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Overview |
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Definition |
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Spontaneous abortion, or miscarriage, is defined as the loss of a clinically
recognized pregnancy that occurs before 20 weeks of gestation; early miscarriage
occurs prior to week 12 while late spontaneous abortion occurs between weeks 12
and 20. Spontaneous abortions are classified as threatened (bleeding or cramping
in the first 20 weeks of gestation), inevitable (bleeding that threatens the
pregnant woman's health), incomplete (partial expulsion of the products
of conception), or complete. Missed abortion refers to a fetus
that has died in utero, which can be confirmed by ultrasonography.
Habitual spontaneous abortion is defined as three or more consecutive
miscarriages. Twenty-two to thirty-three percent of spontaneous abortions occur
before clinical recognition as a pregnancy; an additional 9% to 14% of
spontaneous abortions occur after pregnancy has been clinically recognized.
Therefore, overall rate of loss following implantation is estimated to be
one-third to one-half of all pregnancies. |
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Etiology |
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Chromosomal abnormalities:
- Up to 60% of spontaneous abortions
- Balanced parental
translocation—phenotypically normal parents, but
abortuses show chromosomal duplications or deficiencies
- Aneuploidy—numerical chromosomal
abnormalities; trisomies, then monosomy X, most common
- Triploidy—early abortions
- Inversions—order of genes is
reversed
Anatomic:
- Congenital distortion of uterine cavity –
e.g. mullerian fusion defects—septate uteri or small
T-shaped uteri; secondary to diethylstilbestrol (DES) exposure; generally a
second trimester miscarriage
- Acquired abnormalities: Asherman's Syndrome (intrauterine adhesions
from surgery and/or curettage); leiomyomas (rare); adenomyosis; endometriosis;
endometritis, which may also cause synechiae; 15% to 30% of those with
intrauterine adhesions have repeated spontaneous abortions
- Incompetent internal cervical os—DES exposed
as well
- Placental
abnormalities—rare
Endocrine:
- Hyperandrogen disorders—including polycystic
ovary syndrome
- Hyperthyroidism, hypothyroidism—antithyroid
antibodies higher in women experiencing repeated fetal loss
- Diabetes mellitus—only if poorly controlled
- Hyperprolactinemia
- Luteal phase defects (LPD)—inhospitable
endometrium possibly from deficient progesterone production; LPD may be
associated with hyperprolactinemia; although clinically plausible, currently
considered an uncommon even unlikely cause as LPD also exists in fertile women
who carry to term and treatment for LPD with progesterone suppositories remains
unproven
Infection:
- Directly via bacterial, viral, parasitic, or fungal
infection
- Indirectly via fever causing elevated core temperature
- Chlamydia trachomatis commonly associated with
endometritis and salpingitis
- Ureaplasma urealyticum and Mycoplasma hominis
– relationship to spontaneous abortion somewhat
controversial
- Herpes simplex may be associated with increased risk for
spontaneous abortion
- Human papillomavirus (HPV) more prevalent in spontaneously aborted
tissue compared to electively terminated pregnancies
- Septic abortion – infected uterine contents
occurring before, during, or after an abortion; generally, the woman is acutely
ill with chills, high fever, leukocytosis, and signs of septicemia and/or
peritonitis; causative agents include E. coli, Enterobacter aerogenes,
Proteus vulgaris, hemolytic streptococci, staphylococci, and anaerobic
organisms; incidence dramatically reduced with legalization of elective
abortions
Autoimmunity:
- Antiphospholipid antibodies (APLA) with high-titer IgG or
IgM—possibly abnormal when directed against negatively
charged phospholipids (e.g., lupus anticoagulant, anticardiolipin)
Anti-Fetal Antibodies:
- Rh-negative (D-negative) women with anti-D antibodies
- Anti-P antibodies in mother rejects Pp fetus early in
gestation
Alloimmune:
- Excessive sharing of HLA antigens between mother and father
Other Causes:
- Time of implantation—preovulatory oocyte
aging and postovulatory gamete aging; conceptus that implants after days 8 to 10
is at increased risk
- Defective spermatozoa
- Stress—possibly a psychocytokine mechanism
– controversial
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Risk Factors |
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- Previous spontaneous abortion
- Increased maternal age
- Cigarette smoking—presence of cotinine in
urine, smoking half a pack a day significantly increases risk
- Alcohol—risk doubles with more than two
drinks a day; paternal alcohol use as well
