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Associations between body mass index and maternal weight gain on the delivery of LGA infants in Chinese women with gestational diabetes mellitus
Journal of Diabetes and Its Complications xxx (2015) xxx–xxx
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Original Article
Associations between body mass index and maternal weight gain on the delivery of LGA infants in Chinese women with gestational diabetes mellitus Qi Chen a, b, J. Wei b, M. Tong b, L. Yu c, A.C. Lee d, Y.F. Gao a, M. Zhao e,⁎ a
The Hospital of Obstetrics & Gynaecology, Fudan University, Shanghai, China Department of Obstetrics & Gynaecology, The University of Auckland, Auckland, New Zealand Department of Anatomy with Radiology, The University of Auckland, Auckland, New Zealand d Section of Epidemiology and Biostatistics, School of Population Health, The University of Auckland, New Zealand e Wuxi Maternity and Child Health Hospital, Nanjing Medical University, Wuxi, China b c
a r t i c l e
i n f o
Article history: Received 17 March 2015 Received in revised form 31 July 2015 Accepted 20 August 2015 Available online xxxx Keywords: Gestational diabetes mellitus Body mass index Large for gestational age Maternal obesity Excessive weight gain
a b s t r a c t Background: Women with gestational diabetes mellitus (GDM) are at increased risk for maternal and fetal complications including delivery of large for gestational age (LGA) infants. Maternal body mass index (BMI) and excessive weight gain during pregnancy are associated with delivery of LGA infants. However, whether maternal BMI and weight gain are associated with LGA infants in women with GDM is unclear. Basic procedures: Data on 1049 pregnant women who developed GDM were collected from a university teaching hospital in China and retrospectively analyzed. Data included maternal BMI, weight gain, incidence of LGA and gestational week at diagnosis. Main findings: The incidence of LGA infants was significantly associated with maternal BMI (p = 0.0002) in women with GDM. The odds of delivery of LGA for obese or overweight pregnant women are 3.8 or 2 times more than normal weight pregnant women. The incidence of LGA infants was also significantly associated with maternal weight gain in women with GDM. The odds ratio of delivery of LGA for pregnant women with excessive weight gain was 3.3 times more than pregnant women with normal weight gain. The effect of weight gain was not significantly different between different maternal BMI. Principal conclusion: The incidence of delivery of LGA infants in Chinese women with GDM who were overweight or obese is higher than Caucasians, Hispanic, and Asian-Americans. The effects of maternal BMI and weight gain on the delivery of LGA infants by women with GDM are additive. © 2015 Elsevier Inc. All rights reserved.
1. Introduction Gestational diabetes mellitus (GDM) is a condition of glucose intolerance during pregnancy (American Diabetes A, 2011), which affects 2%–18% of healthy pregnancies depending on ethnicity and geographic area (Hunt & Schuller, 2007). Women with GDM are at increased risk of maternal and fetal complications including preeclampsia, preterm birth, caesarean section and delivery of large for gestational age (LGA) infants (Casey, Lucas, McIntire, & Leveno, 1997; Yang, Cummings, O'Connell, & Jangaard, 2006). In addition, women with unmanaged GDM are at risk of developing type 2 diabetes mellitus later in life (Bellamy, Casas, Hingorani, & Williams, 2009; Knight, Pressman, Hackney, & Thornburg, 2012).
Conflicts of Interest statement: None of the authors have a conflict of interest. ⁎ Corresponding author at: 48 Huaishu Street, Wuxi, China, Wuxi Maternity and Children Hospital, Nanjing Medical University, China. Tel.: +86 13611691734. E-mail address: [email protected] (M. Zhao).
The precise mechanisms underlying gestational diabetes remain unknown, but risk factors for developing GDM include maternal age, maternal obesity before pregnancy, pre-gestational diabetes mellitus and a family history of type 2 diabetes. In addition, a recent metaanalysis also found an association between excessive weight gain during pregnancy, in particular during the first trimester, and the risk of developing GDM (Ruifrok et al., 2014). The amount of weight gain during pregnancy can affect the immediate and future health of pregnant women and their infants. Being an LGA infant is a risk factor for developing diabetes, obesity and cancer later in life (Walsh & McAuliffe, 2012). Delivery of LGA infants increases the risk of delivery complications including prolonged labor, shoulder dystocia and cesarean section (Walsh & McAuliffe, 2012). Preterm birth is a major cause of perinatal mortality and long-term morbidity (McCormick, 1985). Studies clearly showed that maternal obesity, maternal excessive weight gain and GDM are associated with the increased risk of pregnancy complications, including delivery of LGA infants and preterm birth (Ferraro et al., 2012; Hinkle et al., 2012; Ornoy, 2011). However, the incidence of
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Please cite this article as: Chen, Q., et al., Associations between body mass index and maternal weight gain on the delivery of LGA infants in Chinese women with gestational dia..., Journal of Diabetes and Its Complications (2015), http://dx.doi.org/10.1016/j.jdiacomp.2015.08.017
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Q. Chen et al. / Journal of Diabetes and Its Complications xxx (2015) xxx–xxx
