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Pregnancy and maternal weight change van der Wijden, C.

2015

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Download date: 26. Sep. 2021 Summary and general8 discussion R1 R2 R3 R4 R5 R6 R7 R8 R9 R10 R11 R12 R13 R14 R15 R16 R17 R18 R19 R20 R21 R22 R23 R24 R25 R26 R27 R28 R29 R30 R31 R32 R33 R34 R35 R36 R37 R38 R39

110 | Chapter 8 Summary and general discussion R1 R2 Pregnancy and maternal weight change is the central theme of this thesis. R3 Pregnancies, and especially those in which women gain weight excessively, are believed to R4 contribute to weight retention, and the subsequent development or worsening of maternal R5 overweight and obesity (1,2). In addition, excessive gestational weight gain contributes to an R6 increased risk of complications for mother and child during pregnancy, delivery, neonatal life R7 and to obesity in the offspring (3-11). R8 The underlying question of this thesis is ‘how gestational weight gain can be influenced and R9 the consequences thereof’. R10 R11 What did we find? R12 Firstly in chapter 2 evidence was gathered on maternal nutrition in the Netherlands resulting R13 in a narrative review. One of the conclusions was that no simple relationship exists between R14 extra energy needs in pregnancy and extra energy intake advised, and that a universal ‘one R15 size fits all’ advice regarding nutrition for well-nourished Dutch women cannot be justified. It R16 might be better to give a personalized advice. R17 Subsequently, in the New Life(style), a randomized controlled trial (chapter 3), the effects R18 were evaluated of individualized counseling regarding physical activity and nutrition in R19 pregnancy on gestational weight gain and retention as the primary outcomes. The counseling R20 intervention had neither an effect on gestational weight gain nor on weight retention at 52 R21 weeks postpartum. In both the intervention and the control group, women had gained on R22 average 11.3 kg from early to late pregnancy, and they were on average 1 kg lighter at 52 R23 weeks postpartum compared to 15 weeks of pregnancy. R24 Because the counseling intervention had no measurable effect on gestational weight gain we R25 further analysed the study population as a cohort and assessed in chapter 4, whether eating R26 style, as well as behavioral determinants (i.e. attitude, social norm and self-efficacy) were of R27 any significance for gestational weight gain. Interestingly, during pregnancy eating style was R28 unstable in 34% of all women. At first sight emotional eaters gained more weight in pregnancy R29 compared to restrained or external eaters. After hierarchical regression analyses none of the R30 eating styles was associated with gestational weight gain. R31 Attitude, social norm, and self-efficacy were not of any significance on gestational weight gain. R32 R33 Not only total weight gain is important, but also, from a public health perspective, what part of R34 this weight gain is attributable to an increase in maternal adipose tissue. Also of importance R35 is whether the increase in maternal adipose tissue is mostly of visceral or subcutaneous R36 nature. In chapter 5 the concurrent validity was estimated between three different proxies of R37 maternal adipose tissue: i.e. serum leptin, BMI and the sum of 4 skinfolds in pregnancy and the R38 R39

