7.2. Lifestyle Management and Weight Control before or during Pregnancy
In the next section, we will present clinical (summarized in ) and animal (summarized in ) studies that have examined the main interventions tested to reduce the impact of maternal obesity and gestational diabetes and how they can break the vicious circle that perpetuates the transmission of obesity and metabolic conditions to the next generations.
7.2.1. Clinical Studies
Regarding lifestyle management during pregnancy, few studies assessing the role of a dietitan intervention alone have been published. A randomized controlled trial undertaken in Belgium enrolled 122 obese pregnant women in 3 groups receiving either nutritional advice from a brochure; the brochure and lifestyle education by a dietitian; or no intervention [103
]. By assessing dietitian intervention using food log book or questionnaires, the authors found that while their intervention positively impacted on nutritional habits of participants, it did not result in any improvement of obstetrical or neonatal outcomes. On the other hand, Wolff et al. showed that when obese pregnant women were assisting to frequent nutritional consultation with a specialized dietitian (ten 1-hour sessions during pregnancy), they gained less gestational weight and reduced their fasting insulin, glucose and leptin concentrations, thus suggesting improved metabolic control [104
]. However, as in the previous paper, similar obstetrical and neonatal complications between intervention and control women were observed. These studies thus suggest that in order to achieve more optimal weight gain during pregnancy with a nutritional approach alone, it seems important that the participant benefits from individualized professional advices.
The results of studies assessing the benefits of exercise alone either before and/or during pregnancy are worth mentioning. In a small cohort of obese pregnant women, Callaway and colleagues showed that even though an increase in energy expenditure of 900
kcal/week was achieved by 28 weeks of gestation with an individualized exercise program, HOMA-IR and GDM outcomes were not different in comparison to the group receiving usual care, and the authors concluded that the efficiency of their intervention was not convincing [105
]. Nevertheless, they showed that by 28 weeks, fasting glucose was significantly reduced and that by 36 weeks, fasting insulin was significantly reduced by 28% in mothers of the intervention group, thus suggesting that these metabolic gains still may show some benefits on a longer-term basis in their children. Clapp et al. also found that in women physically active before pregnancy, those who sustained intensive activity throughout pregnancy gain less gestational weight than those who stopped physical activity at the beginning of pregnancy [106
]. Moreover, they showed beneficial effects on the newborns such as reduced birth weight, ponderal index, percent body fat and fat mass. Moreover, these benefits were maintained at 5 years of age as these children had reduced weight, ponderal index and skinfolds as well as presented improved neurodevelopmental skills. A recent paper reviewing prospective, retrospective and cross-sectional studies assessing prepregnancy and early pregnancy physical activity in over 35.000 and 4.400 participants, respectively, suggested that these women were at reduced risk of GDM [118
Other trials aimed to improve maternal, neonatal and long-term offspring outcomes by lifestyle management. Indeed, it was shown by Artal and colleagues that, in obese women with GDM, the addition of physical activity to improved dietary habits resulted in less gestational gain weight when compared to the effect of diet alone, without compromising neonatal outcomes [107
]. Quinlivan and colleagues performed a randomized-controlled trial enrolling overweight or obese Australian pregnant participants allocated to standard care or a 4-step approach consisting of a visit with an interdisciplinary team including: (1) an obstetrician for continuity of maternal care, (2) a food technologist for nutritional habits and for providing food information, (3) a nurse performing weight measurements and (4) a psychologist to evaluate signs of depression and anxiety [108
]. This interdisciplinary lifestyle intervention lead to a significant reduction in gestational weight gain (7.0 versus 13.8
kg) and in the incidence of GDM (6 versus 29%), as compared to standard care. In spite of these clinically significant differences in obstetrical outcomes, neonate weights were similar between the 2 groups. Similarly, a group of Finland's pregnant women at risk for GDM, based on the results of an OGTT performed during first trimester, were randomised to the intervention group, consisting of dietary and physical activity counselling, or in the control group [109
]. Weight gain was slightly, although not significantly, reduced in the intervention group (11.4 versus 13.9; P
= 0.06), but no difference was observed between groups regarding glucose tolerance during 2nd trimester. However, although obstetrical and neonatal outcomes were similar between groups, they showed a slight, but significant increase birth weight in the intervention versus close follow-up group. Other studies have shown that lifestyle improvement by nutritional or physical activity behavioural modifications during pregnancy resulted in recommended gestational weight gain or lower gain than with control intervention [110
]. Altogether, these trials and others (including review [122
] and meta-analysis [123
]) suggest that it is feasible to improve weight management and/or the metabolic state of obese or at-risk women during pregnancy, without negative impact on fetal outcomes. However, results are somewhat scarce, controversial and inconsistent regarding the impact on maternal and fetal medical complications, and long-term follow-up studies are lacking in order to determine whether they have long lasting metabolic benefits on the offspring.