- Caffeine—see section entitled
Nutrition
- Cocaine—hair tests mildly correlate to
greater risk but urine tests did not; therefore, this issue is controversial;
possible that long-term use is more predictive of miscarriage (as indicated by
positive hair tests) than acute exposure
- Increased homocysteine levels (see section entitled
Nutrition)
- Exposure to x-rays (greater than 10 rads)
- Environmental—excessive exposure to lead,
mercury, ionizing radiation, organic solvents
- Intrauterine device – increased risk of
septic abortion
- Serious maternal illness
- Flight attendants working more than 74 hours/month during pregnancy;
possibly secondary to increased gravitational forces, circadian rhythm
disruption, noise and vibration, ozone, decompression episodes, fatigue,
chemical exposure, ionizing radiation exposure
- Maternal or paternal handling of anti-neoplastic agents
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Signs and Symptoms |
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- Embryonic heart rate below 90 beats per minute at 6 to 8 weeks of
gestation
- Bleeding
- Uterine cramping
- Cervical dilation
- Fever
- Shock
- Passage of necrotic fetal
tissue
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Differential
Diagnosis |
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- Ectopic pregnancy
- Molar pregnancy
- Cervical or vaginal lesions
- Membranous dysmenorrhea
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Diagnosis |
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Physical Examination |
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- Comprehensive medical, genetic, and social history of both
parents
- Assessment for signs of metabolic illness and
hyperandrogenism
- Pelvic examination—including assessment of
uterine size and shape, evidence of DES or trauma
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Laboratory Tests |
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- Human chorionic gonadotropin (hCG)—chemical
detection of pregnancy; levels >2,000 mIU/ml and lack of gestational sac
indicates loss – to make the diagnosis
- Karyotyping—determines chromosomal
abnormalities
- Hematocrit—to evaluate extent of bleeding
To evaluate possible etiology:
- Serum assay for thyroid-stimulating hormone (TSH)
- Lupus anticoagulant, IgG and IgM iosotopes of anticardiolipin and of
antiphosphatidylserine—for immunologic
assessment
- Cervical culture, Gram's staining of endometrial
smears—reveals infection
- Endometrial biopsy—examines effect of
progesterone on endometrium with luteal phase defects
- Serum progesterone level from mid-luteal
phase—best predictor of low
progesterone
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Pathology/Pathophysiology |
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Necrotic fetal debris—with or without chromosomal
abnormalities; fetal death may precede miscarriage by several
weeks |
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Imaging |
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- Ultrasound for uterine and fetal evaluation to make diagnosis of
spontaneous abortion; to assess for possible etiology –
e.g. polycystic ovaries or anatomic abnormality
- Sonohysterography identifies mullerian lesions
- Sonohysterosalpingography differentiates between a bicornuate and
septate uterus; reveals tubal patency
- MRI for uterine evaluation may be useful but
costly
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Other Diagnostic
Procedures |
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- Ultrasound-guided amniocentesis or chorionic villus
sampling—for prenatal genetic diagnosis or before
uterine evacuation to increase likelihood of fetal, not maternal, karyotyping
- Hysteroscopy evaluates uterine cavity
- Laparoscopy differentiates between a bicornuate and septate uterus
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Treatment Options |
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Treatment Strategy |
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Genetic counseling is advised for parents with inborn chromosomal
abnormalities. Necrotic uterine contents must be removed (naturally or
surgically) to avoid complications. Recognizing that spontaneous abortion may be
associated with a grieving process, counseling both partners during this process
is essential. In vitro fertilization, embryo transfer, or artificial
insemination are used with unexplained, recurrent loss and parental
translocations involving homologous chromosomes. |
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Drug Therapies |
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- Anti-D immunoglobulin—if only mother is
Rh-negative; 50 mcg first trimester, 300 mcg thereafter; plasmapheresis also
