Accepted Article
Received Date : 11-Feb-2014 Accepted Date : 07-May-2014 Article type
: Main Research Article
Impact of gestational weight gain on fetal growth in obese glycemic mothers: A comparative study
Running title: effect of GWG on fetal growth
Agzail S. Elhddad1, Fiona Fairlie2 & Hany Lashen1
1
Academic Unit of Reproductive and Developmental Medicine, Human Metabolism Department, Medical School, University of Sheffield, Sheffield, 2Royal Hallamshire Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
Corresponding author: Hany Lashen Academic Unit of Reproductive and Developmental Medicine, Human Metabolism Department, Medical School, University of Sheffield, The Jessop Wing, Sheffield S10 2SF, UK. E-mail: [email protected]
Authors have no conflict of interest.
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/aogs.12427 This article is protected by copyright. All rights reserved.
Accepted Article
Abstract Objective: To assess the pattern of gestational weight gain (GWG) and its effect on fetal growth among normogylycemic obese and lean mothers. Design: Prospective longitudinal study. Setting: Teaching hospitals, Sheffield, UK. Population: 46 euglycemic obese and 30 lean mothers and their offspring. Method: The contrast slope of GWG was calculated and its impact on fetal growth trajectory and birth anthropometry examined in both groups. Results: The GWG contrast slope trended significantly upward in both groups, however, it was ssteeper among lean mothers (p=0.003), particularly in second trimester. Lean mothers had a biphasic GWG pattern with a higher early weight gain (p=0.02) whereas obese mothers had a monophasic GWG. Both groups had similar third trimester GWG. The GWG contrast slope was influenced by early pregnancy maternal anthropometry in the obese group only. Nonetheless, the obese mothers’ glucose and insulin indices had no significant relation to GWG. GWG had a significant positive relation with intrauterine femur length (r=0.32, p=0.04) and abdominal circumference (r=0.42, p=0.006) growth trajectories, as well as birthweight standard deviation scores (r=0.32, p=0.036) and the ponderal index (r=0.45, p= 0.003) in the obese mothers. Conclusions: Gestational weight gain among lean mothers is biphasic and significantly higher than for their obese counterparts, but without effect on fetal growth. The obese mothers’ monophasic weight gain was influenced by their anthropometry, but not by their insulin or glucose indices and impacted on the growth of their babies.
Key words Maternal obesity, gestational weight gain, intrauterine growth trajectory, birth anthropometry, fetal growth
Abbreviations ACT
abdominal circumference trajectory
BMI
body mass index
FLT
femur length trajectory
GWG
gestational weight gain
HCT
head circumference trajectory
HOMA-IR
Homeostasis Model Assessment- Insulin Resistance
PI
ponderal index
SDS
standard deviation score
This article is protected by copyright. All rights reserved.
Accepted Article
Key message Obese mothers’ weight gain in pregnancy appears to be influenced by their body mass and size, but not by their insulin or glucose levels, and it impacts on the growth of their babies.
Introduction Abnormal birthweight is associated with higher perinatal morbidity and mortality and may adversely affect long-term health (1-3). Birthweight, an indicator of fetal growth, is influenced by the maternal body mass index (BMI) and also gestational weight gain (GWG) (4-6). Both maternal BMI (7) and GWG are on the increase and both are associated with adverse pregnancy outcome (8). Abnormal weight gain, below or above the 1990 Institute of Medicine (IOM) recommended guidelines, has been reported to negatively impact on pregnancy outcome in mother and baby (9). However, not only the overall weight gain, but also the weekly rate of weight accumulation was reported to affect pregnancy outcome (10). In a population based-cohort study, limiting GWG among obese mothers was found to reduce the risk of delivering large-for-gestational age babies and other adverse pregnancy outcomes (11). Furthermore, excessive GWG has been reported to correlate with the offspring’s BMI, abdominal fat and adverse cardiovascular risk factors in childhood and adulthood (12, 13). On the maternal side, excessive GWG increased the women’s risk of long-term weight gain and obesity (14). High maternal pre-gestational BMI has been found to be associated with excessive GWG (15). However, others reported that lean mothers had a significantly higher GWG compared to obese mothers (16, 17). The objectives of this prospective longitudinal study were to comparatively assess the pattern of GWG among normogylycemic obese and lean mothers and to assess the relation between GWG and fetal intrauterine growth rate and anthropometry at birth.
