Original Article
Maternal adiposity and blood pressure in pregnancy: varying relations by ethnicity and gestational diabetes Wai-Yee Lim a, Kenneth Kwek b,c, Yap-Seng Chong d, Yung-Seng Lee e,f, Fabian Yap b,c, Yiong-Huak Chan g, Keith M. Godfrey h,i, Peter D. Gluckman f,j, Seang-Mei Saw a,c,, and An Pan a,c,
Objective: Greater maternal adiposity is a potentially modifiable risk factor for elevated blood pressure during pregnancy; however, the association has been little studied in Asian populations, and no study has evaluated potential differences in the adiposity-blood pressure relation between ethnic groups or interaction with gestational diabetes. Methods: We performed a cross-sectional evaluation of a Singapore mother-offspring cohort comprising 799 pregnant Chinese, Malay and Indian women. Data on body weight, height, skinfold thickness and glycaemia (oral glucose tolerance test) were collected during the 2nd trimester; peripheral SBP and DBP were measured using an oscillometric device and central pressures by noninvasive radial applanation tonometry. The associations between adiposity measures BMI and sum of skinfold thickness and blood pressure outcomes were examined by linear regression with adjustment for potential confounders. Results: Higher maternal BMI was associated with elevated peripheral and central pressures: the increases in pressure (mmHg) for each kg/m2 increase in BMI were 1.19 (95% confidence interval, 1.03–1.36) for peripheral SBP, 0.76 (0.63–0.89) for peripheral DBP, 1.02 (0.87–1.17) for central systolic pressure and 0.26 (0.16–0.37) for central pulse pressure. The associations were generally stronger in Chinese women (P-interaction ¼ 0.03 for central pulse pressure) and individuals with gestational diabetes (P-interaction ¼ 0.03 for DBP and P-interaction ¼ 0.046 for central systolic pressure). Similar patterns of results were found when using skinfold thickness as the measure of adiposity. Conclusion: Maternal adiposity is associated with higher peripheral and central blood pressures during pregnancy. Stronger associations in Chinese women and individuals with gestational diabetes warrant further investigation. Keywords: central blood pressure, ethnicity, gestational diabetes, obesity, peripheral blood pressure, pregnancy Abbreviations: CAPP, central pulse pressure; CASP, central systolic pressure; CI, confidence interval; GDM, gestational diabetes
caesarean delivery [1,2]. The pathophysiology of hypertension in pregnancy is unclear, and a number of risk factors have been proposed, including older maternal age, smoking, nulliparity, previous abortions, multiple pregnancy and obesity [3,4]. Previous studies have mainly focused on the relation between obesity and peripheral blood pressures in pregnancy, but less is known for central blood pressures, which is of interest because they reflect different cardiovascular adaptations compared with peripheral pressures [5,6]. Meanwhile, most studies of the obesity-blood pressure relation have been conducted in whites, and studies in Asian women and particularly pregnant women are very limited. Furthermore, no study has specifically assessed differences in the obesity-blood pressure relation within Asian pregnant women of different ethnicities. The three major Asian ethnic groups, Chinese, Indian and Malay, composed of more than 43% of the total global population, and obesity has increasingly become a major public health problem in the three ethnicities [7,8], with important implications for adverse pregnancy outcomes in the populations and potential long-term impact on the mothers and their offspring [9,10]. Some studies suggest that there are ethnic differences in predisposition to obesity within Asians [11], and obesity may be differentially related to insulin resistance and inflammatory markers among Chinese, Malays and Indians [12].
Journal of Hypertension 2014, 32:857–864 a Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, bKK Women’s and Children’s Hospital, cYong Loo Lin School of Medicine, National University of Singapore and National University Health System, dDepartment of Obstetrics & Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, e Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, fSingapore Institute for Clinical Sciences, Agency for Science and Technology Research (A’STAR), gMedicine Dean’s Office, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, hMedical Research Council Lifecourse Epidemiology Unit, University of Southampton, iNIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK and jLiggins Institute, University of Auckland, Auckland, New Zealand
Correspondence to Dr An Pan, Saw Swee Hock School of Public Health, National University of Singapore, 16 Medical Drive, Singapore 117597, Republic of Singapore. Tel: +65 6516 4972; fax: +65 6779 1489; e-mail: [email protected].