possibly therapeutic in the case of anti-fetal antibodies
- Antibiotics—in case of chlamydia or
ureaplasm, should treat both partners with doxycycline 100 mg po bid x 7 days to
eradicate infection and avoid spontaneous abortion in the future; if mother is
pregnant, use amoxicillin 500 mg po tid x 7 days instead; in case of
endometritis, cefoxitin (2 g IV, every 6 to 8 hours) for moderately severe
infection; in the case of sepsis or septic shock secondary to septic abortion,
clindamycin (900 mg IV, q 8 hours), ampicillin (2 g IV, q 6 hours), and an
aminoglycoside; prophylactic antibiotics should be used prior to certain
surgeries or procedures such as hysterosalpingogram
- Estrogen supplementation—following
intrauterine adhesion surgery; 2.5 mg/day for 30 days with 10 mg/day
medroxyprogesterone during last 10 days, which stimulates endometrial
growth
- Aspirin (81 mg/day) followed by low-molecular-weight heparin (2,500 or
5,000 U/day) after confirmed pregnancy for antiphospholipid syndrome
- Vaginal progesterone suppositories—for LPD 25
mg/bid starting at time of basal body temperature elevation, for 6 to 8
weeks
- Immunotherapy with paternal or third-party leukocytes or trophoblast
membranes—for alloimmune disease;
controversial
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Surgical Procedures |
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- D & C to evacuate necrotic debris
- Uteroplasty corrects mullerian fusion defects; controversial
- Resection of intrauterine septum and cervical
cerclage—with DES exposure, uterine anomalies
- Lysis under hyperscopic
visualization—followed by an intrauterine device to
reduce reapposition for intrauterine adhesions
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Complementary and Alternative
Therapies |
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There is a strong association between dietary and lifestyle factors and the
risk of spontaneous abortion; preconceptional counseling, therefore, should
include discussion of diet and lifestyle in relation to known risk factors
including avoidance of caffeine and abstinence from alcohol and recreational
drugs. In addition, while there is no definitive scientific support, there are
case reports suggesting the usefulness of Chinese herbal medicines in preventing
recurrent spontaneous abortions secondary to autoimmune abnormalities.
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Nutrition |
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Clinically, many naturopathic and other doctors recommend the use of vitamin
B complex 50 mg per day with additional vitamin B6 and folic acid 800
to 1,000 mcg per day. These practices for prevention of spontaneous abortion are
supported by studies suggesting a connection between impaired
methionine-homocysteine metabolism and recurrent miscarriages.
Increased homocysteine levels, caused by a dysfunctional
methionine-homocysteine metabolism, have been implicated in spontaneous
abortion, placental abruption, and neural tube defects. Cofactors in methionine
metabolism include folic acid, vitamins B12 and B6, and
betaine. The fetus, the neonate, and the pregnant woman all have increased
requirements of folic acid and B12; therefore, they are also more
likely to be deficient in these vitamins (Miller and Kelly 1996).
Impaired methionine metabolism may negatively impact other important
nutritional constituents such as coenzyme Q10 which may not be synthesized in
sufficient quantity in the case of too little folic acid, cobalamin and betaine.
Two studies comparing women with a threatened or completed spontaneous abortion
with women who had a normal, term pregnancy suggest that CoQ10 levels are
significantly decreased in women with negative pregnancy outcomes.
Supplementation with cofactors for methionine metabolism (e.g., folic acid or
its active form folinic acid; vitamin B12 or its active form
methylcobalamin together with riboflavin-5'-phosphate) may be useful in
preventing spontaneous abortion (Miller and Kelly 1996).
The deleterious effects associated with elevated homocysteine levels have
been illustrated in a case report of a woman with five consecutive spontaneous
abortions and in a retrospective study of 100 women with recurrent early
miscarriages of unknown cause. Evaluations of homocysteine levels in these women
revealed significant hyperhomocysteinemia, with levels inversely correlated with
serum folate and C677T homozygous genotype carrier status. The C677T mutation
occurs in the 5,10-methylene tetrahydrofolate reductase (MTHFR) gene, which
plays a central role in folate metabolism. Supplementation for 1 month with 15
mg daily folic acid and 500 mg daily B6 resulted in restoration of
normal homocysteine levels and successful pregnancy outcome in the single case
study (Quere et al. 1998).
