Pregnancy is a unique time when the female body is undergoing physiologic and metabolic changes that support fetal development. These physiologic and metabolic changes are recognized in gestational weight gain (GWG), which includes gains in
Nicholas T. Broskey and Kara L. Marlatt are the co-first author.
N. T. Broskey · K. L. Marlatt · L. M. Redman (*)
Reproductive Endocrinology and Women’s Health Lab, Pennington Biomedical Research Center, Baton Rouge, LA, USA
e-mail: [email protected]; [email protected]; [email protected]
maternal and fetal body mass, as well as growth of placental tissue and alterations in amniotic fluid. Indeed, increased medical attention is placed on optimizing mater- nal and fetal outcomes and as such, body composition is recognized as an important modulator of these outcomes in a pregnant woman and her offspring.
Common methods used to assess body composition in a pre-gravid female can- not be directly applied to the pregnant female without adequate adjustments or con- sideration of the drastic deviation in normal body composition. Additionally, while non-invasive and less cumbersome methods of assessing body composition, particu- larly fat mass (FM) and fat-free mass (FFM), are necessary in research and clinical settings, certain methods are clearly more superior to others. Herein many of the common methods to assess body composition are described, as well as their consid- eration for measurement in pregnant women. Finally, changes in body composition throughout pregnancy using these techniques are also discussed.
Methods of Assessment
Anthropometry
Anthropometry via skinfold thickness measurement is a non-invasive method of assessing body composition that is suitable for field research given its use of highly mobile, non-specialized equipment. Specifically, skinfold thickness measurements provide an estimated size of the subcutaneous fat depot directly under the skin. The summation of skinfold thickness measurements at particular areas of the body can be used to obtain an estimation of total subcutaneous body fat. Extensive training and expertise of the technician is necessary to accurately assess skinfold thickness and ensure a high level of reliability both within an individual over time (pregnancy) and also between individuals. Moreover, the appropriate use of necessary equip- ment such as anthropometry tape (Gullick), stadiometer, weight scale, skinfold cali- pers, anthropometer, and segmometer is critical to locate the anatomical site for measurement, and thereby obtain reliable and consistent results while minimizing measurement error.
Pregnancy presents a unique challenge for assessing skinfold thickness due to both tissue expansion and stretch. The increase in individual skinfold thickness dur- ing pregnancy is often greater in underweight women compared to overweight women, and greater at central sites compared to those located in the periphery.
Taggart and colleagues demonstrated the absolute change (millimeters) in individ- ual skinfold thickness at seven anatomical sites (i.e., suprailiac, scapular, costal, biceps, knee-cap, mid-thigh, triceps) occurs between 10 and 30 weeks gestation, yet all sites but thigh, showed little change or decreased thickness from 30 to 38 weeks [1]. Similar observations were reported by Pipe et al. using the summation of four anatomical sites (i.e., triceps, biceps, subscapular, suprailiac); however, slight increases were observed up to 36–38 weeks due to greater gains at the suprailiac site [2]. Additionally, the increase in skinfold thickness during pregnancy is often greater, on average, among primiparae than among multiparae women [1].
Few studies use skinfold thickness during pregnancy to estimate total fat mass.
Equations to estimate body composition from skinfold thickness also use weight and body composition (FM, FFM). While some published models claim to explain a high percentage of the variability in predicting FM or percent body fat, these mod- els cannot be extrapolated across pregnancy, and instead serve to estimate fat mass only at designated time periods [3, 4]. One important anthropometric study [2]
detailed skinfold thickness measures at six different sites across multiple time points before and during pregnancy and related total body fat; however, others have reported that only mediocre multiple correlation coefficients were observed [5].
Similar results have been demonstrated [6, 7], and collectively conclude that use of equations to estimate total body fat from skinfold thickness may be useful in certain groups; however, they are inappropriate for most clinical and research purposes.
With precision being maintained, repeated assessment of subcutaneous fat with skinfold thickness throughout pregnancy can be useful in research and clinical settings.
Bioelectrical Impedance
Bioelectrical Impedance (BIA) is a commonly used non-invasive method that is based on assumptions and relationships in the electrical properties of biological tis- sues. Typically, BIA is performed by placing electrodes on the ankle and wrist, allowing for the flow of low-amperage current to travel throughout the body. The conductivity of the electrical current is determined by the amount of water the bio- logical tissue contains. Tissues with high water content (e.g., muscle) are more con- ductive than tissue with less water content (e.g., bone, fat) and, therefore, the volume of conductive tissue can be calculated from the resistance of the electrical signal throughout body parts. BIA, therefore, allows for an estimation of total body water and subsequently, estimations of FM and FFM. A similar principle to BIA is bio- impedance spectroscopy, which allows for estimation of intracellular and extracel- lular water and thus, total body water (TBW) by summing the two cellular water compartments.