these independent risk factors varies depending on the ethnicity of the population and geographical region (Health N.C.C.f.W.s.a.C.s, 2008). In addition, it is unclear whether overweight women or obese women with GDM are at increased risk of having an LGA infant or preterm delivery in comparison to normal or underweight women with GDM. Whether there is an additive effect on delivery of LGA infants in women with GDM who are obese and also have excessive weight gain is not clear. Our previous study and other studies reported lower maternal body mass index (BMI) in Asian and Chinese populations (Fisher, Kim, Sharma, Rochat, & Morrow, 2013; Xiao et al., 2014). Therefore in this study, we investigated the association between maternal body mass index (BMI) and gestational weight gain on the delivery of LGA infants in Chinese women with GDM. 2. Material and methods This investigation conforms to the principles outlined in the Declaration of Helsinki. This study was approved by the Ethics Committee of The Hospital of Obstetrics & Gynaecology, Fudan University, Shanghai, China. 2.1. Study population This retrospective analysis of prospectively acquired data was performed in the Department of Obstetrics, The Hospital of Obstetrics and Gynaecology, Fudan University, which is the largest specialized Obstetrics and Gynaecology teaching hospital in China and serves a diverse urban and rural population. In this study, data on all pregnancies complicated by gestational diabetes mellitus (GDM) admitted between April 2010 and July 2012 were collected from the mother’s medical records. Oral glucose tolerance tests (OGTT) were measured by a 1 step approach. A 75 g glucose load was administrated after fasting glucose and plasma glucose levels were measured after 1 and 2 h. GDM was diagnosed if either of the glucose values fell at or above the specific glucose threshold (≥ 5.1 mmol/L for fasting, ≥ 10.0 mmol/L at 1 h, ≥ 8.5 mmol/L at 2 h). The maternal age, gestational week at diagnosis, gestational week at delivery, parity, maternal body mass index (BMI), maternal weight gain, birth weight and the glucose levels of GDM patients were recorded. Pregnant women with pre-existing diabetes mellitus were excluded. Gestational weight gain was calculated from gestational weight at delivery and maternal weight at first booking (around 11–13 weeks of gestation). Body mass index (BMI) was calculated as a ratio of maternal weight and height (kg/m2) at the first booking. All the patients were then divided into underweight, normal weight, overweight and obese groups according to the WHO classification of BMI for Asian/Indian women. The BMIs for underweight, normal weight, overweight and obese are under 18.5 kg/m2, 18.5–22.9 kg/m 2, 23–27.4 kg/m2 or over 27.5 kg/m 2, respectively. Large for gestational age (LGA) infants were defined as birth weight ≥ 90th percentile for gestational age (Alexander, Himes, Kaufman, Mor, & Kogan, 1996). Excessive weight gain was defined as gestational weight gain greater than the upper range of Institute of Medicine (IOM) 2009 guidelines for each pre-pregnancy BMI category (Rasmussen, Catalano, & Yaktine, 2009). All women with GDM received a recommendation for their diet during pregnancy. For those women who had poor glycemic control despite dietary and lifestyle intervention, insulin therapy was given. The targets for insulin treatment are fasting glucose level ≤3.3– 5.6 mmol/L and two hour post-prandial ≤ 6.7 mmol/L. 2.2. Statistical analysis This study included all the GDM patients (N = 1049) who presented to the Hospital of Obstetrics & Gynaecology, Fudan University, the largest specialized Obstetrics & Gynaecology teaching
hospital in China, between April 2010 and July 2012. Of the 1049 total study population, 293 (27.9%) women had excessive weight gestational gain. Assuming 6.5% (no excessive weight gain) vs 13.5% (excessive weight gain) of pregnant women will deliver LGA babies (Kim, Sharma, Sappenfield, Wilson, & Salihu, 2014), 287 subjects per group will provide 80% power with a two sided Type I error rate of 5%. The effects of maternal BMI and weight gain and their interaction adjusting for maternal age on delivery of LGA infants in women with GDM were assessed with multiple logistic regression using SAS, version 9.4 (SAS Institute Inc., Cary, NC, USA). The association between maternal BMI with maternal weight gain and gestation weeks at GDM diagnosis was assessed using Chi-square test. P-value of b0.05 was considered statistically significant. 3. Results During the study period, the total number of live births was 12,498. Of these live births, 1049 (8.4%) mothers developed GDM. The clinical characteristics of women with GDM (n = 1049) are summarized in Table 1. The median maternal age of women with GDM was 29 (range 18–43) years old. The median week of gestation at diagnosis and at delivery was 25 +3 (range 13 +1–38 +6) and 38 +4 (27 +3–41 +6), respectively. Of the 1049 women with GDM, considering each factor individually, we found that 47.3% were overweight or obese, 293 (27.9%) women had excessive gestational weight gain, and 97 (9.2%) women delivered LGA infants (Table 1). The delivery of LGA according to the maternal BMI or maternal excessive weight gain is summarized in Table 2. We then analyzed the factors which potentially associate with delivery of LGA in women with GDM. Multiple logistic regression analysis result (Table 3) shows that there was no significant association between maternal age and delivery of LGA (p = 0.5338) in women with GDM. However there was a very strong statistically significant association of maternal BMI with delivery of LGA (p = 0.0002) among women with GDM. The odds of delivery of LGA for obese pregnant women are 3.8 times the odds for normal weight pregnant women (OR = 3.8 with 95% CI: 2.0– 7.0), while the odds of delivery of LGA for overweight pregnant women are 2.0 times the odds for normal weight pregnant women (OR = 2.0 with 95% CI: 1.2–3.3). But there is no statistically significant difference in the odds ratio of delivery of LGA between underweight and normal weight mothers. In addition, there is a very strong statistically significant association between maternal weight gain and delivery of LGA (Table 3, p ≤ 0.0001). The odds of delivery of LGA for pregnant women with excessive weight gain are 3.3 times (95% CI: 2.1–5.1) the odds of delivery of LGA for pregnant women with normal weight gain
Table 1 Clinical characteristics of women with GDM.
Maternal age (years old, median/range) Parity (number) 0 1 2 Mean BMI (before pregnancy, kg/m2) Under weight (number, %) Normal (number, %) Overweight (number, %) Obese (number, %) Gestation week at diagnosis (median/range) Gestation week at delivery (median/range) Birth weight (g, median/range) Total weight gain (kg, medium/range) Excessive weight gain (number, %) LGA (number, %)
N = 1049 29 (18–43) 959 88 2 22.6 (15.7–38.8) 62 (5.9%) 493 (46.8%) 374 (35.8%) 120 (11.5%) 25+4 (13+1–38+6) 38+4 (27+3–41+6) 3360 (825–5080) 12 (0–59) 293 (27.9%) 97 (9.2%)
BMI: body mass index; LGA: larger for gestational age.