Although supplementation with folic acid prior to and during pregnancy
particularly for prevention of neural tube defects is standard practice, it is
not entirely without controversy. As one author writes, a few studies have
suggested a slightly increased risk of miscarriage among users of prenatal
vitamins, multivitamins, or folic acid supplements, particularly if their use
began before conception. It is questionable whether supplementation actually
increases risk of miscarriage or simply prolongs a pregnancy that might have
miscarried earlier; it is also difficult to determine from these particular
studies whether it was folate or another factor contributing to the incidence of
spontaneous abortion (Windham et al. 2000).
Other nutrients with a potential role in spontaneous abortion include
selenium, magnesium, glutathione, beta-carotene, and vitamins A and E. Subacute,
chronic, and marginal deficits in magnesium may contribute to impaired
reproductive function, including miscarriage. In one small study, six women with
a history of unexplained infertility or early miscarriage, whose red blood cell
(RBC) magnesium levels failed to normalize after 4 months of oral magnesium
supplementation, were compared with a similar group of controls whose levels did
normalize. Levels of RBC GSH-Px, a selenium-dependent, antioxidant enzyme, were
found to be significantly lower in the non-normalized group, suggesting a role
for selenium deficiency in magnesium depletion. Within 8 months of normalizing
their RBC-magnesium levels with either magnesium or magnesium/selenium
supplements, all 12 of the previously infertile women conceived and delivered
normal healthy babies (Howard et al. 1994).
While magnesium deficiency is conventionally managed with magnesium
supplementation, these researchers suggest that normalization of magnesium
depletion may require supplementation with selenium as well. Magnesium depletion
appears to be secondary to increased permeability of cell membranes caused by
oxidative damage. According to this explanation, the selenoenzyme GSH-Px is
essential to cellular antioxidant activity, and a deficiency of selenium may
compromise the integrity of cell membranes. Other possible explanations are that
selenium improves magnesium absorption, or that enhanced selenium status
optimizes reproductive function by some other mechanism not identified in this
particular study (Howard et al. 1994).
Other studies have confirmed the association between antioxidant status and
spontaneous abortion. In a preliminary study, 40 women presenting with first
trimester miscarriage were matched with 40 nonpregnant healthy volunteers and 40
women in their first trimester of pregnancy. Healthy volunteers had normal blood
levels of selenium with the exception of one volunteer with a marginally low
level. All women in the healthy pregnant control group delivered healthy babies
and had decreased selenium levels compared with nonpregnant controls. However,
still lower selenium levels were found in the women who miscarried in the first
trimester. The loss of antioxidant activity associated with selenium deficiency
may have contributed to miscarriage in this group (Gabbe 1996). Similarly, blood
samples of 40 women with habitual spontaneous abortion compared with those of 40
healthy fertile women revealed increased lipid peroxidation and lower levels of
vitamins A and E and beta-carotene in the spontaneous abortion group. Levels of
glutathione were significantly higher in the women with habitual abortion
(Simsek et al. 1998).
Caffeine is known to cross the placenta readily; its impact on pregnancy is
not entirely understood. Whereas the plasma half-life of caffeine in healthy
adults is 2.5 to 4.5 hours, the half-life increases to 10.5 hours in pregnant
women and 32 to 149 hours in the newborn. A prospective cohort study of 3135
pregnant women showed that moderate-to-heavy caffeine users (> 151 mg
daily) were significantly more likely to experience late first- or
second-trimester spontaneous abortion when compared with nonusers or light
users. Light caffeine use (1 to 150 mg daily) was associated with increased risk
for abortion only in women for whom there was a history of spontaneous abortion.
(Note: one cup of coffee has 107 mg of caffeine, one cup of tea has 34 mg, and
one glass of cola has 47 mg.) Coffee was the main source of caffeine in
moderate-to-heavy users; light users were more likely to derive caffeine from
tea and other sources. It is possible that some other component of coffee other
than caffeine is responsible for the increased risk of spontaneous abortion
(Srisuphan and Bracken 1986).