INTRODUCTION
H
igh blood pressure affects 10–12% of pregnancies, and it is associated with adverse pregnancy outcomes including eclampsia, preterm birth and
Journal of Hypertension
Seang-Mei Saw and An Pan contributed equally to the writing of this article.
Received 20 September 2012 Accepted 28 November 2013 J Hypertens 32:857–864 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. DOI:10.1097/HJH.0000000000000096
www.jhypertension.com
857
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Lim et al.
Therefore, we examined the association of maternal adiposity with peripheral and central blood pressures as measures of arterial compliance in a large cohort of South Asian pregnant women in Singapore. As the cohort members were from three major ethnic groups (Chinese, Malay and Indian), we also aimed to investigate whether the associations were modified by ethnicity. Lastly, as obesity and gestational diabetes are prevalent in Asian women [13], we assessed their independent and joint associations with blood pressures across ethnicities of South Asian women.
METHODS Study participants The study participants were drawn from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort study [14], which composed of 1162 pregnant women recruited from KK Women’s and Children’s Hospital and National University Hospital during 2009 and 2010. We recruited pregnant women who were Singapore citizens or permanent residents, and who conceived naturally and intended to deliver at the two hospitals. We only included pregnant women who were Chinese, Malay or Indian with homogenous parental ethnic background. Women with type 1 diabetes, on chemotherapy or psychotropic drugs were excluded. Among the 893 (76.8%) women who attended the GUSTO 2nd trimester study visit for blood pressures and radial pulse waves measurement, 64 women were excluded because of poor measurement of radial pulse wave forms and 30 women because of missing information on age, weight or height measurements. Therefore, data from 799 (89.5%) women were available for analysis. No significant differences in age and BMI were found between women who were included and excluded from analysis because of poor measurement of radial pulse wave forms (data not shown). The GUSTO study was approved by the SingHealth and National Health Group Institutional and Domain Specific Review Boards.
Blood pressure measurement The blood pressure and anthropometric measurements were performed at mean 27 1.2 weeks of gestation during the GUSTO 2nd trimester study visit. Research coordinators were trained prior to commencement of fieldwork, and standard operating procedures were adopted. Participants were required to abstain from caffeine intake for at least 30 min prior to blood pressure measurement. Brachial SBP and DBP pressures were measured thrice at 30–60 s intervals with an oscillometric device MC3100 (HealthSTATS International Pte Ltd, Singapore). We applied the A-pulse tonometer (BPro, HealthSTATS International Pte Ltd, Singapore) on the radial artery of the same arm, for continuous sampling of radial artery waveforms over 1 min following standard procedures [15,16]. These waveforms were calibrated with the averaged brachial pressures to derive the central aortic systolic pressure (CASP). Central aortic pulse pressure (CAPP) was calculated based on the difference between CASP and DBP [17]. The BPro device has shown high agreement and correlation (r2 ¼ 0.98) with invasive central aortic pressures measurements [15,16]. 858
www.jhypertension.com
Adiposity measures (body mass index and skinfold thickness) Maternal height and weight were measured during the 2nd trimester study visit. Height was measured twice to the nearest 0.1 cm, barefooted in the horizontal Frankfort plane using a Seca 213 Portable Stadiometer (SECA, Hamburg, Germany). Weight was measured to the nearest 0.1 kg using a calibrated weighing scale (SECA 803 electronic flat scale: SECA, Hamburg, Germany). Measurements were repeated if readings differed by more than 1 cm and 0.2 kg, respectively, and the average of all three readings were used. BMI (kg/m2) was calculated as weight in kilograms divided by square of height in meters. Skinfold thicknesses were measured at four sites (biceps, triceps, subscapular and suprailiac) following standard procedures [18] using Holtain Tanner/Whitehouse skinfold calipers (Holtain Ltd, Crymych, United Kingdom). All measurements were made in triplicate to nearest 0.2 mm, and the readings were averaged. The sum of skinfold thickness was derived by summating the averaged skinfold thicknesses of the four sites.
Covariates Established risk factors for hypertension were assessed by questionnaire as potential confounders: maternal age, ethnicity, education, parity and preexisting chronic hypertension. Glycaemic status in pregnancy was ascertained using a 75 mg oral glucose tolerance test performed at the same study visit; gestational diabetes was defined as fasting plasma glucose of 7.0 mmol/l or greater or 2-h glucose of 11.1 mmol/l or greater according to the WHO classification [19].
