One of the most exciting and biologically highly plausible reasons for the childhood obesity epidemic may well be that current generations are far more susceptible to obesity because of “epigenetic programming”.

Simply put, the notion is that exposure to an adverse fetal environment, as in the case of maternal obesity, diabetes or hypertension during pregnancy, can lead to a lifelong change in the genetic program of the offspring, making them genetically more prone to obesity.

Thus, although the children are born with the same genetic code as their parents, whether or not certain genes are “more” or “less” active, is determined by the fetal (and possibly early post-natal) environment.

While these “epigenetic” changes are well documented in animal studies, exactly which genes are affected in the context of intergenerational transmission of obesity is not clear.

A study by Luigi Bouchard and colleagues from Université de Montréal, Canada, just published online in Diabetes Care, suggests that one of the modified genes may well be leptin, a key regulator of energy balance.

The researchers examined placental tissues as well as maternal and cord blood samples from 48 women, 23 of who had gestational impaired glucose tolerance (= gestational pre-diabetes).

Not only was there a positive association between the DNA methylation levels of the offspring’s leptin gene (measured in the placenta) and the glucose response to an oral glucose test, but there was also a negative relationship to placental leptin gene expression.

DNA methylation is a form of “epigenetic” modification that determines the extent to which a given gene is expressed in vivo. Thus although the genetic code or DNA sequence for that gene may be identical between two individuals, variations in DNA methylation will determine how “active” this gene is in a given individual.

The authors conclude that impaired glucose tolerance during pregnancy is associated with epigentic modification of the leptin gene with potential functional impacts that could in part account for the detrimental health effects associated with fetal programming such as long-term increased risk of developing obesity and type 2 diabetes.

As I have noted before, obesity may well start in the womb, which is why recent recommendations have focussed on improving maternal health, including the prevention of excess weight gain during pregnancy, as a key strategy to reduce childhood obesity.

AMS
Edmonton, Alberta

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Bouchard L, Thibault S, Guay SP, Santure M, Monpetit A, St-Pierre J, Perron P, & Brisson D (2010). Leptin Gene Epigenetic Adaptation to Impaired Glucose Metabolism during Pregnancy. Diabetes care PMID: 20724651

While the phenomenon of depression during and following pregnancy in women is widely appreciated (and often associated with weight gain and/or antenatal weight retention), the effect of pregnancy on mood of fathers is less appreciated.

A recent study by James Paulson and Sharnail Bazemore from the Virginia Medical School, Norfolk, VA, just published in the Journal of the American Medical Association, throws new light on this interesting issue.

The researchers performed a meta-analysis of 43 studies that documented depression in fathers between the first trimester and the first postpartum year involving 28 004 participant.

Although there was substantial heterogeneity between the rates of paternal depression between studies, the average rate of paternal depression in the antenatal period (during pregnancy) was abour 10% but increased to about 25% during the 3 to 6-month postpartum period (after birth).

While paternal depression was more likely in the presence of maternal depression, this was by no means a strong predictor of paternal mood disorder.

These findings have important implications.

Not only is it important to also be wary of mood disorders in expecting and new fathers (especially if the mother has mood problems), but these mood disorders in fathers may need to be addressed.

This is of particular importance given the emerging evidence that paternal depression may have substantial emotional, behavioural and developmental effects on the infant.

Furthermore, it may well be that paternal peripartum depression could contribute to weight gain in dads.

Thus, prevention, screening and interventions for depression should likely be focussed on the couple rather than on the individual parent.

AMS
Oslo, Norway

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Paulson JF, & Bazemore SD (2010). Prenatal and postpartum depression in fathers and its association with maternal depression: a meta-analysis. JAMA : the journal of the American Medical Association, 303 (19), 1961-9 PMID: 20483973

Yesterday, at the Second Canadian Student Obesity meeting, currently being held in Ottawa, Kristi Adamo from the University of Ottawa and the Children’s Hospital of Eastern Ontario presented the Keynote dinner presentation on “Balancing Work and Life on the Pathway of a Research Scientist“.

Kristi Adamo has a background in nutrition, exercise physiology and genetics of obesity. Her interests lie in the irregular metabolic function associated with childhood obesity and the role diet and exercise may play in predisposition or prevention. She has particular interest in early intervention to prevent child obesity and is focusing on intervening during the gestational period and halting the intergenerational cycle of obesity.

In fact, several of the presentations at this meeting emphasized the fascinating biology of how early fetal development and influences in the first weeks and months after birth can change the lifelong risk for obesity by changing how genes are switched on or off through mechanisms like imprinting and how maternal and environmental influences during this critical period can change how the complex circuitry of appetite and reward are “hardwired” into the brain.

