Home | About us | Editorial board | Search | Ahead of print | Current issue | Archives | Submit article | Instructions | Subscribe | Contacts | Advertise | Login 
Search Article 
Advanced search 
  Users Online: 2922 Home Print this page Email this page Small font sizeDefault font sizeIncrease font size  

Table of Contents
Year : 2013  |  Volume : 17  |  Issue : 1  |  Page : 60-68

In utero fuel homeostasis: Lessons for a clinician

Department of Neonatology, St. John's Medical College Hospital, Bangalore, Karnataka, India

Date of Web Publication27-Feb-2013

Correspondence Address:
P. N Suman Rao
Department of Neonatology, St. John's Medical College Hospital, Indiranagar, Bangalore, Karnataka
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2230-8210.107851

Rights and Permissions

Fetus exists in a complex, dynamic, and yet intriguing symbiosis with its mother as far as fuel metabolism is concerned. Though the dependence on maternal fuel is nearly complete to cater for its high requirement, the fetus is capable of some metabolism of its own. The first half of gestation is a period of maternal anabolism and storage whereas the second half results in exponential fetal growth where maternal stores are mobilized. Glucose is the primary substrate for energy production in the fetus though capable of utilizing alternate sources like lactate, ketoacids, amino acids, fatty acids, and glycogen as fuel under special circumstances. Key transporters like glucose transporters (GLUT) are responsible for preferential transfers, which are in turn regulated by complex interaction of maternal and fetal hormones. Amino acids are preferentially utilized for growth and essential fatty acids for development of brain and retina. Insulin, insulin like growth factors, glucagon, catecholamines, and letpin are the hormones implicated in this fascinating process. Hormonal regulation of metabolic substrate utilization and anabolism in the fetus is secondary to the supply of nutrient substrates. The knowledge of fuel homeostasis is crucial for a clinician caring for pregnant women and neonates to manage disorders of metabolism (diabetes), growth (intrauterine growth restriction), and transitional adaptation (hypoglycemia).

Keywords: Fetus, fuel, glucose, metabolism

How to cite this article:
Rao PS, Shashidhar A, Ashok C. In utero fuel homeostasis: Lessons for a clinician. Indian J Endocr Metab 2013;17:60-8

How to cite this URL:
Rao PS, Shashidhar A, Ashok C. In utero fuel homeostasis: Lessons for a clinician. Indian J Endocr Metab [serial online] 2013 [cited 2021 Sep 18];17:60-8. Available from: https://www.ijem.in/text.asp?2013/17/1/60/107851

   Introduction Top

The maintenance of a balanced and continuous supply of nutrients from the mother to the fetus throughout gestation is critical in maintaining a healthy, viable, and optimally growing fetus. For many years even after oxygen was discovered by Lavoisier, [1] it was assumed that the fetus had no metabolism of its own. Now it is well understood that the placenta and fetal liver work as a coordinated multi-organ system to supply nutrients to meet fetal metabolism and growth. [2] Enormous attempts have been made subsequently to understand the fetal metabolism in a very low oxygen environment (pO 2 16-27 mmHg)-'Mount Everest in utero' concept.

Estimation of fetal oxygen consumption may be used as a direct indicator of the fetal metabolism. Though the fetus has a great capacity for anaerobic metabolism using lactate, ketone bodies, amino acids effectively, the energy processes operate essentially through oxidative pathways. Based on fetal oxygen consumption, a fetus expends 55 kcal/kg/day. [3] The immense advancement in understanding fetal and perinatal fuel homeostasis is due to methodological advances in kinetic studies using stable isotopic tracers in conjunction with mass spectrometric quantification. [4]

   Carbohydrate Metabolism Top


The fetus has been described as a 'glucose-dependent parasite.' Carbohydrate is the primary fuel for the fetus, accounting for about 80% of fetal energy consumption. The remaining 20% of fetal energy needs is provided by lactate, amino acids, and others. Fetal glucose utilization rates (5-7 mg/kg/min) are higher than in adults (2-3 mg/kg/min). The placenta maintains a continuous uninterrupted supply in utero-the hallmark of fetal life-by the process of facilitated diffusion. The three key points in this complex regulation of fetal glucose metabolism are: [5]

  1. Maintenance of maternal glucose concentration by increasing maternal glucose production and development of relative maternal glucose intolerance and insulin resistance.
  2. Placental transfer of maternal glucose to the fetus, buffered by placental glucose utilization.
  3. Fetal insulin production and enhancement of glucose utilization in sensitive tissues.

The fetal glucose is almost all of maternal origin and is generally 10-20 mg/dl less than maternal levels (70-80% of maternal levels). This gradient favors transfer of glucose to the fetus. Fluctuations in maternal blood glucose are rapidly reflected in parallel changes in fetal glucose concentration. Though uterine, placental and fetal glucose uptake are related to maternal glucose concentrations, the partition of uterine glucose uptake into fetal and uteroplacental glucose uptakes is regulated by fetal glucose concentrations and is independent of maternal glucose availability [Figure 1]. [5] With increasing age and size of the fetus, the placenta successfully supplies more glucose by:
Figure 1: Uterine, fetal, and uteroplacental glucose uptake rates as functions of maternal (a, b) or fetal (c) arterial plasma glucose concentrations in pregnant sheep (reproduced from Ref 5)

Click here to view

  1. Increase in maternal-fetal glucose gradient as fetal glucose levels decrease due to increase in insulin dependent uptake of glucose by adipose tissue and skeletal muscle.
  2. Increase in placental glucose transport (PGT) capacity by an increase of the fetal glucose transporters.