Summary and general discussion | 111 R1 postpartum period. Because of the high correlation between the three methods, all methods R2 seem to be equally suitable to estimate changes in maternal body fat during pregnancy and R3 the year thereafter. However, none of the three methods is capable of differentiating between R4 visceral or subcutaneous adipose tissue. R5 R6 In chapter 6 we analyzed in a longitudinal cohort study the relationship between lifestyle R7 factors and maternal weight change and pregnancy outcomes. Sedentary behavior, physical R8 activity, sleeping patterns and BMI at 15 weeks of pregnancy were not related to gestational R9 weight gain and pregnancy outcomes. Breastfeeding was not related to weight retention. R10 Smoking during pregnancy was related to less weight retention (-5.1 kg) and lighter babies R11 (-323 gram). We also found that many women quit smoking before getting pregnant (41% of R12 76), but that around 50% of them started again after having given birth. R13 Some women (9%) lost >5% of their weight before getting pregnant, possibly preparing R14 themselves to be fit for pregnancy. In our study the women who had lost weight, had more R15 weight retention 52 weeks after delivery (4.9 kg) and delivered heavier babies (377 gram), R16 compared to women with more stable weight before pregnancy. We cannot explain the latter R17 finding, i.e. the heavier babies. The higher weight retention might be explained by a larger R18 yo-yo effect in the women who had lost substantial weight before pregnancy. That is, they R19 returned to their weight from before losing weight before pregnancy. These results show R20 that one needs to extend the study period well beyond pregnancy (i.e. > 1 year) to study R21 relationships between lifestyle factors and maternal weight change and pregnancy outcomes. R22 Total physical activity ( with moderate-to-vigorous intensity physical activity being part of this) R23 and energy expenditure determine energy balance and therefore body weight. In chapter 7 we R24 studied the relationship between moderate-to-vigorous intensity physical activity (MVPA) and R25 body weight. Not surprisingly, we found that MVPA decreased during pregnancy. However, R26 in our study MVPA was neither related to weight gain in pregnancy nor to weight retention. R27 Perhaps such a relationship could not be established because the group of women had very R28 low levels of MVPA. Another explanation could be that gestational weight gain cannot be R29 influenced so easily, because of the physiological processes taking place during pregnancy R30 overruling external stimuli. R31 It is known, mostly from training intervention studies, that PA has an effect on hormones R32 related to energy homeostasis (12-14). Was there any effect of MVPA on these hormones R33 in pregnancy in our study group? The only significant difference between women with levels R34 of MVPA above the median, compared to women with MVPA below the median, was a lower R35 fasting insulin and BMI at 15 weeks of gestation. At no other point in pregnancy or postpartum, R36 significant differences were observed in hormonal markers between women with MVPA below R37 or above the median for MVPA. R38 R39

112 | Chapter 8 What did we learn? R1 In our study we approached the issue of pregnancy and maternal weight change from various R2 perspectives. R3 Most studies reporting on gestational weight change restrict themselves to pregnancy. R4 In our view, aside from weight change in pregnancy, weight change after and even before R5 pregnancy is important as well. Gestational weight gain itself might not be that important R6 for the development of maternal obesity and may be difficult to influence (15,16). Perhaps R7 maternal weight gain during pregnancy is more ‘fixed’ in order to ensure fetal development, R8 and cannot be changed much under ‘normal’ (body weight) conditions. The model for weight R9 change of calories-in, calories-out in pregnancy might thus be too simple. R10 The mother’s metabolism is modified from the beginning of pregnancy, independent of R11 lifestyle (17-19). It is known that during pregnancy the developing fetus demands more and R12 more nutrients. The placenta increases the production of Growth Hormone (GH) and of R13 Human Placental Lactogen (HPL) through pregnancy, leading to reduced insulin sensitivity R14 and therefore, to increasing maternal glucose levels, which finally lead to an increase in the R15 adipose tissue lipolytic activity (19). In the beginning the mother gains weight and maternal R16 adipose tissue increases (20,21). Cholesterol and triglyceride levels increase also during R17 pregnancy, with an increment in free fatty acids (FFAs) mostly near delivery (17-19). Those R18 FFA may easily cross the placenta to guarantee a constant supply of nutrients for the fetus. R19 Leptin, a hormone produced by white adipose tissue seems to be important in regulating R20 nutrition and the energy-consuming processes of reproduction, pregnancy and lactation R21 (22,23). In pregnancy, leptin sensitivity decreases and a state of leptin resistance develops R22 resulting in a stimulation of food intake and maternal energy storage (24-27). R23 But apart from the maternal effects of leptin, leptin might play a role in the fetal programming R24 via epigenetic variation (28,29).1 R25 R26 The effect of maternal weight change during pregnancy on early-life programming of the fetus R27 was not the topic of this thesis. We limited ourselves to birth weight. But in studies on fetal R28 programming maternal weight dynamics even before conception in normal weight women R29 play a role (30). It was reported that in normal weight women (BMI <25 kg/m) weight loss R30 before pregnancy was associated with newborns small for gestational age and, independent R31 of maternal BMI, a positive association was reported between weight loss before pregnancy R32 and gestational diabetes and hypertension (30). In our study, however, the women who had R33 lost weight before pregnancy, gave birth to significantly heavier babies (377 gram; 95% CI 94 R34 to 661 gram). R35 1 Epigenetics is mostly the study of heritable changes that are not caused by changes in the DNA R36 sequence; to a lesser extent, epigenetics also describes the study of stable, long-term alterations in R37 the transcriptional potential of a cell that are not necessarily heritable. Unlike simple genetics based on changes to the DNA sequence (the genotype), the changes in gene expression or cellular phenotype of R38 epigenetics have other causes, thus use of the term epi- (Greek: επί- over, outside of, around) -genetics. R39 Ref Wikipedia.

