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Timing of Excessive Pregnancy-Related Weight Gain and Offspring Adiposity at Birth

Davenport, Margie H., PhD; Ruchat, Stephanie-May, PhD; Giroux, Isabelle, RD, PhD; Sopper, Maggie M., PhD; Mottola, Michelle F., PhD, FACSM

doi: 10.1097/AOG.0b013e31829a3b86
Original Research
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OBJECTIVE: To evaluate whether the timing of excessive maternal weight gain in a cohort of women following current guidelines for healthy living during pregnancy affects neonatal adiposity at birth.

METHODS: One hundred seventy-two healthy women who were at least 18 years old with body mass indexes (BMIs) of at least 18.5 were recruited between 16 weeks and 20 weeks of gestation. The cohort followed healthy living guidelines during pregnancy and were retrospectively grouped according to 2009 Institute of Medicine guidelines for weight gain in the first and second halves of pregnancy: 1) appropriate gestational weight gain (ie, within Institute of Medicine recommendations) in the first and second halves of pregnancy (“overall appropriate”); 2) appropriate gestational weight gain in the first half of pregnancy and excessive gestational weight gain in the second half of pregnancy (“late excessive”); 3) excessive gestational weight gain in the first half of pregnancy and appropriate gestational weight gain in the second half of pregnancy (“early excessive”); and 4) excessive gestational weight gain throughout pregnancy (“overall excessive”). Primary measures included neonatal weight, length, BMI, and body fat at birth measured 6–18 hours after delivery. Neonatal body fat greater than 14% was considered excessive.

RESULTS: Neonates of women who gained excessively in the first half of pregnancy exhibited greater heel-crown length, birth weight, and excessive body fat (“early excessive” 17.5±3.1%, “overall excessive” 18.7±3.3%) compared with those born to women who gained appropriately (“overall appropriate” 13.2±4.1%; “late excessive” 14.7±3.3%; P<.01). Neonates of women who gained excessively in the first half of pregnancy had an increased risk (odds ratio [OR] 2.64, 95% confidence interval [CI] 1.35–5.17) of elevated body fat at birth compared with neonates of women with total excessive weight gain (OR 1.49, 95% CI 0.80–2.79).

CONCLUSION: Timing of excessive weight gain is an important factor influencing neonatal morphometrics. Prevention of early excessive weight gain should be encouraged in the period before conception and reinforced early in pregnancy.

LEVEL OF EVIDENCE: II

Timing of excessive gestational weight gain is an important factor influencing adiposity at birth.

Physical Activity and Diabetes Laboratory, Faculty of Physical Education and Recreation, the Women and Children's Health Research Institute, and the Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada; the R. Samuel McLaughlin Foundation–Exercise & Pregnancy Laboratory, School of Kinesiology, Faculty of Health Sciences, the Department of Anatomy and Cell Biology, Schulich School of Medicine, and the Children's Health Research Institute, Western University, London, Ontario, Canada; and the Nutrition Program, Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada.

Corresponding author: Margie H. Davenport, PhD, Physical Activity and Diabetes Laboratory, 1-059D Li Ka Shing Centre for Health Research Innovation, University of Alberta, Edmonton, Alberta, Canada T6G 2E1; e-mail: margie.davenport@ualberta.ca.

Financial Disclosure The authors did not report any potential conflicts of interest.

Funded by the Canadian Institutes of Health Research (CIHR). Dr. Davenport was supported by the CIHR Doctoral Research Award and the Heart and Stroke Foundation/CIHR Focus on Stroke Fellowship. Dr. Ruchat was supported by a Canadian Diabetes Association Fellowship.

The authors thank Dr. Craig Steinback for critical review of the manuscript.

