How is Maternal pelvic dimensions and neonatal size

  Abstract

  INTRODUCTION

 There is compelling evidence that growth patterns in early life predict diverse components of health or disease risk in later life, as summarized in the ‘developmental origins of adult health disease’ (DOHaD) hypothesis [1]. Classic studies of rodents in the 1960 s identified ‘sensitive periods’ or ‘critical windows’ during early development, during which growth patterns generated a long-term impact on later body size and composition [2]. The specific role of nutrition in these effects was demonstrated experimentally in animals, by administering low-protein or low-energy diets during pregnancy [3, 4]. In humans, observational studies from the 1990 s onwards have likewise linked variability in size at birth with the risk of non-communicable diseases (NCDs), including stroke, hypertension, type II diabetes and cardiovascular disease [1, 5].

 Initially, most attention was directed to the high NCD risk among those of low birth weight (<2500 g), seemingly implicating ‘fetal under-nutrition’ as the primary pathophysiological mechanism [6]. This interpretation received support from long-term follow-up studies of those exposed in utero to maternal famine during the Dutch Hunger Winter, in 1944–45 [7]. Notably, however, similar analysis of those gestated during the Leningrad siege (1941–44) failed to replicate the Dutch findings [8]. A crucial difference was that the Dutch experienced only a brief and well-defined period of starvation, followed by rapid restoration of food supplies, whereas Leningrad experienced severe famine for several years. Dutch fetuses exposed to maternal famine are likely to have experienced catch-up growth after birth, an established independent risk factor for NCDs [9].

 Exactly how maternal nutrition during pregnancy shapes NCD risk in the offspring is also controversial from other perspectives. First, the association between birth weight and later NCD risk holds across the entire spectrum of birth weight, so that each additional increment of birth weight is associated with lower risk [5, 10]. On this basis, overt fetal malnutrition does not appear to be the key mechanism. Second, circulating maternal nutrient levels during pregnancy show negligible association with birth weight [11, 12], though a few studies have linked specific factors such as maternal glycaemic load or fish intake during pregnancy with birth weight [13, 14]. Maternal protein-energy supplementation during pregnancy typically results in relatively modest birth weight increments [15], though increases of 200–300 g have been reported among the most malnourished mothers [16, 17]. Collectively, these studies suggest that maternal diet during pregnancy can impact fetal growth, but that the magnitude of the effect tends to be modest.

 More generally, the majority of evidence linking early plasticity with later NCD risk relates not to maternal or fetal nutrition, rather to early growth variability. Moreover, recent large cohort studies indicate that among adults living a healthy lifestyle, there is little association of birth weight variability with adult NCD risk, whereas among adults with unhealthy lifestyle (obese, sedentary, unhealthy diet, smoking) birth weight is inversely associated with NCD risk [18, 19]. These data fit a ‘capacity-load’ model of NCD aetiology, in which the long-term capacity for homeostasis develops in fetal life and infancy in association with the magnitude of early growth, and NCD risk becomes elevated if those with low capacity subsequently acquire a high metabolic load [20, 21]. In high-income populations, where low birth weight is often followed by catch-up growth [9], there may be an inherent tendency for those with low capacity to acquire elevated load, elevating their NCD risk.

 Natural selection broadly favours larger neonates, due to their better survival in post-natal life [22, 23], though very high birth weights contradict this trend and indicate excess adiposity. The fact that median birth weight is substantially lower than the level at which survival is maximized indicates a tendency for mothers to constrain fetal growth, which may promote maternal genetic fitness over that of each individual offspring [23, 24]. Classic studies by Ounsted and colleagues indicated inter-generational transmission of a mechanism constraining fetal growth through the female line, indicating that paternal effects were negligible when maternal constraint is severe [25, 26]. While genetic factors might contribute, these analyses also indicated the involvement of non-genetic mechanisms. Of relevance here, recent studies indicate a striking developmental pattern in the heritability in growth. Twin studies show that the heritability of adult height approaches ∼90% [27], contrasting markedly with that for birth weight of ∼30% [28]. However, both before and after birth, the heritability of growth is higher, as demonstrated in Fig. 1 [29, 30]. There is a profound dip in heritability around the time of birth, of which the inevitable counterpart is that phenotype is more plastic during late fetal life and early infancy. A key question is, why should plasticity increase at such a vulnerable stage of the life-course