Fetal glucose transporters [Table 1]
Table 1: Distribution of glucose transporters

Click here to view

The facilitated glucose diffusion is mediated by a family of structurally similar proteins known as the glucose transporters (GLUT) encoded by a family of genes SCL2A and expressed in a tissue-specific manner [Table 1]. GLUT 1 is the dominant isoform in most fetal tissues and the placenta. [6] Basal membrane GLUT 1 is the rate limiting step in fetal glucose levels. The maternal side of the placenta has a 5-fold greater increase in GLUT 1 than the fetal side. Insulin, insulin-like growth factors (IGF), and other hormones and peptides regulate its activity and expression. GLUT 1 in the placenta are not saturated until 198-235 mg/dl maternal glucose- levels that are significantly above the usual maternal blood glucose level. [7] This may indeed be a protective mechanism from adverse effects of severe hyperglycemia. With increasing gestational age, the placental glucose transfer is enhanced by increase in GLUT 1 and GLUT 3. GLUT 3 is more efficient, has very strong affinity to glucose and may be responsible for glucose transfer at very low glucose concentrations. GLUT 4 expressions are upregulated by hypoglycemia and hypoinsulinemia in skeletal muscle and adipose tissue, in contrast to no change in the brain, and downregulated with hyperglycemia.

Alternate fuels

The energy expenditure of the fetus as measured by oxygen consumption is 55 kcal/kg/day and the glucose uptake accounts for only 32 kcal/kg/d. Even if the supply of glucose is reduced, fetal oxygen consumption remains normal as the fetus is fully capable of using other substrates such as lactate, ketoacids, amino acids, fatty acids, and glycogen as fuel [Figure 2] and [Figure 3]. [8] Routinely, approximately 40-50% of the transported glucose is used by placenta for oxidation or converted to glycogen and lactate. The fetus uses this lactate along with glucose for fat and glycogen synthesis (accretion needs). With increasing gestation, maternal lipolysis provides fuel for the mother and also gluconeogenic precursors for the fetus. Normally, gluconeogenesis and ketogenesis are not seen in the fetus when substrate supply is adequate.
Figure 2: Energy substrates transported to and deposited in the fetus

Click here to view
Figure 3: Energy and nutrient substrates transfer to fetus (adapted from Ref 8)

Click here to view


In the third trimester, some of the energy and substrate available to the fetus are channeled from meeting needs for ongoing growth and development to energy storage. [9] The fetal liver contains the full complement of enzymes required for the synthesis and breakdown of glycogen and is the main glycogen storehouse (2-3 times adult), followed by heart (10 times adult), and skeletal muscle (3-5 times adult). However, only the liver contains sufficient glucose-6-phosphatase for the release of glucose in the circulation. Net synthesis or degradation of glycogen in the fetus is controlled by the functional balance between glycogen synthase and glycogen phosphorylase. The total content of these two enzymes is relatively constant over gestation. Fetal hyperglycemia increases fetal glycogen deposition by activating glycogen synthase via insulin. Hypoglycemia, glucagon, and cyclic adenosine monophosphate (cAMP) can induce the fetal liver to release glucose by activation of phosphorylase. The glycogenolytic action of glucagon is suppressed by insulin.

Preterm infants have an abbreviated or no third trimester and thus have limited glycogen stores. Fetuses that are growth-restricted on the basis of limited metabolic fuel availability and uteroplacental insufficiency will use these fuels for growth and not for glycogen synthesis.


Hepatic GNG is completely absent in utero and appears in the immediate newborn period. [10] The fetus also has all the four key hepatic enzymes involved in GNG, although their levels are lower than those in adults especially phosphoenolpyruvate carboxykinase (PEPCK), which, at least in the rat, is not expressed in utero and appears immediately after birth. GNG can be induced in utero by maternal starvation, prolonged hyperglycemia in mother and by cAMP infusion in the fetus. At birth, thyroid, cortisol, and catecholamines stimulate GNG. GNG may be impaired in preterm infants and intra uterine growth restricted (IUGR) infants due to lower PEPCK activity and reduced gluconeogenetic precursors.

   Lipid Metabolism Top

The land mammal with the highest fat content is the human fetus. It increases from 0.5% of body weight in early gestation to 3.5% by 28 weeks to 16-18% by term. [11] During early gestation, embryonic and fetal lipids are derived from maternal free fatty acids (FFA), whereas in advanced gestation there is a gradual shift to de novo synthesis in fetal tissue.