Material and methods The project was approved by the Local Research Ethics Committee in Sheffield, approval number 08/41308/198 dated 16/12/2008. Written informed consent was obtained from the mothers at the commencement of the study. The study was conducted in a tertiary center in a university-based teaching hospital. The study participants were recruited in their first trimester, from pregnant women aged between 18 and 40 years who were either primiparous or had one previous live birth. Women with prepregnancy medical problems or who developed antenatal complications, likely to affect fetal growth, were excluded. Only obese (BMI >30 kg/m2) or lean women (BMI 19-25) were invited to take part. Maternal body weight (kg) and height (m) were measured using an electronic weighing device and a fixed stadiometer respectively. BMI was calculated using Quetlet index [BMI= weight (kg) /height 2 (m)] and the cut-offs proposed by theWorld Health Organization for BMI (18) were used to identify obese and lean women. The waist and hip circumferences were measured in the first trimester using
This article is protected by copyright. All rights reserved.
Accepted Article
inelastic pocket tape measure and the waist to hip ratio was calculated by dividing the waist circumference by the hip circumference. Maternal body weight was recorded in each trimester. The women were seen at their first (booking) antenatal visit [V1], at second trimester (24-28 weeks) [V2] and third trimester (36-38 weeks) [V3]. Only those who attended prior to their 14th week of gestation at V1 were included in the study so that the early pregnancy maternal anthropometry would be more reflective of pre-pregnancy measures. All obese mothers underwent a 75g oral glucose tolerance test at 24-28 weeks gestation and diabetic mothers were excluded. Insulin was also assayed in the fasting and 2-hour postprandial samples. Insulin resistance index was calculated using the Homeostasis Model Assessment- Insulin Resistance (HOMA-IR). The use of the HOMA-IR for assessment of insulin resistance has been previously described (19).
Fetal intrauterine growth was assessed via serial measures of femur length and abdominal and head circumferences in the second and third trimesters using trans-abdominal ultrasound scanning performed by a single experienced investigator. The growth trajectories of the femur length (FLT), abdominal circumference (ACT) and head circumference (HCT) were calculated using the formula [100 * (measurement at 3rd trimester – measurement at 2nd trimester)/measurement at 2nd trimester]. The formula was obtained from http://www.ehow.com/how_4532706_calculate-growthrate-percent-change.html. Birthweight, crown-heel length and head circumference were recorded at birth. Birthweight was measured with an electronic self-calibrating scale (SECA, Birmingham, UK). Supine crown-heel length was measured using a length board Rollameter-60 (provided by Harlow health care). An inelastic measuring tape was used to measure the fetal head circumference (a maximum front-occipital circumference). Ponderal index (PI), an index of the baby’s adiposity (20), was calculated using the following formula PI= 100*[weight (gm)/crown heel length3 (cm)]. Placental weight was also recorded. Birthweight, crown-heel length and head circumference were converted to standard deviation scores (SDS) to adjust for the variations in birthweight due to gender and gestational age. http://homepage.mac.com/tjcole/FileSharing1.html.
Insulin was determined by Direct Chemiluminescence Immunoassay using Siemens ADVIA Centaur automated analysers (Siemens AG. Erlangen, Germany) . It is a solid phase, two-site Chemiluminescent Immunometric Assay. The test is highly specific for insulin with no cross-reactivity with proinsulin, glucagon, c-peptide, secretin or gastrin-1. The Beckman Coulter DxC 800 System GLUCm method was used to determine glucose concentration by an oxygen rate method employing the Beckman Coulter Oxygen electrode (Beckman Coulter Inc., Brea, CA, USA).