Please cite this article as: Chen, Q., et al., Associations between body mass index and maternal weight gain on the delivery of LGA infants in Chinese women with gestational dia..., Journal of Diabetes and Its Complications (2015), http://dx.doi.org/10.1016/j.jdiacomp.2015.08.017
Q. Chen et al. / Journal of Diabetes and Its Complications xxx (2015) xxx–xxx Table 2 The numbers of delivery of LGA in women with GDM by maternal weight gain or maternal BMI.
Weight gaina Normal Excessive BMI Underweight Normal overweight Obese a
Normal (number, row %)
LGA (number, row %)
Total (n = 1049) (N, col %)
713 (94.44%) 238 (81.23%)
42 (5.56%) 55 (18.77)
755 293
60 (96.77%) 467 (94.73%) 328 (87.7%) 97 (80.83%)
2 (3.23%) 26 (5.27%) 46 (12.3%) 23 (19.17%)
62 (5.9%) 493 (47%) 374 (36.7%) 120 (11.4%)
There was one woman with missing data in the weight gain category.
during pregnancy. The interaction effect of maternal BMI and excessive weight gain on delivery of LGA infants is not significant suggesting that the effect of weight gain on delivery of LGA infants is not significantly different between different maternal BMIs with excessive weight gain and vice versa. We then investigated whether maternal BMI is associated with gestational weight gain in women with GDM (Table 4). Chi Square test showed that the distribution of weight gain is significantly different between different maternal weight categories (p b 0.0001). 6.5% of underweight pregnant women with GDM had excessive weight gain, while 40.6% of overweight and 33.6% of obese women had excessive weight gain. We also analyzed whether maternal BMI was associated with the gestational weeks at diagnosis of GDM. As shown in Table 4, the majority of women with GDM (n = 790, 75.3%) were diagnosed between 24 and 28 weeks of gestation and the association between maternal BMI and gestational weeks at diagnosis is highly significant (Table 4, p = 0.003). We found that 25.8% of obese women with GDM were diagnosed before 24 weeks of gestation, while only 13.4% of normal weight women were diagnosed before 24 weeks of gestation. 4. Discussion Maternal, perinatal and neonatal complications are strongly associated with gestational diabetes mellitus (GDM). The incidence of GDM in China has increased since 2000 and this has become an important public problem in China (Leng et al., 2015; Zhang et al., 2011). In this study, conducted in the largest Obstetrics and Gynaecology university teaching hospital in China, our data show that the incidence of GDM was 8.4% over the 28 month study period. This incidence of GDM is similar to other studies in Asian populations (Kim et al., 2012), but higher than the incidence of GDM in United Kingdom (3.5%) (Health N.C.C.f.W.s.a.C.s, 2008) and the United States (7%) (Anonymous, 2003). Incidence of GDM seems to depend on
Table 3 Odds ratios and 95% confidence intervals for delivery of LGA in women with GDM, multiple logistic regressions. Odds ratio estimates Effect
Point Estimate
95% Wald Confidence Limits
Pr N ChiSq
Maternal age (years) Maternal BMI (referent to normal)
0.98
0.921
1.043
0.5338 0.0002
Obese Overweight Underweight
3.773 1.965 0.744
2.032 1.168 0.171
7.006 3.306 3.246
b0.0001 0.0109 0.6942 b0.0001
Excess
3.294
2.112
5.14
Maternal weight gain (referent to normal)
3
factors such as ethnicity and geographical regions (Health N.C.C.f.W.s.a.C.s, 2008). Although the incidence of obesity is lower in Chinese and Asian women compared with other ethnicities (Fisher et al., 2013; Xiao et al., 2014), in this study our data show that 47.3% of women with GDM were overweight or obese. This suggests that similar to Caucasians (Chu et al., 2007), maternal obesity is associated with a substantially higher incidence of GDM in the Chinese population. Gestational diabetes mellitus can affect the developing fetus throughout the pregnancy. A number of studies suggest that women with GDM in general are at increased risk of delivering LGA infants, which may lead to delivery complications as well as complications later on in life (Crowther et al., 2005; Maso, Piccoli, Parolin, Restaino, & Alberico, 2014). In the current study our data show that 9.2% of women with GDM delivered LGA infants, which is similar to a recent study which showed that 10.3% of Spanish women with GDM delivered LGA infants (Guillen et al., 2014). However, our result shows that the incidence of delivery of LGA in Chinese women with GDM was lower than the incidence of delivery of LGA (17.3%) in Caucasian women (including African-American, Asian or PacificAmerican) with GDM in the United States (Kim et al., 2014). Studies have shown that maternal obesity is positively correlated with the risk of delivery of LGA infants in women regardless of GDM (Ehrenberg, Mercer, & Catalano, 2004; Retnakaran et al., 2012). When combining the two risk factors (GDM and maternal obesity) on the delivery of LGA infants, a recent study showed that the incidence of delivery of LGA infants in Caucasian women with GDM was 9.2% (normal weight) or 10.4% (overweight) or 16.4% (class I obesity) (Kim et al., 2014). In comparison, our data show a lower incidence (5.3%) of LGA infants born to normal weight women with GDM. However, our data also show that the odds of delivery of LGA infants born to women with GDM who were overweight or obese were 2 times or 3.8 times higher than the odds of delivery of LGA infants born to women with normal weight. This result was similar with the odds of delivery of LGA infants born to African-American women with GDM who were overweight or obese (3.2 times), but higher than Caucasian (White) (1.2 times), Hispanic (1.4 times) and Asian or Pacific-American women (1.8 times) (Kim et al., 2014). Taken together our data suggest that Chinese women with GDM who were overweight or obese are at higher risk for delivery of LGA infants than Caucasian and other ethnicity women compared with underweight or normal weight women with GDM. Excessive gestational weight gain, in particular during the first trimester, is associated with an increased risk for delivery of LGA infants in women with GDM (Cheng et al., 2008). The amount of weight gained during pregnancy can affect the immediate