Physiological Adaptations of Pregnancy Affecting the Nervous System

ABSTRACT

Physiological adaptations of pregnancy affect neurological function in health and disease. Women often experience self-limited sensory abnormalities that resolve shortly after delivery. More important, pregnancy can predispose to the onset or deterioration of permanent neurological disorders. Lastly, complications of pregnancy may develop in patients with preexisting neurological disease. Therefore, a basic knowledge of reproductive physiology can guide clinicians in the diagnosis and management of the pregnant patient with neurological symptoms. This clinical review highlights the modifications that affect the nervous system, including neuroanatomy, reproductive endocrinology, immunology, systemic and cerebral circulations, metabolism, and coagulation profile. The widespread role of sex steroids in many of these adaptations is addressed to illustrate the complex interactions of human reproductive biology.

KEYWORDS

Physiology - pregnancy - nervous system

REFERENCES

• 1 Munson M L. Births, marriages, divorces, and deaths: provisional data for 2005. In: National Vital Statistics Reports. Vol. 54. Hyattsville, MD; National Center for Health Statistics 2006
• 2 Cunningham F, Leveno K J, Bloom S L. Williams Obstetrics. 22nd ed. New York; McGraw-Hill Companies Inc 2005
• 3 Hirabayashi Y, Shimizu R, Fukuda H, Saitoh K, Igarashi T. Soft tissue anatomy within the vertebral canal in pregnant women.  Br J Anaesth. 1996;  77 153-156
• 4 Cibils L A, Hendricks C H. Uterine contractility on the first day of the puerperium.  Am J Obstet Gynecol. 1969;  103 238-243
• 5 Eogan M, O'Brien C, Carolan D, Fynes M, O'Herlihy C. Median and ulnar nerve conduction in pregnancy.  Int J Gynaecol Obstet. 2004;  87 233-236
• 6 Speroff L, Fritz MA Clinical Gynecologic Endocrinology and Infertility. 7th ed. Philadelphia; Lippincott Williams & Wilkins 2005
• 7 Albrecht E D, Aberdeen G W, Pepe G J. The role of estrogen in the maintenance of primate pregnancy.  Am J Obstet Gynecol. 2000;  182 432-438
• 8 Albrecht E D, Aberdeen G W, Pepe G J. Estrogen elicits cortical zone-specific effects on development of the primate fetal adrenal gland.  Endocrinology. 2005;  146 1737-1744
• 9 Pepe G J, Davies W A, Albrecht E D. Activation of the baboon fetal pituitary-adrenocortical axis at midgestation by estrogen: enhancement of fetal pituitary proopiomelanocortin messenger ribonucleic acid expression.  Endocrinology. 1994;  135 2581-2587
• 10 Datta S, Hurley R J, Naulty J S et al.. Plasma and cerebrospinal fluid progesterone concentrations in pregnant and nonpregnant women.  Anesth Analg. 1986;  65 950-954
• 11 Robinson B G, Emanuel R L, Frim D M, Majzoub J A. Glucocorticoid stimulates expression of corticotropin-releasing hormone gene in human placenta.  Proc Natl Acad Sci U S A. 1988;  85 5244-5248
• 12 Majzoub J A, McGregor J A, Lockwood C J, Smith R, Taggart M S, Schulkin J. A central theory of preterm and term labor: putative role for corticotropin-releasing hormone.  Am J Obstet Gynecol. 1999;  180 S232-S241
• 13 Beyenburg S, Stoffel-Wagner B, Bauer J et al.. Neuroactive steroids and seizure susceptibility.  Epilepsy Res. 2001;  44 141-153
• 14 Murphy D D, Cole N B, Greenberger V, Segal M. Estradiol increases dendritic spine density by reducing GABA neurotransmission in hippocampal neurons.  J Neurosci. 1998;  18 2550-2559
• 15 Murphy D D, Cole N B, Segal M. Brain-derived neurotrophic factor mediates estradiol-induced dendritic spine formation in hippocampal neurons.  Proc Natl Acad Sci U S A. 1998;  95 11412-11417
