Normal and abnormal maternal metabolism during pregnancy

doi:10.1016/j.siny.2008.09.004

Seminars in Fetal and Neonatal Medicine

Volume 14, Issue 2, April 2009, Pages 66-71

https://doi.org/10.1016/j.siny.2008.09.004 Get rights and content

Summary

Metabolic adaptations during pregnancy are essential to meet the physiological demands of pregnancy as well as adequate growth and development of the fetus. There has been considerable interest in carbohydrate metabolism during pregnancy, with diabetes, the main disorder of glucose metabolism, a considerable focus for research. Whereas disorders of protein and lipid metabolism are recognised during pregnancy, their influence has received less attention. Fasting glucose values fall in early pregnancy with a rise in plasma free fatty acids, enhanced ketogenesis and a fall in plasma amino acids. Decreased hepatic insulin sensitivity in later pregnancy plays a key role in bringing about the appropriate changes in carbohydrate, lipid and amino acid metabolism which are essential for normal fetal development and survival.

Section snippets

Metabolism in normal women

The concept of ‘metabolism’ to describe the chemical changes continually occurring in the cells of living matter dates back to the 18th century. It involves the process by which food or nutritive matter is built up into living material (anabolism), or by which protoplasm is broken down to simpler material (catabolism). Claude Bernard had emphasised the constancy of the internal environment or milieu intérieur, and gradually a detailed understanding has been built up of the biochemical processes

Fasting plasma glucose and the response to glucose ingestion in normal subjects

This review will emphasise the somewhat different biochemical mechanisms which come into action during the normal fasting state (also confusingly called ‘post-absorptive’), and those which occur within a few hours of food ingestion (‘absorption’). When fasting, most glucose uptake is by tissues which are not sensitive to insulin control – the brain, red blood cells and splanchnic tissues.² Overall glucose uptake is precisely matched by the rate of endogenous glucose production, primarily by the

Impaired fasting glucose (IFG) and glucose intolerance (IGT)

The diagnostic concepts of IFG and IGT as distinct intermediate states between normality and overt diabetes mellitus have been emphasised recently. Epidemiological studies suggest that these categories represent largely distinct subpopulations, with different metabolic characteristics. In both cases impaired insulin sensitivity (or insulin resistance) and impaired beta cell function can be demonstrated, which are primary defects in type 2 diabetes mellitus. However, subjects with IFG have

Maternal adaptation to pregnancy

There are two underlying adaptations to the pregnant state, which may be regarded as being necessary to facilitate optimum development of the fetus. It has been known for many years that fasting glucose values fall in early pregnancy, and that there is a progressive rise in postprandial glucose and its associated insulin response in later pregnancy (Fig. 1, Fig. 2, Fig. 3). Norbert Freinkel in Chicago synthesised a number of interrelated maternal metabolic observations into his concepts of

Lipid metabolism in pregnancy

Normal pregnancy is hyperlipidemic. All circulating lipids are increased, but the greatest rise is in the triglyceride components. Changes in lipid metabolism are accompanied by functional and morphological changes in the adipocytes. Hypertrophy of these cells accommodates the increased fat storage during the first two trimesters of pregnancy.¹ The number of insulin receptors on the adipocytes increases in the first part of pregnancy and returns to non-pregnant levels by term. As the

Amino acid and protein metabolism in pregnancy

Although amino acids are required by both mother and fetus for energy and for growth, in most cases the maternal plasma concentrations fall during pregnancy.¹⁸ Total protein content of serum falls within the first trimester and reaches a plateau at mid-pregnancy (around 1 g/dL below non-pregnant levels). This is related to increased placental uptake, increased insulin levels, hepatic diversion of amino acids for gluconeogenesis, and transfer of amino acids to the fetus for use in glucose

Energy balance

There is a surprising degree of uncertainty regarding the overall energy balance of a normal pregnancy, due to the difficulty in making accurate measurements. Estimates of the energy cost range from 80 000 kcal to an actual saving of 10 000 kcal in different parts of the world. The original calculations by Hytten in Newcastle upon Tyne in England¹⁹ considered the additional maternal and fetoplacental tissues gained, and the additional energy requirements such as cardiac output during a pregnancy.

Maternal glucose homeostasis

Overall, as glucose is the major substrate for the human fetus throughout pregnancy, carbohydrate metabolism has been the main focus for physiological and pathophysiological research. Fetal glucose levels are 15–20% lower than in the mother, and maternal glycaemia is regulated by her insulin production. This will depend not only on the balance between the insulin secretion from the pancreatic beta cells and subsequent insulin clearance, but also on the effective action of that insulin on the

Changes in the postpartum period

After childbirth, carbohydrate metabolism is somewhat labile. Fasting plasma glucose appears to fall in the first few days of the postpartum period. Harris studied²⁶ 12 healthy women and found the mean fasting plasma glucose to be 3.9 mmol/L (70.7 mg/dL) on the second postpartum day compared to 4.2 mmol/L (75.4 mg/dL) in late pregnancy and 4.1 mmol/L (74.5 mg/dL) on the fifth day postpartum.²⁸ A larger cross-sectional study by McDonald et al.²⁹ found that the mean fasting glucose fell from 3.4 mmol/L

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Normal and abnormal maternal metabolism during pregnancy

Summary

Section snippets

Metabolism in normal women

Fasting plasma glucose and the response to glucose ingestion in normal subjects

Impaired fasting glucose (IFG) and glucose intolerance (IGT)

Maternal adaptation to pregnancy

Lipid metabolism in pregnancy

Amino acid and protein metabolism in pregnancy

Energy balance

Maternal glucose homeostasis

Changes in the postpartum period

Meta

Am J Obstet Gynecol

Lancet

Am J Obstet Gynecol

Meta

Am J Obstet Gynecol

Lancet

Am J Obstet Gynecol

Carbohydrate, fat, and protein metabolism

Preservation of pancreatic B-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk hispanic women

Diabetes

Subclinical abnormalities of glucose metabolism in subjects with previous gestational diabetes

Am J Obstet Gynecol

The Freinkel legacy

Some aspects of the metabolic and hormonal adaptation to pregnancy

Acta Endocrinol

Maternal physiologic adaptations to early human pregnancy

Lancet

Weight gain in pregnancy