Lesson 1: Preconception Considerations for Childhood Obesity

Table of Contents


Introduction

When discussing childhood obesity, and childhood health overall, considerations begin prior to the child being conceived. The preconception period in this context refers to the months prior to conception. The Nutrition and Weight Management course as well as the General Exercise course on this website are mostly appropriate for potential parents in the preconception stage; you can read through those courses to see what to do to live a healthy life regarding nutrition and exercise. There are a few additional considerations when intending to have a child; I discuss these below as they pertain to childhood obesity.

Regarding fathers, the main idea is that paternal health and lifestyle choices can influence sperm and seminal fluid in several ways; these alterations can carry forward to the developing  embryo, fetus, and child. Regarding mothers, the overall influence may be stronger as maternal health and lifestyle factors will influence the in-utero environment and the supply of nutrients for the developing embryo and fetus. All of this collectively can influence long-term health outcomes.

Note: It is rather difficult to study this rigorously in humans. To do so you would need to alter certain variables (ie, parental food choices), perform biological measurements on the growing fetus and subsequent child, and then follow these individuals for an extended period of time to see if there are any long-term differences. While conceptually feasible, this is not very practical, particularly due to the long length of time that is needed as well as the difficulty in performing many measurements on a fetus and young child safely. Thus, much of the experimental research is done on rodents (who have much shorter life cycles than humans). Much of the human data is either observational in nature (ie, tracking outcomes in children of mothers with different prepregnancy body mass indexes (“BMIs”)) or assesses intermediate measures (ie, provide males with various diets and determine the resulting epigenetic changes in sperm).

If “epigenetics” is a new term to you, it essentially describes methods of genetic variation that do not include actual changes of your underlying DNA sequences. For example:

  • certain DNA base pairs can be methylated – this can alter the way that transcription factors bind to them and impact gene expression
  • histones can be altered (ie, via acetylation) – this can make it more or less difficult to transcribe genes that are in close proximity to an altered histone
  • non-coding RNAs can interact with DNA or other genetic elements to additionally alter gene expression

The field of epigenetics research is relatively young and much more research is needed to determine what impact all of this has on obesity.(Ouni, 2020; Rasmussen, 2021)


Transgenerational influence

A recent review described some of the evidence that obesity risk can transcend generations via various epigenetic mechanisms.(King, 2020) The authors note:

  • In mice there is substantial evidence that exposure to ancestral obesity leads to increased weight gain in future generations.
  • In rats several environmental toxicants can induce a transgenerational obesity phenotype multiple generations in the future; the authors particularly emphasize that this has been shown with dichlorodiphenyltrichloroethane (“DDT”, a pesticide) causing the great-grandchildren of the exposed rats to develop obesity, even though the children and grandchildren did not see this effect.
    • The authors also mention that in the 1940s and 1950s in the US there was widespread use of DDT; perhaps that has contributed to today’s obesity epidemic?
  • Daughters of women who experienced the Dutch Hunger Winter of World War II in utero had 1.8 times more chronic disease as adults compared to nonexposed women, while grandchildren of fathers who experienced it tended to develop an increased BMI later in life.
  • In a town in Northern Sweden, paternal ancestral nutrition appeared to significantly influence the incidence of cardiovascular disease and diabetes mellitus in grandchildren.

A 2022 systematic review and meta-analysis (“SR/MA”) found that when grandparents have obesity this increases the odds of grandchildren having obesity; in the subset of the studies that were included in the MA the odds ratio was 1.79.(Kanmiki, 2022)

  • When removing one outlier study the odds ratio decreased to 1.70 and was only borderline statistically significant (95% confidence interval: [0.95, 2.46]), but higher quality studies showed stronger associations in general.

If you are unfamiliar with odds ratios, they are somewhat similar to relative risks. A relative risk is generally determined prospectively and describes the change in risk due to some variable. If the relative risk was 1.79, there would be a 79% increased risk. If the relative risk was 2.00, then there would be a 100% increased risk, or the risk would be 2 times as high (twice as high). If the relative risk was 0.68, there would be a 1-0.68 = 32% decreased risk.