The benefits of controlling adequately maternal hyperglycemia during pregnancy are now well established and have influenced international guidelines on the diagnosis and treatment of gestational hyperglycaemic disorders. The Australian Carbohydrate Intolerance in Pregnant Women (ACHOIS) study showed that in women with mild impaired glucose tolerance but treated with dietary advices and if needed, insulin, macrosomia incidence and serious neonatal complications were significantly reduced as compared to the routine care group [112
]. However, intervention was associated with higher admission to neonatal care unit and increased rate of labor induction although caesarean rate were similar. This intervention was not associated with any change in BMI in children at 4-5 years of age between groups [113
]. In a randomized controlled trial held in the US, Landon and colleagues showed similar results in women with mild gestational diabetes enrolled in the intervention group consisting of a dietary intervention, self-monitoring of blood glucose and, if needed, insulin therapy [114
]. In comparison to control group who received usual care, the intervention did not result in improved neonatal complications as in the ACHOIS study, but it resulted in better fetal growth, as shown by reduced incidence of macrosomia, large-for-gestational age as well as fetal fat mass [114
]. Unlike the ACHOIS study, this trial found a reduction in preeclampsia, caesarean and shoulder dystocia. Results of the long-term follow-up of the offspring are not yet available. However, in 71 children assessed between 7–11 years of age, Malcolm and colleagues found that interventions in women with gestational diabetes aiming for either minimal or tight glycemic control during pregnancy [115
] were equally effective for the prevention of impaired glucose tolerance [116
]. However, this conclusion needs to be interpreted with caution because no control group was included and this study was limited by its relatively small sample size.
Since carbohydrates are the main determinant of postprandial blood glucose level [124
], intervention trials were assessed or are presently being held to establish the effect of low glycemic index diet during pregnancy on neonatal outcomes [125
]. Accordingly, one interventional study conducted in healthy pregnant women proposed that low glycemic index diet reduces the incidence of macrosomia [117
]. In pregnancies complicated by GDM, it is generally accepted that a low glycemic index diet is indicated because it was shown to facilitate glucose control without compromising obstetric and fetal outcomes [127
]. In a recent systematic review of literature on low glycemic index diet, Louie et al. proposed that until results of larger randomised control trials are available, low glycemic index diet should not be introduced into clinical practice, except for mothers with GDM, because data are not consistent and supported by large cohorts [129
In brief, these clinical intervention trials showed some benefits in terms of improved gestational weight gain but few provided convincing data for better impact on the neonates. However, limitations include mainly small number of participants (lack of power) and possible publication bias. As it is otherwise satisfactory to observe that these interventions were not detrimental to the fetus, the next question arising is whether they have a long lasting impact on later childhood obesity or metabolic function.
7.2.2. Animal Studies
Although the impact of gestational obesity and diabetes on the offspring is well described, human trials conducted to determine whether maternal interventions could break down the vicious cycle on future generation are still at their infancy. Therefore, only animal studies can help us to make some inferences for the moment. In fact, the potential beneficial impact of nutritional intervention were reported in the yellow Agouti mice and in rats born to fat-fed mothers. In the yellow Agouti mice, authors showed that in utero
exposure to the dietary antioxidant genistein, at levels present in human adult populations consuming high-soy diets, reduces obesity by altering the epigenome in those mice [119
]. In addition, offspring born from dams fed a fat Westernized diet developed by 2 weeks of age greater adiposity and glucose intolerance than those born from dams fed the control diet [120
]. However, offspring born from dams fed the Westernized diet and supplemented with antioxidant normalized their fat mass as well as their leptin, glucose, insulin and non-esterified fatty acid blood concentrations to levels similar to the control group.
Zambrano and colleague showed that giving a normal chow to obese female rats 1 months prior to mating and throughout pregnancy and lactation in comparison to obese rats who were kept on the obesogenic diet throughout entire study period resulted in dams with lower gestational weight gain but in offspring of similar phenotype and weight from birth to 150 days of age [121
]. These results are in agreement with the previously reported literature in human where maternal interventions with the aim to reduce gestational weight gain had no effect on the foetuses birth weight. However, by 21 days of age, offspring born to mothers on the intervention arm significantly improved their high fat mass, hypertriglyceridemia, hyperleptinemia, hyperinsulinemia and insulin resistance, in comparison to rats born from untreated obese dams, and almost to the same levels as in rats born from non-obese dams. By 150 days of age, improvements in leptinemia, fat mass and adipocyte cell size were still observable [121
These results suggest that maternal intervention aimed at reducing gestational weight gain has tremendous long lasting metabolic effects on the offspring, even if fetal and neonatal profile were similar or slightly changed. It is therefore possible to extrapolate that even though interventions in humans did not result in improved newborn phenotype, beneficial effects on the intrauterine milieu may have long lasting effect on adulthood health of the offspring.