Statistical analysis The data distribution was assessed using the Shapiro-Wilk test (21). Maternal GWG in the second trimester was calculated by subtracting maternal weight in V1 from that in V2 and was labelled
This article is protected by copyright. All rights reserved.
Accepted Article
GWG-1. Similarly, maternal GWG in the third trimester was calculated by subtracting maternal weight in V2 from that in V3 which was labelled GWG-2. To analyse the overall longitudinal trend in weight changes the approach of Matthews et.al (22) was used, whereby the slope of the maternal weight in the three trimesters was calculated. Subsequently, the linear contrast of gestational weight was calculated to summarise the trend in GWG in each individual which takes into account the different weight changes in the second and third trimesters. A single sample t-test on the linear contrasts was computed which tested a null hypothesis that the mean linear contrast was equal to zero (i.e. on average there is no trend up or down over time) against an alternative hypothesis that the mean linear contrast was not equal to zero (i.e. on average there is a trend up or down over time). The calculated slopes as well as GWG-1 and GWG-2 were compared between the obese and lean groups using t-test or Mann-Whitney test according to the data distribution. The GWG slope was correlated with fetal anthropometry and intrauterine growth trajectories and maternal early pregnancy anthropometry in each group using Spearman or Pearson correlation analyses according to the nature of data distribution. Further, the obese mothers’ GWG slope was correlated with their fasting and postprandial insulin and glucose and HOMA-IR.
The intrauterine calculated growth trajectories and birth anthropometry were compared between the babies of the obese and lean mothers using the Student’s t-test or the Mann-Whitney U-test according to the data distribution. Logistic regression analysis was used to correlate the categorical to continuous variables where appropriate. Fisher’s exact test was used to compare proportions. The statistical analyses were carried out using the SPSS-18 (SPSS, Chicago, IL, USA). A p value of 4000 g) was 10/46 (21%) and 1/30 (3%) in the obese and lean groups respectively and the difference was significant (p=0.042).
As shown in Table 1 and Fig. 1 the GWG slope was significant in both lean [(t=14.6, p
Received Date : 11-Feb-2014 Accepted Date : 07-May-2014 Article type
: Main Research Article
Impact of gestational weight gain on fetal growth in obese glycemic mothers: A comparative study
Running title: effect of GWG on fetal growth
Agzail S. Elhddad1, Fiona Fairlie2 & Hany Lashen1
1
Academic Unit of Reproductive and Developmental Medicine, Human Metabolism Department, Medical School, University of Sheffield, Sheffield, 2Royal Hallamshire Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
Corresponding author: Hany Lashen Academic Unit of Reproductive and Developmental Medicine, Human Metabolism Department, Medical School, University of Sheffield, The Jessop Wing, Sheffield S10 2SF, UK. E-mail: [email protected]
Authors have no conflict of interest.
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/aogs.12427 This article is protected by copyright. All rights reserved.
Accepted Article
Abstract Objective: To assess the pattern of gestational weight gain (GWG) and its effect on fetal growth among normogylycemic obese and lean mothers. Design: Prospective longitudinal study. Setting: Teaching hospitals, Sheffield, UK. Population: 46 euglycemic obese and 30 lean mothers and their offspring. Method: The contrast slope of GWG was calculated and its impact on fetal growth trajectory and birth anthropometry examined in both groups. Results: The GWG contrast slope trended significantly upward in both groups, however, it was ssteeper among lean mothers (p=0.003), particularly in second trimester. Lean mothers had a biphasic GWG pattern with a higher early weight gain (p=0.02) whereas obese mothers had a monophasic GWG. Both groups had similar third trimester GWG. The GWG contrast slope was influenced by early pregnancy maternal anthropometry in the obese group only. Nonetheless, the obese mothers’ glucose and insulin indices had no significant relation to GWG. GWG had a significant positive relation with intrauterine femur length (r=0.32, p=0.04) and abdominal circumference (r=0.42, p=0.006) growth trajectories, as well as birthweight standard deviation scores (r=0.32, p=0.036) and the ponderal index (r=0.45, p= 0.003) in the obese mothers. Conclusions: Gestational weight gain among lean mothers is biphasic and significantly higher than for their obese counterparts, but without effect on fetal growth. The obese mothers’ monophasic weight gain was influenced by their anthropometry, but not by their insulin or glucose indices and impacted on the growth of their babies.