and future health of women and their infants. A recent study showed that the incidence of delivery of LGA infants was significantly higher in women with excessive weight gain, regardless of whether they had GDM (Scifres, Feghali, Althouse, Caritis, & Catov, 2014) or not (Kim et al., 2014). Our data show that the odds of delivery of LGA infants were significantly higher (3.3 times) in GDM women with excessive weight gain compared to GDM women without excessive weight gain. Compared with the study of (Kim et al. (2014)), the odds of delivery of LGA infants born to Chinese women with GDM with excessive weight gain (3.3 times) were lower than the incidence of LGA infants born to African-American with GDM with excessive weight gain (6.8 times). However, our observation is similar with the odds of delivery of LGA infants born to women of other ethnicities (Caucasian, Hispanic and Asian or Pacific-American) with GDM with excessive weight gain (odds: 2.8–4.1 times). Our data suggest that Chinese women with GDM and excessive weight gain during pregnancy have similar risk for delivery of LGA infants compared with other major ethnicities. In our current study, our data show that there was a significant association between maternal BMI and maternal weight gain. Therefore we also investigated whether the combination of maternal obesity and excessive weight gain is correlated with the incidence of
Please cite this article as: Chen, Q., et al., Associations between body mass index and maternal weight gain on the delivery of LGA infants in Chinese women with gestational dia..., Journal of Diabetes and Its Complications (2015), http://dx.doi.org/10.1016/j.jdiacomp.2015.08.017
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Q. Chen et al. / Journal of Diabetes and Its Complications xxx (2015) xxx–xxx
Table 4 The association between BMI, maternal weigh gain and gestation week at diagnosis in women with GDM. Maternal BMI
Maternal weight gain Total (n, %) Normal (n, %) Excess (n, %) Diagnosis week Before 24 weeks (n, %) 24 to 28 weeks (n, %) After 28 weeks (n, %) Birth weight (g, median/range) a
Total
Under weight (b18.5 kg/m2)
Normal weight (18.5–22.9 kg/m2)
Overweight (23–27.4 kg/m2)
Obesea (N27.5 kg/m2)
1049 (100%) 755 (72.04%) 293 (27.96%)
62 (5.9%) 58 (93.55%) 4 (6.45%) +3 (15+1–37+6) 25 9 (14.52%) 48 (77.42%) 5 (8.06%) 3210 (1295–4760)
493 (46.8 %) 396 (80.32%) 97 (19.68%) 25+4 (14+1–36+6) 66 (13.39%) 393 (79.72%) 34 (6.9%) 3310 (980–4665)
374(35.8%) 222 (59.36%) 152 (40.64%) 25+4 (14+1–38+6) 61 (16.31%) 276 (73.8%) 37 (9.89%) 3410 (825–5080)
120 (11.5%) 79 (66.39%) 40 (33.61%) +4 25 (13+1–35+6) 31 (25.83%) 73 (60.83%) 16 (13.33%) 3480 (1450–4700)
Chi square test p-value b0.0001
167 (15.92%) 790 (75.31%) 92 (8.77%)
0.003
There was one woman with missing data in the weight gain category.
delivery of LGA infants. Our data show that the interaction effect of weight gain is not significantly different between different maternal BMIs, suggesting that there is an additive effect of maternal BMI and excessive weight gain on the delivery of LGA in Chinese women with GDM. Gestational diabetes rarely causes any clinical symptoms; however, 15%–60% women with GDM develop type 2 diabetes mellitus within 5–15 years postpartum (Kim, Newton, & Knopp, 2002). Therefore, early diagnosis and treatment of GDM can significantly reduce the risk for pregnancy complications and prevent development of type 2 diabetes mellitus later in life (Moyer, 2014). However, whether GDM should be screened systematically or upon risk factors is controversial, and currently, screening tests are generally performed between 24 and 28 weeks of gestation in women at no risk of developing GDM. Screening tests for GDM may need to be performed before 24 weeks of gestation in high risk pregnant women but there is little evidence about the benefits and harms of screening before 24 weeks of gestation (Moyer, 2014). A recent study indicated that diagnosis of GDM before 24 weeks of gestation is associated with preterm birth (Ngai et al., 2014). In our current study, our data show that there was a statistically significant association between maternal BMI and the gestation weeks at diagnosis of GDM. 25.8% of obese GDM women were diagnosed before 24 weeks while only 13.4% of normal weight GDM women were diagnosed before 24 weeks. This suggests that earlier screening test for GDM diagnosis (before 24 weeks) may be necessary for obese women. There are some limitations to this study in terms of generalizing the findings to China as a whole. All data were obtained from a university teaching hospital in the largest city in China over 28 months, which limited the sample size. The associations between maternal BMI, maternal weight gain and delivery of LGA infants in women with GDM may vary between regions and socioeconomic levels in China. In addition, we do not have the data for how many GDM patients have received insulin treatment in the hospital database; therefore we are not able to analyze whether receiving insulin treatment is associated with the delivery of LGA infant which may help us to better understand the results shown in this study.
5. Conclusion In this study, we analyzed the associations between maternal BMI, gestational weight gain, and the delivery of LGA infants in Chinese women with GDM. We found that Chinese women with GDM who were overweight or obese are at higher risk for delivery of LGA infants than Caucasian and women of other ethnicities, and Chinese women with GDM who had excessive weight gain have the same risk for delivery of LGA infant compared with other ethnicities. There was an additive effect of maternal BMI and maternal weight gain on the delivery of LGA infant in women with GDM. In addition, screening
tests for GDM in obese women may be useful prior to 24 weeks of gestation for early treatment.
Acknowledgments This study was supported by the Chinese National Nature Sciences Foundation (grant number 81100437 to M Zhao). All the authors thank Dr. Joanna James from The University of Auckland for reviewing the manuscript. We also would like to thank Dr. Greg Gamble from The University of Auckland for statistical assistance.