Odds ratios are generally determined retrospectively. It is not quite accurate to say an odds ratio of 1.79 means there is a 79% increased risk, but the basic idea is similar. Depending on the range of values seen in individual studies when combining them in a meta-analysis, there may be a large degree of uncertainty in the estimate. If the 95% confidence interval for the individual estimate crosses 1.00, then this is said to not be statistically significant.

Thus, as the above review had an estimate of 1.70 with a confidence interval of [0.95, 2.46] after removing the one outlier study, there is a 70% increased odds of obesity when grandparents have obesity but this result is not quite statistically significant. Therefore, there may actually be no increased risk of obesity when grandparents have obesity. However, as higher quality studies had stronger associations, this implies there is a true increased risk. Performing additional high quality large studies will provide more data that will help refine the estimate and shrink the size of the confidence interval to provide a better notion of what the true increased odds are.

If you want more examples, click here for odds ratios and click here for relative risk.

Note: This transgenerational risk alone may be playing a large role in the increasing obesity epidemic. When a generation starts to gain weight and develop obesity their children and grandchildren potentially became more prone to developing obesity themselves. This risk would compound with each future generation while the overall rates of obesity continue to increase. As our modern-day obesity rates are the highest they have ever been, any epigenetic alterations that have occurred may be adding fuel to this fire, counteracting the large amount of research and public discussion regarding how to lose weight and maintain a healthy body composition. This doesn’t make combating the obesity epidemic hopeless, but this may make the fight a lot harder today than it was 60 years ago.


Environmental exposures

The research literature does not generally indicate that prenatal exposure to pesticides or other environmental exposures has any bearing on child weight outcomes, with one exception: smoke exposure.(Vrijheid, 2020; Pinos, 2021)

Both prenatal maternal smoking and secondhand smoke exposure have been associated with increased child BMI. For people on the fence regarding quitting smoking, knowing this can impact the health of their future children may be the additional motivational factor needed to kick the habit.


Maternal weight status

A 2020 retrospective longitudinal cohort study examined the relationship of various maternal characteristics (excessive gestational weight gain (“GWG”), age, education, household income, race or ethnicity, medical conditions, prepregnancy BMI, gestational diabetes mellitus (“GDM”), and more) with child weight outcomes between ages 2-6 years.(Wang, 2020) Overall, the most influential factors on excessive weight gain in children were prepregnancy maternal obesity followed by prepregnancy maternal overweight, and these larger effects were independent of the child’s BMI at age 2 (implying a longer-term impact distinct from their influence on early life weight). Much weaker but still significant were maternal type 1 diabetes, type 2 diabetes, or GDM requiring medication treatment.

This last study shows that not only is prepregnancy maternal weight status important for influencing childhood weight outcomes, but it is potentially the most important modifiable factor. A 2019 SR/MA attempted to determine how influential this factor is, assessing the impact of maternal prepregnancy BMI on subsequent child overweight and obesity.(Heslehurst, 2019) This included 79 studies, and in the subset of studies included in the MA the authors found:

  • Maternal overweight and obesity had odds ratios of 1.41 and 1.80, respectively, for child overweight.
  • Maternal overweight and obesity had odds ratios of 1.89 and 3.64, respectively, for child obesity.
  • Maternal overweight and obesity had odds ratios of 1.65 and 2.69, respectively, for child overweight + obesity.
    • The fact that the odds ratios are higher for childhood obesity than overweight or overweight + obesity implies that there is a stronger relationship of maternal overweight or obesity with childhood obesity than with childhood overweight.

Another consideration is the change (if any) in maternal weight status between pregnancies. A 2020 review examined the influence of weight gain during the interpregnancy interval (“IPI”, between the delivery of one child and conception of the next) on birth and later child weight outcomes.(Alwan, 2020) The literature suggests that with greater BMI gain in the IPI there is an increasing risk of a subsequent child being born large for gestational age, while increasing weight loss between pregnancies can increase the risk of a subsequent child being born small for gestational age. A few studies have found that increased IPI weight gain does lead to greater odds of childhood obesity as well.