In a validation study for pregnant women, Lof and Forsum [8] utilized wrist-to- ankle bioimpedance spectroscopy during various stages of pregnancy (14 and 32 weeks, 2 weeks postpartum) and reported similar estimates of TBW measured by BIA versus deuterium dilution (the gold standard) early in pregnancy, but the esti- mate of TBW by BIA was underestimated later in pregnancy.
The inherent problem with BIA is that this measurement of body composition is based on TBW, which changes during the course of pregnancy. Therefore, in addi- tion to fluid shifts associated with pregnancy that have a wide degree of inter- and intra-individual variation, hydration status can also affect BIA measurement [9].
Standardization of time of day is therefore important, as well as understanding the hydration status of the individual. Changes in TBW also happen concomitantly with changes in overall composition, adding to the problem of precision and accuracy, bringing into question the feasibility of BIA to measure body composition throughout pregnancy. Otherwise, BIA is a rapid, non-invasive, and inexpensive
method to estimate body composition that is suitable in field settings. Unfortunately, it is unable to decipher between maternal and fetal contributions.
Densitometry
Whole-body densitometry is a non-invasive method to obtain body density of the maternal–fetal unit as a whole. Unfortunately, densitometry is currently unable to separate both the maternal and fetal contribution. Densitometry can be estimated in water (known as hydrodensitometry or underwater weighing), or it can be estimated in air (known as air-displacement plethysmography). Relying on the assumption that the density of FM is constant (0.900 g/cm3) and that FFM density depends on relative contributions of bone, protein, and water, and is estimated as 1.100 g/cm3 in men and women in the pre-gravid state [16], whole-body densitometry commonly applies the equation of Siri to estimate FM [15]:
FM kg Body Mass TBD D FFM D FM D FFM
( )
= æèç ö
ø÷´
( )
( ) ( )
é
ë 100
100 100
1 1
– – êêê
êê
ù
û úú úú
® æèç ö
ø÷´é - ëê
ù ûú Body Mass
TBD 100
495 450
where TBD = total body density, D(FM) = density fat mass (or 0.90 g/cm3), D(FFM)
= 1.10 g/cm3
Moreover, densitometry is thereby based on a 2C model of body composition where body mass is assumed to be a function of FM and FFM (combined). Hence, FFM is derived by subtracting the calculated FM from the total body mass of the individual.
The estimation of FM and FFM during pregnancy with 2C models, though, is more complex because of the well-documented changes in FFM density. In the early stages of pregnancy, small changes in FFM are predominantly due to the expansion of maternal tissue; the growth of these maternal tissues minimally affects the density of FFM. In later stages of pregnancy, however, the density of FFM is reduced due to the increased growth of fetal tissues that have higher water content and subsequently a lower density [17]. The accumulation of water in preg- nancy is gradual, non-linear, and highly variable in women, and may even plateau or decline in late pregnancy [18, 19]. While some scholars suggest that FFM den- sity is the same at 10 weeks when compared to the pre-gravid state (or 1.100 g/cm3) [4, 20], others suggest that FFM density decreases during the first trimester to approximately 1.099 g/cm3 [10]. Table 1 documents the estimated FFM density throughout pregnancy. To provide more accurate estimates of FM and FFM by 2C models applied at the different stages of pregnancy, the appropriate density of FFM should be substituted into densitometry equations (i.e., Siri). Without adjusting
densitometry equations for pregnancy-specific FFM density, FFM will be underes- timated and result in an overestimation of FM.
Careful steps to enhance measurement accuracy through protocol standardization can indeed be implemented; however, estimating body composition via whole- body densitometry is unfortunately prone to high degrees of variability in pregnancy.
Namely, van Raaij et al. demonstrated how the presence of clinical edema can impact hydration and thus, the density of FFM [10]. The temporal relationship of edema adds further complexity to the quantification of FFM density. And while the presence of clinical edema may not be visibly present, the existence of edema may indeed be physically present. Nonetheless, van Raaij et al. [10] and their application of the changes in body composition contributions of Hytten and Leitch to approximate FFM density has become widely recognized as the most well-established method to estimate FFM density during pregnancy [21]. Additionally, while the estimates for FFM density may appear to be relatively consistent throughout the literature, studies are needed to understand the degree to which these FFM densities might be impacted by maternal age, race, and body size as measured by body mass index (BMI).