Researchers have recently reported on a marked positive dose-response
relation between coffee consumption and plasma total homocysteine (Nygard et al.
1997). In view of a role for aberrant homocysteine metabolism in negative
pregnancy outcomes (as discussed earlier), a coffee-homocysteine correlation may
provide a mechanism for increased risk of spontaneous abortion among heavy
coffee drinkers. However, further research is needed to investigate the possible
connection between homocysteine levels, coffee consumption, and pregnancy.
A recent retrospective study examining the link between miscarriage and
stillbirths and a high intake of persistent organochlorine compounds due to
ingestion of contaminated fish found no association (Axmon et al. 2000).
Examples of POCs are polychlorinated biphenyls (PCBs) and DDT
(dichlorodiphenyltrichlorothane). Higher blood levels of PCBs were previously
reported in women hospitalized for miscarriage as compared with women who
carried full-term (Leoni et al. 1989). |
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Herbs |
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Western herbs may be beneficial in resolving underlying endocrine
abnormalities and may also play a role in stress reduction; however, these have
not yet been explored in relation to spontaneous abortion specifically.
Autoimmune abnormalities have been successfully treated with Traditional
Chinese Medicine. Twelve patients positive for antinuclear antibodies (ANA) and
one or more antiphospholipid antibodies (APLA) were admitted into treatment; all
had experienced recurrent spontaneous abortion during the first trimester.
Preconceptional administration of Sairei-to (a modified, Japanese version of the
Chinese herbal preparation Chan ling-tang) resulted in normalization of APLA
values in all but one of the patients within 2 months of treatment. Sairei-to
was continued throughout the prenatal course and discontinued after delivery.
Corticosteroids and aspirin were not administered during this time. In 9 out of
11 patients, these levels continued to be negative throughout the course of
Sairei-to. In the other two cases, levels increased and became positive. Ten
patients delivered healthy babies following a normal prenatal course. Two of the
patients whose APLA re-elevated or remained positive experienced recurrent
miscarriage (Takakuwa et al. 1996).
There are case reports in Chinese journals of women with recurrent
spontaneous abortion secondary to elevated autoantibodies and/or allo-antibodies
including anti-zona pellucida, APLA, and anti-ABO blood group antibodies being
treated successfully with Chinese herbal preparations (Li et al. 1997). Such
reports suggest that, for the appropriate patient with a history of one or more
spontaneous abortions, referral to a traditional medical practitioner is not
unreasonable. |
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Homeopathy |
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While information regarding the use of homeopathy for prevention of recurrent
spontaneous abortion was not found in the literature, a licensed and certified
homeopath would evaluate each individual and determine the appropriate
constitutional homeopathic treatment, which may be useful in supporting the
person's overall health. |
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Acupuncture |
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Although not necessarily recorded in the medical literature, acupuncturists
report clinical success in treating women with a history of spontaneous abortion
leading to future term pregnancies. The mechanism of success is possibly related
to resolution of underlying endocrine abnormalities and may also play a role in
stress reduction. |
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Patient Monitoring |
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- Monitor until miscarriage is complete
- Postconception monitoring is
critical
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Other
Considerations |
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Prevention |
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- Avoid known risks as described above
- Abortus karyotyping for clues to etiology and likelihood of
recurrence
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Complications/Sequelae |
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- Retained necrotic tissue may become infected and could possibly result
in pelvic abscess, septic shock, or death
- Feelings of depression and guilt are quite common, as well as fear and
concern with the next pregnancy
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Prognosis |
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- Fetal chromosomal abnormality—present in 45%
to 60% of first abortus and 75% of second abortuses
- Fetal chromosomal normality—second loss has
75% chance of normality
- Recurrent miscarriage—approximately 1%; risk
for subsequent loss is 24% after two, 30% after three, and 40% after four
consecutive losses
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References |
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Axmon A, Rylander L, Stromberg U, Hagmar L. Miscarriages and stillbirths in
women with a high intake of fish contaminated with persistent organochlorine
compounds. Int Arch Occup Environ Health. 2000;73(3):204-208.
Barrington JW, Lindsay P, James D, Smith S, Roberts A. Selenium deficiency
and miscarriage: a possible link? Br J Obstet Gynaecol.
