Genetic Evidence for Causal Relationships Between Maternal Obesity-Related Traits and Birth Weight

Tyrrell, Jessica; Richmond, Rebecca C; Palmer, Tom; Feenstra, Bjarke; Rangarajan, Janani; Metrustry, Sarah; Cavadino, Alana; Paternoster, Lavinia; Armstrong, Loren L.; Silva, N. Maneka G. De; Wood, Andrew R.; Horikoshi, Momoko; Geller, Frank; Myhre, Ronny; Bradfield, Jonathan P.; Kreiner‐Møller, Eskil; Huikari, Ville; Painter, Jodie N.; Hottenga, Jouke‐Jan; Allard, Catherine; Berry, Diane J.; Bouchard, Luigi; Das, Shikta; Evans, David M.; Hákonarson, Hákon; Hayes, M. Geoffrey; Heikkinen, Jani; Hofman, Albert; Knight, Bridget; Lind, Penelope A.; McCarthy, Mark I.; McMahon, George; Medland, Sarah E.; Melbye, Mads; Morris, Andrew P.; Nodzenski, Michael; Reichetzeder, Christoph; Ring, Susan M.; Sebért, Sylvain; Sengpiel, Verena; Sørensen, Thorkild I A; Willemsen, Gonneke; Geus, Eco J. C. de; Martin, Nicholas; Spector, Tim D.; Power, Christine; Järvelin, Marjo‐Riitta; Bisgaard, Hans; Grant, Struan F A; Nøhr, Ellen Aagaard; Jaddoe, Vincent W. V.; Jacobsson, Bo; Murray, Jeffrey C.; Hocher, Berthold; Hattersley, Andrew T.; Scholtens, Denise M.; Smith, George Davey; Hivert, Marie‐France; Felix, Janine F.; Hyppönen, Elina; Frayling, Timothy M.; Lawlor, Debbie A.; Freathy, Rachel M.

doi:10.1001/jama.2016.1975

Cited by 234 publications

(217 citation statements)

References 55 publications

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“…This may seem surprising because GDM is a known risk factor for macrosomia of the newborn, at least if untreated [4,8,49]. In our study, women with GDM had comparable glucose levels to women without GDM, therefore a good glucose control of mothers with GDM during pregnancy in combination with the reduced duration of gestation might explain the similar birth weight results.…”

Section: Discussionsupporting

confidence: 46%

Fetal Serum Metabolites Are Independently Associated with Gestational Diabetes Mellitus

Reichetzeder

Prehn

et al. 2018

Cell Physiol Biochem

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Background/Aims: Gestational diabetes (GDM) might be associated with alterations in the metabolomic profile of affected mothers and their offspring. Until now, there is a paucity of studies that investigated both, the maternal and the fetal serum metabolome in the setting of GDM. Mounting evidence suggests that the fetus is not just passively affected by gestational disease but might play an active role in it. Metabolomic studies performed in maternal blood and fetal cord blood could help to better discern distinct fetal from maternal disease interactions. Methods: At the time of birth, serum samples from mothers and newborns (cord blood samples) were collected and screened for 163 metabolites utilizing tandem mass spectrometry. The cohort consisted of 412 mother/child pairs, including 31 cases of maternal GDM. Results: An initial non-adjusted analysis showed that eight metabolites in the maternal blood and 54 metabolites in the cord blood were associated with GDM. After Benjamini-Hochberg (BH) procedure and adjustment for confounding factors for GDM, fetal phosphatidylcholine acyl-alkyl C 32:1 and proline still showed an independent association with GDM. Conclusions: This study found metabolites in cord blood which were associated with GDM, even after adjustment for established risk factors of GDM. To the best of our knowledge, this is the first study demonstrating an independent association between fetal

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Section: Discussionsupporting

confidence: 46%

Fetal Serum Metabolites Are Independently Associated with Gestational Diabetes Mellitus

Reichetzeder

Prehn

et al. 2018

Cell Physiol Biochem

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“…A study among 30,487 mother-offspring pairs from 18 cohort studies showed that a genetically higher maternal BMI was associated with a higher birth weight, which suggests that genetically higher maternal BMI may be causally related to birth weight [78] . On the contrary, a study of 4,091 mother-offspring pairs, showed no association of maternal FTO with childhood fat mass at the age of 9 years, which suggest that maternal obesity may not be causally related to childhood adiposity outcomes [69] .…”