Free fatty acids

Placental transfer of triglycerides is null. Essential fatty acids such as ω-6 linoleic and ω-3 α linolenic acids derived from maternal diet are made available to the fetus by the action of the lipoprotein receptors and lipase activities in the placenta. Fatty acid binding protein on placental membrane (FABP pm) preferentially takes up long chain polyunsaturated fatty acids (LC-PUFAs) in the favored sequence of docosahexaenoic (DHA) > α-linolenic > linoleic > oleic > arachidonic acid (ARA). [12],[13] Intrauterine requirements ω-6 and ω-3 fatty acids in the human fetus during the last trimester of fetal development through the early weeks of life have been estimated to be 400 and 50 mg/kg/day, respectively. Though the fetus has a significant capacity for production of DHA and ARA from ω-3 α linolenic and ω-6 linoleic acids, respectively, is this enough throughout gestation? [14] It is suggested that maternal supplementation with DHA may improve neurodevelopmental outcome in offspring. [15]

Lipogenesis is very active in the fetus through the fatty acid synthetase pathway. The high insulin to glucagon ratio in the fetus promotes lipogenesis. The increased maternal nutrition in late gestation uniquely enhances brown fat development and the content of uncoupling protein-1 (UCP-1). These stores are vital postdelivery and UCP-1 allows for rapid lipid mobilization and energy production after birth. [16]


Maternal glycerol is preferentially used for glucose synthesis, saving other gluconeogenic substrates, like amino acids, for fetal growth.

Ketone bodies

Though ketogenesis is not active in the fetus, maternal ketone bodies are readily transferred transplacentally and the fetus can use them as fuel and as lipogenic substrates during maternal starvation, caloric restriction, high fat diet, or diabetes. [17] The fasting and fed states during pregnancy are depicted in [Figure 4]. Prolonged ketonemia may have neurological implications to the fetus.
Figure 4: Fasting and fed states in pregnancy (adapted from Ref 8)

Click here to view

   Protein Metabolism Top

Protein is the essential building block. Accumulation of protein results in most of the increase in fetal weight till about 26 weeks gestation. However, no protein is transported across the placenta. Amino acids are actively transported to the fetus by Na + /K + -ATPase and H + dependent transporter proteins resulting in higher fetal concentrations of amino acids (fetal-maternal plasma concentration ratios 1-5). Protein molecules as small as albumin and as large as gamma globulin pass from maternal to fetal plasma by pinocytosis. [8]

In utero accretion of proteins is highest during the third trimester of pregnancy at 3.6-4.8 g/kg/day. Matching this in the extreme preterm infant postnatally for optimal growth is indeed a very difficult task! In addition to the 10 essential amino acids, fetus needs cysteine, histidine, and taurine. The placenta also produces ammonia that is used by the fetal liver for additional protein synthesis. Some critical amino acids are not transferred across the placenta, but are produced in the placenta. This may be a safety feature as some amino acids like glutamate and aspartate are toxic, so the placenta can produce only the amounts that are needed by the fetus.

These amino acids are used for oxidation, protein, glycogen and fat accretion, and for growth. The amino acids contributes significantly as fuel in the fetus as evidenced by: [18]

  1. Excess uptake of amino acids relative to rate of deposition in fetal protein
  2. High rate of fetal urea production
  3. Direct measurement of labeled CO 2 production and excretion during fetal infusions with carbon labeled stable isotope amino acids.

Fetal protein synthesis is dependent on both amino acid and energy supplies. During positive energy balance, glucose utilization as fuel substitutes for amino acids. Insulin promotes nitrogen accretion. During maternal hypoaminoacidemia, as long as the fetal glucose supply is normal, growth is not affected. Conversely during maternal fasting, increased proteolysis occurs but protein synthesis is normal. It is only on prolonged energy and protein restriction, that protein synthesis is reduced to a great extent. [19],[20]

In this reciprocal manner, glucose supply and amino acid metabolism are closely balanced and protein accretion and growth are variables that less vital than fetal oxidative metabolism. Thus the fetus develops mechanisms that tend to keep its energy metabolism relatively constant, while growth is, at times of deficient energy supply, expendable. [5]

   Maternal Metabolism Top

The effect of pregnancy on maternal metabolism can be studied in two time frames:

Anabolic first half of gestation

The increased caloric intake sustains fetal growth and facilitates maternal fat deposition under normal insulin secretion.

Catabolic second half of gestation

In this period of exponential fetal growth, with the continuous transfer of glucose and nutrients to the fetus, the fasting maternal glucose and amino acids are lower. Maternal fat stores are mobilized and the resulting hypertriglyceridemia or 'floating fuel' is beneficial to both mother and baby. Increasing insulin resistance (20-60%) is integral to this phase, resulting in three times the pregravid insulin levels (diabetogenic state). Increasing human placental lactogen, progesterone, and estrogen are partly responsible for the insulin resistance. This can unmask a tendency toward diabetes mellitus. These changes are seen when the conceptus rapidly increases in mass from 20 to 24 weeks of pregnancy. The maternal metabolic processes and the underlying hormonal changes are shown in [Table 2]. The 'accelerated starvation' of the mother guarantees fuel to the fetus at the mother's expense.
Table 2: Maternal metabolic processes and hormonal changes

Click here to view

   Endocrine Regulation of Fetal Metabolism Top

Hormonal regulation of metabolic substrate utilization and anabolism in the fetus is secondary to the supply of nutrient substrates.


Insulin appears in the fetal circulation as early as 10-12 weeks gestational age. Fetal glucose metabolism is relatively independent of the insulin-glucagon regulatory mechanisms. Insulin is more important for enhancing growth than for regulating metabolic fuels during fetal life. Insulin stimulates the growth of specific tissues (e.g., adipose, hepatic, connective, skeletal, and cardiac muscle).