The prevalence of obesity and associated adverse perinatal outcomes in obstetric populations are increasing.1,2 Current epidemiologic evidence suggests that the intrauterine environment plays an important role in the developmental origins of adult disease including the in utero programming of obesity and diabetes mellitus.3,4 This fetal origin of obesity hypothesis is supported by a strong association between increased maternal prepregnancy weight and excessive gestational weight gain with increased neonatal birth weight and adiposity, which predicts elevated body mass index (BMI, calculated as weight (kg)/[height (m)]2) in childhood.5–11 Evidence from animal models of obesity has also linked maternal overnutrition during pregnancy with offspring obesity later in life.12–14

Current guidelines developed by the Institute of Medicine to prevent adverse maternal and neonatal outcomes detail the recommended total gestational weight gain during pregnancy based on prepregnancy BMI.15 Regardless of prepregnancy BMI, all women are recommended to gain 0.5–2.0 kg in the first trimester, whereas weekly gestational weight gain in the second and third trimesters is based on prepregnancy BMI.15 The Institute of Medicine recommends that health care providers discuss with their pregnant patients appropriate weight gain guidelines as well as individualized nutrition and physical activity strategies to prevent excessive gestational weight gain.15 Although the influence of total weight gain during pregnancy has been described, the timing of overnutrition and resulting excessive gestational weight gain on neonatal outcome at birth has not been examined. Therefore, our aim was to evaluate whether the timing of excessive maternal weight gain in a cohort of women following current guidelines for healthy living during pregnancy affects neonatal adiposity at birth.16,17 We hypothesized that excessive weight gain during the second half of pregnancy would increase body fat deposition in the neonate because this is when the majority of fat deposition occurs during fetal growth and development.

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MATERIALS AND METHODS

Between 1995 and 2011, 172 healthy, nonsmoking women (prepregnancy BMI at least 18.5 and at least 18 years old) between 16 weeks and 20 weeks of gestation were recruited through physician and midwife referrals, posters, and newspaper advertisements in London, Ontario, Canada. Women with multiple gestations, chronic disease (ie, gestational diabetes mellitus, preeclampsia), or contraindications to exercise were excluded.16 Ethics approval was obtained from the Human Research Ethics Board for Health Sciences at the University of Western Ontario, and written informed consent was obtained from participants.

After being medically prescreened (PARmed-X for Pregnancy)16 by their primary health care providers at study entry (16–20 weeks of gestation), information was collected on maternal age, parity, week of gestation (confirmed by routine ultrasonography), maternal height, and self-reported prepregnancy weight. Prepregnancy weight and height were used to calculate prepregnancy BMI. Body weight at study entry was measured and rounded to the nearest 0.1 kg.

All participants were encouraged to follow a basic exercise program reflecting healthy active living during pregnancy.16–20 The basic program consisted of aerobic exercise three to four times per week beginning with 25 minutes, building 2 minutes per week until 40 minutes per session was achieved (including a 5-minute warm-up and cool down).20

Each participant received nutrition information designed to meet nutritional needs and promote healthy weight gain during pregnancy after baseline measures were assessed. Nutritional recommendations included: 1) a total energy intake between 1,800 and 2,000 kcal/d−1 (7,520 and 8,360 kJ/d−1); 2) 210 g per day (40–55% of total daily energy intake) of complex sources of carbohydrates; 3) 30% of total daily energy intake as fat substituting monounsaturated and polyunsaturated fatty acids for saturated and transfatty acids; and 4) the balance of total daily energy intake from low-fat protein sources spread over three meals and three to four snacks per day.20,21

Total maternal gestational weight gain was scored against the 2009 Institute of Medicine guidelines for weight gain during pregnancy to determine whether excessive weight was gained based on prepregnancy BMI.15 Total maternal gestational weight gain was calculated as last measured weight before delivery (generally the week before delivery, but always less than 1 month before delivery) minus prepregnancy weight. Early maternal gestational weight gain was determined to be the difference between body weight at 16–20 weeks of gestation (study entry) and prepregnancy weight. Excessive early maternal gestational weight gain was calculated as measured weight at study entry–prepregnancy weight–(2.0 kg+[X *{week of gestation at study entry–12}]), where 2.0 kg is the maximum recommended weight gain in the first trimester (up to 12 weeks of gestation) and X is the maximum recommended weekly weight gain based on prepregnancy BMI (18.5–24.9: 0.45 kg/week; 25.0–29.9: 0.32 kg/week; 30.0 or more: 0.27 kg/week15). Late maternal weight gain was calculated as the difference between last body weight measured before delivery and body weight measured at 16–20 weeks of gestation (study entry).

