Nutrition in Pregnancy Affects Metabolic and Respiratory Outcomes in Offspring

By Giovanni Piedimonte, MD

The prevalence of both obesity (17 percent) and asthma (9.6 percent) in children continues to rise in the United States.1 While pathophysiologic links between obesity and asthma have been proposed, such linkage remains controversial.2

Nutrition’s role in the asthma-obesity link

My colleagues and I previously demonstrated in a study of 18,000 school-age children that those with asthma tend to have higher serum triglyceride levels and higher rates of insulin resistance, regardless of body mass.3 This finding brought forth a potentially game-changing idea: Early abnormalities of lipid and glucose metabolism may be associated with the development of asthma, confounding asthma’s epidemiologic link to obesity.

Building on this population-based correlation, we subsequently undertook an animal study to determine whether maternal nutrition in pregnancy affects postnatal metabolic and respiratory outcomes in offspring. The study, recently published in Pediatric Research4 and funded in part by a grant from the National Institutes of Health, was fueled by the likelihood that both obesity and asthma begin in utero and in early childhood. Therefore, nutritional factors — especially prenatal and early infant diet — may play a role in the pathogenesis of both conditions.

In this follow-on study, we sought to determine if fetal exposure to a maternal high-fat hypercaloric diet (HFD) — even in the absence of maternal obesity prior to pregnancy — could result in a predisposition to pathological airway responses to environmental challenges.

Study highlights

Using a rat strain without a genetic predisposition to obesity, we fed dams an HFD or a control diet (CD) during pregnancy and lactation. We compared the offspring in terms of:

• Metabolic profiles
• Inflammatory status
• Neurotrophic pathways
• Lung function in early versus adult life

The offspring of the HFD and CD dams also were exposed to the most common respiratory pathogen in infancy, respiratory syncytial virus (RSV), to evaluate the interactions between maternal and environmental factors on postnatal lung function.

Our findings included the following:

• Pups born from HFD dams developed that persisted throughout development.
• Cytokine expression analysis of lung tissues from newborns born to HFD dams revealed a strong proinflammatory pattern.
• Gene expression of neurotrophic factors and receptors was upregulated in lungs of weanlings born to HFD dams.
• HFD dams delivered pups that were prone to develop more severe RSV disease following infection.

Based on these findings, we concluded that maternal nutrition in pregnancy is a critical determinant of airway inflammation and hyperreactivity in offspring.

Take-home points

This study demonstrated that changing to an HFD in a normal-weight dam during gestation leads to offspring with abnormal metabolic profiles, chronic airway inflammation and increased susceptibility to RSV infection. Pups born to mothers fed an HFD during pregnancy had hypertriglyceridemia and increased body fat without a corresponding change in body weight.

One of the most important findings of this study is that increased availability of nutrients to the placenta was associated with airway inflammation and hyperreactivity during development.

Because this was an animal study, we were able to analyze the lung mechanics without obesity as a mechanical confounder, which allowed us to confirm our previously described population-based association of abnormal pulmonary function with elevated triglycerides.3

This study did have limitations, including the fact that we did not investigate variables related to maternal metabolism, such as gestational weight gain. In addition, since the dams were on the HFD prior to delivery for only about three weeks, we had to use a diet that would be considered extreme for humans.

Clinical implications: Early interventions look more compelling

In this study, we developed a new model of airway inflammation and hyperreactivity induced by prenatal dietary imbalance. While we cannot ethically achieve this same model in clinical research, the clinical implications are clear, especially in light of our earlier population-based study:3 A greater focus on the diet and metabolic health of pregnant women could have a significant impact on the global epidemics of childhood obesity and asthma — more so than other, more expensive postnatal prevention strategies or therapies.

When considered with our earlier population-based study in school-age children,3 the results of this animal study clearly suggest that public health interventions must occur as early in life as possible — especially in pregnant women and young children. Enormous resources are currently spent on treating the manifestation of diseases, yet the only way to stop them efficiently is to deal with them at the source. The consequences of a mother’s health — including nutrition — during pregnancy are not only important, but long-lasting.

At Cleveland Clinic, we have two programs in place focused on early nutritional and other health interventions that could serve as models for other centers. Our Healthy Expectations program gives women the support and information they need to optimize their weight and health before and during pregnancy, as well as after delivery. And Cleveland Clinic Children’s Be Well Kids Clinic brings together a comprehensive team of clinicians and researchers with expertise in childhood weight management to help children and families develop strategies and create plans for healthy lifestyle changes.

Our continuing research will focus on maternal and early-life nutrition as well as additional studies predicated on the notion that indoor and outdoor pollution (e.g., tobacco smoke, fine particles), bacterial or viral infections, psychological or physical traumas, or anything else a mother encounters in the environment during gestation can affect the well-being of a fetus or child and also have long-term health consequences in adulthood.

References

1. Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011–2012. JAMA. 2014;311:806-814.
2. Shore SA. Obesity and asthma: possible mechanisms. J Allergy Clin Immunol. 2008;121:1087-1093.
3. Cottrell L, Neal W, Ice C, Perez MK, Piedimonte G. Metabolic abnormalities in children with asthma. Am J Respir Crit Care Med. 2011;183:441-448.
4. Griffiths PS, Walton C, Samsell L, Perez MK, Piedimonte G. Maternal high-fat hypercaloric diet during pregnancy results in persistent metabolic and respiratory abnormalities in offspring. Pediatric Res. 2015 Nov 5 [Epub ahead of print].

Dr. Piedimonte, a pediatric pulmonologist, is Chairman and Physician-in-Chief of Cleveland Clinic Children’s as well as President of Cleveland Clinic Children’s Hospital for Rehabilitation. He can be contacted at piedimg@ccf.org or 216.444.2344.