Key words Maternal obesity, gestational weight gain, intrauterine growth trajectory, birth anthropometry, fetal growth
Abbreviations ACT
abdominal circumference trajectory
BMI
body mass index
FLT
femur length trajectory
GWG
gestational weight gain
HCT
head circumference trajectory
HOMA-IR
Homeostasis Model Assessment- Insulin Resistance
PI
ponderal index
SDS
standard deviation score
This article is protected by copyright. All rights reserved.
Accepted Article
Key message Obese mothers’ weight gain in pregnancy appears to be influenced by their body mass and size, but not by their insulin or glucose levels, and it impacts on the growth of their babies.
Introduction Abnormal birthweight is associated with higher perinatal morbidity and mortality and may adversely affect long-term health (1-3). Birthweight, an indicator of fetal growth, is influenced by the maternal body mass index (BMI) and also gestational weight gain (GWG) (4-6). Both maternal BMI (7) and GWG are on the increase and both are associated with adverse pregnancy outcome (8). Abnormal weight gain, below or above the 1990 Institute of Medicine (IOM) recommended guidelines, has been reported to negatively impact on pregnancy outcome in mother and baby (9). However, not only the overall weight gain, but also the weekly rate of weight accumulation was reported to affect pregnancy outcome (10). In a population based-cohort study, limiting GWG among obese mothers was found to reduce the risk of delivering large-for-gestational age babies and other adverse pregnancy outcomes (11). Furthermore, excessive GWG has been reported to correlate with the offspring’s BMI, abdominal fat and adverse cardiovascular risk factors in childhood and adulthood (12, 13). On the maternal side, excessive GWG increased the women’s risk of long-term weight gain and obesity (14). High maternal pre-gestational BMI has been found to be associated with excessive GWG (15). However, others reported that lean mothers had a significantly higher GWG compared to obese mothers (16, 17). The objectives of this prospective longitudinal study were to comparatively assess the pattern of GWG among normogylycemic obese and lean mothers and to assess the relation between GWG and fetal intrauterine growth rate and anthropometry at birth.
Material and methods The project was approved by the Local Research Ethics Committee in Sheffield, approval number 08/41308/198 dated 16/12/2008. Written informed consent was obtained from the mothers at the commencement of the study. The study was conducted in a tertiary center in a university-based teaching hospital. The study participants were recruited in their first trimester, from pregnant women aged between 18 and 40 years who were either primiparous or had one previous live birth. Women with prepregnancy medical problems or who developed antenatal complications, likely to affect fetal growth, were excluded. Only obese (BMI >30 kg/m2) or lean women (BMI 19-25) were invited to take part. Maternal body weight (kg) and height (m) were measured using an electronic weighing device and a fixed stadiometer respectively. BMI was calculated using Quetlet index [BMI= weight (kg) /height 2 (m)] and the cut-offs proposed by theWorld Health Organization for BMI (18) were used to identify obese and lean women. The waist and hip circumferences were measured in the first trimester using
This article is protected by copyright. All rights reserved.
Accepted Article
inelastic pocket tape measure and the waist to hip ratio was calculated by dividing the waist circumference by the hip circumference. Maternal body weight was recorded in each trimester. The women were seen at their first (booking) antenatal visit [V1], at second trimester (24-28 weeks) [V2] and third trimester (36-38 weeks) [V3]. Only those who attended prior to their 14th week of gestation at V1 were included in the study so that the early pregnancy maternal anthropometry would be more reflective of pre-pregnancy measures. All obese mothers underwent a 75g oral glucose tolerance test at 24-28 weeks gestation and diabetic mothers were excluded. Insulin was also assayed in the fasting and 2-hour postprandial samples. Insulin resistance index was calculated using the Homeostasis Model Assessment- Insulin Resistance (HOMA-IR). The use of the HOMA-IR for assessment of insulin resistance has been previously described (19).
