarean section. According to a retrospective cohort study of 5,162 pregnant women by Lynch et al. (2008), the rate of vaginal delivery was progressively reduced with increasing BMI, with significant reductions by 33.5% and 23.6% observed for morbidly obese primigravida and multigravida, respectively. In our study, vaginal delivery rate in the normal weight group was higher than that in the obese group, with statistical significance. The caesarean delivery rate was 1.28-fold and 1.36-fold higher in the obese group than the overweight and normal weight group, respectively; the emergency caesarean delivery rate was 1.56-fold and 1.67-fold higher in the obese group and overweight group when compared with the normal weight group, respectively. The increased incidence of caesarean delivery for GDM pregnant women, which at the same time would increase the risk for abnormal fetal heart rate and other labour abnormalities, was very likely attributed to the obesity-associated pregnancy complications. Large-for-gestational-age (LGA) newborns and fetal macrosomia are serious obstetric complications of GDM (SchaeferGraf et al. 2002; Leipold et al. 2005; Olmos et al. 2012). In our study of women with GDM, the risk of LGA newborns was 2.04fold and 2.5-fold greater in the obese group than the normal weight and overweight groups, respectively. The risk of fetal macrosomia in the obese and overweight groups was 5.09-fold and 2.63-fold greater than that in the normal weight group, respectively. GDM could lead to fetal overgrowth, which in turn results in LGA newborns and macrosomia. It is reported that GDM might be transmittable to the next generation, even with good glycaemic control in the diabetic mother (McLean et al. 2006). Obese women with GDM more likely than normal weight pregnant women with insulin resistance, to have fetal hyperinsulinaemia, which subsequently influences fetal lipid metabolism. The increased chance of fetal growth disorders would increase the likelihood of LGA newborns and fetal macrosomia. As reported in other studies we found that, obesity is still a risk factor for adverse outcomes of pregnancy in patients with good glycaemic control (Joy et al. 2012). To our knowledge, there is increased risk of infertility and other pregnancy outcomes in obese women of childbearing age. Unfortunately, there is increasing evidence to support the intergenerational transmission of obesity. In recent years, the incidence of GDM in China has increased significantly and the pre-pregnancy BMI of GDM pregnant women is strongly associated with adverse pregnancy outcomes. Therefore, it is possible to reduce the maternal risk by controlling the body weight. Clinicians should provide more comprehensive prenatal counselling and offer adequate health education for obese women of childbearing age, in order to reduce the risk of complications during pregnancy. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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