Thus for e.g., Lindsay Naef from McGill University talked about her experiments in rats showing that exposure to high-fat diets during early development results in increased reward value of fatty foods in adult animals or Christian Rueda-Clausen from the University of Alberta, who talked about how intrauterine growth restriction increases the susceptibility to diet-induced obesity and insulin resistance.

For this very reason, other presentations examined interventions to improve diet and physical activity during pregnancy with a focus on limiting weight gain to the levels recommended by the Institute of Medicine and other organisations. As pointed out by Zach Ferraro (one of the student organisers from the University of Ottawa), not only do mothers with overweight and obesity end up gaining far more than the recommended amount of weight during gestation, but that this is also associated with an almost 6-fold higher risk of having a “supersized” baby that will eventually grow into a “supersized” adult.

So while Adamo spoke about her own pursuit of work-life balance by focussing on what she loves doing, she noted that as a mother, her professional interest on the environmental impact of fetal and early postnatal development is quite complementary to her personal goal of raising her own children in the most healthy way possible.

AMS
Ottawa, Ontario

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Walker CD, Naef L, d’Asti E, Long H, Xu Z, Moreau A, & Azeddine B (2008). Perinatal maternal fat intake affects metabolism and hippocampal function in the offspring: a potential role for leptin. Annals of the New York Academy of Sciences, 1144, 189-202 PMID: 19076377

I have often blogged about the impact of excess weight in pregnancy on both the health of the mother and the infant.

The need to manage gestational diabetes, a frequent complication in overweight and obese women, is well established but the evidence for mild cases is less clear.

This question was now addressed by Mark Landon and colleagues on behalf of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network in a paper just published in the New England Journal of Medicine.

This multicenter trial randomised a total of 958 women who were in the 24th to 31st week of gestation and who met the criteria for mild gestational diabetes mellitus (i.e., an abnormal result on an oral glucose-tolerance test but a fasting glucose level below 95 mg per deciliter [5.3 mmol per liter]) to usual prenatal care (control group) or dietary intervention, self-monitoring of blood glucose, and insulin therapy, if necessary (treatment group).

Although there were no significant differences in the primary outcome consisting of a composite of stillbirth or perinatal death and neonatal complications, including hyperbilirubinemia, hypoglycemia, hyperinsulinemia, and birth trauma, there were significant reductions with treatment as compared with usual care in several prespecified secondary outcomes, including mean birth weight (3302 vs. 3408 g), neonatal fat mass (427 vs. 464 g), the frequency of large-for-gestational-age infants (7.1% vs. 14.5%), birth weight greater than 4000 g (5.9% vs. 14.3%), shoulder dystocia (1.5% vs. 4.0%), and cesarean delivery (26.9% vs. 33.8%).

Interestingly, while the intervention group only gained 2.8 Kg during the pregnancy, the control group gained 5 Kg.

Treatment of mild gestational diabetes mellitus also reduced the rates of preeclampsia and gestational hypertension (combined rates for the two conditions, 8.6% vs. 13.6%; P=0.01).

The authors conclude that although treatment of mild gestational diabetes mellitus may not significantly reduce the frequency of stillbirth, perinatal death and several neonatal complications, it does reduce the risks of fetal overgrowth, shoulder dystocia, cesarean delivery, and hypertensive disorders.

Obviously, the findings cannot be attributed to the effects of the intervention on weight alone, however, they do support the notion that limiting weight gain during pregnancy in overweight and obese women, may be beneficial for both mother and child.

AMS
Edmonton, Alberta.

Regular readers of these pages are aware of my concerns about how excess weight gain in pregnancy can adversely affect both mother and infant (click here for previous posts on this).

This issue is now addressed in a comprehensive new guideline from the Institute of Medicine that reexamines this issue (click here for summary of guideline). This guideline follows on the heels of previous recommendation from the American Dietetic Association and the American Society for Nutrition, published last year.

The report not only sets new levels for weight gain in pregnancy, but also addresses the issue of preconceptual weight given that one of the most important modifiers of pregnancy weight gain and its impact on a mother’s and her baby’s health is a woman’s weight at the start of pregnancy.

The two major differences to previous guidelines are: firstly, the recommendations are now based on the WHO BMI categories rather than the now obsolete Metropolitan Life Insurance tables. Second, the new guidelines include a specific and relatively narrow range of recommended gain for obese women.

It will remain to be seen how successfully these recommendation will be translated into practice.

AMS
Montreal, Quebec