Fetal intrauterine growth was assessed via serial measures of femur length and abdominal and head circumferences in the second and third trimesters using trans-abdominal ultrasound scanning performed by a single experienced investigator. The growth trajectories of the femur length (FLT), abdominal circumference (ACT) and head circumference (HCT) were calculated using the formula [100 * (measurement at 3rd trimester – measurement at 2nd trimester)/measurement at 2nd trimester]. The formula was obtained from http://www.ehow.com/how_4532706_calculate-growthrate-percent-change.html. Birthweight, crown-heel length and head circumference were recorded at birth. Birthweight was measured with an electronic self-calibrating scale (SECA, Birmingham, UK). Supine crown-heel length was measured using a length board Rollameter-60 (provided by Harlow health care). An inelastic measuring tape was used to measure the fetal head circumference (a maximum front-occipital circumference). Ponderal index (PI), an index of the baby’s adiposity (20), was calculated using the following formula PI= 100*[weight (gm)/crown heel length3 (cm)]. Placental weight was also recorded. Birthweight, crown-heel length and head circumference were converted to standard deviation scores (SDS) to adjust for the variations in birthweight due to gender and gestational age. http://homepage.mac.com/tjcole/FileSharing1.html.
Insulin was determined by Direct Chemiluminescence Immunoassay using Siemens ADVIA Centaur automated analysers (Siemens AG. Erlangen, Germany) . It is a solid phase, two-site Chemiluminescent Immunometric Assay. The test is highly specific for insulin with no cross-reactivity with proinsulin, glucagon, c-peptide, secretin or gastrin-1. The Beckman Coulter DxC 800 System GLUCm method was used to determine glucose concentration by an oxygen rate method employing the Beckman Coulter Oxygen electrode (Beckman Coulter Inc., Brea, CA, USA).
Statistical analysis The data distribution was assessed using the Shapiro-Wilk test (21). Maternal GWG in the second trimester was calculated by subtracting maternal weight in V1 from that in V2 and was labelled
This article is protected by copyright. All rights reserved.
Accepted Article
GWG-1. Similarly, maternal GWG in the third trimester was calculated by subtracting maternal weight in V2 from that in V3 which was labelled GWG-2. To analyse the overall longitudinal trend in weight changes the approach of Matthews et.al (22) was used, whereby the slope of the maternal weight in the three trimesters was calculated. Subsequently, the linear contrast of gestational weight was calculated to summarise the trend in GWG in each individual which takes into account the different weight changes in the second and third trimesters. A single sample t-test on the linear contrasts was computed which tested a null hypothesis that the mean linear contrast was equal to zero (i.e. on average there is no trend up or down over time) against an alternative hypothesis that the mean linear contrast was not equal to zero (i.e. on average there is a trend up or down over time). The calculated slopes as well as GWG-1 and GWG-2 were compared between the obese and lean groups using t-test or Mann-Whitney test according to the data distribution. The GWG slope was correlated with fetal anthropometry and intrauterine growth trajectories and maternal early pregnancy anthropometry in each group using Spearman or Pearson correlation analyses according to the nature of data distribution. Further, the obese mothers’ GWG slope was correlated with their fasting and postprandial insulin and glucose and HOMA-IR.
The intrauterine calculated growth trajectories and birth anthropometry were compared between the babies of the obese and lean mothers using the Student’s t-test or the Mann-Whitney U-test according to the data distribution. Logistic regression analysis was used to correlate the categorical to continuous variables where appropriate. Fisher’s exact test was used to compare proportions. The statistical analyses were carried out using the SPSS-18 (SPSS, Chicago, IL, USA). A p value of 4000 g) was 10/46 (21%) and 1/30 (3%) in the obese and lean groups respectively and the difference was significant (p=0.042).
As shown in Table 1 and Fig. 1 the GWG slope was significant in both lean [(t=14.6, p
