Miscarriage

Miscarriage
Classification and external resources

A complete spontaneous abortion at about six weeks from conception, i.e. eight weeks from the last menstrual period (LMP)
ICD-10 O03
ICD-9 634
MedlinePlus 001488
eMedicine topic list
MeSH D000022

Miscarriage or spontaneous abortion is the spontaneous end of a pregnancy at a stage where the embryo or fetus is incapable of surviving independently, generally defined in humans at prior to 20 weeks of gestation. Miscarriage is the most common complication of early pregnancy.[1][2]

Contents

Terminology

Very early miscarriages—those that occur before the sixth week LMP (since the woman's Last Menstrual Period)—are medically termed early pregnancy loss[3] or chemical pregnancy.[4] Miscarriages that occur after the sixth week LMP are medically termed clinical spontaneous abortion.[3]

In medical (and veterinary) contexts, the technical term "abortion" refers to any process by which a pregnancy ends with the death and removal or expulsion of the fetus, regardless of whether it is spontaneous or intentionally induced. Many women who have had miscarriages, however, object to the term "abortion" in connection with their experience, because in everyday English the word is strongly associated with induced abortions. In recent years there has been discussion in the medical community about avoiding the use of this term in favor of the less ambiguous term "miscarriage".[5] In 2005 the European Society for Human Reproduction and Embryology (ESHRE) published a paper aiming to facilitate an update and revision of nomenclature used to describe early pregnancy events.[6]

Labour resulting in live birth before the 37th week of pregnancy is termed "premature birth", even if the infant dies shortly afterward. The limit of viability at which 50% of fetus/infants survive longterm is around 24 weeks, with moderate or major neurological disability dropping to 50% only by 26 weeks.[7] Although long-term survival has never been reported for infants born from pregnancy shorter than 21 weeks and 5 days,[8] fetuses born as early as the 16th week of pregnancy may sometimes live for some minutes after birth.[9]

A fetus that dies while in the uterus after about the 20–24th week of pregnancy is termed a "stillbirth"; the precise gestational age definition varies by country. Premature births or stillbirths are not generally considered miscarriages, though usage of the terms and causes of these events may overlap.

Miscarriage of a fetus is also called intrauterine fetal death (IUFD).

Classification

The clinical presentation of a threatened abortion describes any bleeding seen during pregnancy prior to viability, that has yet to be assessed further. At investigation it may be found that the fetus remains viable and the pregnancy continues without further problems.

Alternatively the following terms are used to describe pregnancies that do not continue:

The following two terms consider wider complications or implications of a miscarriage:

The physical symptoms of a miscarriage vary according to the length of pregnancy:[13]

Signs and symptoms

The most common symptom of a miscarriage is bleeding;[14] bleeding during pregnancy may be referred to as a threatened abortion. Of women who seek clinical treatment for bleeding during pregnancy, about half will go on to have a miscarriage.[15] Symptoms other than bleeding are not statistically related to miscarriage.[14]

Miscarriage may also be detected during an ultrasound exam, or through serial human chorionic gonadotropin (HCG) testing. Women pregnant from ART methods, and women with a history of miscarriage, may be monitored closely and so detect a miscarriage sooner than women without such monitoring.

Several medical options exist for managing documented nonviable pregnancies that have not been expelled naturally.

Psychological

Although a woman physically recovers from a miscarriage quickly, psychological recovery for parents in general can take a long time. People differ greatly in this regard: some are able to move on after a few months, but others take more than a year. Still others may feel relief or other less negative emotions. A questionnaire (GHQ-12 General Health Questionnaire) study following women having miscarried showed that half (55%) of the miscarrying women presented with significant psychological distress immediately, 25% at 3 months; 18% at 6 months, and 11% at 1 year after miscarriage.[16]