A glucose load elicits a very sluggish fetal insulin response in the nondiabetic mother [Figure 5]. With chronic hyperglycemia, insulin is reduced. [5],[21] But in contrast, the fetus of a diabetic mother with pulsatile hyperglycemia responds with a brisk insulin release. [22] Excessive insulin secretion during fetal life resulting from such conditions as maternal diabetes causes the disproportionate growth of insulin-sensitive tissues, resulting in macrosomia. The anabolic effect of insulin is enhanced by a separate direct effect of insulin on mitogen activated protein kinase (MAPK). Lack of insulin, as in infants with transient neonatal diabetes mellitus, always is accompanied by fetal growth restriction. Chronic maternal malnutrition depresses insulin and stimulates release of fetal glucagon.
Figure 5: Effect of maternal hyperglycaemia on the fetus in normal and diabetic pregnancies (adapted from Ref 7) A Normal pregnancy, B Diabetic pregnancy

Click here to view

Insulin like growth factors- IGF-1 and IGF-II

IGFs from the liver have autocrine, paracrine, and endocrine functions. Both IGF-I and IGF-II increase with gestational age. In early gestation, IGF-II is predominant and in later gestation, IGF-I, regulated by nutrient availability promotes growth with insulin and glucose. IGF-I is more responsive to insulin, thyroxine, and glucocorticoids than IGF II. Further, the effect of IGFs on fetal growth is amplified or attenuated by the IGF binding proteins (IGFBPs), which are regulated by nutritional and endocrine signals. In growth restricted fetuses, IGF-I is low. [23] Disruption of the IGF I, IGF II, or IGF I receptor gene retards fetal growth. Silver-Russel syndrome characterized by IUGR, poor postnatal growth, relative microcephaly, triangular face, and feeding difficulties is associated with low levels of IGF II due to hypomethylation defects and maternal uni-parental disomy.

Growth hormone

Growth hormone is abundant in fetal life. It has been suggested as a stimulator of fetal hepatic glycogen synthesis. It may affect insulin/glucose metabolism in a way similar to its postnatal diabetogenic action. However, its action on fetal skeletal growth is negligible due to less receptors. The phenotype resulting from GH deficiency is unremarkable except for micropenis, hypoglycemia, and perhaps a small reduction in birth length.


Glucagon is abundant in fetal life. The number of fetal hepatic glucagon receptors is decreased and insulin receptors higher. This promotes insulin mediated anabolism and decrease glucagon induced catabolism. Critical glucagon/insulin ratio is important for inducing gluconeogenic enzymes. A balance between these two hormones controls gluconeogenic enzyme induction during perinatal life. Cord clamping triggers an increase in glucagon secretion and insulin secretion slowly decreases. This is the trigger for glycogenolysis and gluconeogenesis in the immediate postnatal period.

Adrenergic hormones

During labor adrenergic mechanisms can stimulate hepatic glycogenolysis.


Fetal leptin, an adipostatic hormone appears by 90 days gestation, increases after 32-34 weeks and closely reflects the increase in size and number of adipocytes. It is important for fetal growth and may act by modulating growth hormone. It decreases rapidly after birth and may help limit energy expenditure and conserve nutrients for growth. Concentrations of leptin are three times higher in large for gestation (LGA) infants and 12 times higher in small for gestation (SGA) infants. Leptin expression is influenced by other hormones, that is, insulin, thyroid hormones, cortisol but its exact role in fetal and neonatal homeostasis is not understood. [24-26]

   Transition to Extra Uterine Life Top

The neonate must become independent after birth, [27] transitioning from a continuous intravenous supply of predominantly glucose as fuel to a variable and intermittent exogenous intake orally that is the hallmark of the neonatal period. This successful adaptation requires not only an immediate catabolic cascade but also adaptation to enteral feeding. The catabolic cascade includes endocrine stress response, surge in glucagon, low insulin, and glucagon ratio. This mobilizes hepatic glycogen and initiates gluconeogenesis, lipolysis, fatty acid β-oxidation with generation of ketone bodies, and proteolysis that generates lactate and other substrates for gluconeogenesis. Ketone bodies and lactate serve as alternative fuels with glucose-sparing effects, and are especially important in maintaining cerebral energy. The neonatal glucose homeostasis is also consistent with the ontogeny of the glucose transporters. After birth, GLUT-3 in the brain and GLUT-4 in the muscle increase. [4],[28] The metabolic transition is summarized in [Table 3]. Lipolytic activity becomes active after delivery especially as the human milk has a high fat content. The fetus and neonate have a high lipoprotein lipase activity in the liver in contrast to the adult. Fifty percent of the caloric intake of the newborn is from lipids.
Table 3: Metabolic transition at birth

Click here to view

   Implications for the Clinician Top

Understanding maternal-placental-fetal metabolism is critical for the management of frequent disorders such as diabetes in pregnancy, IUGR, preterm, and maladaptations at birth.


Blood glucose concentration falls rapidly after birth, reaching a nadir by 1 h of age and then rising to stabilize by 3 h of age. Small energy stores, delayed maturation of gluconeogenesis, hyperinsulinemia, or increased demands, may hamper the normal metabolic transition and lead to hypoglycemia. Under these conditions, the most vital organ, the brain, tries to maintain the metabolism by increasing blood supply and glucose transfer to brain, using alternate fuels such as lactate, fatty acids, ketone bodies. [29] Monitoring of at risk infants, prevention, and early treatment of hypoglycemia are critical to prevent adverse neurodevelopmental outcome.

