<<

. 20
( 51 .)



>>

restriction occurring in early-to-mid-gestation will reliably induce pregnancy loss
in the common marmoset. Energy restriction during early marmoset pregnancy
results in reduced free estradiol and cortisol in the maternal circulation, suggesting
that food restriction does not act as a classical stressor and that perhaps endocrine
function of the placenta is impaired by the restriction (Tardif et al., 2005). In one
early-restricted pregnancy complete aborted material was recovered. The weight
and crown-rump length of the collected twin fetuses were less than expected for
the estimated gestational age (83 days), based on published measures of fetuses
collected at day 80 (Chambers and Hearn, 1985). The placental weight was also less
than expected based upon published measures; however, the placental disk areas
were similar to the expected area.
The same energy restriction initiated in late pregnancy did not reliably induce
pregnancy loss, though it did result in pre-term delivery in a third of pregnancies,
a ¬gure higher than that expected in normal, non-manipulated pregnancies
(Tardif et al., 2004). These ¬ndings contrast with those for rodents and sheep and
suggest that the marmoset may be particularly sensitive to early-to-mid-pregnancy
energy restrictions. The mechanism behind this sensitivity is not yet elucidated.
In addition, the variation and relationships among maternal parameters, birth
condition, infant growth and subsequent adult weight in the common marmoset
indicate potential for this species to be a useful model of the links among birth
weight, subsequent growth, and latter adult vulnerability to disease. Among mar-
moset females between 2 and 7 years old, older females generally produced infants
with higher birth weights. Low maternal weight was associated with slower early
infant growth, but not with low birth weight. This might re¬‚ect a greater con-
straint on females due to the costs of lactation as opposed to the costs of gestation
(Tardif et al., 2001). However, long bone growth did appear to be related to mater-
nal weight, as infants of larger mothers had greater knee“heel lengths. Twins that
were smaller than average at birth were more likely to be small as adults. This was
not true, however, for triplets, implying that the mechanisms that produce a small
infant likely differ between twin and triplet pregnancies in this species (Tardif and
Bales, 2004).


Conclusions

Maternal nutrient intake and nutritional status can affect pregnancy outcome in a
myriad of ways. In the context of this book we have focused on how they might
affect the timing of birth and fetal growth and development. There would appear
107 Maternal nutrition and metabolic control of pregnancy


to be a U-shaped distribution relating energy stores in pregnant women and the
risk of an adverse pregnancy outcome. Both maternal undernutrition and overnu-
trition (obesity) can negatively affect later health in offspring.
The metabolic signals and markers of at-risk pregnancy are not well under-
stood. The IGF system plays a major role in fetal growth, and growth hormones
produced by the placenta affect maternal and placental physiology in pregnant
women. Placental growth hormone is regulated by maternal serum glucose, and
maternal serum pGH, IGF-1, and IGF-2 are lower in pregnancies complicated by
IUGR. Recent ¬ndings indicate that in normal pregnancies the gestational age of
peak placental GH concentration in maternal serum is associated with total length
of gestation and that women who give birth to lighter children have lower serum
pGH concentrations at term (Chellakooty et al., 2004).
Leptin, often primarily considered a hormone of energy homeostasis and a reg-
ulator of food intake, appears to have multiple functions in pregnancy, from ovu-
lation through implantation and maintenance of pregnancy. Leptin produced by
the placenta is secreted into both maternal and fetal compartments. Low maternal
leptin is associated with early pregnancy loss. Leptin may also have important
functions in fetal growth and development.
The CRH is perhaps the most intriguing of the hormones discussed in this
chapter, at least from an evolutionary perspective. Only anthropoid primates pro-
duce placental CRH, and among our anthropoid relatives only our closest relatives,
the chimpanzee and gorilla, share the human pattern of exponentially increasing
maternal CRH from early-to-mid-pregnancy until parturition (Smith et al., 1999).
Preterm birth is associated with both increased maternal serum CRH from early
in pregnancy, and an accelerated rate of increase of serum CRH concentration
(McLean et al., 1995; Leung et al., 2001). The evidence is consistent with serum
CRH concentration functioning as a ˜clock™, that is set early in pregnancy, and pre-
dicts the timing of parturition (McLean et al., 1995).
Placental CRH is secreted into both the maternal and fetal compartments,
although fetal concentrations are signi¬cantly lower than maternal. Placental CRH
may stimulate the maternal pituitary-adrenal axis, and almost certainly stimulates
the fetal pituitary-adrenal axis and the fetal adrenal directly (Smith et al., 1998). In
vitro studies have shown that human placental CRH can be stimulated by cate-
cholamines (Petraglia et al., 1989). In vivo studies have shown associations
between CRH and cortisol and ACTH (Goland et al., 1992; 1994). Thus, it is pos-
sible that maternal stress responses can affect and be affected by placental CRH.
The primate fetal adrenal produces cortisol and androgens, primarily DHEA-S,
which then feedback to the placenta. Cortisol stimulates placental CRH produc-
tion, and DHEA-S is converted to estrogen. Thus, a positive feedback loop is estab-
lished that results in increasing production of estrogen as pregnancy progresses.
108 M. L. Power and S. D. Tardif