Tip: This is one of several reasons why it is better to avoid gaining excess weight during pregnancy; if you gain more weight during pregnancy then you will have more to lose after the pregnancy to avoid increasing the risk of negative health consequences. The impact on child weight outcomes is discussed further in the next lesson.

Note: While parental obesity may increase the risk of childhood obesity, at least in one study it did not worsen the treatment success rate in a childhood obesity intervention trial.(Martínez-Villanueva, 2019) This is encouraging as it shows being a parent with obesity does not preclude you from helping your children adopt healthier habits to improve their body composition and it shows that worse health outcomes are not inevitable.


Paternal weight status

Three recent reviews indicate that paternal weight status also has implications for offspring obesity risk.(Campbell, 2019; Eberle, 2020; Billah, 2022) This is hypothesized to occur via several potential mechanisms, including epigenetic changes in sperm, increased DNA damage, increased reactive oxygen species, reduced mitochondrial function, or alterations in the seminal fluid with a greater inflammatory profile.

All of these reviews systematically surveyed the literature, finding paternal obesity contributes to the risk of several adverse health outcomes including obesity throughout childhood and even into adulthood. While it is difficult to disentangle the impact of paternal BMI from the environment that may have mediated the increase in BMI and that is subsequently shared with the child offspring, some of the research including various animal studies indicates that paternal BMI has an independent effect on increased obesity risk in the offspring.

The following figure highlights some of the findings, showing that paternal obesity and other cardiometabolic risk factors carry over to increase the risk of the same health conditions in the offspring who then grow up with these conditions, leading to perpetuation of the cycle.

Reproduced from: Eberle C, Kirchner MF, Herden R, Stichling S. Paternal metabolic and cardiovascular programming of their offspring: A systematic scoping review. PLoS One. 2020 Dec 31;15(12):e0244826. doi: 10.1371/journal.pone.0244826. PMID: 33382823; PMCID: PMC7775047.

Tip: The most recent review listed above also highlights animal model interventions demonstrating that improved nutrition and/or exercise with weight loss in the preconception phase does lead to health benefits in the offspring.(Billah, 2022) The authors make a point that in humans the duration of spermatogenesis is 74 days; thus any intervention to yield significant health benefits would likely need to start at least 3 months prior to the time of conception to ensure the physiologic changes are able to take affect when the sperm begin to develop, and if it turns out that it is additionally helpful to achieve significant weight loss prior to the onset of spermatogenesis then interventions likely need to begin multiple months prior to this time point for an optimal effect.

Alternatively, changes in the seminal fluid likely will not require as long of an intervention. We need more studies to help determine the time course of when males can begin healthier lifestyle habits to have a meaningful beneficial impact on their sperm (with respect to influencing child health outcomes).

Note: Paternal metabolic status, as indicated by an increasing number of metabolic syndrome components, also contributes modestly to preterm delivery, low birth weight, and a necessity for admission to the neonatal intensive care unit once born (~19-28% higher odds when most or all components of metabolic syndrome are present).(Kasman, 2020) This can additionally contribute to child health outcomes and childhood obesity risk.


Preconception nutrition, exercise, and working towards a healthy weight

Two 2020 reviews highlight the various lines of evidence (mostly in rodent studies) indicating that dietary and exercise lifestyle choices made by fathers in the preconception period can influence sperm epigenetic profiles, affect semen quality, and reprogram health for future generations.(Kusuyama, 2020; Marcho, 2020) A 2021 review similarly emphasizes the role of paternal nutrition, providing evidence that this can impact sperm methylation and small noncoding RNA content and that in mice studies this has been shown to influence offspring methylation patterns, metabolism, and may influence cardiometabolic risk factors long-term.(Dimofski, 2021)

A 2021 review highlights how at least in rodent studies paternal diet and exercise habits in the preconception period, maternal diet and exercise habits during pregnancy and after delivery (if breastfeeding), and offspring early-life exercise habits can all lead to epigenetic and other modifications that decrease the risk of obesity and potentially improve skeletal muscle fitness and cardiometabolic risk factors long-term.(Beleza, 2021)

Considerations for weight loss:

A 2021 review highlights that both maternal and paternal obesity are associated with negative offspring health effects.(Hieronimus, 2021) Both the sperm and the oocytes are impacted by obesity potentially due to chronic exposure to altered hormones and metabolites associated with obesity while they are maturing. However, there is some evidence that the negative effects can be diminished by adopting healthier nutrition habits. The authors note that while health guidelines recommend normalization of body weight prior to pregnancy, there is no consensus regarding a reasonable amount of weight loss and safe strategies to work towards this. The authors highlight some concerning lines of evidence regarding preconception weight loss, such as:

  • Severe weight loss with bariatric surgery prior to conception is associated with a higher risk of prematurity, small birth size, and neonatal intensive care unit utilization.
  • Weight reduction in women with obesity prior to infertility treatment may increase the rate of subsequent miscarriage.
  • One cohort study found a restrictive diet and weight loss prior to pregnancy resulted in increased GWG.

The authors suggest that while supervised weight loss prior to pregnancy may be beneficial for women with overweight and obesity, overly health-conscious women with normal weight who adopt similar advice may have a higher risk of developing nutritional deficiencies and having infants who are small for gestational age (which has been associated with subsequent negative health effects). Ultimately, the authors state more research needs to be done to determine to what extent preconception weight loss is safe.

Of note, a recent international guideline on preconception, pregnancy, and postpartum obesity stated a realistic target is to aim for 5-10% weight loss over a 6 month period prior to conception, but the authors did not state this was a maximum safe rate.(McAuliffe, 2020) They did note that the preconception period is an opportunity for intensive nutrition and weight optimization, so perhaps faster weight loss is still advisable if it can be done in a healthy manner. A separate review of several clinical practice guidelines similarly did not find any concrete recommendations regarding weight loss in the preconception period.(Harrison, 2021)

Tip: So how fast should people with obesity lose weight prior to conception? I showed literature above indicating this has health benefits but I also cited literature indicating concerns.

  • Regarding the bariatric surgery concern, people who undergo bariatric surgery typically lose weight very rapidly, and for this reason it is generally recommended to delay becoming pregnant for at least 12-18 months, and potentially longer, after undergoing bariatric surgery.(McAuliffe, 2020)
  • If you lose weight at a more sensible rate, which I will speculate may be 0.5-1% of your body weight weekly if done in a healthy manner, this may be less likely to generate unhealthy outcomes.
    • I want to emphasize this is speculation on my part; 1% body weight loss per week may still be too fast even if doing things “optimally”, though as shown in Lesson 3 of the Nutrition and Weight Management course this does seem safe for general health. I would be surprised if 0.5% weight loss per week led to any negative health outcomes assuming high-quality macronutrient and micronutrient intake otherwise. We need studies to compare the effects of different rates of weight loss preconception.
      • Taking a prenatal vitamin to help ensure adequate micronutrient intake is generally advisable if attempting to become pregnant; if you’re actively restricting calories to lose weight then additional supplementation may also be warranted and you can discuss this with your healthcare provider.
    • It is well-established that even 5% weight loss can lead to significant health benefits, with greater benefits seen at 10-15%. If you lose 0.5-1% of your body weight weekly, you can get to the 5-10% range in 2-3 months, and then you can consider maintaining your current weight for an additional 2-3 months to help minimize any potential harmful effects of active weight loss prior to attempting to conceive.
  • Lastly, any beneficial lifestyle changes you make to improve your health prior to conception will be very helpful moving forward assuming you are able to maintain these new lifestyle habits long-term. This will help mitigate any negative impact from previous lifestyle choices, decrease the likelihood of excessive GWG during pregnancy, and aid in your future child developing healthy lifestyle habits.

Conclusion

It is very clear that many things occur before one’s conception that can influence their health long-term. Body weight status, health status, and lifestyle habits (nutrition, exercise, pollutant/toxin exposure, etc) seem to all play roles in shaping life moving forward. From a practical standpoint some of this is not going to be in your control but much of it will be. If you work to live healthily for several months prior to conceiving a child this will likely increase your child’s chances of developing healthily long-term, and at any point in time if you are able to adopt a healthier lifestyle that you can maintain this will help mitigate the risks of any adverse preconception exposures.

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References

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