Abstract
Objective.
To characterize changes in body composition during obese pregnancy.
Methods.
Fifty-four healthy women with obesity (class 1, 30–34.9 kg/m2: n=25, class 2, 35–39.9 kg/m2: n=21, class 3, ≥40.0 kg/m2: n=8) expecting a singleton pregnancy were studied. Body composition was measured in early (13–16 weeks), mid (24–27 weeks) and late pregnancy (35–37 weeks) using air displacement plethysmography, stable isotopes and skinfold thickness measurements. Fasting glucose, insulin, and leptin were measured.
Results.
The gain in fat-free mass was lower in the second trimester compared to the third (2.7±0.2 to 5.3±0.2 kg, P<0.001), whereas fat mass accumulation declined over time (0.6±0.3 to −0.7±0.4 kg, P=0.005). Women with class 1 and 2 obesity gained 1.1±0.7 kg fat mass during pregnancy, while women with class 3 obesity lost 4.1±0.6 kg (both, P<0.001). The difference in fat accumulation between obesity classes were observed only in the second trimester (P=0.02). Gestational weight gain associated positively with changes in plasma concentrations of insulin, leptin and insulin resistance (all, P<0.01).
Conclusions.
Gestational weight gain in pregnancy differs by obesity class and trimester. Women with class 3 obesity gain less body weight and fat mass. Fat mass gain is most likely preventable in the second trimester.
Keywords: Pregnancy, Obesity, Body Composition, Doubly labeled water, Air Displacement Plethysmography
Introduction
For women with obesity, the 2009 Institute of Medicine guidelines suggest that optimal pregnancy outcomes can be achieved when gestational weight gain is 5–9 kilograms (1). Unfortunately, two out of every three women with obesity gain more weight than recommended (2) increasing the risks of obesity and type 2 diabetes mellitus in both the mother and her baby (3, 4, 5, 6, 7).
The Institute of Medicine guidelines acknowledge insufficient data prevented the current weight gain guidelines from providing independent weight gain recommendations for each obesity class. Since then, epidemiological studies suggest the inverse association between maternal BMI and healthy weight gain observed in non-obese women (1, 8), also continues with obesity severity (9, 10, 11, 12, 13, 14). Thereby, opposed to the 5–9 kg weight gain currently recommended for all women with obesity, optimal pregnancy outcomes may require further weight gain restrictions for women with a BMI greater than 35 kg/m2, and weight maintenance or even weight loss for women with a BMI greater than 40 kg/m2.
To advance the management of gestational weight gain in women with obesity, the contributions of fat mass, fat-free mass and fetal mass to weight gain need to be understood. Among non-obese women, fat mass is the most variable component of gestational weight gain (8, 15). In women with obesity, only few studies have assessed the partitioning of gestational weight gain (16, 17), but none has assessed differences by obesity class and trimester.
To address these gaps, the aim of this prospective, observational study is to measure body composition in women with mild to severe obesity throughout pregnancy. We hypothesized that weight gain would be inversely associated with obesity class and that fat mass would be the most variable component.
Methods
Study Design:
This is a pre-planned secondary analysis of a prospective observational study on the determinants of weight gain in obese pregnancy (16). Seventy-two women with obesity (BMI≥30 kg/m2) were enrolled prior to 15 weeks gestation. Participants completed three study visits commensurate with the beginning (13–16 weeks) and end of the second trimester (24–27 weeks) and end of the third trimester (35–37 weeks). Differences in weight gain and changes in fat mass, fat-free mass and fetal growth were assessed by obesity class (class 1: 30.0–34.9 kg/m2, class 2: 35–39.9 kg/m2, class 3: ≥40.0 kg/m2). The primary outcome was weight gain and the change in fat mass from early (13–16 weeks) to late (35–37 weeks) gestation, measured by a 3-compartment model (using densitometry combined with hydrometry). Secondary outcomes included changes in body components other than fat mass, trimester-specific changes in body composition, metabolic biomarkers, and subcutaneous adipose tissue assessed by skinfold thickness measurements. The study was approved by the Pennington Biomedical Research Center Institutional Review Board, and participants provided written informed consent prior to participation.
