Lesson 3: Pregnancy - Medical Conditions, Birth Size, and Other Considerations

Introduction

In the last lesson I discussed how during pregnancy food intake can potentially influence child health and flavor preferences. I also discussed the association of maternal weight status and weight change during pregnancy with childhood obesity and noted that the literature generally suggests the long-term impact is mediated via changes in appetite as well as childhood adiposity. In this lesson I will discuss additional considerations, including maternal medical conditions, pregnancy number and delivery method, infant birth size, and environmental exposures. I will also go over the literature regarding pregnancy interventions to see what effect actively working on some of these risk factors may have on future child health outcomes.

Impact of various maternal medical conditions on child weight

Various medical conditions are associated with obesity to some degree during pregnancy, and besides impacting the pregnant woman they may impact the offspring as well.

Gestational diabetes mellitus (“GDM”)

A 2021 publication performed two meta-analyses (“MAs”); the first included 49 cohort studies and evaluated the association of maternal GDM and the risk of childhood overweight at different developmental stages, while the second included 4 randomized controlled studies and evaluated the effect of lifestyle interventions for GDM during pregnancy and the subsequent risk of childhood overweight^{(Gao, 2021)}:

In the 1^st MA the pooled results indicated that for children born to mothers with GDM the relative risk of developing overweight was 1.45; in adulthood they had a BMI that was 1.5 points higher than children not born to mothers with GDM. Of note, preconception overweight/obesity was not a confounder; this risk was distinct from baseline obesity status.
- The authors note several potential mechanisms for these associations. Maternal GDM will lead to higher levels glucose which transfer to the fetus; the fetus then will make more insulin and synthesize more tissue, including adipose tissue, as a result. This additionally may alter other fetal hormones such as leptin and contribute to epigenetic changes.
In the 2^nd MA there was no impact of intensive management of GDM during pregnancy regarding child weight outcomes (over a maximum of 9 years follow-up). Possible explanations include the interventions may not have been effective enough, there may have been alterations (ie, epigenetic) not influenced by the intervention, or perhaps environmental factors and lifestyle choices explain the association rather than GDM itself.

Thus, it seems more beneficial to try to prevent the development of gestational diabetes by exercising regularly (discussed later in this lesson), minimizing added sugar, and preventing excess gestational weight gain (“GWG”). If you do develop gestational diabetes despite taking appropriate preventive measures (and this can happen through no fault of your own), discuss with your healthcare provider what you should do to help optimize your blood glucose control.

Preeclampsia

A 2021 systematic review and meta-analysis (“SR/MA”) including 44 articles evaluated the association of preeclampsia with various outcomes, finding that in offspring this associates with small increases in body mass index (“BMI”), waist-to-hip ratio, waist circumference, hip circumference, subscapular and triceps skin folds, a 45% increased risk of obesity, and a 42% increased risk of hypertension.^{(Bi, 2021)} There did not seem to be a significant impact on diabetes risk (though there was a trend for an increased risk), cholesterol, or triglycerides.

Note: In the preeclampsia analysis noted above a 45% increased risk of obesity seems quite large, but this was compiled from only 5 studies at an average age of ~9 years. Regarding the small increase in BMI, this was determined from 19 studies and on average the BMI increased by 0.22; children under age 10 years had no increase in BMI and children >10 years old had an average increase of 0.46. Thus, one group of studies indicates no increase in BMI under age 10 and another indicates a significant increase in obesity risk; it is hard to reconcile this as discussed in Lesson 10 obesity is typically defined by BMI. More studies are needed, but potentially the overall effect is rather minimal.

It’s possible preeclampsia increases the risk of being born small for gestational age (“SGA”), which may lead to excessive catch-up growth (“CUG”) and increase the obesity risk later in life; this is discussed further below and in Lesson 7.

