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
Lydia K LeeM.D.
Clinical Fellow of Maternal Fetal Medicine, Department of Obstetrics, Gynecology,
and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School
75 Francis Street, Boston, MA 02115
eMail: Lydia.Lee@cshs.org