Elevated maternal serum CRH appears to signal a metabolic disruption of preg-
nancy in humans. Whether CRH is merely a marker of an at-risk pregnancy, or an
effector molecule that is causal to the pathology is unclear.
Maternal malnutrition could affect placental CRH production in a number of
ways. Fetal undernutrition could result in a stress response by the fetal HPA axis,
resulting in increased fetal glucocorticoids that would feed back to the placenta
and increase CRH production. Maternal malnutrition could down regulate pla-
cental 11 -hydroxysteroid dehydrogenase type 2, exposing both the fetus and the
placenta to effectively higher concentrations of maternal glucocorticoids. Habitual
short-term maternal starvation could increase maternal serum glucocorticoid
concentration, stimulating placental CRH production, which then stimulates the
fetal adrenals, leading to increased fetal cortisol and DHEA-S production, which in
turn stimulates placental CRH production. All of these hypotheses are plausible, if
simplistic.



R E F E R E N C ES


Agarwal, S., Agarwal, A., Bansal, A. K., Agarwal, D. K. and Agarwal, K. N. (2002). Birth weight
patterns in rural undernourished pregnant women. Indian Pediatr., 39, 244“53.
Arduini, D. and Rizzo, G. (1990). Normal values of pulsatility index from fetal vessels: a cross-
sectional study on 1556 health fetuses. J. Perinat. Med., 18, 165“72.
Bajoria, R., Sooranna, S. R., Ward, S. and Hancock, M. (2002). Placenta as a link between amino
acids, insulin-IGF axis, and low birth weight: evidence from twin studies. J. Clin. Endocrinol.
Metab., 87, 308“15.
Baldelli, R., Dieguez, C. and Casanueva, F. F. (2002). The role of leptin in reproduction: experi-
mental and clinical aspects. Ann. Med., 34(1), 5“18.
Barker, D. J. P. (2001). The malnourished baby and infant. Br. Med. Bull., 60, 69“88.
Bertram, C., Trowern, A. R., Copin, N., Jackson, A. A. and Whorwood, C. B. (2001). The mater-
nal diet during pregnancy programs altered expression of the glucocorticoid receptor and
type 2 11beta-hydroxysteroid dehydrogenase: Potential molecular mechanisms underlying
the programming of hypertension in utero. Endocrinology, 142(7), 2841“53.
Bloom¬eld, F. H., Oliver, M. H., Hawkins, P. et al. (2004). Periconceptional undernutrition in
sheep accelerates maturation of the fetal hypothalamic-pituitary-adrenal axis in late gestation.
Endocrinology 145, 4278“85.
Bowman, M. E., Lopata, A. et al. (2001). Corticotropin-releasing hormone-binding protein in
primates. Am. J. Primatol., 53, 123“30.
Butte, N. F., Hopkinson, J. M., Nicolson, M. A. (1997). Leptin in human reproduction: serum lep-
tin levels in pregnant and lactating women. J. Clin. Endocrinol. Metab., 82, 585“89.
Castracane, V. D. and Henson, M. C. (2002). When did leptin become a reproductive hormone?
Semin. Reprod. Med., 20, 89“92.
109 Maternal nutrition and metabolic control of pregnancy