Maternal infection and antibiotic use

Regarding infections and antibiotics use, a 2021 SR/MA including 10 studies found that in general prenatal antibiotic use was associated with at most a small increased risk of childhood overweight and obesity.^{(Solans, 2021)} Potentially more importantly, in the subgroup of women who received at least 3 courses there was a more substantial 31% increased risk. However, a 2020 study that assessed the association of maternal infection and maternal antibiotic use during pregnancy with child overweight for up to 10 years found that those who developed infections without antibiotic use had a ~10% greater risk of childhood obesity while antibiotic use itself was not associated with this risk.^{(Li, 2020)} Thus, multiple maternal infections may increase the risk of childhood obesity while short courses of antibiotics may not have a significant additional effect.

Impact of pregnancy number, birth order, and siblings

A 2018 SR/MA attempted to quantify the impact of birth order and the number of siblings on the risk of overweight/obesity (in childhood or as adults), finding^{(Meller, 2018)}:

Regarding birth order, 6 studies showed higher odds of overweight/obesity with lower birth order (the 1st born would have a birth order of 1, 2^nd born a birth order of 2, etc), 1 showed the opposite, and 8 showed no association, with an overall pooled odd’s ratio = 1.47 (suggesting lower birth order has higher odds of developing overweight/obesity).
Regarding the number of siblings, 6 studies showed lower odds of developing overweight/obesity with a greater number of siblings, 1 showed the opposite, and 7 had no association, with an overall pooled odd’s ratio = 1.46 (suggesting having fewer siblings increases the odds of developing overweight/obesity).
Of the 9 studies evaluating both factors, a higher risk of developing overweight/obesity was consistently seen in children without any siblings relative to children with siblings, whereas when only looking at children with siblings the 1^st born compared to later born children did not have an increased risk.

Thus, it seems being an only child increases the risk of developing overweight/obesity. The authors speculate this may be due to permanent physiologic changes in women after their first pregnancy (which seems unlikely given no impact was seen in the 1st born compared to later-born siblings) or due to only children having higher nutrient intake than children with siblings. This is plausible if children without siblings have more food available; they also may exercise less without sibling interaction.

A separate 2018 SR also evaluated the influence of birth order and number of siblings; they evaluated fewer studies and had some contrasting results.^{(Park, 2018)} Here being an only child also increased the risk of obesity, similar to above. Additionally, having fewer siblings associated with unhealthy eating habits as well as inadequate sleep and exercise. In contrast to the above review, 6 studies were found that evaluated the influence of birth order and 4 of them suggested that being a youngest child increased the risk of obesity, 1 suggested no difference, and 1 suggested being an oldest child increased the risk of obesity. Thus, depending on the subset of studies that are evaluated the birth order may or may not be influential, but more consistently it does seem that children without siblings are at an increased risk of obesity.

Lastly, a 2021 study evaluated the impact of various maternal factors as well as birth order on birth weight in children with siblings and in comparison to children without siblings.^{(Bohn, 2021)} The authors found:

Children with a birth order of 3 or higher were born ~180g heavier than 1^st born children, and children born 2^nd were also heavier than the 1^st born children to a smaller degree.
There were no differences between only children and 1^st born children in families with multiple births.
While maternal preconception BMI did increase with each pregnancy, the actual amount of weight gained during pregnancy decreased with each successive birth.
Maternal preconception BMI and preconception weight gain did contribute to birth weight as well but this was independent of birth order in their multivariate analysis.

Thus, in this study birth order had a greater impact on birth weight than all of the considered maternal factors.

Note: It may seem like the more recent study contrasted the above reviews to a degree, but keep in mind the above reviews were evaluating overweight and obesity as outcomes (at any age) while in the more recent study the authors were evaluating the impact on birth weight specifically, which is a very different metric.

Impact of delivery method

A 2022 SR/MA evaluated 11 studies to determine the impact of caesarean section vs. vaginal delivery on obesity risk in young adults (age ≥18 years).^{(Quecke, 2022)} Initially there was a 30% increased risk of obesity with caesarean sections, but when adjusting for various confounding variables there was only a 22% increased risk. However, when only looking at the subset of studies that could be adjusted for maternal prepregnancy BMI (and when making this adjustment), the relative risk ratio was 1.08 with a 95% confidence interval of [0.92, 1.27]. This implies that caesarean sections do not increase the risk of obesity relative to vaginal delivery, rather women with higher prepregnancy BMIs are more likely to have cesarean sections, and it is the higher prepregnancy BMI that contributes to the increased risk of obesity.