Section: Causality or Confoundingmentioning

confidence: 99%

Childhood Health Consequences of Maternal Obesity during Pregnancy: A Narrative Review

Gaillard

Santos²,

Duijts

et al. 2016

Ann Nutr Metab

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Background: Obesity is a major public health problem among women of reproductive age. In a narrative review, we examined the influence of maternal obesity during pregnancy on fetal outcomes and childhood adiposity, cardio-metabolic, respiratory and cognitive-related health outcomes. We discuss results from recent studies, the causality and potential underlying mechanisms of observed associations and challenges for future epidemiological studies. Summary: Evidence from observational studies strongly suggests that maternal pre-pregnancy obesity and excessive gestational weight gain are associated with increased risks of fetal pregnancy complications and adverse childhood cardio-metabolic, respiratory and cognitive-related health outcomes. It remains unclear whether these associations are due to intrauterine mechanisms or explained by confounding family-based sociodemographic, lifestyle and genetic factors. The underlying mechanisms have mainly been assessed in animal studies and small human studies, and are yet to be further explored in large human studies. Key Message: Maternal obesity is an important modifiable factor during pregnancy that is associated with a variety of adverse offspring health outcomes. Further studies are needed to explore the causality and underlying mechanisms of the observed associations. Ultimately, preventive strategies focused on reducing maternal obesity and excessive weight gain during pregnancy may reduce common diseases in future generations.

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“…Furthermore, literature suggests a complex genetic association, as SGA offspring more commonly occurs in women themselves born SGA [32,36]. Increases in birth weight are typically associated with maternal obesity and gestational or pre-gestational diabetes [37][38][39]. Moreover, a very recent study provided genetic evidence for a causal relationship between maternal obesityrelated traits and offspring birth weight [37].…”

Section: Overnutritionmentioning

confidence: 99%

“…Increases in birth weight are typically associated with maternal obesity and gestational or pre-gestational diabetes [37][38][39]. Moreover, a very recent study provided genetic evidence for a causal relationship between maternal obesityrelated traits and offspring birth weight [37]. Large for gestational age (LGA) offspring usually displays an increased body fat mass and an increased risk for metabolic disease in later life [37,40,41].…”

Section: Overnutritionmentioning

confidence: 99%

“…Moreover, a very recent study provided genetic evidence for a causal relationship between maternal obesityrelated traits and offspring birth weight [37]. Large for gestational age (LGA) offspring usually displays an increased body fat mass and an increased risk for metabolic disease in later life [37,40,41]. Current evidence suggests that either being born with a reduced or an increased birth weight increases disease risk in later life.…”

Section: Overnutritionmentioning

confidence: 99%

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Developmental Origins of Disease - Crisis Precipitates Change

Reichetzeder

Putra

et al. 2016

Cell Physiol Biochem

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The concept of developmental origins of diseases has gained a huge interest in recent years and is a constantly emerging scientific field. First observations hereof originated from epidemiological studies, linking impaired birth outcomes to adult chronic, noncommunicable disease. By now there is a considerable amount of both epidemiological and experimental evidence highlighting the impact of early life events on later life disease susceptibility. Albeit far from being completely understood, more recent studies managed to elucidate underlying mechanisms, with epigenetics having become almost synonymous with developmental programming. The aim of this review was to give a comprehensive overview of various aspects and mechanisms of developmental origins of diseases. Starting from initial research foci mainly centered on a nutritionally impaired intrauterine environment, more recent findings such as postnatal nutrition, preterm birth, paternal programming and putative interventional approaches are summarized. The review outlines general underlying mechanisms and particularly discusses mechanistic explanations for sexual dimorphism in developmental programming. Furthermore, novel hypotheses are presented emphasizing a non-mendelian impact of parental genes on the offspring's phenotype.

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Genetic Evidence for Causal Relationships Between Maternal Obesity-Related Traits and Birth Weight

Cited by 234 publications

References 55 publications

Fetal Serum Metabolites Are Independently Associated with Gestational Diabetes Mellitus

Fetal Serum Metabolites Are Independently Associated with Gestational Diabetes Mellitus

Childhood Health Consequences of Maternal Obesity during Pregnancy: A Narrative Review

Developmental Origins of Disease - Crisis Precipitates Change

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