1996;103(2):130-132.
Gabbe SG, ed. Obstretrics—Normal and Problem
Pregnancies. 3rd ed. New York, NY: Churchill Livingston; 1996.
Howard JM, Davies S, Hunnisett A. Red cell magnesium and glutathione
peroxidase in infertile women: effects of oral supplementation with magnesium
and selenium. Magnes Res. 1994;7(1):49-57.
Klebanoff MA, Levine RJ, DerSimonian R, Clemens JD, Wilkins DG. Maternal
serum paraxanthine, a caffeine metabolite, and the risk of spontaneous abortion.
N Engl J Med. 1999;341(22):1639-1644.
Leoni V, Fabiani L, Marinelli G, et al. PCB and other organochlorine
compounds in blood of women with or without miscarriage: a hypothesis of
correlation. Ecotoxicol Environ Saf. 1989;17(1):1-11.
Li DJ, Li CJ, Zhu Y. Treatment of integrated traditional and western medicine
in recurrent spontaneous abortion of immune abnormality type [in Chinese].
Chung Kuo Chung Hsi I Chieh Ho Tsa Chih. 1997;17(7):390-392.
Miller AL, Kelly GS. Methionine and homocysteine metabolism and the
nutritional prevention of certain birth defects and complications of pregnancy.
Altern Med Rev. 1996;1(4):220-235.
Ness RB, Grisso JA, Hirschinger N, et al. Cocaine and tobacco use and the
risk of spontaneous abortion. N Engl J Med. 1999;340(5):333-339.
Nygard O, Refsum H, Ueland PM, et al. Coffee consumption and plasma total
homocysteine: The Hordaland Homocysteine Study. Am J Clin Nutr.
1997;65(1):136-143.
Quere I, Bellet H, Hoffet M, Janbon C, Mares P, Gris JC. A woman with five
consecutive fetal deaths: case report and retrospective analysis of
hyperhomocysteinemia prevalence in 100 consecutive women with recurrent
miscarriages. Fertil Steril. 1998;69(1):152-154.
Rosen P, Barkin R, eds. Emergency Medicine: Concepts and Clinical
Management. 4th ed. St. Louis, Mo: Mosby-Year Book; 1998.
Ryan KJ, ed. Kistner's Gynecology & Women's Health. 7th ed. St.
Louis, Mo: Mosby, Inc.; 1999.
Simsek M, Naziroglu M, Simsek H, Cay M, Aksakal M, Kumru S. Blood plasma
levels of lipoperoxides, glutathione peroxidase, beta carotene, vitamin A and E
in women with habitual abortion. Cell Biochem Funct.
1998;16(4):227-231.
Srisuphan W, Bracken MB. Caffeine consumption during pregnancy and
association with late spontaneous abortion. Am J Obstet Gynecol.
1986;154(1):14-20.
Takakuwa K, Yasuda M, Hataya I, et al. Treatment for patients with recurrent
abortion with positive antiphospholipid antibodies using a traditional Chinese
herbal medicine. J Perinat Med. 1996;24(5):489-494.
Wilcox AJ, Baird DD, Weinberg CR. Time of implantation of the conceptus and
loss of pregnancy. N Engl J Med. 1999;340(23):1796-1799.
Windham GC, Shaw GM, Todoroff K, Swan SH. Miscarriage and use of
multi-vitamins or folic acid. Am J Med Genet.
2000;90(3):261-262. |
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Copyright © 2000 Integrative Medicine
Communications This publication contains
information relating to general principles
of medical care that should not in any event be construed as specific
instructions for individual patients. The publisher does not accept any
responsibility for the accuracy of the information or the consequences arising
from the application, use, or misuse of any of the information contained herein,
including any injury and/or damage to any person or property as a matter of
product liability, negligence, or otherwise. No warranty, expressed or implied,
is made in regard to the contents of this material. No claims or endorsements
are made for any drugs or compounds currently marketed or in investigative use.
The reader is advised to check product information (including package inserts)
for changes and new information regarding dosage, precautions, warnings,
interactions, and contraindications before administering any drug, herb, or
supplement discussed herein. | |