Besides the feeling of loss, a lack of understanding by others is often important. People who have not experienced a miscarriage themselves may find it hard to empathize with what has occurred and how upsetting it may be. This may lead to unrealistic expectations of the parents' recovery. The pregnancy and miscarriage are hardly mentioned any more in conversation, often because the subject is too painful. This can make the woman feel particularly isolated. Inappropriate or insensitive responses from the medical profession can add to the distress and trauma experienced, so in some cases attempts have been made to draw up a standard code of practice.[17]

Interaction with pregnant women and newborn children is often also painful for parents who have experienced miscarriage. Sometimes this makes interaction with friends, acquaintances and family very difficult.[18]

Causes

Miscarriages can occur for many reasons, not all of which can be identified. Some of these causes include genetic, uterine or hormonal abnormalities, reproductive tract infections, and tissue rejection.

First trimester

Most clinically apparent miscarriages (two thirds to three-quarters in various studies) occur during the first trimester.[19][20]

Chromosomal abnormalities are found in more than half of embryos miscarried in the first 13 weeks. A pregnancy with a genetic problem has a 95% probability of ending in miscarriage. Most chromosomal problems happen by chance, have nothing to do with the parents, and are unlikely to recur. Chromosomal problems due to a parent's genes are, however, a possibility. This is more likely to have been the cause in the case of repeated miscarriages, or if one of the parents has a child or other relatives with birth defects.[21] Genetic problems are more likely to occur with older parents; this may account for the higher miscarriage rates observed in older women.[22]

Another cause of early miscarriage may be progesterone deficiency. Women diagnosed with low progesterone levels in the second half of their menstrual cycle (luteal phase) may be prescribed progesterone supplements, to be taken for the first trimester of pregnancy.[21] No study has shown that general first-trimester progesterone supplements reduce the risk of threatened miscarriage (when a mother might already be losing her baby),[23] and even the identification of problems with the luteal phase as contributing to miscarriage has been questioned.[24]

Second trimester

Up to 15% of pregnancy losses in the second trimester may be due to uterine malformation, growths in the uterus (fibroids), or cervical problems.[21] These conditions may also contribute to premature birth.[19]

One study found that 19% of second trimester losses were caused by problems with the umbilical cord. Problems with the placenta may also account for a significant number of later-term miscarriages.[25]

General risk factors

Pregnancies involving more than one fetus are at increased risk of miscarriage.[21]

Uncontrolled diabetes greatly increases the risk of miscarriage. Women with controlled diabetes are not at higher risk of miscarriage. Because diabetes may develop during pregnancy (gestational diabetes), an important part of prenatal care is to monitor for signs of the disease.[21]

Polycystic ovary syndrome is a risk factor for miscarriage, with 30-50% of pregnancies in women with PCOS being miscarried in the first trimester. Two studies have shown treatment with the drug metformin to significantly lower the rate of miscarriage in women with PCOS (the metformin-treated groups experienced approximately one-third the miscarriage rates of the control groups).[26] However, a 2006 review of metformin treatment in pregnancy found insufficient evidence of safety and did not recommend routine treatment with the drug.[27]

High blood pressure during pregnancy, known as preeclampsia, is sometimes caused by an inappropriate immune reaction (paternal tolerance) to the developing fetus, and is associated with the risk of miscarriage. Similarly, women with a history of recurrent miscarriages are at risk of developing preeclampsia.[28]

Severe cases of hypothyroidism increase the risk of miscarriage. The effect of milder cases of hypothyroidism on miscarriage rates has not been established. The presence of certain immune conditions such as autoimmune diseases is associated with a greatly increased risk of miscarriage.[21] The presence of anti-thyroid autoantibodies is associated with an increased risk of miscarriage with an odds ratio of 3.73 and 95% confidence interval 1.8–7.6.[29]

Certain illnesses (such as rubella, chlamydia and others) increase the risk of miscarriage.[21]

Tobacco (cigarette) smokers have an increased risk of miscarriage.[30] An increase in miscarriage is also associated with the father being a cigarette smoker.[3] The husband study observed a 4% increased risk for husbands who smoke fewer than 20 cigarettes/day, and an 81% increased risk for husbands who smoke 20 or more cigarettes/day.