Subsequently, a 2023 SR/MA evaluated the same 11 studies as the prior one plus an additional 3, finding the odds of developing overweight or obesity in adulthood after being born by cesarean section were 1.19 (with a 95% confidence interval of [1.08, 1.30], but this was only significant in females (odds 1.32 with a 95% confidence interval of [1,00, 1.75]) and not in males (odds ratio 1.00).^{(Chiavarini, 2023)} This latter analysis however did not consider maternal prepregnancy BMI, and considering that made the prior analysis’s findings no longer statistically significant I expect the same would occur here.

Impact of infant birth size and body composition on child health

Several health-related aspects of pregnancy and maternal body composition can impact infant birth size in various ways.^{(Heslehurst, 2022)} For example, GDM typically correlates with infants being born relatively large (as stated above, when the fetus experiences higher glucose levels more insulin is secreted which drives increased growth), while maternal smoking typically correlates with infants being born relatively small (smoking can lead to decreased blood flow and thus decreased nutrient delivery to the growing fetus). It is worth considering what impact birth size has on future child health outcomes. However, birth size in isolation may not tell the whole story; infant body composition may also play a role and any connection between birth size and subsequent rapid weight gain (“RWG”) may also be informative.

Thus, I include some of the more relevant recent literature here. You can click on the expandable box if you want to read through brief synopses of each publication; I include a summary paragraph below. I will underline some of the main findings of birth size while I will bold some of the main findings or thoughts regarding the weight gain trajectory after birth. I discuss RWG in more detail in Lesson 7; I am discussing it to some degree here as it is associated with infant birth size in some of the cited publications.

Click here for summaries of recent publications regarding the impact of birth size on child weight outcomes

In summary:

Low birth weight is associated with decreased muscle mass and increased fat mass in young adulthood, while being born SGA is associated with an increased risk of type 2 diabetes mellitus (“T2DM”); it is unclear if this may be mediated by RWG.
High birth weight is associated with an increased risk of obesity and T2DM, particularly if there is no deceleration in the rate of weight gain in early life. However, being born large for gestational age (“LGA”) by length (but not weight) or by mothers without overweight, obesity, or diabetes mellitus does not lead to an increased risk of RWG.
A higher body fat percentage at birth is associated with an increased risk of childhood obesity.
Preterm birth itself is associated with an increased risk of future obesity, potentially mediated by RWG.

Unfortunately, from what I can tell, relatively few studies have attempted to disentangle birth size from the subsequent growth trajectories. It is possible that the in utero environment leads to fetal programming that makes RWG more likely. As a healthier pregnancy with respect to maternal body composition and GDM should lead to better infant birth size outcomes and potentially a lower risk of RWG, a healthier pregnancy is worth striving for to decrease the risk of childhood obesity and adverse cardiometabolic outcomes.

Note: Regarding the increased risk of obesity from prematurity mentioned above, it’s worth considering if this may be mediated by birth size, as premature infants are frequently born relatively small.

A 2019 SR/MA found that prematurity itself is associated with slight increases in BF%, blood pressure, glucose levels, and total cholesterol, but not BMI, waist circumference, waist-to-hip ratio, triglycerides, HDL-cholesterol, or LDL-cholesterol.^{(Markopoulou, 2019)} When looking at the subset of studies that attempted to disentangle the impact of being born premature with and without being born SGA, there were no differences between the two groups, meaning being born premature increases cardiometabolic risks independent of the birth size itself.

Environmental and in utero exposures

Pretty much any substance that is within the maternal bloodstream can make it at least to the placenta and potentially to the embryo or fetus. While consumed nutrients transfer to the growing child, other substances can have an effect as well.