Summary and general discussion | 113 R1 The change in maternal energy homeostasis in pregnancy is of vital importance for the fetus R2 and so it might not easily be influenced. Under extreme conditions, such as under- and over- R3 nutrition, this change in energy homeostasis might be influenced, affecting the fetus (31,32). R4 Whether the effect of under- and over-nutrition acts on the fetus via epigenetics by modifying R5 energy homeostasis, maternal body weight gain or the amount and function of adipose tissue, R6 is not clear at this point in time. R7 If maternal weight gain in pregnancy is more ‘fixed’ in order to ensure fetal development, and R8 cannot be changed much under normal conditions, the importance of gestational weight gain R9 related to obesity for the mother and her offspring is challenged. Perhaps nutritional status R10 e.g. over- and underweight, of the mother before and during pregnancy might be even of more R11 importance. This nutritional status might act on certain genes of the gamete or fetus, modifying R12 their expression, so-called epigenetics (32-37). Differences in expression of genes may lead R13 to differences in the development of fetal organs, including brain development, and to different R14 crosstalk between fetal neurotransmitters involved in the energy homeostasis (38-44). These R15 epigenetic changes might lead to a higher risk for developing obesity in the offspring (45,46). R16 R17 Apart from weight change in pregnancy and nutritional status, maternal body composition R18 as such might act on fetal programming (47). In the study of Kent, birth weight correlated R19 positively with maternal fat-free mass and not with adiposity. The author suggested “that, in R20 nondiabetic women, interventions intended to reduce fat mass during pregnancy may not R21 prevent large-for-gestational-age neonates and revised guidelines for gestational weight gain R22 in obese women may not prevent large-for-gestational-age neonates” (47). R23 R24 Many scientists and health care providers consider pregnancy as “a window of opportunity” R25 for the fetus and for introducing healthy behaviour to the mother (46,48,49). But if a change in R26 health behaviour has been achieved it is not known how sustainable that change will be. For R27 example changing addictive behaviour in pregnancy is sometimes successful by means of an R28 intensive approach (49-52). In our study the limited sustainability of a behavioural change was R29 illustrated by the fact that of the 31 women who stopped smoking in the year before getting R30 pregnant, about half (16) started again after delivering their lighter baby’s. R31 For that reason we should not limit the observation period regarding the effect of a lifestyle R32 intervention to pregnancy alone. Lifestyle interventions and weight management should not R33 just focus on pregnancy, but should be extended beyond pregnancy (53,54). R34 R35 We have introduced measuring the effect of eating style in our study. Many studies on weight R36 change mainly considered food intake and physical activity. But food intake (and thus energy R37 intake) is related to determinants of food intake, such as eating style, attitude and self- R38 esteem. When studying weight and weight changes, such determinants should be identified. R39