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Please cite this article as: Chen, Q., et al., Associations between body mass index and maternal weight gain on the delivery of LGA infants in Chinese women with gestational dia..., Journal of Diabetes and Its Complications (2015), http://dx.doi.org/10.1016/j.jdiacomp.2015.08.017
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Original Article
Associations between body mass index and maternal weight gain on the delivery of LGA infants in Chinese women with gestational diabetes mellitus Qi Chen a, b, J. Wei b, M. Tong b, L. Yu c, A.C. Lee d, Y.F. Gao a, M. Zhao e,⁎ a
The Hospital of Obstetrics & Gynaecology, Fudan University, Shanghai, China Department of Obstetrics & Gynaecology, The University of Auckland, Auckland, New Zealand Department of Anatomy with Radiology, The University of Auckland, Auckland, New Zealand d Section of Epidemiology and Biostatistics, School of Population Health, The University of Auckland, New Zealand e Wuxi Maternity and Child Health Hospital, Nanjing Medical University, Wuxi, China b c
a r t i c l e
i n f o
Article history: Received 17 March 2015 Received in revised form 31 July 2015 Accepted 20 August 2015 Available online xxxx Keywords: Gestational diabetes mellitus Body mass index Large for gestational age Maternal obesity Excessive weight gain
a b s t r a c t Background: Women with gestational diabetes mellitus (GDM) are at increased risk for maternal and fetal complications including delivery of large for gestational age (LGA) infants. Maternal body mass index (BMI) and excessive weight gain during pregnancy are associated with delivery of LGA infants. However, whether maternal BMI and weight gain are associated with LGA infants in women with GDM is unclear. Basic procedures: Data on 1049 pregnant women who developed GDM were collected from a university teaching hospital in China and retrospectively analyzed. Data included maternal BMI, weight gain, incidence of LGA and gestational week at diagnosis. Main findings: The incidence of LGA infants was significantly associated with maternal BMI (p = 0.0002) in women with GDM. The odds of delivery of LGA for obese or overweight pregnant women are 3.8 or 2 times more than normal weight pregnant women. The incidence of LGA infants was also significantly associated with maternal weight gain in women with GDM. The odds ratio of delivery of LGA for pregnant women with excessive weight gain was 3.3 times more than pregnant women with normal weight gain. The effect of weight gain was not significantly different between different maternal BMI. Principal conclusion: The incidence of delivery of LGA infants in Chinese women with GDM who were overweight or obese is higher than Caucasians, Hispanic, and Asian-Americans. The effects of maternal BMI and weight gain on the delivery of LGA infants by women with GDM are additive. © 2015 Elsevier Inc. All rights reserved.
1. Introduction Gestational diabetes mellitus (GDM) is a condition of glucose intolerance during pregnancy (American Diabetes A, 2011), which affects 2%–18% of healthy pregnancies depending on ethnicity and geographic area (Hunt & Schuller, 2007). Women with GDM are at increased risk of maternal and fetal complications including preeclampsia, preterm birth, caesarean section and delivery of large for gestational age (LGA) infants (Casey, Lucas, McIntire, & Leveno, 1997; Yang, Cummings, O'Connell, & Jangaard, 2006). In addition, women with unmanaged GDM are at risk of developing type 2 diabetes mellitus later in life (Bellamy, Casas, Hingorani, & Williams, 2009; Knight, Pressman, Hackney, & Thornburg, 2012).
Conflicts of Interest statement: None of the authors have a conflict of interest. ⁎ Corresponding author at: 48 Huaishu Street, Wuxi, China, Wuxi Maternity and Children Hospital, Nanjing Medical University, China. Tel.: +86 13611691734. E-mail address: [email protected] (M. Zhao).
The precise mechanisms underlying gestational diabetes remain unknown, but risk factors for developing GDM include maternal age, maternal obesity before pregnancy, pre-gestational diabetes mellitus and a family history of type 2 diabetes. In addition, a recent metaanalysis also found an association between excessive weight gain during pregnancy, in particular during the first trimester, and the risk of developing GDM (Ruifrok et al., 2014). The amount of weight gain during pregnancy can affect the immediate and future health of pregnant women and their infants. Being an LGA infant is a risk factor for developing diabetes, obesity and cancer later in life (Walsh & McAuliffe, 2012). Delivery of LGA infants increases the risk of delivery complications including prolonged labor, shoulder dystocia and cesarean section (Walsh & McAuliffe, 2012). Preterm birth is a major cause of perinatal mortality and long-term morbidity (McCormick, 1985). Studies clearly showed that maternal obesity, maternal excessive weight gain and GDM are associated with the increased risk of pregnancy complications, including delivery of LGA infants and preterm birth (Ferraro et al., 2012; Hinkle et al., 2012; Ornoy, 2011). However, the incidence of
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Please cite this article as: Chen, Q., et al., Associations between body mass index and maternal weight gain on the delivery of LGA infants in Chinese women with gestational dia..., Journal of Diabetes and Its Complications (2015), http://dx.doi.org/10.1016/j.jdiacomp.2015.08.017
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Q. Chen et al. / Journal of Diabetes and Its Complications xxx (2015) xxx–xxx