Extreme preterm neonate

Neonatal intensive care units now routinely take care of 24-28 weeks. The glucose homeostasis in extreme preterm neonates is precarious. On one hand, they are at risk for hypoglycemia and need glucose infusion right from birth. But they are also unable to completely suppress endogenous glucose production even with high glucose infusions. This hepatic unresponsiveness combined with diminished pancreatic β cell response predisposes the extreme premature infant to hyperglycemia. [4] The range of euglycemia of 50-145 mg/dl may represent a more acceptable range for term and preterm neonates, except in micropremies. Providing adequate proteins and calories to match intrauterine accretion is also a big challenge in these infants.

   Maternal Diabetes Top

Pederson's hypothesis

Increased fetal glucose supply from the placenta increases fetal insulin secretion, [30] which augments fetal glucose and lactate accretion. The hyperinsulinemia promotes lipogenesis and macrosomia. Rather than chronic hyperglycemia, it is pulsatile hyperglycemia that results in glucose stimulated insulin secretion (GSIS). Despite normal HbA 1C , infant of diabetic mothers may be macrosomic due to poorly controlled postprandial sugars. A more severe acute hyperglycemia can initiate such profound metabolic changes to result in fetal acidosis and death. Close monitoring of maternal blood sugars is therefore vital to prevent neonatal complications in infant of diabetic mothers.

   Intra Uterine Growth Restricted Top

Impaired placental growth and function resulting in decreased energy substrate rather than dysregulated fetal endocrine responses is the primary defect in IUGR. [31] Lower lipolysis in the mother has been shown to reduce substrate availability in IUGR. [32] The PGT capacity is reduced due to a small placenta and reduction in glucose transporters. Owens, et al. [33] demonstrated impaired glucose stimulated insulin secretion in sheep fetus with impaired placental function. IUGR fetuses are not able to produce adequate amount of insulin due to reduced β islet number and size, by lengthening G1, S, and G2 stages of interphase and decreasing mitosis near term. Limesand, et al
. [22] demonstrated that plasma insulin concentrations in the IUGR fetuses are 64% lower at baseline and 77% lower after GSIS. The IUGR fetus copes in two ways: [5],[34]

  1. Upregulation of mechanisms regulating glucose utilization

    1. Glycogenolysis
    2. Gluconeogenesis
    3. Use of alternate fuels
    4. Increase in GLUT 1 in placenta and GLUT 4 in skeletal muscles

  2. Downregulation of mechanisms regulating growth

One question that needs to be answered urgently is-Can we intervene to prevent growth restriction in utero and thereby alter the potential metabolic problem?

   Fetal Origin of Adult Disease Top

Fetal over nutrition and under nutrition have been implicated in the genesis of the metabolic syndrome and is the deep focus of preventive medicine. Macrosomic infants of diabetic mothers may exhaust their insulin reserves in the face of hyperglycemia secondary to obesity and insulin resistance. [5]

IUGR infants probably have a low β cell mass and this coupled with the added insulin resistance of obesity later in life leads to the metabolic syndrome (the thrifty phenotype hypothesis). For each 1-inch decrease in abdominal circumference at birth, serum cholesterol and LDL-C concentrations in older adults are increased by approximately 10 mg/dl. [35] A meta-analysis including 147,000 persons has shown inverse relation between birth weight and subsequent development of ischemic heart disease, with a 10-20% lower risk observed per kilogram higher birth weight. [36]

Fetal hypoglycemia in the absence of impaired fetal growth has also been found to be associated with lower insulin secretion. [37],[38] Obesity-induced insulin resistance, altered expression of GLUT 4, defective oxidative phosphorylation, genetic mutations, and increased adrenocorticomedullary activity have all been evaluated in the pathophysiology of fetal origin of adult diseases.

   Conclusions Top

The human fetus is capable of controlling and partitioning energy to some extent through many complex, dynamic processes. Glucose is the primary fuel for fetal metabolism. However, the fetus is capable of utilizing lactate, amino acids, ketone bodies and others too. Continuous supply of fetal nutrients rather than hormones control fuel homeostasis. Oversupply of undersupply of nutrients can permanently program the fetal metabolism adversely.

   Acknowledgments Top

Dr. Saudamini Nesargi for her support in reviewing the manuscript.