• 16 Landgren S, Aasly J, Backstrom T, Dubrovsky B, Danielsson E. The effect of progesterone and its metabolites on the interictal epileptiform discharge in the cat's cerebral cortex.  Acta Physiol Scand. 1987;  131 33-42
• 17 Majewska M D, Harrison N L, Schwartz R D, Barker J L, Paul S M. Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor.  Science. 1986;  232 1004-1007
• 18 Luisi S, Petraglia F, Benedetto C et al.. Serum allopregnanolone levels in pregnant women: changes during pregnancy, at delivery, and in hypertensive patients.  J Clin Endocrinol Metab. 2000;  85 2429-2433
• 19 Hsu F C, Smith S S. Progesterone withdrawal reduces paired-pulse inhibition in rat hippocampus: dependence on GABA(A) receptor alpha4 subunit upregulation.  J Neurophysiol. 2003;  89 186-198
• 20 Moran M H, Smith S S. Progesterone withdrawal I: pro-convulsant effects.  Brain Res. 1998;  807 84-90
• 21 Smith S S, Gong Q H, Hsu F C, Markowitz R S, ffrench-Mullen J M, Li X. GABA(A) receptor alpha4 subunit suppression prevents withdrawal properties of an endogenous steroid.  Nature. 1998;  392 926-930
• 22 Meher S, Duley L. Progesterone for preventing pre-eclampsia and its complications.  Cochrane Database Syst Rev. 2006;  (4) CD006175
• 23 Zeisler H, Sator M O, Joura E A. Serum levels of progesterone in patients with preeclampsia.  Wien Klin Wochenschr. 2000;  112 362-364
• 24 Walsh S W. Progesterone and estradiol production by normal and preeclamptic placentas.  Obstet Gynecol. 1988;  71 222-226
• 25 Colmers W F, El Bahh B. Neuropeptide Y and Epilepsy.  Epilepsy Curr. 2003;  3 53-58
• 26 Petraglia F, Coukos G, Battaglia C et al.. Plasma and amniotic fluid immunoreactive neuropeptide-Y level changes during pregnancy, labor, and at parturition.  J Clin Endocrinol Metab. 1989;  69 324-328
• 27 Murphy S P, Choi J C, Holtz R. Regulation of major histocompatibility complex class II gene expression in trophoblast cells.  Reprod Biol Endocrinol. 2004;  2 52
• 28 Moffett A, Loke C. Immunology of placentation in eutherian mammals.  Nat Rev Immunol. 2006;  6 584-594
• 29 Lin H, Mosmann T R, Guilbert L, Tuntipopipat S, Wegmann T G. Synthesis of T helper 2-type cytokines at the maternal-fetal interface.  J Immunol. 1993;  151 4562-4573
• 30 Yoneyama Y, Sawa R, Suzuki S, Yoneyama K, Doi D, Araki T. Relationship between adenosine deaminase activity and cytokine-secreting T cells in normal pregnancy.  Obstet Gynecol. 2002;  100 754
• 31 Somerset D A, Zheng Y, Kilby M D, Sansom D M, Drayson M T. Normal human pregnancy is associated with an elevation in the immune suppressive CD25 + CD4 + regulatory T-cell subset.  Immunology. 2004;  112 38-43
• 32 Szekeres-Bartho J, Kilar F, Falkay G, Csernus V, Török A, Pacsa A S. The mechanism of the inhibitory effect of progesterone on lymphocyte cytotoxicity: I. Progesterone-treated lymphocytes release a substance inhibiting cytotoxicity and prostaglandin synthesis.  Am J Reprod Immunol Microbiol. 1985;  9 15-18
• 33 Druckmann R, Druckmann M A. Progesterone and the immunology of pregnancy.  J Steroid Biochem Mol Biol. 2005;  97 389-396
• 34 Prieto G A, Rosenstein Y. Oestradiol potentiates the suppressive function of human CD4 CD25 regulatory T cells by promoting their proliferation.  Immunology. 2006;  118 58-65
• 35 Confavreux C, Hutchinson M, Hours M M, Cortinovis-Tourniaire P, Moreau T. Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group.  N Engl J Med. 1998;  339 285-291
• 36 Langer-Gould A, Garren H, Slansky A, Ruiz P J, Steinman L. Late pregnancy suppresses relapses in experimental autoimmune encephalomyelitis: evidence for a suppressive pregnancy-related serum factor.  J Immunol. 2002;  169 1084-1091
• 37 Palaszynski K M, Liu H, Loo K K, Voskuhl R R. Estriol treatment ameliorates disease in males with experimental autoimmune encephalomyelitis: implications for multiple sclerosis.  J Neuroimmunol. 2004;  149 84-89