these independent risk factors varies depending on the ethnicity of the population and geographical region (Health N.C.C.f.W.s.a.C.s, 2008). In addition, it is unclear whether overweight women or obese women with GDM are at increased risk of having an LGA infant or preterm delivery in comparison to normal or underweight women with GDM. Whether there is an additive effect on delivery of LGA infants in women with GDM who are obese and also have excessive weight gain is not clear. Our previous study and other studies reported lower maternal body mass index (BMI) in Asian and Chinese populations (Fisher, Kim, Sharma, Rochat, & Morrow, 2013; Xiao et al., 2014). Therefore in this study, we investigated the association between maternal body mass index (BMI) and gestational weight gain on the delivery of LGA infants in Chinese women with GDM. 2. Material and methods This investigation conforms to the principles outlined in the Declaration of Helsinki. This study was approved by the Ethics Committee of The Hospital of Obstetrics & Gynaecology, Fudan University, Shanghai, China. 2.1. Study population This retrospective analysis of prospectively acquired data was performed in the Department of Obstetrics, The Hospital of Obstetrics and Gynaecology, Fudan University, which is the largest specialized Obstetrics and Gynaecology teaching hospital in China and serves a diverse urban and rural population. In this study, data on all pregnancies complicated by gestational diabetes mellitus (GDM) admitted between April 2010 and July 2012 were collected from the mother’s medical records. Oral glucose tolerance tests (OGTT) were measured by a 1 step approach. A 75 g glucose load was administrated after fasting glucose and plasma glucose levels were measured after 1 and 2 h. GDM was diagnosed if either of the glucose values fell at or above the specific glucose threshold (≥ 5.1 mmol/L for fasting, ≥ 10.0 mmol/L at 1 h, ≥ 8.5 mmol/L at 2 h). The maternal age, gestational week at diagnosis, gestational week at delivery, parity, maternal body mass index (BMI), maternal weight gain, birth weight and the glucose levels of GDM patients were recorded. Pregnant women with pre-existing diabetes mellitus were excluded. Gestational weight gain was calculated from gestational weight at delivery and maternal weight at first booking (around 11–13 weeks of gestation). Body mass index (BMI) was calculated as a ratio of maternal weight and height (kg/m2) at the first booking. All the patients were then divided into underweight, normal weight, overweight and obese groups according to the WHO classification of BMI for Asian/Indian women. The BMIs for underweight, normal weight, overweight and obese are under 18.5 kg/m2, 18.5–22.9 kg/m 2, 23–27.4 kg/m2 or over 27.5 kg/m 2, respectively. Large for gestational age (LGA) infants were defined as birth weight ≥ 90th percentile for gestational age (Alexander, Himes, Kaufman, Mor, & Kogan, 1996). Excessive weight gain was defined as gestational weight gain greater than the upper range of Institute of Medicine (IOM) 2009 guidelines for each pre-pregnancy BMI category (Rasmussen, Catalano, & Yaktine, 2009). All women with GDM received a recommendation for their diet during pregnancy. For those women who had poor glycemic control despite dietary and lifestyle intervention, insulin therapy was given. The targets for insulin treatment are fasting glucose level ≤3.3– 5.6 mmol/L and two hour post-prandial ≤ 6.7 mmol/L. 2.2. Statistical analysis This study included all the GDM patients (N = 1049) who presented to the Hospital of Obstetrics & Gynaecology, Fudan University, the largest specialized Obstetrics & Gynaecology teaching
hospital in China, between April 2010 and July 2012. Of the 1049 total study population, 293 (27.9%) women had excessive weight gestational gain. Assuming 6.5% (no excessive weight gain) vs 13.5% (excessive weight gain) of pregnant women will deliver LGA babies (Kim, Sharma, Sappenfield, Wilson, & Salihu, 2014), 287 subjects per group will provide 80% power with a two sided Type I error rate of 5%. The effects of maternal BMI and weight gain and their interaction adjusting for maternal age on delivery of LGA infants in women with GDM were assessed with multiple logistic regression using SAS, version 9.4 (SAS Institute Inc., Cary, NC, USA). The association between maternal BMI with maternal weight gain and gestation weeks at GDM diagnosis was assessed using Chi-square test. P-value of b0.05 was considered statistically significant. 3. Results During the study period, the total number of live births was 12,498. Of these live births, 1049 (8.4%) mothers developed GDM. The clinical characteristics of women with GDM (n = 1049) are summarized in Table 1. The median maternal age of women with GDM was 29 (range 18–43) years old. The median week of gestation at diagnosis and at delivery was 25 +3 (range 13 +1–38 +6) and 38 +4 (27 +3–41 +6), respectively. Of the 1049 women with GDM, considering each factor individually, we found that 47.3% were overweight or obese, 293 (27.9%) women had excessive gestational weight gain, and 97 (9.2%) women delivered LGA infants (Table 1). The delivery of LGA according to the maternal BMI or maternal excessive weight gain is summarized in Table 2. We then analyzed the factors which potentially associate with delivery of LGA in women with GDM. Multiple logistic regression analysis result (Table 3) shows that there was no significant association between maternal age and delivery of LGA (p = 0.5338) in women with GDM. However there was a very strong statistically significant association of maternal BMI with delivery of LGA (p = 0.0002) among women with GDM. The odds of delivery of LGA for obese pregnant women are 3.8 times the odds for normal weight pregnant women (OR = 3.8 with 95% CI: 2.0– 7.0), while the odds of delivery of LGA for overweight pregnant women are 2.0 times the odds for normal weight pregnant women (OR = 2.0 with 95% CI: 1.2–3.3). But there is no statistically significant difference in the odds ratio of delivery of LGA between underweight and normal weight mothers. In addition, there is a very strong statistically significant association between maternal weight gain and delivery of LGA (Table 3, p ≤ 0.0001). The odds of delivery of LGA for pregnant women with excessive weight gain are 3.3 times (95% CI: 2.1–5.1) the odds of delivery of LGA for pregnant women with normal weight gain
Table 1 Clinical characteristics of women with GDM.
Maternal age (years old, median/range) Parity (number) 0 1 2 Mean BMI (before pregnancy, kg/m2) Under weight (number, %) Normal (number, %) Overweight (number, %) Obese (number, %) Gestation week at diagnosis (median/range) Gestation week at delivery (median/range) Birth weight (g, median/range) Total weight gain (kg, medium/range) Excessive weight gain (number, %) LGA (number, %)
N = 1049 29 (18–43) 959 88 2 22.6 (15.7–38.8) 62 (5.9%) 493 (46.8%) 374 (35.8%) 120 (11.5%) 25+4 (13+1–38+6) 38+4 (27+3–41+6) 3360 (825–5080) 12 (0–59) 293 (27.9%) 97 (9.2%)
BMI: body mass index; LGA: larger for gestational age.