Excessive late pregnancy weight gain was calculated as last measured weight before delivery–measured weight at study entry–(week of gestation of last weight before delivery–week of gestation at study entry)*X, where X is the recommended weekly weight gain based on prepregnancy BMI.15

Neonatal body weight was recorded from medical records at birth. Neonatal morphometrics were measured 6–18 hours after delivery. Length and circumference morphometrics were measured to the nearest 0.5 cm.22,23 Neonatal crown–heel length was measured on a flat, hard surface and used the tonic neck reflex to prevent flexion of the leg. Neonatal BMI was calculated. The suprailiac skinfold was measured on the left side in the midaxillary line above the crest of the ilium to the nearest millimeter using calipers.22,23 The skin, but not the underlying muscle, was gently grasped with the thumb and index finger approximately 2.5 cm apart. The skin was lifted away from the body and the caliper was placed perpendicular to the skinfold and allowed to gently squeeze the skinfold using the technique outlined by Catalano et al22 and Dauncey et al.23

Neonatal fat mass was calculated using the methods of both Catalano et al22 and Dauncey et al.23 The Catalano method is based on comparisons of the Dauncey method and measurements of total body electrical conductivity and validated by estimates of fat mass using total body electrical conductivity.22 Because both methods yielded similar results, for the purpose of the present study, neonatal body fat was expressed using the Catalano method. Percent body fat was calculated as 100×fat mass/birth weight. Based on the Catalano method, these authors suggested that neonatal fat typically constitutes 12–14% of total birth weight at term; therefore, body fat greater than 14% was considered excessive.22

All data are expressed as mean±standard deviation unless otherwise stated. The strength of the association among maternal prepregnancy BMI, maternal total weight gain, neonatal birth weight, neonatal BMI, and body fat were determined using the Pearson product-moment correlation coefficient. The partial correlation between total maternal weight gain and neonatal body fat was also conducted after controlling for maternal prepregnancy BMI. Descriptive analysis was performed using a one-way analysis of variance. Tukey's post hoc analysis was used to compare means when main effects were found to be significant using analysis of variance.

To examine the influence of timing of maternal gestational weight gain on neonatal body fat, participants were separated into four groups: 1) appropriate gestational weight gain (ie, within Institute of Medicine recommendations) in the first and second halves of pregnancy (“overall appropriate”); 2) appropriate gestational weight gain in the first half of pregnancy and excessive gestational weight gain in the second half of pregnancy (“late excessive”); 3) excessive gestational weight gain in the first half of pregnancy and appropriate gestational weight gain in the second half of pregnancy (“early excessive”); and 4) excessive gestational weight gain throughout pregnancy (“overall excessive”). The effect of timing of maternal gestational weight gain on neonatal body fat was performed by analysis of covariance in which neonatal body fat was the dependent variable, timing of maternal gestational weight gain was the fixed factor, and maternal prepregnancy BMI (continuous), total gestational weight gain (continuous), maternal age (continuous), gestational age at delivery (continuous), and neonatal sex were the covariates. Bonferroni post hoc analysis was used to compare main effects found to be significant using analysis of covariance. Finally, to examine whether total gestational weight gain or timing of gestational weight gain better predicted neonatal body fat at birth, two linear regression equations were developed and coefficient of determinations (R2) calculated. The first equation included neonatal body fat as the dependent variable and prepregnancy BMI, total gestational weight gain, maternal age, gestational age at delivery, and neonatal sex as independent variables. The second equation included neonatal body fat as the dependent variable and prepregnancy BMI, timing of maternal gestational weight gain, maternal age, gestational age at delivery, and neonatal sex as independent variables. Fisher z-test was used to determine whether there were significant differences between the two equations. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) to determine the effect of early excessive weight gain on the presence of neonatal adiposity of at least 14% using a two-by-two contingency table. Furthermore, the effect of total excessive weight gain on the presence of neonatal adiposity of at least 14% was assessed by using a two-by-two contingency table. Statistical analyses were performed using SPSS 16.0. Statistical significance was assumed at P<.05. Despite a relatively small sample size, all comparisons were appropriately powered (power of performed test with α=0.05 was at least 0.9 for all analyses using G*Power 3.1.5).