Pesticides and pollutants

A 2021 SR/MA found that prenatal exposure to some of the persistent organic pollutants in our environment is associated with an increased risk of childhood obesity.^{(Stratakis, 2021)} It is thought these can act as endocrine disruptors and increase the volume and number of existing adipocytes (fat cells) while altering hormonal control of appetite and satiety. This was also indicated in separate recent reviews, specifically noting that bisphenol A and phthalates may be culprits.^{(Lobstein, 2021; Rodgers, 2021; Abulehia, 2022)} Distinctly, a 2021 SR regarding prenatal & postnatal exposure to pesticides on obesity risk in offspring included 9 animal studies and 25 human studies and found in general lots of mixed and conflicting results, noting that more research is needed.^{(Pinos, 2021)}

Nonetheless, one toxicant that does have significant supporting evidence is smoke exposure (also mentioned in Lesson 1 regarding the preconception period); both paternal smoking preconception and maternal smoking during pregnancy have been associated with negative effects such as increased offspring body fat, increased childhood obesity, and increased risk of T2DM.^{(Fernandez-Twinn, 2019; O’Connor, 2020; Vrijheid, 2020; Hou, 2022)}

Hormones

There are additional hormonal factors that can influence child growth^{(Rodgers, 2021)}:

Excess testosterone exposure in utero can increase the risk of polycystic ovarian syndrome (“PCOS”) in females, while in animal studies excess androgen exposure can increase white adipose tissue size and promote a pro-inflammatory state. As PCOS is associated with increased testosterone levels, this can propagate through generations.
Maternal stress, which increases glucocorticoid exposure (ie, cortisol) for the growing embryo and fetus, has also been noted to have negative effects.
- This impact of maternal stress was also noted in a review regarding intrauterine programming of obesity and T2DM, where prenatal bereavement (a stressful condition for the fetus) associated with greater T2DM incidence later in life.^{(Fernandez-Twinn, 2019)}

Insulin is another hormone of consideration, but this does not directly transfer from the mother to the embryo/fetus; rather excess glucose can transfer to the fetus and the fetus will secrete excess insulin in response. Increased cortisol and insulin exposure can collectively contribute to increased adipocyte differentiation.^{(Rasmussen, 2021)}

Pregnancy interventions

As it is clear that maternal choices during pregnancy can impact the health of the developing embryo and fetus, several research trials of pregnancy interventions have been performed to determine what can be done to improve the likelihood of better child health outcomes. I include some of the more recent review articles here.

General lifestyle interventions

A 2019 review found there was very little evidence of effective interventions during pregnancy to benefit the risk of later childhood obesity onset.^{(Grobler, 2019)}
A 2021 SR/MA found that lifestyle interventions in pregnancy generally did not impact early childhood growth outcomes in any meaningful way, though the authors note that many of the interventions had small effects on the pregnant women themselves.^{(Raab, 2021)} It is possible that more impactful interventions would have a larger influence on child growth outcomes.
A 2021 SR/MA evaluated if lifestyle interventions during pregnancy in women with overweight or obesity impacted neonatal adiposity, finding overall no impact on this outcome, birth weight, or fat-free mass.^{(Baroni, 2021)}
A 2021 meta-review of SRs of lifestyle interventions for reducing GWG in pregnant women with overweight or obesity found collectively almost all studied interventions had at most minimal impact, generally reducing GWG by at most 2.4 kg and not impacting the risk of GDM, preeclampsia, c-section, preterm delivery, being born LGA, or being born SGA.^{(Fair, 2021)}
A 2021 SR/MA examined individual participant data regarding the impact of dietary and/or lifestyle interventions in pregnancy for women with overweight or obesity on child weight outcomes at age 3-5 years.^{(Louise, 2021)} The authors found ~30% of children had a BMI >90th percentile both in the intervention and the control groups with no differences between them. When correcting for multiple hypothesis testing the interventions did not lead to any significant changes in child or maternal anthropometric outcomes, maternal diet, or child diet and activity levels, and any changes that were otherwise seen for maternal outcomes were likely clinically insignificant. Even when there were some differences in GWG these weight differences did not persist at 3-5 years follow-up.
A 2022 review notes that interventions targeting pregnant women with overweight or obesity generally do not impact GWG gain or infant health.^{(Dodd, 2022)}
A 2023 review of prenatal interventions found in general no strong evidence that prenatal dietary, exercise, or combined interventions result in any long-term effects on offspring adiposity.^{(Fortin-Miller, 2023)}

So it seems unfortunately that research trials of interventions during pregnancy do not show significant improvements in maternal or child health outcomes. However, as indicated above this may be because the interventions themselves were not very effective. Thus, it is unclear if there would be clinically meaningful benefits from truly effective interventions.