Participants:
Eligible women were 18–40 years old, had obesity (BMI≥30 kg/m2 at ≤15 weeks of gestation), a confirmed viable, singleton pregnancy (>6 weeks gestation) and reported no current or history of disease, use of medication or supplements that would interfere with study outcomes (18). To study women with obesity who were otherwise healthy, participants were excluded for smoking, alcohol intake, drug use (prescription or recreational), hypertension (>160/110 mmHg), diabetes (HbA1c≥6.5%), severe anemia (Hb<8 g/dL and/or Hct <24%). Women that developed pre-eclampsia (n=4) were excluded from the analysis due to prescribed bedrest and evidence of edema which would interfere with weight gain outcomes. Participants were recruited from January 2015 to January 2017 through community and social media advertisements and referrals by local midwives and obstetricians as previously described.
Body Composition:
Methods have been described in detail previously (18). Body weight and composition were measured after an overnight fast. Body weight was measured in a clinic gown on an electronic scale, and body volume in spandex clothing by air displacement plethysmography (ADP, BodPod®, COSMED, Concord, CA). Body volume was corrected for thoracic gas volume estimated by BodPod software and a pregnancy-related decline of 100 mL per trimester (19), as validated in more recent studies (20, 21). Total body water was measured by stable isotope dilution using doubly-labeled water (DLW) over 7 days (1.25g of 10% enriched H218O and 0.10g of 99.9% enriched 2H2O per kg) (8). Body water was calculated as mean estimate of using 0-intercepts of 2H and 18O-isotopes, and using the mean of the measured individual and trimester-specific group-average ND/NO-ratios. Fat mass was calculated per 3-Compartment model per Siri and Catalano (8, 22, 23): FM=2.118*BV–0.78*TBW–1.354*BW, where FM=fat mass (kg), BV=body volume (L), TBW=total body water (L), and BW=body weight (kg).
To allow weight and body composition change to be partitioned by trimester, body composition was also measured mid gestation (24–27 weeks) using air displacement plethysmography to obtain a 2-compartment model. Hydration and density of fat-free mass were estimated based on van Raaij-data (24) using hFFM=0.724+0.00008484*GA+0.00001435*GA2, and dFFM=1.10.00002988*GA-0.00000731*GA2, in which hFFM is hydration of fat-free mass in (L/kg), GA is gestational age (weeks), and dFFM is density of fat-free mass (kg/L) (8).
Subcutaneous adipose tissue deposition was assessed with skinfold thickness at six sites (triceps, biceps, subscapular, iliac crest, mid-thigh, mid-calf) using Harpenden skinfold calipers (Baty International, West Sussex, UK) by two trained assessors who were re-certified annually. Thickness at each site was measured in duplicate, or triplicate if the first two measurements deviated by >20%, which is the tolerance limit stated by NHANES (25). The two closest measurements were used for calculations.
Fetal Weight:
Fetal weight was estimated by 3-D ultrasound assessments (GE Logiq E9, GE Medical Systems; Milwaukee, WI, and 4D View, GE Healthcare) with measurements of head circumference, biparietal diameter, abdominal circumference, and femoral length and volume (26), obtained by the same sonographer.
Metabolic Biomarkers:
A fasting blood sample was collected in the morning following a standardized dinner and 12 hour fast for measurement of glucose (DXC600, Beckman Coulter Inc., Brea, CA), insulin (ELISA, Immulite 2000, Siemens, Broussard, LA) and leptin (RIA, Millipore, Burlington, MA).
Statistics:
Data are reported as frequencies and means with standard errors (SEM) based on a linear model. Least square means from the linear models were used to test differences between obesity classes (primary outcome) with a p-value less than 0.05 considered as statistically significant. Changes in body weight and body composition components are reported in kilograms throughout the observation period, but each was analyzed appropriately as changes in grams per week (data in Supplemental Material). Post-hoc testing was only performed, if the main effect of obesity class was significant. Associations between anthropometric and metabolic measures were performed using Pearson’s Correlation Coefficient. We performed linear regression to determine the contribution of fat mass and fat-free mass (independent variables, expressed as standardized ß, in %) to the variability of gestational weight gain (dependent variable). Analyses were carried out using SAS, Version 9.4 (SAS Institute, Cary, NC).