Cocaine use increases miscarriage rates.[30] Physical trauma, exposure to environmental toxins, and use of an IUD during the time of conception have also been linked to increased risk of miscarriage.[31]

Antidepressants specially paroxetine and venlafaxine can lead to spontaneous abortion.[32][33]

Further information: Advanced maternal age

The age of the mother is a significant risk factor. Miscarriage rates increase steadily with age, with more substantial increases after age 35.[34][35]

Suspected risk factors

Several factors have been correlated with higher miscarriage rates, but whether they cause miscarriages is debated. No causal mechanism may be known, the studies showing a correlation may have been retrospective (beginning the study after the miscarriages occurred, which can introduce bias) rather than prospective (beginning the study before the women became pregnant), or both.

Autoimmune disease

Some research suggests autoimmunity as a possible cause of recurrent or late-term miscarriages.[36] Autoimmune disease occurs when the body's own immune system acts against itself. Therefore, in the case of an autoimmune-induced miscarriage the woman's body attacks the growing fetus or prevents normal pregnancy progression.[37][38] Further research has also suggested that autoimmune disease can cause genetic abnormalities in embryos which in turn can lead to miscarriage.[39]

Morning sickness

Nausea and vomiting of pregnancy (NVP, or morning sickness) are associated with a decreased risk of miscarriage. Several mechanisms have been proposed for this relationship, but none are widely agreed on.[40] Because NVP may alter a woman's food intake and other activities during pregnancy, it may be a confounding factor when investigating possible causes of miscarriage.

Exercise

One such factor is exercise. A study of over 92,000 pregnant women found that most types of exercise (with the exception of swimming) correlated with a higher risk of miscarriage prior to 18 weeks. Increasing time spent on exercise was associated with a greater risk of miscarriage: an approximately 10% increased risk was seen with up to 1.5 hours per week of exercise, and a 200% increased risk was seen with over 7 hours per week of exercise. High-impact exercise was especially associated with the increased risk. No relationship was found between exercise and miscarriage rates after the 18th week of pregnancy. The majority of miscarriages had already occurred at the time women were recruited for the study, and no information on nausea during pregnancy or exercise habits prior to pregnancy was collected.[41]

Caffeine

Caffeine consumption has also been correlated to miscarriage rates, at least at higher levels of intake. A 2007 study of over 1,000 pregnant women found that women who reported consuming 200 mg or more of caffeine per day experienced a 25% miscarriage rate, compared to 13% among women who reported no caffeine consumption. 200 mg of caffeine is present in 10 oz (300 mL) of coffee or 25 oz (740 mL) of tea. This study controlled for pregnancy-associated nausea and vomiting (NVP or morning sickness): the increased miscarriage rate for heavy caffeine users was seen regardless of how NVP affected the women. About half of the miscarriages had already occurred at the time women were recruited for the study.[42] A second 2007 study of approximately 2,400 pregnant women found that caffeine intake up to 200 mg per day was not associated with increased miscarriage rates (the study did not include women who drank more than 200 mg per day past early pregnancy).[43] A prospective cohort study in 2009 showed no increased risk.[44]

Diagnosis

A miscarriage can be confirmed via ultrasound and by the examination of the passed tissue. When looking for microscopic pathologic symptoms of miscarriage, one looks for the products of conception. Microscopically, these include villi, trophoblast, fetal parts, and background gestational changes in the endometrium. Genetic tests may also be performed to look for abnormal chromosome arrangements.

Management

Blood loss during early pregnancy is the most common symptom of both miscarriage and of ectopic pregnancy. Pain does not strongly correlate with miscarriage, but is a common symptom of ectopic pregnancy.[14] In the case of concerning blood loss, pain, or both, transvaginal ultrasound is performed. If a viable intrauterine pregnancy is not found with ultrasound, serial βHCG tests should be performed to rule out ectopic pregnancy, which is a life-threatening situation.[45][46]

If the bleeding is light, making an appointment to see one's doctor is recommended. If bleeding is heavy, there is considerable pain, or there is a fever, then emergency medical attention is recommended to be sought.

