High Birth Weight and Hormone-Associated Cancer in Mothers
The idea of intrauterine or fetal factors being the cause of several prevalent noninfectious diseases in adults has recently gained the status of an axiom. One of the most thoroughly studied predictors is birth weight (BW). Although many published studies point at relations between BW and later adult morbidity or mortality, much less attention is paid to associations between baby BW and maternal morbidity. Available data suggest a sort of dichotomy in these relationships. Thus, cardiovascular risk is higher in mothers of babies with a reduced BW, while cancer risk, mainly of the breast and some other hormone-dependent cancers, is often higher among mothers of babies with a large BW (newborn macrosomia). This review addresses possible causes and endocrine mechanisms of this topic and suggests a 'particular' and 'general' solution for arising controversy. Emphasis is placed on a probable competition between chronic diseases (mainly, between female hormone-related cancer and cardiovascular pathology) within the concept of multiple causes of death. These associations should be remembered while studying the relation between offspring BW and maternal predisposition to hormone-associated cancers and other noncommunicable diseases.
Although many chronic diseases including cardiovascular disorders and cancer are more common in older adults, their causal factors often occur during the earlier stages of ontogenesis. Therefore, deviations in the physical parameters of newborns are often viewed as the first signs of apparent or, more often, occult pathology of both the child and mother. The importance of these factors to the child is partly reflected by popular concepts such as thrifty genotype, thrifty phenotype, developmental plasticity, compensatory or 'catch-up' growth and fetal programming. The 'fetal, or developmental, origin of adult diseases' is currently in the focus of attention. Its significance is confirmed by multiple published studies often based on integral indices, such as birth weight (BW) at term. The occasionally published critique of these views does not compromise the general idea of human noncommunicable diseases as a complex condition originating, at least partly, from in utero factors.
However, some of the critical arguments are quite convincing, leading to the "causal inference in this domain remains a serious challenge" and "the reported associations may be biased rather than causal" conclusions. In a comment to a large Danish publication regarding U-shaped rather than linear association of BW, with later adult mortality owing to circulatory diseases and other causes, Basso pointed, that "we should be cautious to not focus excessively on fetal growth," while speaking of adult outcomes. In another commentary to the same paper Lawlor added that, "This area of research needs to move away from simply describing the association of BW with disease/health outcomes. Instead, we must aim to understand whether there are modifiable risk factors during the developmental period that are importantly causally related to later disease outcomes". Therefore, the discussed subject should be reviewed in all its complexity, taking in account the mechanisms and possible factors leading to the development of chronic noninfectious conditions, such as cardiovascular diseases (CVDs) and hormone-associated cancers.
Meanwhile, the 'birth weight is forever' concept is still popular, not only because BW is an important indicator of both biological traits and socioeconomic circumstances, but also because of its apparent relationship with distant manifestations of human pathological conditions, although its exact machinery is not yet clear. Moreover, as the attention of 'developmental origin of chronic noncommunicable diseases' proponents is traditionally focused on low BW (LBW) babies, they mostly overlook the opposite side of the weight spectrum. However, recent trends suggest that high BW (HBW; more than 4000 g at birth) babies are becoming more prevalent than LBW babies; hence, the HBW group is beginning to attract more attention.
This review is based on long-term experience of studying chronic disease-related aspects of HBW. After a brief discussion of BW relation to later adult pathological conditions, the article will mainly concentrate on the other side of the problem: the association of babies' BW with the morbidity of their parents, particularly their mothers. Finally, possible causes of opposite associations of newborn macrosomy with maternal morbidity rate due to hormone-associated cancer and CVDs will be discussed.
Abstract and Introduction
Abstract
The idea of intrauterine or fetal factors being the cause of several prevalent noninfectious diseases in adults has recently gained the status of an axiom. One of the most thoroughly studied predictors is birth weight (BW). Although many published studies point at relations between BW and later adult morbidity or mortality, much less attention is paid to associations between baby BW and maternal morbidity. Available data suggest a sort of dichotomy in these relationships. Thus, cardiovascular risk is higher in mothers of babies with a reduced BW, while cancer risk, mainly of the breast and some other hormone-dependent cancers, is often higher among mothers of babies with a large BW (newborn macrosomia). This review addresses possible causes and endocrine mechanisms of this topic and suggests a 'particular' and 'general' solution for arising controversy. Emphasis is placed on a probable competition between chronic diseases (mainly, between female hormone-related cancer and cardiovascular pathology) within the concept of multiple causes of death. These associations should be remembered while studying the relation between offspring BW and maternal predisposition to hormone-associated cancers and other noncommunicable diseases.
Introduction
Although many chronic diseases including cardiovascular disorders and cancer are more common in older adults, their causal factors often occur during the earlier stages of ontogenesis. Therefore, deviations in the physical parameters of newborns are often viewed as the first signs of apparent or, more often, occult pathology of both the child and mother. The importance of these factors to the child is partly reflected by popular concepts such as thrifty genotype, thrifty phenotype, developmental plasticity, compensatory or 'catch-up' growth and fetal programming. The 'fetal, or developmental, origin of adult diseases' is currently in the focus of attention. Its significance is confirmed by multiple published studies often based on integral indices, such as birth weight (BW) at term. The occasionally published critique of these views does not compromise the general idea of human noncommunicable diseases as a complex condition originating, at least partly, from in utero factors.
However, some of the critical arguments are quite convincing, leading to the "causal inference in this domain remains a serious challenge" and "the reported associations may be biased rather than causal" conclusions. In a comment to a large Danish publication regarding U-shaped rather than linear association of BW, with later adult mortality owing to circulatory diseases and other causes, Basso pointed, that "we should be cautious to not focus excessively on fetal growth," while speaking of adult outcomes. In another commentary to the same paper Lawlor added that, "This area of research needs to move away from simply describing the association of BW with disease/health outcomes. Instead, we must aim to understand whether there are modifiable risk factors during the developmental period that are importantly causally related to later disease outcomes". Therefore, the discussed subject should be reviewed in all its complexity, taking in account the mechanisms and possible factors leading to the development of chronic noninfectious conditions, such as cardiovascular diseases (CVDs) and hormone-associated cancers.
Meanwhile, the 'birth weight is forever' concept is still popular, not only because BW is an important indicator of both biological traits and socioeconomic circumstances, but also because of its apparent relationship with distant manifestations of human pathological conditions, although its exact machinery is not yet clear. Moreover, as the attention of 'developmental origin of chronic noncommunicable diseases' proponents is traditionally focused on low BW (LBW) babies, they mostly overlook the opposite side of the weight spectrum. However, recent trends suggest that high BW (HBW; more than 4000 g at birth) babies are becoming more prevalent than LBW babies; hence, the HBW group is beginning to attract more attention.
This review is based on long-term experience of studying chronic disease-related aspects of HBW. After a brief discussion of BW relation to later adult pathological conditions, the article will mainly concentrate on the other side of the problem: the association of babies' BW with the morbidity of their parents, particularly their mothers. Finally, possible causes of opposite associations of newborn macrosomy with maternal morbidity rate due to hormone-associated cancer and CVDs will be discussed.
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