Caufriez, A., Frankenne, F., Hennen, G. and Copinschi, G. (1993). Regulation of maternal IGF-I
by placental GH in normal and abnormal pregnancy. Am. J. Physiol., 265, E572“7.
Chambers, P. L. and Hearn, J. P. (1985). Embryonic, foetal and placental development in the
common marmoset monkey (Callithrix jacchus). J. Zool. Lond., 207, 545“61.
Chehab, F. F., Lim, M. E. and Lu, R. (1996). Correction of the sterility defect in homozygous
obese female mice by treatment with human recombinant leptin. Nat. Genet., 12, 318“20.
Chellakooty, M., Vansgaard, K., Larsen, T. et al. (2004). A longitudinal study of intrauterine
growth and the placental growth hormone (GH)-insulin-like growth factor I axis in maternal
circulation: association between placental GH and fetal growth. J. Clin. Endocrinol. Metab.,
89, 384“91.
Daenzer, M., Ortmann, S., Klaus, S. and Metges, C. C. (2002). Prenatal high protein exposure
decreases energy expenditure and increases adiposity in young rats. J. Nutr., 132, 142“4.
Dallman, M. F., Pecoraro, N., Akana, S. F. et al. (2003). Chronic stress and obesity: a new view of
“comfort food”. Proc. Natl. Acad. Sci. USA, 100(20), 11696“701.
De Onis, M., Blossner, M. and Villar, J. (1998). Levels and patterns of intrauterine growth restric-
tion in developing countries. Eur. J. Clin. Nutr., 52(Suppl 1), S5“15.
Domali, E. and Messinis, I. E. (2002). Leptin in pregnancy. J. Mater. Fetal Neonatal Med., 12(4),
222“30.
Eastman, N. T. (1947). Prematurity from the viewpoint of the obstetrician. Am. Pract., 1, 343.
Ebbs, J. H., Tisdall, F. F. and Scott, W. A. (1941). The in¬‚uence of prenatal diet on the mother and
child. J. Nutr., 22, 515“21.
Felig, P. and Lynch, V. (1970). Starvation in human pregnancy: hypoglycemia, hypoinsulinemia,
and hyperketonemia. Science, 170, 990“2.
Galan, H. L., Hussey, M. J., Chung, M. et al. (1998). Doppler velocimetry of growth-restricted
fetuses in an ovine model of placental insuf¬ciency. Am. J. Obstet. Gynecol., 178, 451“6.
Gluckman, P. D. and Pinal, C. S. (2003). Regulation of fetal growth by the somatotrophic axis.
J. Nutr., 133(Suppl), 1741S“6S.
Glynn, L., Wadhwa, P. D., Dunkel Schetter, C. and Sandman, C. A. (2001). When stress happens
matters: the effects of earthquake timing on stress responsivity in pregnancy. Am. J. Obstet.
Gynecol., 184, 637“42.
Goland, R. S., Wardlaw, S. L., Stark, R. I., Brown, L. S. J. and Frantz, A. G. (1986). High levels of
corticotropin-releasing hormone immunoreactivity in maternal and fetal plasma during
pregnancy. J. Clin. Endocrinol. Metab., 63, 1199“203.
Goland, R. S., Wardlaw, S. L. and Fortman, J. D. (1992). Plasma corticotropin-releasing factor
concentrations in the baboon during pregnancy. Endocrinology, 131, 1782“6.
Goland, R. S., Jozak, S. and Conwell, I. (1994). Placental corticotropin-releasing hormone and
the hypercortisolism of pregnancy. Am. J. Obstet. Gynecol., 171, 1287“91.
Goland, R. S., Tropper, P. J., Warren, W. B., Stark, R. I., Jozak, S. M. and Conwell, I. M.
(1995). Concentrations of corticotropin-releasing hormone in the umbilical cord blood
of pregnancies complicated by preeclampsia. Reproduction Fertility and Development, 7,
1227“30.
Goldenberg, R. L. (2003). The plausibility of micronutrient de¬ciency in relationship to peri-
natal infection. J. Nutr., 133, 1645S“8S.
110 M. L. Power and S. D. Tardif