• 38 Pritchard J A. Changes in the blood volume during pregnancy and delivery.  Anesthesiology. 1965;  26 393-399
• 39 Wilson M, Morganti A A, Zervoudakis I et al.. Blood pressure, the renin-aldosterone system and sex steroids throughout normal pregnancy.  Am J Med. 1980;  68 97-104
• 40 van Oppen A C, van der Tweel I, Alsbach G P, Heethaar R M, Bruinse H W. A longitudinal study of maternal hemodynamics during normal pregnancy.  Obstet Gynecol. 1996;  88 40-46
• 41 Mabie W C, DiSessa T G, Crocker L G, Sibai B M, Arheart K L. A longitudinal study of cardiac output in normal human pregnancy.  Am J Obstet Gynecol. 1994;  170 849-856
• 42 Robson S C, Dunlop W, Boys R J, Hunter S. Cardiac output during labour.  Br Med J (Clin Res Ed). 1987;  295 1169-1172
• 43 Robson S, Hunter S, Boys R, Dunlop W, Bryson M. Changes in cardiac output during epidural anaesthesia for caesarean section.  Anaesthesia. 1989;  44 475-479
• 44 Bucklin B A, Hawkins J L, Anderson J R, Ullrich F A. Obstetric anesthesia workforce survey: twenty-year update.  Anesthesiology. 2005;  103 645-653
• 45 Robson S C, Boys R J, Hunter S, Dunlop W. Maternal hemodynamics after normal delivery and delivery complicated by postpartum hemorrhage.  Obstet Gynecol. 1989;  74 234-239
• 46 Salonen Ros H, Lichtenstein P, Bellocco R, Petersson G, Cnattingius S. Increased risks of circulatory diseases in late pregnancy and puerperium.  Epidemiology. 2001;  12 456-460
• 47 Belfort M A, Tooke-Miller C, Allen Jr J C et al.. Changes in flow velocity, resistance indices, and cerebral perfusion pressure in the maternal middle cerebral artery distribution during normal pregnancy.  Acta Obstet Gynecol Scand. 2001;  80 104-112
• 48 Williams K, Wilson S. Maternal middle cerebral artery blood flow velocity variation with gestational age.  Obstet Gynecol. 1994;  84 445-448
• 49 Zeeman G G, Hatab M, Twickler D M. Maternal cerebral blood flow changes in pregnancy.  Am J Obstet Gynecol. 2003;  189 968-972
• 50 Sarrel P M. The differential effects of oestrogens and progestins on vascular tone.  Hum Reprod Update. 1999;  5 205-209
• 51 Ferro J M, Canhao P, Stam J, Barinagarrementeria F. Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT).  Stroke. 2004;  35 664-670
• 52 Kim R J, Becker R C. Association between factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations and events of the arterial circulatory system: a meta-analysis of published studies.  Am Heart J. 2003;  146 948-957
• 53 Cumming A M, Tait R C, Fildes S, Yoong A, Keeney S, Hay C R. Development of resistance to activated protein C during pregnancy.  Br J Haematol. 1995;  90 725-727
• 54 Clark P, Walker I D, Greer I. Acquired activated protein-C resistance in pregnancy and association with increased thrombin generation and fetal weight.  Lancet. 1999;  353 292-293
• 55 Davison J M, Lindheimer M D. Volume homeostasis and osmoregulation in human pregnancy.  Baillieres Clin Endocrinol Metab. 1989;  3 451-472
• 56 Lindheimer M D, Davison J M. Osmoregulation, the secretion of arginine vasopressin and its metabolism during pregnancy.  Eur J Endocrinol. 1995;  132 133-143
• 57 Dahlman T, Sjoberg H E, Bucht E. Calcium homeostasis in normal pregnancy and puerperium. A longitudinal study.  Acta Obstet Gynecol Scand. 1994;  73 393-398
• 58 Pitkin R M, Reynolds W A, Williams G A, Hargis G K. Calcium metabolism in normal pregnancy: a longitudinal study.  Am J Obstet Gynecol. 1979;  133 781-790
• 59 Sanders R, Konijnenberg A, Huijgen H J, Wolf H, Boer K, Sanders G T. Intracellular and extracellular, ionized and total magnesium in pre-eclampsia and uncomplicated pregnancy.  Clin Chem Lab Med. 1999;  37 55-59