Results
Of 72 women enrolled, we obtained complete primary outcome-data of fifty-four subjects (16). The average BMI at enrollment (11.3±0.3 weeks) was 35.8±0.7 kg/m2, ranging from 30.2 kg/m2 to 57.1 kg/m2. Twenty-five women (46%) were classified as class 1 obesity, 21 (39%) as class 2 obesity, and 8 (15%) as class 3 obesity (Figure 1A). Demographic characteristics were not different between obesity classes (Table 1). As expected, with increasing obesity, women had more fat mass (in kg and as percent).
Figure 1. Enrollment BMI Distribution, Gestational Weight Gain and its Components.
Women with class 1, 2 and 3 obesity are presented in white, grey and black, respectively. Data is presented as frequency (A), individual data points (B-F), and as mean±SEM (G). (A) Enrollment BMI was assessed <15 weeks gestation. (B-F) Linear regressions were performed to assess associations between enrollment BMI and change in body weight (B), fat mass (c), fat-free mass (D), water (E) and fetal size (F). Body composition was measured using air displacement plethysmography, doubly-labelled water, and fetal weight by 3D-ultrasound.
Table 1.
Subjects Characteristics
| Class 1, n=25 | Class 2, n=21 | Class 3, n=8 | P | |
|---|---|---|---|---|
| Maternal Demographics | ||||
| Age, years | 27.4 ± 0.9 | 26.7 ± 1.0 | 30.3 ± 1.6 | 0.18 |
| Parity, n (0, 1, ≥2) | 8, 8, 9 | 12, 8, 1 | 3, 3, 2 | 0.15 |
| Race, n (AA, W, O) | 10, 14, 1 | 9, 10, 2 | 3, 4, 1 | 0.91 |
| Education, n (1, 2, 3) | 3, 17, 5 | 4, 13, 4 | 1, 4, 3 | 0.25 |
| Poverty-to-Income-Ratio | 3.7 ± 0.5 | 3.5 ± 0.6 | 4.1 ± 0.9 | 0.84 |
| Maternal Anthropometrics | ||||
| Gestational Age, weeks | 11.8 ± 0.4 | 11.1 ± 0.5 | 10.4 ± 0.8 | 0.23 |
| Body Height, m | 163.1 ± 1.6 | 163.9 ± 1.7 | 164.5 ± 2.8 | 0.89 |
| Body Weight, kg | 85.3 ± 2.1 | 99.1 ± 2.2 | 122.0 ± 3.6 | <.001 |
| Body-Mass-Index, kg/m2 | 32.0 ± 0.5 | 36.9 ± 0.5 | 45.0 ± 0.8 | <.001 |
| Pregnancy Complications | ||||
| Gestational Diabetes Mellitus, n | 2 (8%) | 4 (20%) | 1 (13%) | 0.54 |
| Gestational Hypertension, n | 0 (0%) | 1 (5%) | 3 (38%) | 0.002 |
| Delivery Outcomes | ||||
| Gestational Age, weeks | 39.4 ± 0.2 | 39.6 ± 0.2 | 39.6 ± 0.4 | 0.74 |
| Anemia, n | 2 (8%) | 0 (0%) | 0 (0%) | 0.30 |
| Labor Type, n (0, 1, 2) | 8, 8, 9 | 3, 17, 1 | 3, 4, 1 | 0.01 |
| Delivery Type, n (1, 2, 3) | 14, 3, 8 | 12, 6, 3 | 4, 1, 3 | 0.43 |
| Shoulder Dystocia, n | 0 (0%) | 0 (0%) | 0 (0%) | |
| Infant Outcomes | ||||
| Fetal Sex, n (F, M) | 11, 14 | 10, 11 | 6, 2 | 0.30 |
| Birth Weight, g | 3349 ± 92 | 3541 ± 100 | 3598 ± 163 | 0.25 |
| Birth Length, cm | 51.0 ± 0.5 | 50.9 ± 0.6 | 50.8 ± 1.0 | 0.99 |
| Infant Size, n (SGA, LGA) | 1, 2 | 0, 5 | 0, 3 | 0.28 |
Education is categorized into High School diploma (1); college (2); post-graduate work (3), Labor Types: no labor (0); spontaneous/augmented (1); induced (2), Delivery Types: spontaneous vaginal (1); caesarean section with labor (2); caesarean section without labor (3), AA, African-American, W, White, O, others; AGA, appropriate for gestational age, LGA, large for gestational age, SGA, small for gestational age. P indicates the statistical significance for a main effect of obesity class. Posthoc comparisons were only performed, if P≤0.05; groups with shared letters are not statistically different from each other.