Underwater Weighing
Underwater weighing is a technique that can apply standard densitometry equations to derive a 2C measure of body mass. With this technique, individuals are com- pletely submerged in a small tank of warm water. The weight of the individual in the water is measured after the individual performs a complete exhalation, to void the lungs and airway of as much residual air volume as possible. Underwater weighing is based off a buoyancy principle formulated by Archimedes, which states that force exerted on an object immersed in water is equal to the weight of the fluid the object displaces [22]. It follows the basic equation:
body volume=
(
weightair–weightwater)
/densitywaterAlthough on its own, underwater weighing provides a 2C estimate of body com- position, underwater weighing has been incorporated into several 4-compartment (4C) models in pregnant women [11, 12]. Underwater weighing has also been mod- eled together with anthropometric measurements of body composition (skinfold thickness triceps, subscapular, suprailiac) during late gestation and shown to predict
Table 1 Changes in fat-free mass density throughout pregnancy (g/cm3)
Study Pre-Gravid 10–14 weeks ~20 weeks 30–32 weeks 35–40 weeks
Van Raaij et al. [10] 1.100 1.099 1.097 1.093 1.087
Fidanza [20] 1.100 1.100 1.097 1.092 1.087
Paxton et al. [4] – 1.100 – – 1.091
Hopkinson et al. [11] – – – – 1.086
91% of the variance in FM [3]. Altering the hydration constants for body density and TBW has been shown to have little impact on measurements of maternal body composition [18]. As pointed out in the previous discussion of densitometry, the major drawback of hydrostatic weighing lies in the estimate of FFM density. Some women may also find it difficult to maximally exhale and undertake complete sub- mersion with occluded nostrils. Nonetheless, underwater weighing is non-invasive and can be performed longitudinally without undue risk.
Air-Displacement Plethysmography (ADP)
ADP is a safe and relatively fast method of quantifying total body density from estimated total body volume, and is therefore becoming a more widely adopted body composition assessment method in vulnerable populations (e.g., pregnant women, infants). ADP is especially applicable where dual-energy X-ray absorpti- ometry techniques are harmful or not recommended. The patented “BodPod” tech- nology (COSMED, Concord, CA, USA) utilizes a dual-chamber model that is based on Boyle’s law, where small contrasts in volume and pressure in each chamber are measured [23]. With correction for thoracic gas and lung volumes by either mea- surement or estimation, total body volume is determined. Thoracic gas volume is measured via an estimation of both functional residual capacity and tidal volume.
While seated inside the measurement chamber, the individual is required to place a plastic tube in the mouth, and with remote coaching from the technician, lightly blow air into a breathing tube connected to the system. Although less accurate, the BodPod software can also predict total lung volume if a direct measurement cannot be adequately obtained by the instrument [24]. An accurate measurement of body volume requires that individuals wear tight-fitting clothing (e.g., lycra swimsuit) to eliminate any residual air from body surface. Table 2 summarizes the relevant BodPod equations that are utilized to estimate FM and FFM.
Advantages of the ADP technique include the high level of safety, therefore allowing repeated measurements across pregnancy, as well as the relative ease and speed of estimating body composition. Disadvantages of the technique in pregnancy are indeed more profound. First, given well-described changes in TBW throughout pregnancy, there is a need to adjust coefficients applied to the estimated FFM den- sity throughout pregnancy to accurately reflect the degree of increased FFM hydra- tion; the manufacturer does not provide these adjustments in the current software.
However, as pointed out earlier, the available FFM density adjustments are outdated and were derived from mostly women of normal weight and without evidence of clinical edema. Second, the ADP technique is not portable, and thus not suitable for field research, and is expensive to operate and maintain. A third disadvantage is the inability to assess body density of a pregnant woman independent of the growing fetus and supporting tissues, which limits the assumptions from BodPod to changes in maternal/fetal tissues. While body composition estimation via a 2C model is accepted, the derived estimate of FM and FFM is subpar compared to 3C or 4C models. It is also likely that measures of FM and FFM by ADP are affected by
variability in the estimation of thoracic gas volume. While seldom discussed in the literature, obtaining an actual measurement of thoracic gas volume by the BodPod is difficult for some individuals, and thus requires the use of predicted equations.
Discrepancies between measured and predicted thoracic gas volume exist and can- not be ignored. For longitudinal measurements, it is important to apply either the measured or estimated thoracic gas volume throughout the assessments to limit this as a potential source of error in the FM and FFM estimations. Finally, residual air may also cause an overestimation of body volume, and adequate attention should be provided to minimize this artifact, especially in pregnant women when the size of the bust and abdomen is changing considerably and could contribute to increased residual air volume.