   References Top

1.Huch R, Huch A. Assessment of oxygenation in the fetus and newborn. J Matern Fetal Neonatal Med 2003;13:76-9.  Back to cited text no. 1
2.Battaglia FC, Thureen PJ. Nutrition of the fetus and premature infant. Nutrition 1997;13:903-6.  Back to cited text no. 2
3.Sinclair JC. Metabolic rate and temperature control in the newborn. In: Goodwin JW, Gooden LO, Chance GW, editors. Perinatal Medicine. Baltimore: Williams and Wilkins; 1976. p. 558-77.  Back to cited text no. 3
4.Cowett RM, Farrag HM. Selected principles of perinatal-neonatal glucose metabolism. Semin Neonatol 2004;9:37-47.  Back to cited text no. 4
5.Hay WW Jr. Placental-fetal glucose exchange and fetal glucose metabolism. Trans Am Clin Climatol Assoc 2006;117:321-39.  Back to cited text no. 5
6.Simmons RE. Cell glucose transport and glucose handling during fetal and neonatal development. In: Polin RA, Fox WW, editors. Fetal and Neonatal Physiology. 4 th ed. Philadelphia: Saunders; 2011:560-8.  Back to cited text no. 6
7.Oakley NW, Beard RW, Turner RC. Effect of sustained maternal hyperglycemia on the fetus in normal and diabetic pregnancies. Br Med J 1972;1:466-9.  Back to cited text no. 7
8.Blackburn ST. Carbohydrate, fat and protein metabolism. In: Blackburn ST, editor. Maternal, fetal, and neonatal physiology. 2 nd ed. St. Louis: Saunders; 2003:599-629.  Back to cited text no. 8
9.Hay WW, Sparks JW. Placental, fetal and neonatal carbohydrate metabolism. Clin Obstet Gynecol 1985;28:473-85.  Back to cited text no. 9
10.Kalhan S, Parimi P. Gluconeogeneis in the fetus and neonate. Semin Perinatol 2000;24:94-106.  Back to cited text no. 10
11.Hendrickse W, Stammers JP, Hull D. The transfer of free fatty acids across the human placenta. Br J Obstet Gynaecol 1985;92:945-53.  Back to cited text no. 11
12.Haggarty P, Page K, Abramovich DR, Ashton J, Brown D. Long-chain polyunsaturated fatty acid transport across the perfused human placenta. Placenta 1997;18:635-42.  Back to cited text no. 12
13.Herrera E, Lasuncion MA. Maternal fetal transfer of lipid metabolites. In: Polin RA, Fox WW, editors. Fetal and Neonatal Physiology. 4 th ed. Philadelphia: Saunders; 2011:560-8.  Back to cited text no. 13
14.Van Aerde JE, Wilke MS, Feldman M, Clandinin MT. Accretion of lipid in the fetus and newborn. In: Polin RA, Fox WW, editors. Fetal and Neonatal Physiology. 4 th ed. Philadelphia: Saunders; 2011:454-70.  Back to cited text no. 14
15.de Groot RH, Hornstra G, van Houwelingen AC, Rumen F. Effect of linolenic acid supplementation during pregnancy on maternal and neonatal polyunsaturated fatty acid status and pregnancy outcome. Am J Clin Nutr 2004;79:251-60.  Back to cited text no. 15
16.Symonds ME, Stephenson T. Maternal nutrient restriction and endocrine programming of fetal adipose tissue development. Biochem Soc Trans 1999;27:97-103.  Back to cited text no. 16
17.Herrera E, Amusquivar E. Lipid metabolism in the fetus and the newborn. Diabetes Metab Res Rev 2000;16:202-10.  Back to cited text no. 17
18.Hay WW Jr, Anderson MS. Fuel homeostasis in the fetus and neonate. In: Degroot LJ, Jameson LJ, editors. Endocrinology. 5 th ed. Philadelphia: Saunders; 2005. p. 3387-405.  Back to cited text no. 18
19.Wilkening RB, Boyle DW, Teng C, Meschia G, Battaglia FC. Amino acid uptake by the fetal ovine hindlimb under normal and euglycemic hyperinsulinemic states. Am J Physiol 1994;266:E72-8.  Back to cited text no. 19
20.Johnson JD, Dunham T, Skipper BJ, Loftfield RB. Protein turnover in diseases of the rat fetus following maternal starvation. Pediatr Res 1986;20:1252-7.  Back to cited text no. 20
21.Carver TD, Anderson SM, Aldoretta PA, Esler AL, Hay WW Jr. Glucose suppression of insulin secretion in chronically hyperglycemic fetal sheep. Pediatr Res 1995;38:754-62.  Back to cited text no. 21
22.Limesand SW, Rozance PJ, Zerbe GO, Hutton JC, Hay WW Jr. Attenuated insulin release and storage in fetal sheep pancreatic islets with intrauterine growth restriction. Endocrinology 2006;147:1488-97.  Back to cited text no. 22
23.Wollmann HA. Growth hormone and growth factors during perinatal life. Horm Res 2000;53:50-4.  Back to cited text no. 23
24.Matsuda J, Yokota I, Iida M, Murakami T, Yamada M, Saijo T, et al. Dynamic changes in serum leptin concentrations during the fetal and neonatal periods. Pediatr Res 1999;45:71-5.  Back to cited text no. 24
25.Hytinantti T, Koistinen HA, Koivisto VA, Karonen SL, Andersson S. Changes in leptin concentration during the early postnatal period. Adjustment to extrauterine life? Pediat Res 1999;45:197-201.  Back to cited text no. 25
26.Schubring C, Siebler T, Kratzsch J, Englaro P, Blum WF, Triep K, et al. Leptin serum concentrations in healthy neonates within the first week of life. Relation to insulin and growth hormone levels, skin fold thickness, BMI and weight. Clin Endocrinol (Oxf) 1999;51:199-204.  Back to cited text no. 26
27.Ward Platt MP, Deshpande S. Metabolic adaptation at birth. Semin Fetal Neonatal Med 2005;10:341-50.  Back to cited text no. 27
28.Sadiq F, Holtzclaw L, Chundu K, Muzaffar A, Devaskar S, Muzzafar A. The ontogeny of the rabbit brain glucose transporter. Endocrinology 1990;126:2417-24.  Back to cited text no. 28
29.Richardson BS, Hohimer AR, Bissonnette JM, Machida CM. Cerebral metabolism in hypoglycemic and hyperglycemic fetal lambs, Am J Physiol 1983;245:R730-6.  Back to cited text no. 29
30.Pedersen J. Diabetes and Pregnancy. Blood sugar of newborn infants. PhD Thesis, Copenhagen, Danish Science Press, 1952.  Back to cited text no. 30
31.Gilbert JS, Brandon E, Vera T. Fetal insulin secretion in late gestation: Does size matter? J Physiol 2007;585:651-2.  Back to cited text no. 31
32.Diderholm B. Perinatal energy metabolism with reference to IUGR and SGA: Studies in pregnant women and newborn infants. Indian J Med Res 2009;130:612-7.  Back to cited text no. 32
[PUBMED]  Medknow Journal  
33.Owens JA, Gatford KL, De Blasio MJ, Edwards LJ, McMillen IC, Fowden AL. Restriction of placental growth in sheep impairs insulin secretion but not sensitivity before birth. J Physiol 2007;584:935-49.  Back to cited text no. 33
34.Thorens B, Mueckler M. Glucose transporters in the 21 st Century. Am J Physiol Endocrinol Metab 2010;298:E141-5.  Back to cited text no. 34
35.Barker DJ, Martyn CN, Osmond C, Hales CN, Fall CH. Growth in utero and serum cholesterol concentrations in adult life. BMJ 1993;307:1524-7.  Back to cited text no. 35
36.Huxley R, Owen CG, Whincup PH, Cook DG, Rich-Edwards J, Smith GD. Is birth weight a risk factor for ischemic heart disease in later life? Am J Clin Nutr 2007;85:1244-50.  Back to cited text no. 36
37.Hay WW Jr. Recent observations on the regulation of fetal metabolism by glucose. J Physiol 2006;572:17-24.  Back to cited text no. 37
38.Rozance PJ, Limesand SW, Wyckoff MH, Hay WW Jr. Chronic hypoglycemia reduces potassium and calcium stimulated insulin secretion in pancreatic islets obtained from fetal sheep. Pediatric Res 2004;55:382A.  Back to cited text no. 38