Please cite this article as: Chen, Q., et al., Associations between body mass index and maternal weight gain on the delivery of LGA infants in Chinese women with gestational dia..., Journal of Diabetes and Its Complications (2015), http://dx.doi.org/10.1016/j.jdiacomp.2015.08.017
Q. Chen et al. / Journal of Diabetes and Its Complications xxx (2015) xxx–xxx Table 2 The numbers of delivery of LGA in women with GDM by maternal weight gain or maternal BMI.
Weight gaina Normal Excessive BMI Underweight Normal overweight Obese a
Normal (number, row %)
LGA (number, row %)
Total (n = 1049) (N, col %)
713 (94.44%) 238 (81.23%)
42 (5.56%) 55 (18.77)
755 293
60 (96.77%) 467 (94.73%) 328 (87.7%) 97 (80.83%)
2 (3.23%) 26 (5.27%) 46 (12.3%) 23 (19.17%)
62 (5.9%) 493 (47%) 374 (36.7%) 120 (11.4%)
There was one woman with missing data in the weight gain category.
during pregnancy. The interaction effect of maternal BMI and excessive weight gain on delivery of LGA infants is not significant suggesting that the effect of weight gain on delivery of LGA infants is not significantly different between different maternal BMIs with excessive weight gain and vice versa. We then investigated whether maternal BMI is associated with gestational weight gain in women with GDM (Table 4). Chi Square test showed that the distribution of weight gain is significantly different between different maternal weight categories (p b 0.0001). 6.5% of underweight pregnant women with GDM had excessive weight gain, while 40.6% of overweight and 33.6% of obese women had excessive weight gain. We also analyzed whether maternal BMI was associated with the gestational weeks at diagnosis of GDM. As shown in Table 4, the majority of women with GDM (n = 790, 75.3%) were diagnosed between 24 and 28 weeks of gestation and the association between maternal BMI and gestational weeks at diagnosis is highly significant (Table 4, p = 0.003). We found that 25.8% of obese women with GDM were diagnosed before 24 weeks of gestation, while only 13.4% of normal weight women were diagnosed before 24 weeks of gestation. 4. Discussion Maternal, perinatal and neonatal complications are strongly associated with gestational diabetes mellitus (GDM). The incidence of GDM in China has increased since 2000 and this has become an important public problem in China (Leng et al., 2015; Zhang et al., 2011). In this study, conducted in the largest Obstetrics and Gynaecology university teaching hospital in China, our data show that the incidence of GDM was 8.4% over the 28 month study period. This incidence of GDM is similar to other studies in Asian populations (Kim et al., 2012), but higher than the incidence of GDM in United Kingdom (3.5%) (Health N.C.C.f.W.s.a.C.s, 2008) and the United States (7%) (Anonymous, 2003). Incidence of GDM seems to depend on
Table 3 Odds ratios and 95% confidence intervals for delivery of LGA in women with GDM, multiple logistic regressions. Odds ratio estimates Effect
Point Estimate
95% Wald Confidence Limits
Pr N ChiSq
Maternal age (years) Maternal BMI (referent to normal)
0.98
0.921
1.043
0.5338 0.0002
Obese Overweight Underweight
3.773 1.965 0.744
2.032 1.168 0.171
7.006 3.306 3.246
b0.0001 0.0109 0.6942 b0.0001
Excess
3.294
2.112
5.14
Maternal weight gain (referent to normal)
3
factors such as ethnicity and geographical regions (Health N.C.C.f.W.s.a.C.s, 2008). Although the incidence of obesity is lower in Chinese and Asian women compared with other ethnicities (Fisher et al., 2013; Xiao et al., 2014), in this study our data show that 47.3% of women with GDM were overweight or obese. This suggests that similar to Caucasians (Chu et al., 2007), maternal obesity is associated with a substantially higher incidence of GDM in the Chinese population. Gestational diabetes mellitus can affect the developing fetus throughout the pregnancy. A number of studies suggest that women with GDM in general are at increased risk of delivering LGA infants, which may lead to delivery complications as well as complications later on in life (Crowther et al., 2005; Maso, Piccoli, Parolin, Restaino, & Alberico, 2014). In the current study our data show that 9.2% of women with GDM delivered LGA infants, which is similar to a recent study which showed that 10.3% of Spanish women with GDM delivered LGA infants (Guillen et al., 2014). However, our result shows that the incidence of delivery of LGA in Chinese women with GDM was lower than the incidence of delivery of LGA (17.3%) in Caucasian women (including African-American, Asian or PacificAmerican) with GDM in the United States (Kim et al., 2014). Studies have shown that maternal obesity is positively correlated with the risk of delivery of LGA infants in women regardless of GDM (Ehrenberg, Mercer, & Catalano, 2004; Retnakaran et al., 2012). When combining the two risk factors (GDM and maternal obesity) on the delivery of LGA infants, a recent study showed that the incidence of delivery of LGA infants in Caucasian women with GDM was 9.2% (normal weight) or 10.4% (overweight) or 16.4% (class I obesity) (Kim et al., 2014). In comparison, our data show a lower incidence (5.3%) of LGA infants born to normal weight women with GDM. However, our data also show that the odds of delivery of LGA infants born to women with GDM who were overweight or obese were 2 times or 3.8 times higher than the odds of delivery of LGA infants born to women with normal weight. This result was similar with the odds of delivery of LGA infants born to African-American women with GDM who were overweight or obese (3.2 times), but higher than Caucasian (White) (1.2 times), Hispanic (1.4 times) and Asian or Pacific-American women (1.8 times) (Kim et al., 2014). Taken together our data suggest that Chinese women with GDM who were overweight or obese are at higher risk for delivery of LGA infants than Caucasian and other ethnicity women compared with underweight or normal weight women with GDM. Excessive gestational weight gain, in particular during the first trimester, is associated with an increased risk for delivery of LGA infants in women with GDM (Cheng et al., 2008). The amount of weight gained during pregnancy can affect the immediate and future health of women