Data analysis Maternal BMI was categorized according to the WHO international classification [20]: underweight (
Maternal adiposity and blood pressure in pregnancy: varying relations by ethnicity and gestational diabetes Wai-Yee Lim a, Kenneth Kwek b,c, Yap-Seng Chong d, Yung-Seng Lee e,f, Fabian Yap b,c, Yiong-Huak Chan g, Keith M. Godfrey h,i, Peter D. Gluckman f,j, Seang-Mei Saw a,c,, and An Pan a,c,
Objective: Greater maternal adiposity is a potentially modifiable risk factor for elevated blood pressure during pregnancy; however, the association has been little studied in Asian populations, and no study has evaluated potential differences in the adiposity-blood pressure relation between ethnic groups or interaction with gestational diabetes. Methods: We performed a cross-sectional evaluation of a Singapore mother-offspring cohort comprising 799 pregnant Chinese, Malay and Indian women. Data on body weight, height, skinfold thickness and glycaemia (oral glucose tolerance test) were collected during the 2nd trimester; peripheral SBP and DBP were measured using an oscillometric device and central pressures by noninvasive radial applanation tonometry. The associations between adiposity measures BMI and sum of skinfold thickness and blood pressure outcomes were examined by linear regression with adjustment for potential confounders. Results: Higher maternal BMI was associated with elevated peripheral and central pressures: the increases in pressure (mmHg) for each kg/m2 increase in BMI were 1.19 (95% confidence interval, 1.03–1.36) for peripheral SBP, 0.76 (0.63–0.89) for peripheral DBP, 1.02 (0.87–1.17) for central systolic pressure and 0.26 (0.16–0.37) for central pulse pressure. The associations were generally stronger in Chinese women (P-interaction ¼ 0.03 for central pulse pressure) and individuals with gestational diabetes (P-interaction ¼ 0.03 for DBP and P-interaction ¼ 0.046 for central systolic pressure). Similar patterns of results were found when using skinfold thickness as the measure of adiposity. Conclusion: Maternal adiposity is associated with higher peripheral and central blood pressures during pregnancy. Stronger associations in Chinese women and individuals with gestational diabetes warrant further investigation. Keywords: central blood pressure, ethnicity, gestational diabetes, obesity, peripheral blood pressure, pregnancy Abbreviations: CAPP, central pulse pressure; CASP, central systolic pressure; CI, confidence interval; GDM, gestational diabetes
caesarean delivery [1,2]. The pathophysiology of hypertension in pregnancy is unclear, and a number of risk factors have been proposed, including older maternal age, smoking, nulliparity, previous abortions, multiple pregnancy and obesity [3,4]. Previous studies have mainly focused on the relation between obesity and peripheral blood pressures in pregnancy, but less is known for central blood pressures, which is of interest because they reflect different cardiovascular adaptations compared with peripheral pressures [5,6]. Meanwhile, most studies of the obesity-blood pressure relation have been conducted in whites, and studies in Asian women and particularly pregnant women are very limited. Furthermore, no study has specifically assessed differences in the obesity-blood pressure relation within Asian pregnant women of different ethnicities. The three major Asian ethnic groups, Chinese, Indian and Malay, composed of more than 43% of the total global population, and obesity has increasingly become a major public health problem in the three ethnicities [7,8], with important implications for adverse pregnancy outcomes in the populations and potential long-term impact on the mothers and their offspring [9,10]. Some studies suggest that there are ethnic differences in predisposition to obesity within Asians [11], and obesity may be differentially related to insulin resistance and inflammatory markers among Chinese, Malays and Indians [12].
Journal of Hypertension 2014, 32:857–864 a Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, bKK Women’s and Children’s Hospital, cYong Loo Lin School of Medicine, National University of Singapore and National University Health System, dDepartment of Obstetrics & Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, e Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, fSingapore Institute for Clinical Sciences, Agency for Science and Technology Research (A’STAR), gMedicine Dean’s Office, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, hMedical Research Council Lifecourse Epidemiology Unit, University of Southampton, iNIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK and jLiggins Institute, University of Auckland, Auckland, New Zealand
Correspondence to Dr An Pan, Saw Swee Hock School of Public Health, National University of Singapore, 16 Medical Drive, Singapore 117597, Republic of Singapore. Tel: +65 6516 4972; fax: +65 6779 1489; e-mail: [email protected].