Total Weight Gain and Body Composition by 3-Compartment Model
On average, women gained 7.8±0.6 kg from 14.9±0.1 to 35.9±0.1 weeks gestation (observation period: 21.1±0.1 weeks). Total weight gain was negatively associated with enrollment BMI (Figure 1B). We observed no difference in total weight gain between women with class 1 and 2 obesity (8.4±0.9 and 8.8±1.0 kg, respectively), but significantly less weight gain was observed in women with class 3 obesity (3.5±1.5 kg, P<0.01 vs both class 1 and 2).
Individual differences in total gestational weight gain were largely explained by changes in fat mass (74%, P<0.001), and less influenced by changes in fat-free mass (26%, P<0.001). The gain in fat mass was significantly lower in women with class 3 obesity as compared to women with class 1 and 2 obesity (class 1: 1.1±0.7, class 2: 1.1±0.7, class 3: −4.1±1.2 kg, both: P<0.001, Figure 1C). Gains in fat-free mass, water accumulation and fetal growth were not different between obesity classes (Figures 1D–F).
Trimester Differences by 2-Compartment Model
Overall (n=54), gestational weight gain tended to be lower in the second trimester compared to the third trimester (3.4±0.4 and 4.4±0.4 kg, P=0.08, Figure 2, Table 2). Higher weight gain in the third trimester was due to a significant increase in fetal weight (0.8±0.03 to 1.9±0.05 kg, P<0.001), and accumulation of fat-free mass (2.7±0.2 to 5.2±0.3 kg, P<0.001). In contrast, fat mass increased in the second trimester and decreased in the third trimester (0.6±0.3 to −0.7±0.4 kg, P=0.005, Figure 2, Table 2).
Figure 2. Components of Gestational Weight Gain by Trimester.
Women were classified as class 1, 2 and 3 obesity at enrollment (<15 weeks gestation). Data is presented as mean±SEM. The average change in body weight (white circles) and its components (stacked bars) was assessed from early pregnancy (14.9±0.1 weeks) to mid-pregnancy (25.1±0.1 weeks) and late pregnancy (35.9±0.1 weeks). Body composition was measured using air displacement plethysmography, doubly-labelled water, and fetal weight by 3D-ultrasound. Total body water accumulation at 24–27 weeks was estimated using hydration constant measured at 35–37 weeks. For statistical analysis, see Table 2.
Table 2.