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

  [Table 1], [Table 2], [Table 3]

This article has been cited by
1 Interpersonal Synchrony in the Context of Caregiver-Child Interactions: A Document Co-citation Analysis
Alessandro Carollo,Mengyu Lim,Vahid Aryadoust,Gianluca Esposito
Frontiers in Psychology. 2021; 12
[Pubmed] | [DOI]
2 Global metabolomic profiling reveals hepatic biosignatures that reflect the unique metabolic needs of late-term mother and fetus
Nipun Saini,Manjot Virdee,Kaylee K. Helfrich,Sze Ting Cecilia Kwan,Susan M. Smith
Metabolomics. 2021; 17(2)
[Pubmed] | [DOI]
3 Effect of amino acid infusion during cesarean delivery on newborn temperature: a randomized controlled trial
Krishna Pokharel,Asish Subedi,Mukesh Tripathi,Binay Kumar Biswas
BMC Pregnancy and Childbirth. 2021; 21(1)
[Pubmed] | [DOI]
4 Pregnancy Outcomes of Women with Hypoglycemia in the Oral Glucose Tolerance Test
Burak Bayraktar,Meriç Balikoglu,Ahkam Göksel Kanmaz
Journal of Gynecology Obstetrics and Human Reproduction. 2020; : 101703
[Pubmed] | [DOI]
5 Adipose tissue development and lipid metabolism in the human fetus: The 2020 perspective focusing on maternal diabetes and obesity
G. Desoye,E. Herrera
Progress in Lipid Research. 2020; : 101082
[Pubmed] | [DOI]
6 Inhibition of Acetyl-CoA Carboxylase Causes Malformations in Rats and Rabbits: Comparison of Mammalian Findings and Alternative Assays
Natasha R Catlin,Christopher J Bowman,Sarah N Campion,Scott D Davenport,William P Esler,Steven W Kumpf,Elise M Lewis,William S Nowland,Trenton T Ross,Donald S Stedman,Christine Stethem,Gregg D Cappon
Toxicological Sciences. 2020;
[Pubmed] | [DOI]
7 Hypoxia with acidosis in extremely preterm born infants was not associated with an increased risk of death or impaired neurodevelopmental outcome at 6.5 years
Mehreen Zaigham,Karin Källén,Karel Maršál,Per Olofsson
Acta Paediatrica. 2019;
[Pubmed] | [DOI]
8 Neonatal Hypoglycemia: A Review
Mahdi Alsaleem,Lina Saadeh,Deepak Kamat
Clinical Pediatrics. 2019; 58(13): 1381
[Pubmed] | [DOI]
9 Kanatli ve Memeli Karacigerinde Karbonhidrat ve Yag Metabolizmasinin Karsilastirilmasi
füsun erhan,Levent ERGÜN
Mehmet Akif Ersoy Üniversitesi Saglik Bilimleri Enstitüsü Dergisi. 2018; 6(1): 33
[Pubmed] | [DOI]
10 Assessment of lactate production as a response to sustained intrapartum hypoxia in large-for-gestational-age newborns
Mehreen Zaigham,Karin Källén,Per Olofsson
Acta Obstetricia et Gynecologica Scandinavica. 2018;
[Pubmed] | [DOI]
11 Perinatal Nutrition and Programmed Risk for Neuropsychiatric Disorders: A Focus on Animal Models
Madison DeCapo,Jacqueline R. Thompson,Geoffrey Dunn,Elinor L. Sullivan
Biological Psychiatry. 2018;
[Pubmed] | [DOI]
12 Life history trade-offs and the partitioning of maternal investment
Jonathan C K Wells
Evolution, Medicine, and Public Health. 2018; 2018(1): 153
[Pubmed] | [DOI]
13 Treatments for women with gestational diabetes mellitus: an overview of Cochrane systematic reviews
Ruth Martis,Caroline A Crowther,Emily Shepherd,Jane Alsweiler,Michelle R Downie,Julie Brown
Cochrane Database of Systematic Reviews. 2018;
[Pubmed] | [DOI]
14 Growing a social brain
Shir Atzil,Wei Gao,Isaac Fradkin,Lisa Feldman Barrett
Nature Human Behaviour. 2018;
[Pubmed] | [DOI]
15 Lifestyle interventions for the treatment of women with gestational diabetes
Julie Brown,Nisreen A Alwan,Jane West,Stephen Brown,Christopher JD McKinlay,Diane Farrar,Caroline A Crowther
Cochrane Database of Systematic Reviews. 2017;