INTRODUCTION
H
igh blood pressure affects 10–12% of pregnancies, and it is associated with adverse pregnancy outcomes including eclampsia, preterm birth and
Journal of Hypertension
Seang-Mei Saw and An Pan contributed equally to the writing of this article.
Received 20 September 2012 Accepted 28 November 2013 J Hypertens 32:857–864 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. DOI:10.1097/HJH.0000000000000096
www.jhypertension.com
857
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Lim et al.
Therefore, we examined the association of maternal adiposity with peripheral and central blood pressures as measures of arterial compliance in a large cohort of South Asian pregnant women in Singapore. As the cohort members were from three major ethnic groups (Chinese, Malay and Indian), we also aimed to investigate whether the associations were modified by ethnicity. Lastly, as obesity and gestational diabetes are prevalent in Asian women [13], we assessed their independent and joint associations with blood pressures across ethnicities of South Asian women.
METHODS Study participants The study participants were drawn from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort study [14], which composed of 1162 pregnant women recruited from KK Women’s and Children’s Hospital and National University Hospital during 2009 and 2010. We recruited pregnant women who were Singapore citizens or permanent residents, and who conceived naturally and intended to deliver at the two hospitals. We only included pregnant women who were Chinese, Malay or Indian with homogenous parental ethnic background. Women with type 1 diabetes, on chemotherapy or psychotropic drugs were excluded. Among the 893 (76.8%) women who attended the GUSTO 2nd trimester study visit for blood pressures and radial pulse waves measurement, 64 women were excluded because of poor measurement of radial pulse wave forms and 30 women because of missing information on age, weight or height measurements. Therefore, data from 799 (89.5%) women were available for analysis. No significant differences in age and BMI were found between women who were included and excluded from analysis because of poor measurement of radial pulse wave forms (data not shown). The GUSTO study was approved by the SingHealth and National Health Group Institutional and Domain Specific Review Boards.
Blood pressure measurement The blood pressure and anthropometric measurements were performed at mean 27 1.2 weeks of gestation during the GUSTO 2nd trimester study visit. Research coordinators were trained prior to commencement of fieldwork, and standard operating procedures were adopted. Participants were required to abstain from caffeine intake for at least 30 min prior to blood pressure measurement. Brachial SBP and DBP pressures were measured thrice at 30–60 s intervals with an oscillometric device MC3100 (HealthSTATS International Pte Ltd, Singapore). We applied the A-pulse tonometer (BPro, HealthSTATS International Pte Ltd, Singapore) on the radial artery of the same arm, for continuous sampling of radial artery waveforms over 1 min following standard procedures [15,16]. These waveforms were calibrated with the averaged brachial pressures to derive the central aortic systolic pressure (CASP). Central aortic pulse pressure (CAPP) was calculated based on the difference between CASP and DBP [17]. The BPro device has shown high agreement and correlation (r2 ¼ 0.98) with invasive central aortic pressures measurements [15,16]. 858
www.jhypertension.com
Adiposity measures (body mass index and skinfold thickness) Maternal height and weight were measured during the 2nd trimester study visit. Height was measured twice to the nearest 0.1 cm, barefooted in the horizontal Frankfort plane using a Seca 213 Portable Stadiometer (SECA, Hamburg, Germany). Weight was measured to the nearest 0.1 kg using a calibrated weighing scale (SECA 803 electronic flat scale: SECA, Hamburg, Germany). Measurements were repeated if readings differed by more than 1 cm and 0.2 kg, respectively, and the average of all three readings were used. BMI (kg/m2) was calculated as weight in kilograms divided by square of height in meters. Skinfold thicknesses were measured at four sites (biceps, triceps, subscapular and suprailiac) following standard procedures [18] using Holtain Tanner/Whitehouse skinfold calipers (Holtain Ltd, Crymych, United Kingdom). All measurements were made in triplicate to nearest 0.2 mm, and the readings were averaged. The sum of skinfold thickness was derived by summating the averaged skinfold thicknesses of the four sites.
Covariates Established risk factors for hypertension were assessed by questionnaire as potential confounders: maternal age, ethnicity, education, parity and preexisting chronic hypertension. Glycaemic status in pregnancy was ascertained using a 75 mg oral glucose tolerance test performed at the same study visit; gestational diabetes was defined as fasting plasma glucose of 7.0 mmol/l or greater or 2-h glucose of 11.1 mmol/l or greater according to the WHO classification [19].
Data analysis Maternal BMI was categorized according to the WHO international classification [20]: underweight (