Changes in Body Composition by Trimester
| Class 1, n=25 | Class 2, n=21 | Class 3, n=8 | P | |
|---|---|---|---|---|
| Body Weight | ||||
| Enrollment, kg | 85.7 ± 1.6a | 99.0 ± 2.1b | 120.9 ± 6.1c | <0.001 |
| Second, kg | 3.5 ± 0.6a, b | 4.1 ± 0.5b | 1.3 ± 0.6 c | 0.04 |
| Third, kg | 4.9 ± 0.6 | 4.6 ± 0.7 | 2.3 ± 0.5 | 0.07 |
| Fetal Weight | ||||
| Enrollment, g | 78 ± 4 | 86 ± 7 | 74 ± 7 | 0.40 |
| Second, kg | 0.8 ± 0.1 | 0.8 ± 0.03 | 0.7 ± 0.1 | 0.84 |
| Third, kg | 1.8 ± 0.1 | 2.0 ± 0.1 | 2.0 ± 0.2 | 0.12 |
| Fat-Free Mass | ||||
| Enrollment, kg | 50.2 ± 1.2a, b | 54.3 ± 1.6b | 59.4 ± 3.5b, c | <0.001 |
| Second, kg | 2.5 ± 0.3 | 2.8 ± 0.5 | 3.4 ± 0.8 | 0.46 |
| Third, kg | 5.1 ± 0.4 | 5.5 ± 0.7 | 4.8 ± 0.7 | 0.71 |
| Fat Mass | ||||
| Enrollment, % | 41.5 ± 0.8a | 45.3 ± 0.8b | 50.7 ± 2.3c | <0.001 |
| Enrollment, kg | 35.6 ± 1.0a | 44.8 ± 1.2b | 61.5 ± 4.8c | <0.001 |
| Second, kg | 0.9 ± 0.5 a | 1.3 ± 0.4 a | −2.1 ± 0.7 b | 0.002 |
| Third, kg | −0.2 ± 0.5 | −0.6 ± 0.8 | −2.5 ± 0.7 | 0.19 |
Women were classified as class 1, 2 and 3 obesity at enrollment (<15 weeks gestation). Data is presented as mean±SEM. The initial measurement of body composition (air displacement plethysmography) was performed in early pregnancy (‘enrollment’, 14.9±0.1 weeks), and the changes are reported for the second trimester (until 25.1±0.1 weeks), and for the third trimester (25.1±0.1 to 35.9±0.1 weeks). The statistical analysis was performed on the change in body mass per week. P indicates the statistical significance for a main effect of obesity class. Posthoc comparisons were only performed, if P≤0.05; groups with shared letters are not statistically different from each other.
The higher gain of fat-free mass and fetal size in the third trimester as compared to the second trimester was consistent for all obesity classes. In contrast, changes in fat mass were significantly different between obesity classes during the second trimester (P=0.002, Table 2, Figure 2). While women with obesity class 3 lost fat mass in the second trimester, women with class 1 and 2 obesity gained fat mass. We observed no differences in the losses of fat mass during the third trimester (P=0.19).
Subcutaneous Adipose Tissue Depots
The results of skinfold thickness measurements are presented in Table 3. Skinfold thickness was larger in women with more severe obesity at all sites, indicating subcutaneous adiposity was associated with maternal BMI (for all sites, r>0.57, P<0.001). Overall (n=54), we did not observe an increase in the sum of skinfolds (P=0.12). Changes in skinfold thickness were inversely related to body size (sum of skinfolds, P=0.04). Women with class 1 obesity had the largest increase in skinfold thickness (23±5 mm) compared to women with class 2 obesity (17±7 mm) and women with class 3 obesity reduced skinfold thickness (−10±14 mm).
Table 3.
Changes in Skinfold Thicknesses by Trimester
| Class 1, n=25 | Class 2, n=21 | Class 3, n=8 | P | |
|---|---|---|---|---|
| Sum | ||||
| Enrollment, mm | 160 ± 5a | 204 ± 5b | 239 ± 8 c | <0.001 |
| Second, mm | 10.4 ± 6.1 | 3.5 ± 6.7 | 1.4 ± 10.8 | 0.67 |
| Third, mm | 12.6 ± 5.7 | 13.3 ± 6.2 | −11.1 ± 10.1 | 0.10 |
| Triceps | ||||
| Enrollment, mm | 25.5 ± 0.9 a | 31.0 ± 1.0 b | 36.5 ± 1.6 c | <0.001 |
| Second, mm | 0.1 ± 1.0 | −1.3 ± 1.1 | −1.7 ± 1.8 | 0.55 |
| Third, mm | 1.2 ± 0.9 | 2.4 ± 1.0 | −0.9 ± 1.7 | 0.25 |
| Biceps | ||||
| Enrollment, mm | 12.9 ± 0.7 a | 17.7 ± 0.8 b | 23.8 ± 1.2 c | <0.001 |
| Second, mm | 1.6 ± 0.7 | −0.2 ± 0.77 | −1.4 ± 1.3 | 0.07 |
| Third, mm | −0.9 ± 0.7 | −0.04 ± 0.7 | −1.1 ± 1.2 | 0.61 |
| Subscapular | ||||