[Pubmed] | [DOI]
16 Oral anti-diabetic pharmacological therapies for the treatment of women with gestational diabetes
Julie Brown,Ruth Martis,Brenda Hughes,Janet Rowan,Caroline A Crowther
Cochrane Database of Systematic Reviews. 2017;
[Pubmed] | [DOI]
17 Insulin for the treatment of women with gestational diabetes
Julie Brown,Luke Grzeskowiak,Kathryn Williamson,Michelle R Downie,Caroline A Crowther
Cochrane Database of Systematic Reviews. 2017;
[Pubmed] | [DOI]
18 Maternal and fetal effects of dexmedetomidine infusion in pregnant ewes anesthetized with sevoflurane
Mauricio Loría Lépiz,Rebecca Sayre,Onkar Sawant,James Barr,Medora Pashmakova,Kevin Washburn,Shannon Washburn
American Journal of Veterinary Research. 2017; 78(11): 1255
[Pubmed] | [DOI]
19 Bio-Behavioral Synchrony Promotes the Development of Conceptualized Emotions
Shir Atzil,Maria Gendron
Current Opinion in Psychology. 2017;
[Pubmed] | [DOI]
20 Effects of rapid temperature fluctuations prior to breeding on reproductive efficiency in replacement gilts
J.S. Johnson,K.L. Martin,K.G. Pohler,K.R. Stewart
Journal of Thermal Biology. 2016; 61: 29
[Pubmed] | [DOI]
21 Pregnancy-induced adaptations of the central circadian clock and maternal glucocorticoids
Michaela D Wharfe,Peter J Mark,Caitlin S Wyrwoll,Jeremy T Smith,Cassandra Yap,Michael W Clarke,Brendan J Waddell
Journal of Endocrinology. 2016; 228(3): 135
[Pubmed] | [DOI]
22 Insulin-like growth factor 1 has multisystem effects on foetal and preterm infant development
Ann Hellström,David Ley,Ingrid Hansen-Pupp,Boubou Hallberg,Chatarina Löfqvist,Linda van Marter,Mirjam van Weissenbruch,Luca A. Ramenghi,Kathryn Beardsall,David Dunger,Anna-Lena Hĺrd,Lois E. H. Smith
Acta Paediatrica. 2016; 105(6): 576
[Pubmed] | [DOI]
23 The Dynamics of Serum Lipid and Lipoprotein Profiles in Growing Foals
Francesca Arfuso,Elisabetta Giudice,Simona Di Pietro,Marco Quartuccio,Claudia Giannetto,Giuseppe Piccione
Journal of Equine Veterinary Science. 2016; 40: 1
[Pubmed] | [DOI]
24 Treatments for women with gestational diabetes mellitus: an overview of Cochrane systematic reviews
Ruth Martis,Julie Brown,Jane Alsweiler,Michelle R Downie,Caroline A Crowther
Cochrane Database of Systematic Reviews. 2016;
[Pubmed] | [DOI]
25 Different intensities of glycaemic control for women with gestational diabetes mellitus
Ruth Martis,Julie Brown,Jane Alsweiler,Tineke J Crawford,Caroline A Crowther
Cochrane Database of Systematic Reviews. 2016;
[Pubmed] | [DOI]
26 Insulin for the treatment of women with gestational diabetes
Julie Brown,Luke Grzeskowiak,Kathryn Williamson,Michelle R Downie,Caroline A Crowther
Cochrane Database of Systematic Reviews. 2016;
[Pubmed] | [DOI]
27 Glucose Homeostasis during Fetal and Neonatal Period
Won Im Cho,Hye Rim Chung
Korean Journal of Perinatology. 2016; 27(2): 95
[Pubmed] | [DOI]
28 Pregnancy in Women With Glycogen Storage Disease Ia and Ib
Iris A. Ferrecchia,Ginny Guenette,Elizabeth A. Potocik,David A. Weinstein
The Journal of Perinatal & Neonatal Nursing. 2014; 28(1): 26
[Pubmed] | [DOI]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
    Carbohydrate Met...
   Lipid Metabolism
   Protein Metabolism
   Maternal Metabolism
    Endocrine Regula...
    Transition to Ex...
    Implications for...
   Maternal Diabetes
    Intra Uterine Gr...
    Fetal Origin of ...
    Article Figures
    Article Tables

 Article Access Statistics
    PDF Downloaded650    
    Comments [Add]    
    Cited by others 28    

Recommend this journal