Goldenberg, R. L., Iams, J. D., Mercer, B. M. et al. (2003). What we have learned about the pre-
dictors of preterm birth. Semin. Perinatol., 27, 185“93.
Harman, C. R. and Baschat, A. A. (2003). Comprehensive assessment of fetal wellbeing: which
Doppler tests should be performed? Curr. Opin. Obstet. Gynecol., 15, 147“57.
Heinonen, S., Taipale, P. and Saarikoski, S. (2001). Weights of placentae from small-for-gestational
age infants revisited. Placenta, 22, 399“404.
Henson, M. C. and Castracane, V. D. (2002). Leptin: roles and regulation in primate pregnancy.
Semin. Reprod. Med., 20(2), 113“22.
Herrmann, T. S., Siega-Riz, A. M., Hobel, C. J., Aurora, C. and Dunkel-Schetter, C. (2001).
Prolonged periods without food intake during pregnancy increase risk for elevated maternal
corticotropin-releasing hormone concentrations. Am. J. Obstet. Gynecol., 185, 403“12.
Howe, D. C., Gertler, A. and Challis, J. R. (2002). The late gestation increase in circulating ACTH
and cortisol in the fetal sheep is suppressed by intracerebroventricular infusion of recombi-
nant ovine leptin. J. Endocrinol., 174, 259“66.
Jaffe, R. B., Mesiano, S., Smith, R. et al. (1998). The regulation and role of fetal adrenal develop-
ment in human pregnancy. Endocrin. Res., 24, 919“26.
Jakimiuk, A. J., Skalba, P., Huterski, R., Haczynski, J. and Magof¬n, D. A. (2003). Leptin messen-
ger ribonucleic acid (mRNA) content in the human placenta at term: relationship to levels of
leptin in cord blood and placental weight. Gynecol. Endocrinol., 17, 311“16.
Jensen, D. M., Damm, P., Sørenson, B. et al. (2003). Pregnancy outcome and prepregnancy
body mass index in 2459 glucose-tolerant anish women. Am. J. Obstet. Gynecol., 189,
239“44.
Keen, C. L., Uriu-Hare, J. Y., Hawk, S. N. et al. (1998). Effect of copper de¬ciency on prenatal
development and pregnancy outcome. Am. J. Clin. Nutr., 67, 1003S“11S.
Keen, C. L., Clegg, M. S., Hanna, L. A. et al. (2003). The plausibility of micronutrient de¬ciencies
being a signi¬cant contributing factor to the occurrence of pregnancy complications. J. Nutr.,
133, 1592S“6S.
Krieger, D. T. (1974). Food and water restriction shifts corticosterone, temperature, activity and
brain amine periodicity. Endocrinology, 95, 1195“1201.
Kuzawa, C. W. and Adair, L. S. (2003). Lipid pro¬les in adolescent Filipinos: relation to birth
weight and maternal energy status during pregnancy. Am. J. Clin. Nutr., 77, 960“6.
Lacroix, M.-C., Guibourdenche, J., Frendo, J.-L., Pidoux, G. and Evain-Brion, D. (2002).
Placental growth hormones. Endocrine, 19, 73“9.
Lesage, J., Blondeau, B., Grino, M., Breant, B. and Dupouy, J. P. (2001). Maternal undernutrition
during late gestation induces fetal overexposure to glucocorticoids and intrauterine growth
retardation, and disturbs the hypothalamo-pituitary adrenal axis in the newborn rat.
Endocrinology, 142, 1692“702.
Leung, T. N., Chung, T. K. H., Madsen, G. et al. (2001). Rate of rise in maternal plasma corti-
cotropin-releasing hormone and its relation to gestational length. Br. J. Obstet. Gynaecol., 108,
527“32.
Masaki, T., Yoshimichi, G., Chiba, S. et al. (2003). Corticotropin-releasing hormone-mediated
pathway of leptin to regulate feeding, adiposity, and uncoupling protein expression in mice.
Endocrinology, 144, 3547“54.
111 Maternal nutrition and metabolic control of pregnancy