| Enrollment, mm | 26.9 ± 0.9 a | 31.7 ± 1.0 b | 38.8 ± 1.6 c | <0.001 |
| Second, mm | 0.1 ± 1.1 | 0.5 ± 1.1 | −0.5 ± 1.9 | 0.89 |
| Third, mm | 1.7 ± 1.0 a | 1.5 ± 1.1a | −5.1 ± 1.7 b | 0.004 |
| Iliac Crest | ||||
| Enrollment, mm | 30.8 ± 1.4 a | 41.3 ± 1.6 b | 46.3 ± 2.5 b | <0.001 |
| Second, mm | 3.9 ± 1.7 | 3.4 ± 2.1 | 2.7 ± 3.5 | 0.95 |
| Third, mm | 5.4 ± 2.2 | 2.8 ± 2.4 | −1.1 ± 3.9 | 0.35 |
| Mid-Thigh | ||||
| Enrollment, mm | 42.0 ± 1.6 a | 55.2 ± 1.7 b | 60.2 ± 2.8 b | <0.001 |
| Second, mm | 3.2 ± 2.2 | 1.3 ± 2.4 | 3.5 ± 3.9 | 0.82 |
| Third, mm | 3.3 ± 1.9 | 3.9 ± 2.0 | −2.6 ± 3.3 | 0.23 |
| Mid-Calf | ||||
| Enrollment, mm | 22.2 ± 1.0 a | 27.2 ± 1.1 b | 33.4 ± 1.8c | <0.001 |
| Second, mm | 1.4 ± 1.1 | −0.4 ± 1.2 | −1.1 ± 1.9 | 0.38 |
| Third, mm | 2.0 ± 1.2 | 2.8 ± 1.3 | −0.3 ± 2.1 | 0.48 |
Women were classified as class 1, 2 and 3 obesity at enrollment (<15 weeks gestation). Data is presented as mean±SEM. The initial measurement of skinfold thicknesses was performed in early pregnancy (14.9±0.1 weeks), and the changes are reported for the second trimester (until 25.1±0.1 weeks), and for the third trimester (25.1±0.1 to 35.9±0.1 weeks). P indicates the statistical significance for a main effect of obesity class. Posthoc comparisons were only performed, if P≤0.05; groups with shared letters are not statistically different from each other.
Significant increases in skinfold thicknesses were observed at the iliac crest (7.0±1.4 mm, P=0.003) and mid-thigh (5.2±1.2 mm, P=0.01). Between obesity classes, only the change in subscapular skinfold thickness significantly differed by obesity class, and was smaller with increased obesity (P=0.002, Table 3).
Metabolic Biomarkers
At enrollment, maternal BMI positively correlated with insulin resistance, i.e. HOMA-IR (r=0.50, P<0.001), insulin (r=0.51, P<0.001), and leptin (r=0.63, P<0.001), but did not correlate with changes in fasting plasma concentrations of glucose, insulin and leptin across pregnancy. We observed significant differences per trimester by obesity class (Figure 3). In women with class 1 and 2 obesity, glucose concentrations decreased during the second trimester (P=0.03), and increased during the third trimester (P<0.05), whereas glucose concentrations remained unchanged in women with class 3 obesity. Increases in insulin concentrations were more pronounced during the third trimester, and not different by obesity class (second trimester, P=0.32; third trimester, P=0.31). Leptin concentrations did not change differently between obesity classes (P=0.15). Fat accumulation during pregnancy were positively associated with changes in fasting plasma concentrations of insulin (r=0.46, P<0.001) and leptin (r=0.72, P<0.001, Figure 3).
Figure 3. Changes in Metabolic Biomarkers in Obese Pregnancy and the Relationship with Gestational Weight and Fat Mass.
Women were classified as obesity class 1 (white circles), 2 (grey circles) and 3 (black circles) at enrollment (<15 weeks gestation). Data is presented as mean±SEM. Plasma concentrations were assessed in early pregnancy (Visit 1, 14.9±0.1 weeks), mid-pregnancy (Visit 2, 25.1±0.1 weeks) and late pregnancy (Visit 3, 35.9±0.1 weeks). Panels A, C, E and G show the measured plasma concentration at each visit; panels B, D, F and H show the associations between fat accumulation during pregnancy and the change in plasma concentrations as percent change from early to late pregnancy. Statistical significance of the difference between obesity classes in early pregnancy is indicated as *, if P<0.05. Linear regression were used to assess the association between weight gain and changes in plasma concentrations.