Imaging
Magnetic Resonance Imaging (MRI)
MRI is an in vivo imaging technique that uses a powerful magnetic field to measure adipose tissue, skeletal muscle, and organ mass. MRI acquisition protocols require that individuals must lie still in a small, enclosed space, often for lengthy periods, while the magnet is running. MRI has several advantages in that it allows for whole- body as well as regional estimates of body composition, and with no exposure to radiation in comparison to DXA. Sohlström and Forsum were one of the first groups
Table 2 Calculations for total body density using air displacement plethysmography Total body
density (TBD) (kg/L)
= Body Mass Body Volume
Body Mass (kg): scale weight derived by BodPod
Body Volume (L): Estimated by BodPod
Body
volume (L) =Vol1+Vol2+( ´TGV)-SAA
2 0 4. Vol1 and Vol2 (L): Lung volume
estimated twice by BodPod via
“Huff” Test
Thoracic Gas Volume (TGV) (L):
Measured or Predicted by BodPod SAA (L): Estimated surface area artifact
Thoracic gas volume (TGV) (L)
Measured TGV = FRC + (0.5 × TV) Predicted TGV (females only) = (0.0360 × Height (cm)) + (0.0031 × Age) − 3.182 + 0.35
Functional Residual Capacity (FRC): Measured by BodPod via
“Huff” test
Tidal Volume (TV): Measured by BodPod via “Huff” test
Predicted TGV (gender-specific, age ≥ 18 years): (Crapo et al. [24]) Surface
area artifact (SAA) (L)
Subjects >110 cm = [71.84 × Body Mass0.425 × Height0.725] × k
Subjects ≤110 cm = [242.65 × Body Mass0.5378 × Height0.725] × k
Subjects >110 cm: (Dubois and Dubois [132])
Subjects ≤110 cm: (Haycock et al.
[133])
Constant k = −0.0000467
to conduct a well-controlled study using MRI in a cohort of 15 Swedish women throughout pregnancy [25]. The MRI showed that of the 7.4 kg gained in pregnancy (to 7 days postpartum), the majority was gained in whole-body subcutaneous adi- pose tissue. Modi et al. also reported a positive correlation between maternal BMI and total adipose tissue gain [26]. A recent cross-sectional analysis of normal weight and overweight/obese pregnant women using MRI to assess body composition at the third trimester [27] found that overweight/obese women had almost two times the amount of total body FM as well as subcutaneous abdominal fat compared to normal-weight women, with no differences in visceral fat between the two groups.
A recent methodological study was performed in obese women during the early second trimester of pregnancy (15–18 weeks) in order to develop a consistent method for calculating subcutaneous and visceral fat area ratios. By varying the thickness and distance of abdominal slices, the group concluded to produce reliable measurements of subcutaneous and visceral fat using MRI between women, the region of interest and acquisition of abdominal slices should be centered above the uterine fundus [28].
MRI research is highly promising in regard to body composition analyses in pregnant women, and will be critical to advance the understanding of the changes in regional fat distribution, particularly fat accumulation within the abdominal com- partment. However, MRI is not without limitations. The most obvious limitation is discomfort attributed to being confined in a small space and position for the scan- ning protocols. Abdominal protocols, while short, can be very difficult and uncom- fortable for pregnant women, especially in the later stages of pregnancy; some protocols require a 15-s breath hold to minimize movement of the chest cavity. In addition, limitations to the field of view will limit accurate abdominal scanning in some women. The MRI scanners can also be noisy; however, newer 3.0 tesla mag- nets are equipped with sound dampeners that reduce noise, and individuals are pro- vided ear protection and plugs as well. The obvious limitation is cost. Many clinical centers charge approximately $600 USD per 30-min of scanning time (sufficient for an abdominal scan), then the cost for analysis of the images is an additional expense.
Manufacturer differences between scanners can introduce problems in standardiz- ing hardware and software among clinical centers. To date, there are no current publications reporting the use of MRI to assess changes in body composition throughout pregnancy; however, two studies employing a whole-body scanning protocol are currently ongoing (MomEE: NCT#01954342; LIFT: NCT#01616147).
Finally, it should be noted that safety of using MRI during the first trimester is ques- tionable and, therefore, estimates of changes in body composition across pregnancy with MRI is only possible from the second trimester onward.
Dual-Energy X-Ray Absorptiometry (DXA)
DXA scans are used to measure total body composition by emitting X-ray beams overhead and throughout the entire body while lying supine. While designed to measure bone mineral density, DXA can also provide measurements of total and