114 | Chapter 8 Knowledge on determinants might help to identify women at risk and can give guidance for R1 intervention development. R2 R3 Methodological considerations R4 Limitations to our study need to be discussed. First of all there is an issue with the sample. R5 Healthy, relatively well-educated women with an average BMI of 23.7 participated in the New R6 Lifestyle study, being capable of maintaining a healthy weight. This selective population may R7 have given a selection bias. R8 The vast majority of the study population was Caucasian. As we know the prevalence of R9 gestational diabetes is different in different ethnic groups. For example in the prevalence is R10 higher in Hindustani Surinamese compared to Caucasian (55, 56). R11 Another limitation was the absolute number of women participating in the study and especially R12 the small number of overweight or obese (BMI ≥ 25) women (21.4%). For instance, Hopkins R13 hypothesized that in normal weight women, PA might not be associated with insulin sensitivity R14 to ensure sufficient nutrients for the fetus, while this association might be present in obese R15 pregnant women, with low insulin sensitivity already at the start of pregnancy and with R16 abundant nutrients available (57). R17 Furthermore, we had neither objective data on energy intake nor objective data on R18 prepregnancy body weight. Although misclassification of self-reported pre-pregnancy BMI is R19 quite common (particularly women with a high BMI underreport their weight (58)), others have R20 shown that in normal weight women, as in our study, self-reported BMI was quite valid (59,60). R21 R22 Implications for future research R23 Efforts to influence maternal weight have been numerous, because abnormal weight change R24 is associated with maternal and fetal morbidity and even mortality. But gestational weight R25 gain cannot be influenced so easily and if limiting gestational weight gain will result in better R26 pregnancy and weight outcomes over the long term is not clear at the moment (15,16). R27 Special attention should be paid to the effect of maternal weight dynamics even outside R28 pregnancy on maternal weight development, but also on early-life programming (30). And not R29 only weight change, but also maternal body composition should be a part of those RCT’s (47). R30 The role of obesity of the father is as yet an unexplored field of study. Recent studies R31 suggested a preconceptional impact of paternal obesity on the epigenetics of the offspring R32 during spermatogenesis (61,62). The effect of maternal obesity on oogenesis is even more R33 unexplored. Therefore, more research is needed on the effect of weight dynamics of both R34 parents on the fetal development and on how expression of genes in the offspring is influenced. R35 Since we know that obesity is also a social disease, as visualized in a large social network in R36 the Framingham study, only focusing on pregnant women and their gestational weight gain R37 without involving their spouses and even families might not be the most successful way to R38 stop the obesity epidemic (63). R39

Summary and general discussion | 115 R1 Based on the above, we recommend to get more insight into the effects of body weight R2 management by conducting RCT’s that assess the long-lasting effects of weight management R3 during and beyond pregnancy on maternal and neonatal health and especially focus on R4 underweight and overweight or obese women. In these RCT’s, the social network (spouse, R5 family, friends) need to be involved. R6 R7 Implications for clinical practice R8 Many uncertainties still exist: the effect of adjusting gestational weight gain according existing R9 guidelines for different weight categories of women; the effect of the timing and the amount R10 of weight loss before getting pregnant and the effect of this weight loss on mother and child; R11 the importance of maternal body composition and the contribution of the father on maternal R12 obesity and obesity of the offspring. R13 Based on our results we have no specific recommendations on this topic, but some general R14 recommendations can be given. R15 Counselling on healthy weight and physical activity should take place not only during, but, R16 more importantly, before and after pregnancy. If women already experience weight problems R17 before trying to conceive, body weight counselling should be commenced. R18 Obese women however, should be encouraged to loose weight long before they try to R19 conceive. Based on our study women should loose weight at least more than 6 months before R20 trying to conceive. R21 R22 Personal view R23 In this thesis, pregnancy and maternal weight change is the central theme. R24 The question I wanted to answer was whether nature or nurture (64-66) influenced maternal R25 weight in pregnancy. A bit naïve perhaps as reality seems to be more complicated. Maternal R26 weight change seems to be more difficult to influence. Short and long term effects must be R27 studied comprehensively. Quoting Traynor “The old dogma of nature versus nurture is dead, R28 but unfortunately it has been replaced by a puzzle even harder to solve” (67). R29 R30 R31 R32 R33 R34 R35 R36 R37 R38 R39

116 | Chapter 8