Exercise during pregnancy

While general lifestyle interventions have not been very effective, the same cannot be said for exercise specifically. I discuss in detail some of the recommendations for performing exercise during pregnancy in Lesson 15 of the General Exercise course. Below I’ve included a couple of reviews highlighting some of the benefits for child health outcomes.

A 2020 review of the effects of maternal and paternal exercise on offspring metabolic health in adulthood noted the following^{(Kusuyama, 2020)}:

Lots of research shows exercise is safe and beneficial during pregnancy. This helps prevent gestational hypertension and GDM, decreases the risk of preterm delivery, normalizes birth weight, decreases neonatal adiposity, and can improve neonatal neurobehavioral outcomes, cardiac autonomic health, and capacity for movement.
Whether there are associations with metabolic health in adulthood has not been studied in humans.
- However, several rodent studies do indicate maternal exercise during pregnancy improves metabolic health in adulthood and also can counteract detrimental effects of parental high-fat diets during pregnancy. Additionally, maternal exercise leads to decreased body weight as offspring age and benefits skeletal muscle, the liver, and the pancreas.

A 2021 SR/MA examined studies evaluating the impact of exercise during pregnancy for mothers with normal weight and obesity on child growth trajectories & obesity risks.^{(Chen, 2021)} This analysis included 99 studies and determined the impact of exercise during pregnancy on various outcomes:

Birth weight (81 studies): no effect was seen.
- However, with high levels of exercise (>810 MET-min per week) birth weight was generally decreased with no increased risk of SGA.
  - If curious, MET-min were defined in Lesson 3 of the General Exercise course.
Preterm birth (32 studies): overall decreased risk of 18%.
SGA (53 studies): overall decreased risk of 18%.
LGA (44 studies): overall decreased risk of 28%.
Childhood weight & obesity risk (7 studies): their data is a little confusing as they mention 7 studies but they actually include 8 studies. Collectively there was no effect, but only 2 studies specifically evaluated the impact on childhood obesity risk and only 1 of these was done with mothers with overweight or obesity.

Thus, the generally advised 500 MET-min/wk of exercise seems safe based on this analysis. Regarding mechanisms, the authors note that pregnant women with obesity have impairment of placental vascular branching & nutrient perfusion. Additionally, aggravated insulin resistance leads to fetal overgrowth, excessive body fat deposition, and accelerated pancreatic beta-cell maturation. Exercise counteracts hyperglycemia & hyperlipidemia by increasing insulin sensitivity and skeletal muscle consumption of glucose & lipids, which may directly mitigate their risks.

Conclusion

There are several insights from the literature discussed in this lesson:

Various maternal medical conditions increase the risk of childhood obesity; working towards having a healthy pregnancy may help mitigate these risks.
Children without siblings seem to have an increased risk of obesity; perhaps this is due to them having greater access to food and less motivation to engage in physical activity without having a sibling for interaction.
The birth method (vaginal vs caesarean section) likely does not impact the risk of childhood obesity.
Low and high birth weights seem to associate with increased risks of obesity, but this may be mediated by the infant growth trajectories after delivery rather than the pregnancy conditions themselves; more research is needed to clarify these points.
Various pollutants and in particular cigarette smoke can increase the risk of childhood obesity.
Maternal stress can have negative effects; exercising regularly may help mitigate stress and will help lead to better birth outcomes.

Now that I have discussed the preconception and pregnancy stages, in the next four lessons I will discuss the infancy/toddler periods and their various associated lifestyle factors that influence future weight management.

Click here to proceed to Lesson 4

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Lesson 3: Pregnancy – Medical Conditions, Birth Size, and Other Considerations

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