Discussion
Pregnancy is a defining period for future health in women and children, with gestational weight gain being one of the most important determinants. We hereby report a natural experiment in an exclusive cohort of pregnant women with obesity who were studied for changes in body composition using state-of-the-art methodologies (air displacement plethysmography and isotope dilution). The present study is novel in that it provides a new understanding of the composition of gestational weight gain specific to each obesity class and trimester. We demonstrated that fat mass accumulation negatively associates with enrollment BMI, but not other components of gestational weight gain. Furthermore, the prospective study design provides novel insights toward understanding the most opportune window for prevention of excess fat accumulation, that is the second trimester. The study also allows recent epidemiological data that challenges recommendations for healthy gestational weight gain by the 2009 Institute of Medicine guidelines to be better interpreted. We show that weight maintenance for women with obesity would require fat mass loss >5kg.
In our study, maternal body size early in pregnancy was negatively associated with gestational weight gain, which is in line with epidemiological studies (9, 10, 11, 12, 13, 14). The inverse association between body size and weight gain is postulated to reflect a biological adaptation of women with increased adiposity to minimize the risk for pregnancy complications and infant outcomes (1, 27). The present study is the first to use gold-standard methodologies, i.e. air displacement plethysmography combined with stable isotope dilution, and show that differences in weight gain during obese pregnancy are largely due to differences in fat accumulation. This data supports the hypothesis that interventions successful in limiting gestational weight gain in obese pregnancy–such as through dietary restriction–would affect fat accumulation, with a minor impact on infant growth, fluid expansion in amniotic fluid and blood and placental development (1, 8, 15, 28). Differences in body composition changes were not associated with pregnancy complications, e.g. gestational diabetes or hypertension (16, 29). To our knowledge, studies in pregnant women with obesity have not yet evaluated the effect of weight gain modification on body composition.
The rate of gestational weight gain was comparable between the second and third trimester for all women, consistent with the pattern in non-obese women (1). However, the composition of weight gain, i.e. fat-free mass and fat mass, differs per trimester. In the second trimester, weight gain is comprised largely of fat mass accumulation whereas, in the third trimester, weight gain is comprised of fat-free mass accumulation, fetal growth and loss of fat. This implies that the second trimester is a more opportune window for limiting excess fat accumulation. This observation is particularly important because fetal adiposity is more susceptible to excess maternal weight gain early in pregnancy (30).
The localization of fat mass deposition is an important measure for understanding the risk of adiposity on metabolic health. Consistent with measurements of whole-body fat mass using plethysmography and isotope dilution, we observed by means of skinfold thickness measurements that changes in subcutaneous adipose tissue were inversely related to obesity class. In specific subcutaneous adipose tissue depots, differences and changes were inconclusive. The most pronounced changes occurred at the iliac crest and on the mid-thigh, but the most pronounced difference between obesity classes were observed at the subscapular site. More objective measures of adipose tissue deposition, such as acquisition by magnetic resonance imaging, are required to inform about storage or mobilization of fat mass. The limitations of imaging techniques include the uncertainty of safety during the first trimester and the costs of acquisition and analysis.
Through this prospective assessment of body composition during obese pregnancy, we show for the first time that weight maintenance or weight loss in pregnant women with obesity would likely be achieved through a reduction of fat mass. Women with class 3 obesity gained 3.5 kg overall, which resulted from 4.1 kg of fat loss and a 7.6 kg increase in fat-free mass. Assuming that fat-free mass accumulation is fairly constant among all women (15, 28), more conservative weight gain recommendations such as weight maintenance would yield 5–8 kg of fat loss during pregnancy. As we recently published, weight maintenance and hence fat loss in pregnancy would require a daily energy deficit of ~300 kcal/d or 10% dietary energy restriction across the second and third trimesters (16). Epidemiological studies have already suggested that a dietary energy deficit is required for women with obesity to minimize risk for gestational hypertension, high birth weight, infant mortality, and delivery complications (9, 10, 11, 12, 13, 14). The long-term effects of such approaches on fetal development remain to be determined.