Whilst bed rest has been advocated in the past to help ensure that the pregnancy might continue, and in one study possibly helped when small subchorionic hematoma had been found on ultrasound scans,[47] the prevailing opinion is that this is of no proven benefit.[48]

No treatment is necessary for a diagnosis of complete abortion (as long as ectopic pregnancy is ruled out). In cases of an incomplete abortion, empty sac, or missed abortion there are three treatment options:

Prevention

Currently there is no known way to prevent an impending miscarriage. However, fertility experts believe that identifying the cause of the miscarriage may help prevent it from happening again in a future pregnancy.[51] In one study, researchers found that use of the supplement dehydroepiandrosterone before and during pregnancy reduced the risk of pregnancy losses.[52]

Epidemiology

Determining the prevalence of miscarriage is difficult. Many miscarriages happen very early in the pregnancy, before a woman may know she is pregnant. Treatment of women with miscarriage at home means medical statistics on miscarriage miss many cases.[15] Prospective studies using very sensitive early pregnancy tests have found that 25% of pregnancies are miscarried by the sixth week LMP (since the woman's Last Menstrual Period).[53][54] However, other sources reports suggest higher rates. One fact sheet from the University of Ottawa states, "The incidence of spontaneous abortion is estimated to be 50% of all pregnancies, based on the assumption that many pregnancies abort spontaneously with no clinical recognition."[55] The NIH reports, "It is estimated that up to half of all fertilized eggs die and are lost (aborted) spontaneously, usually before the woman knows she is pregnant. Among those women who know they are pregnant, the miscarriage rate is about 15-20%." [56] Clinical miscarriages (those occurring after the sixth week LMP) occur in 8% of pregnancies.[54]

The risk of miscarriage decreases sharply after the 10th week LMP, i.e. when the fetal stage begins.[57] The loss rate between 8.5 weeks LMP and birth is about two percent; loss is “virtually complete by the end of the embryonic period."[58]

The prevalence of miscarriage increases considerably with age of the parents. One study found that pregnancies from men younger than 25 years are 40% less likely to end in miscarriage than pregnancies from men 25–29 years. The same study found that pregnancies from men older than 40 years are 60% more likely to end in miscarriage than the 25–29-year age group.[59] Another study found that the increased risk of miscarriage in pregnancies from older men is mainly seen in the first trimester.[60] Yet another study found an increased risk in women, by the age of 45, on the order of 800% (compared to the 20–24 age group in that study), 75% of pregnancies ended in miscarriage.[61]

In other animals

Miscarriage occurs in all animals that experience pregnancy. There are a variety of known risk factors for miscarriage in non-human animals. For example, in sheep, it may be caused by crowding through doors, or being chased by dogs.[62] In cows, miscarriage (i.e. spontaneous abortion) may be caused by contagious disease, such as Brucellosis or Campylobacter, but can often be controlled by vaccination.[63] Other diseases are also known to target animals for miscarriage. Spontaneous abortion occurs in pregnant Prairie Voles when their mate is removed and they are exposed to a new male,[64] an example of the Bruce effect, although this effect is seen less in wild populations than in the laboratory.[65] Female mice that had spontaneous abortions showed a sharp rise in the time spent with unfamiliar males preceding the abortion.[66]

ICD10 codes

N96
O03.0-O06.4
O02.1
O20.0

See also

References

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External links

Pathology of pregnancy, childbirth and the puerperium (O, 630–679)
Pregnancy
Pregnancy with
abortive outcome
Other, predominantly
related to pregnancy
Maternal care related to the
fetus and amniotic cavity
Labor
Puerperal
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Maternal death · Concomitant conditions: Diabetes mellitus, SLE

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mthr/fetu/infc, epon

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