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RESULTS

Maternal and neonatal characteristics are presented in Table 1. As expected, maternal prepregnancy BMI was correlated with total maternal weight gain (r=−0.229, P=.001), neonatal birth weight (r=0.158, P=.043), neonatal BMI (r=0.180, P=.020), and neonatal body fat (r=0.152, P=.046). The correlation between total maternal weight gain and neonatal body fat remained significant after controlling for maternal prepregnancy BMI (r=0.135, P=.047).

Table 1

Table 1

For 52% of participants, total gestational weight gain was excessive. However, there was no difference in neonatal body fat at birth between women who gained an appropriate compared with excessive amount of total gestational weight gain when stratified by prepregnancy BMI (Fig. 1). As expected, the frequency of neonates with a birth weight of at least 4,000 g (macrosomia) increased from 5.2% to 12.1% to 28.5% for women with a normal, overweight, and obese prepregnancy BMI, respectively (P<.01 between obese and normal and overweight). Only two neonates were born with a body weight less than 2,500 g (both in the “overall excessive” group; one normal weight, one obese, nonsignificant).

Fig. 1

Fig. 1

To assess the effect of timing of gestational weight gain, maternal and neonatal characteristics were separated by the timing of excessive gestational weight gain (ie, early compared with late gestation; Table 2). Maternal characteristics were not different between groups. Total gestational weight gain was appropriate for “overall appropriate” and excessive for the “overall excessive” group; however, 45% of “late excessive” and 55% of “early excessive” had excessive total gestational weight gain. Neonates born to women who gained excessively in the first half of pregnancy (“early excessive” and “overall excessive”) exhibited a greater birth weight, crown–heel length, and excessive neonatal body fat compared with women who gained an appropriate amount of weight in the first half of pregnancy (“overall appropriate” and “late excessive”; Table 2). Furthermore, neonates of women who gained excessively in the first half of pregnancy exhibited excessive body fat (“early excessive” 17.5±3.1%; “overall excessive” 18.7±3.3%) compared with those born to women who gained appropriately (“overall appropriate” 13.2±4.1%; “late excessive” 14.7±3.3%; P<.01). These differences remained significant after controlling for maternal prepregnancy BMI, total maternal weight gain, maternal age, gestational age at delivery, and neonatal sex (neonatal body fat: F=19.2, P<.01; Fig. 2; birth weight: F=94.0, P<.01).

Table 2

Table 2

Fig. 2

Fig. 2

Because approximately half of the women in the “late excessive” and “early excessive” groups had excessive total gestational weight gain, we conducted a post hoc subanalysis to compare neonatal body fat between women who had total excessive weight gain and those who had total appropriate gestational weight gain (regardless of timing of gestational weight gain) in each of the two groups (Fig. 2B). This analysis revealed that neonatal body fat was not different whether total gestational weight gain was excessive or appropriate within the “late excessive” or “early excessive” group. This is internally consistent with the regression analyses, which demonstrated that the equation including timing of maternal gestational weight gain better predicted neonatal body fat (R2=0.328, F=14.529, Z=2.42, P<.01) than the equation including total maternal gestational weight gain (R2=0.077, F=2.485, P=.034). Neonates of women who gained excessively in the first half of pregnancy had an increased risk (OR 2.64, 95% CI 1.35–5.17) of elevated body fat at birth compared with neonates of women with total excessive weight gain (OR 1.49, 95% CI 0.80–2.79).

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DISCUSSION

Contrary to our hypothesis, we found that timing of excessive gestational weight gain in the first half of pregnancy is a strong predictor of excessive neonatal body fat at birth. This finding was further supported by the regression analysis and OR, which also demonstrated that timing of excessive gestational weight gain was more important than total excessive gestational weight gain in predicting excessive neonatal adiposity. These data indicate a direct linkage between the early maternal intrauterine environment and subsequent neonatal adiposity and obesity at birth. Implementing preventive measures in the period before conception or in early pregnancy may be necessary to prevent early excessive gestational weight gain and its potential detrimental effects on the neonate.