McIntyre, H. D., Serek, R., Crane, D. I. et al. (2000). Placental growth hormone (GH), GH-bind-
ing protein, and insulin-like growth factor axis in normal, growth-retarded, and diabetic preg-
nancies: correlations with fetal growth. J. Clin. Endocrinol. Metab., 85, 1143“50.
McLean, M., Bistis, A., Davies, J. J. et al. (1995). A placental clock controlling the length of
human pregnancy. Nat. Med., 1, 460“3.
Merali, Z., McIntosh, J., Kent, P., Michaud, D. and Anisman, H. (1998). Aversive and appetitive
events evoke the release of corticotropin-releasing hormone and bombesin-like peptides at
the central nucleus of the amygdala. J. Neurosci., 18, 4758“66.
Merali, Z., Michaud, D., McIntosh, J., Kent, P. and Anisman, H. (2003). Differential involvement
of amydaloid CRH system(s) in the salience and valence of the stimuli. Progress in Neuro-
Psychopharmacology & Biological Psychiatry, 27, 1201“12.
Metzgar, B. E., Ravnikar, V., Vileisis, R. A. and Freinkel, N. (1982). Accelerated starvation and the
skipped breakfast in late normal pregnancy. Lancet, 1, 588“92.
Nayak, N. R. and Giudice, L. C. (2003). Comparative biology of the IGF system in endometrium,
deciduas, and placenta and clinical implications for foetal growth and implantation disorders.
Placenta, 24, 281“96.
Pepe, G. J., Waddell, B. J. and Albrecht, E. D. (1990). Activation of the baboon fetal
hypothalamic“pituitary“adrenocortical axis at midgestation by estrogen-induced changes in
placental corticosteroid metabolism. Endocrinology, 127, 3117“23.
Perkins, A. V., Eben, F., Wolfe, C. D., Schulte, H. M. and Linton, E. A. (1993). Plasma measure-
ment of corticotrophin-releasing hormone-binding protein in normal and abnormal human
pregnancy. J. Endocrinol., 149“57.
Petraglia, F., Sutton, S. and Vale, W. (1989). Neurotransmitters and peptides modulate the release
of immunoreactive corticotropin-releasing factor from cultured human placental cells. Am. J.
Obstet. Gynecol., 160, 247“51.
Romero, R., Chaiworapongsa, T. and Espinoza, J. (2003). Micronutrients and intrauterine infec-
tion, preterm birth and the fetal in¬‚ammatory response syndrome. J. Nutr., 133, 1668S“73S.
Ruth, V., Hallman, M. and Laatikainen, T. (1993). Corticotropin-releasing hormone and cortisol
in cord plasma in relation to gestational age, labor, and fetal distress. Am. J. Perinatol., 10,
115“18.
Sasaki, A., Shinkawa, O. and Yoshinaga, K. (1989). Placental coricotropin-releasing hormone
may be a stimulator of maternal pituitary adrenocorticotropic hormone secretion in humans.
J Clin. Invest., 84, 1997“2001.
Sayers, S. and Powers, J. (1997). Risk factors for aboriginal low birthweight, intrauterine growth
retardation and preterm in the Darwin Health Region. Aust. New Zeal. J. Public Health, 21,
524“30.
Schroder, H. J. (2003). Models of fetal growth restriction. Eur. J. Obstetr. Gynecol. Reprod. Biol.,
110(Suppl 1), S29“39.
Seckl, J. R. (1998). Physiologic programming of the fetus. Clin. Perinatol., 25, 939“64.
Siega-Riz, A. M., Herrmann, T. S., Savitz, D. A. and Thorp, J. M. (2001). Frequency of eating
during pregnancy and its effect on preterm delivery. Am. J. Epidemiol., 153, 647“52.
Siega-Riz, A. M., Promislow, J. H. E., Savitz, D. A., Thorp, Jr., J. M. and McDonald, T. (2003).
Vitamin C intake and the risk of preterm delivery. Am. J. Obstetr. Gynecol., 189, 519“25.
112 M. L. Power and S. D. Tardif


Smith, R., Chan, E.-C., Bowman, M. E., Harewood, W. J. and Phippard, A. F. (1993).
Corticotropin-releasing hormone in baboon pregnancy. J. Clin. Endocrinol. Metab., 76, 1063“8.

<<

. 20
( 51 .)



>>