The negative association between maternal BMI and weight gain suggests the existence of signals related to obesity may limit gestational weight gain. Insulin resistance was more pronounced in women with class 3 obesity early in pregnancy (16). However, the potential benefit of insulin resistance on weight gain is secondary, because we (29) and others (31) have shown that dysglycemia in early pregnancy increases the risk for gestational diabetes development, offspring insulin resistance (32) and other pregnancy complications such as impaired placental metabolism, preeclampsia and fetal overgrowth (33). The observed increases in insulin resistance during pregnancy associated with weight gain are likely a result of increased fat accumulation rather than a cause for weight gain. Increased fat accumulation strongly associated with changes in leptin concentrations during pregnancy. Thereby, increased leptin concentrations may provide an important mediator of the association between maternal and infant fat accumulation, because maternal leptin concentrations have been associated with infant adiposity in multiple studies (34, 35, 36).
The findings of this study are strengthened by the inclusion of exclusively obese women and the use of multiple objective measures of body composition. The use of this comprehensive battery of state-of-the-art methodologies for nutrition research limits the available sample size, which especially in women with class 3 obesity, is small. However, these results are robust. Using the applied methods, we are limited in our ability to distinguish between maternal and fetal components to gestational weight gain, or to specify fetal adiposity, which is likely small (<0.5 kg) (37). Thoracic gas volume was estimated, but not measured, because in this cohort of women with obesity, only half of the measurements produced reliable data (73/162, 45%), while this appears to be less problematic in non-obese women (71–94%) (20, 21, 38). We acknowledge that findings on the determinants of weight gain are correlational in nature and causality cannot be inferred. Measurements of subcutaneous adipose tissue depots are prone to high variability and other important determinants of adipose tissue deposition such as body shape (apple vs pear) or insulin sensitivity need to be considered. However, the measurements were executed by two annually certified investigators to ensure minimal systematic error.
To conclude, we demonstrate that the inverse association between maternal BMI and gestational weight gain persists in women with obesity. The differences in weight gain between obesity classes is explained by differences in fat gain as opposed to fat-free mass and fetal growth. We have previously demonstrated that these differences occur as a result of differences in energy balance (16), but the metabolic and behavioral determinants of energy balance are highly variable between women. Fat mass accumulation was higher in the second trimester as compared to the third, which implies that prevention strategies will likely have increased efficacy when initiated early in pregnancy. Adhering to healthy weight gain trajectories may offer an unexpected opportunity to reduce adiposity in obese pregnancy due to fat loss. However, it is premature to call for adjustments of gestational weight gain recommendations, because future studies must assess the effects of low gestational weight gain in women with obesity on other outcomes such as infant development and lactation.
What is already known about this subject?
Healthy gestational weight gain is inversely related to body size
Fat mass is the most variable component of gestational weight gain in non-obese pregnancy
What does your study add?
Weight and body composition changes during pregnancy differ by obesity class
Fat mass is gained during the second trimester, but not third
‘Inadequate’ weight gain is the result of fat loss
Acknowledgements
We would like to thank our study participants and acknowledge administrative support from Porsha Vallo, Natalie Comardelle, and technical assistance of Dr. Jennifer Rood, Dr. Owen Carmichael, Kori Murray, Loren Cain, Kimberly Landry, Stephen Lee, Melissa Erickson, and Brian Gilmore.
The dataset pertaining to the current study is available upon written request. Resources will be shared in accordance with appropriate data use agreements and IRB approvals for secondary analyses. Further information and requests for resources and reagents should be directed to and will be fulfilled by the Lead Contact, Leanne Redman (leanne.redman@pbrc.edu).
Funding: This study was funded by the National Institutes of Health (R01DK099175; Redman) and Core support via U54GM104940; Ryan, P30DK072476; Ravussin.
Footnotes
Trial registered at Clinicaltrials.gov:
Disclosures: The authors declared no conflict of interest.
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