The potential mechanisms linking excessive early gestational weight gain and excessive neonatal adiposity have not been determined. Although this may simply be a reflection of the neonate’s inheritance of the maternal propensity to gain weight, a study of 150,000 women demonstrated that even small increases in weight between pregnancies elevated the risk of subsequent large-for-gestational-age neonates.24 This suggests that environmental factors play an important role in neonatal growth. The results of the present study support this hypothesis because early excessive gestational weight gain gave rise to an increased prevalence of macrosomia in this cohort. Cetin et al25 suggested that nutrition during the period around conception may also be an important factor in fetal organ development. In fact, overnutrition and undernutrition, which alter the maternal metabolic environment in the first few weeks of pregnancy, may induce epigenetic changes in DNA methylation, which could increase the risk of chronic disease, including obesity later in life.26 Catalano et al27 examined the influence of pregravid, early, and late gestation maternal metabolism on neonatal adiposity at birth. The authors demonstrated that pregravid insulin sensitivity was strongly correlated to fat mass at birth and suggested that this decreased insulin sensitivity may influence early placental development by altering lipid and cytokine gene expression, which affect placental nutrient transfer later in pregnancy.27,28 Although the timing of excessive gestational weight gain was not assessed in these previous studies,27 early excessive gestational weight gain may induce a similar decrease in insulin sensitivity29,30 and potentially alter the hormonal milieu of the intrauterine environment, affecting fetal adiposity.

Few studies have examined the timing of overnutrition during pregnancy on fetal outcome. The Avon Longitudinal Study of Parents and Children demonstrated that any weight gain in the first 14 weeks of gestation was associated with elevated neonatal adiposity at 9 years of age; however, only excessive weight gain of at least 500 g per week between 14 weeks and 36 weeks of gestation was associated with increased adiposity after 9 years.31 In contrast, the effects of undernutrition in early compared with late gestation on fetal adiposity have been studied in both human and animal models. The best known human model examining the timing of undernutrition during pregnancy is the Dutch Hunger Famine Studies. Nutritional restriction in the first trimester was related to increased rates of obesity in the neonates, whereas famine later in pregnancy resulted in decreased rates of obesity.32 Animal evidence has demonstrated that events occurring during the period around conception can directly affect fetal growth and development at the end of pregnancy. Bloomfield et al33 studied the influence of undernutrition during the period around conception on the fetal hypothalamic–pituitary–adrenal axis before birth in sheep. They demonstrated that undernutrition early in pregnancy resulted in accelerated maturation of the hypothalamic–pituitary–adrenal axis, which is essential for the maturation of organ systems and intrauterine homeostasis. Taken together, these data support the evidence that events occurring early in gestation may have an effect on the short-term (ie, at birth) and long-term health of the neonate and growing child.

There are several strengths to this study. First, our study used repeated measures, which allowed us to directly measure maternal body weight at two points during pregnancy to assess maternal weight gain. Second, we assessed neonatal body composition (using the published techniques of Catalano et al22 and Dauncey et al23) 6–18 hours after birth to reduce the effect of postpartum influences. The major limitation of the present study was that prepregnancy weight was not measured; however, self-reported prepregnancy weight has been validated to be similar to measured prepregnancy weight and was unlikely to have affected our results.9 Another limitation was the timespan of the study; however, all women had access to the same health care because this did not change over the years, and all women were given the same information on healthy living during pregnancy. Finally, Catalano et al22 suggest that neonatal fat typically constitutes 12–14% of total body weight at term. Therefore, using a similar methodology in the present study, we defined neonatal body fat above 14% as excessive; however, we recognize that this may be an arbitrary definition.

In conclusion, our results demonstrate that excessive gestational weight gain in the first half of pregnancy was associated with excessive body fat accumulation in the neonate at birth, suggesting an important role of the early maternal in utero environment on fetal programming of obesity. As such, prevention of early excessive gestational weight gain with healthy lifestyle counseling starting before conception or as soon as pregnancy is confirmed may be necessary to prevent the potential deleterious effects of early excessive gestational weight gain on obesogenic adiposity development in the fetus, future child, and adult.

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