Potentially the most important public health issue relating to pregnancy is the epidemiological association between birth weight and adult disease susceptibility (cardiovascular disease, diabetes, and hypertension). The highest risk is associated with the lowest birth weight but, because of the nature of the normal distribution, in terms of the numbers potentially affected in adult life, it is the small variations in the normal birth weight range that have the largest public health implications. A causal connection between birth weight and adult disease has been proposed in the 'fetal origins' hypothesis, which is that fetal undernutrition in middle to late gestation leads to disproportionate fetal growth and programs later disease susceptibility. The close association between birth weight and placental weight has led to speculation that the placenta may limit fetal growth within the normal weight range. However, the available evidence suggests that the capacity of the human placenta to transport macronutrients exceeds the fetal requirement and that a considerable proportion of transport function would have to be lost before it became limiting for fetal growth.
True intrauterine growth restriction (IUGR) resulting from utero-placental insufficiency is a serious pathology that is associated with a greatly increased risk of adverse outcomes including perinatal mortality and morbidity, impaired mental, visual and aural development, autism, and cerebral palsy. IUGR is often detected indirectly by measuring abnormal umbilical artery flow velocity waveforms and/or abnormal fetal heart rate. The abnormal waveforms are thought to result from increased vascular resistance associated with abnormal arter-iolar tree and villi branching and a reduction in the villous capillary tree. Pregnancies in which these abnormalities are observed are also associated with fetal hypoxia and reduced concentrations of glucose and amino acids in the fetal circulation and reduced activity of the system A amino acid transporter within the placenta. However, in vitro studies have shown that the hypoglycemia observed in some IUGR fetuses is not caused by a decreased glucose transport capacity within the placenta (expression and activity of GLUT1) and IUGR fetuses are actually hypertriglyceridemic compared to their appropriately grown counterparts. The fetal blood concentrations of the trace elements are also either normal or elevated in IUGR. Thus, while it is possible that the placenta from IUGR fetuses may limit the supply of amino acids there is no evidence that placental delivery is the first limiting factor in the supply of glucose, lipids, or trace elements. IUGR is a complicated syndrome in which almost all aspects of placental and fetal metabolism are altered and many researchers have emphasized the primary importance of the fetal hypoxia and its effects on fetal metabolism rather than a simple limitation of placental nutrient transfer capacity.
There is considerable uncertainty about the magnitude of the problem of IUGR. The lowest 5% of weight-for-gestational-age babies (defined according to well-nourished fetal growth centile charts) are referred to as small for gestational age (SGA) but babies in this range need not be growth retarded but may be naturally small and have no increased risk of adverse outcome. A further complication is that a baby born within the normal birth weight range could have suffered growth retardation in utero if its genetic potential was for a higher birth weight. The true incidence of IUGR resulting from utero-placental insufficiency is therefore unknown but if it is defined in relation to umbilical flow or fetal heart rate abnormalities then it is only a fraction of even those in the lowest 5% of weight-for-gestational-age that are affected by uteroplacental insufficiency. At the other end of the spectrum babies that are large-for-gestational-age (LGA) are at higher risk of adverse obstetric outcomes and early developmental problems but there is no evidence that LGA or macrosomic babies are produced as a result of a primary alteration in the placenta.
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