and their infants. A recent study showed that the incidence of delivery of LGA infants was significantly higher in women with excessive weight gain, regardless of whether they had GDM (Scifres, Feghali, Althouse, Caritis, & Catov, 2014) or not (Kim et al., 2014). Our data show that the odds of delivery of LGA infants were significantly higher (3.3 times) in GDM women with excessive weight gain compared to GDM women without excessive weight gain. Compared with the study of (Kim et al. (2014)), the odds of delivery of LGA infants born to Chinese women with GDM with excessive weight gain (3.3 times) were lower than the incidence of LGA infants born to African-American with GDM with excessive weight gain (6.8 times). However, our observation is similar with the odds of delivery of LGA infants born to women of other ethnicities (Caucasian, Hispanic and Asian or Pacific-American) with GDM with excessive weight gain (odds: 2.8–4.1 times). Our data suggest that Chinese women with GDM and excessive weight gain during pregnancy have similar risk for delivery of LGA infants compared with other major ethnicities. In our current study, our data show that there was a significant association between maternal BMI and maternal weight gain. Therefore we also investigated whether the combination of maternal obesity and excessive weight gain is correlated with the incidence of
Please cite this article as: Chen, Q., et al., Associations between body mass index and maternal weight gain on the delivery of LGA infants in Chinese women with gestational dia..., Journal of Diabetes and Its Complications (2015), http://dx.doi.org/10.1016/j.jdiacomp.2015.08.017
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Q. Chen et al. / Journal of Diabetes and Its Complications xxx (2015) xxx–xxx
Table 4 The association between BMI, maternal weigh gain and gestation week at diagnosis in women with GDM. Maternal BMI
Maternal weight gain Total (n, %) Normal (n, %) Excess (n, %) Diagnosis week Before 24 weeks (n, %) 24 to 28 weeks (n, %) After 28 weeks (n, %) Birth weight (g, median/range) a
Total
Under weight (b18.5 kg/m2)
Normal weight (18.5–22.9 kg/m2)
Overweight (23–27.4 kg/m2)
Obesea (N27.5 kg/m2)
1049 (100%) 755 (72.04%) 293 (27.96%)
62 (5.9%) 58 (93.55%) 4 (6.45%) +3 (15+1–37+6) 25 9 (14.52%) 48 (77.42%) 5 (8.06%) 3210 (1295–4760)
493 (46.8 %) 396 (80.32%) 97 (19.68%) 25+4 (14+1–36+6) 66 (13.39%) 393 (79.72%) 34 (6.9%) 3310 (980–4665)
374(35.8%) 222 (59.36%) 152 (40.64%) 25+4 (14+1–38+6) 61 (16.31%) 276 (73.8%) 37 (9.89%) 3410 (825–5080)
120 (11.5%) 79 (66.39%) 40 (33.61%) +4 25 (13+1–35+6) 31 (25.83%) 73 (60.83%) 16 (13.33%) 3480 (1450–4700)
Chi square test p-value b0.0001
167 (15.92%) 790 (75.31%) 92 (8.77%)
0.003
There was one woman with missing data in the weight gain category.
delivery of LGA infants. Our data show that the interaction effect of weight gain is not significantly different between different maternal BMIs, suggesting that there is an additive effect of maternal BMI and excessive weight gain on the delivery of LGA in Chinese women with GDM. Gestational diabetes rarely causes any clinical symptoms; however, 15%–60% women with GDM develop type 2 diabetes mellitus within 5–15 years postpartum (Kim, Newton, & Knopp, 2002). Therefore, early diagnosis and treatment of GDM can significantly reduce the risk for pregnancy complications and prevent development of type 2 diabetes mellitus later in life (Moyer, 2014). However, whether GDM should be screened systematically or upon risk factors is controversial, and currently, screening tests are generally performed between 24 and 28 weeks of gestation in women at no risk of developing GDM. Screening tests for GDM may need to be performed before 24 weeks of gestation in high risk pregnant women but there is little evidence about the benefits and harms of screening before 24 weeks of gestation (Moyer, 2014). A recent study indicated that diagnosis of GDM before 24 weeks of gestation is associated with preterm birth (Ngai et al., 2014). In our current study, our data show that there was a statistically significant association between maternal BMI and the gestation weeks at diagnosis of GDM. 25.8% of obese GDM women were diagnosed before 24 weeks while only 13.4% of normal weight GDM women were diagnosed before 24 weeks. This suggests that earlier screening test for GDM diagnosis (before 24 weeks) may be necessary for obese women. There are some limitations to this study in terms of generalizing the findings to China as a whole. All data were obtained from a university teaching hospital in the largest city in China over 28 months, which limited the sample size. The associations between maternal BMI, maternal weight gain and delivery of LGA infants in women with GDM may vary between regions and socioeconomic levels in China. In addition, we do not have the data for how many GDM patients have received insulin treatment in the hospital database; therefore we are not able to analyze whether receiving insulin treatment is associated with the delivery of LGA infant which may help us to better understand the results shown in this study.
5. Conclusion In this study, we analyzed the associations between maternal BMI, gestational weight gain, and the delivery of LGA infants in Chinese women with GDM. We found that Chinese women with GDM who were overweight or obese are at higher risk for delivery of LGA infants than Caucasian and women of other ethnicities, and Chinese women with GDM who had excessive weight gain have the same risk for delivery of LGA infant compared with other ethnicities. There was an additive effect of maternal BMI and maternal weight gain on the delivery of LGA infant in women with GDM. In addition, screening
tests for GDM in obese women may be useful prior to 24 weeks of gestation for early treatment.
Acknowledgments This study was supported by the Chinese National Nature Sciences Foundation (grant number 81100437 to M Zhao). All the authors thank Dr. Joanna James from The University of Auckland for reviewing the manuscript. We also would like to thank Dr. Greg Gamble from The University of Auckland for statistical assistance.
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