Miscarriage

For usage in law, see Miscarriage of justice.
Miscarriage

An ultrasound showing an empty sac, a gestational sac containing a yolk sac but no embryo. This is a type of miscarriage.
Classification and external resources
Specialty Obstetrics and gynecology
ICD-10 O03
ICD-9-CM 634
OMIM 614389
DiseasesDB 29
MedlinePlus 001488
eMedicine topic list
Patient UK Miscarriage
MeSH D000022

Miscarriage, also known as spontaneous abortion and pregnancy loss, is the natural death of an embryo or fetus before it is able to survive independently.[1][2] Some use the cutoff of 20 weeks of gestation after which fetal death is known as a stillbirth.[2] The most common symptoms of a miscarriage is vaginal bleeding with or without pain.[1] Sadness, anxiety, and guilt may occur.[3] Tissue or clot like material may also come out of the vagina.[4]

Risk factors for miscarriage include an older parent, previous miscarriage, exposure to tobacco smoke, obesity, diabetes, and drug or alcohol use, among others.[5][6] In those under the age of 35 the risk is about 10% while it is about 45% in those over the age of 40.[1] Risk begins to increase around the age of 30.[5] About 80% of miscarriages occur in the first 12 weeks of pregnancy (the first trimester). The underlying cause in about half of cases involves chromosomal abnormalities. Other conditions that can produce similar symptoms include an ectopic pregnancy and implantation bleeding.[1] Diagnosis of a miscarriage may involve checking to see if the cervix is open or closed, testing blood levels of human chorionic gonadotropin (hCG), and an ultrasound.[7]

Prevention is occasionally possible with good prenatal care. Avoiding drugs and alcohol, infectious diseases, and radiation may prevent miscarriage.[8] No specific treatment is usually needed during the first 7 to 14 days.[6][9] Most miscarriage will complete without additional interventions.[6] Occasionally the medication misoprostol or a procedure such as vacuum aspiration is required to remove the failed pregnancy.[9][10] Women who are rhesus negative may require Rho(D) immune globulin.[6] Pain medication may be beneficial.[9] Emotional support may help with negative emotions.[9]

Miscarriage is the most common complication of early pregnancy.[11] Among females who know they are pregnant, the miscarriage rate is roughly 10% to 20% while rates among all fertilisation is around 30% to 50%.[1][5] About 5% of females have two miscarriages in a row.[12] Some recommend not using the term "abortion" in discussions with those experiencing a miscarriage in an effort to decrease distress.[13]

Signs and symptoms

The most common symptom of a miscarriage is vaginal bleeding.[14] This can vary from light spotting or brownish discharge to heavy bleeding and bright red blood. The bleeding may come and go over several days. However, light vaginal bleeding is relatively common during the first trimester of pregnancy (the first 12 weeks) and does not necessarily indicate a miscarriage.

Bleeding during pregnancy may be referred to as a threatened miscarriage. Of those who seek clinical treatment for bleeding during pregnancy, about half will miscarry.[15] Symptoms other than bleeding are not statistically related to miscarriage.[14]

Miscarriage may be detected during an ultrasound exam, or through serial human chorionic gonadotropin (HCG) testing. Those who became pregnant using assisted reproductive technology methods, and those with a history of miscarriage may be monitored closely, and may be diagnosed with miscarriage sooner.

Causes

Miscarriage may 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. Miscarriage caused by invasive prenatal diagnosis (chorionic villus sampling (CVS) and amniocentesis) is rare (about 1%).[16][17]

First trimester

Most clinically apparent miscarriages (two-thirds to three-quarters in various studies) occur during the first trimester.[18][19][20] About 30% to 40% of all fertilized eggs miscarry, often before the pregnancy is known.[1] The embryo typically dies before the pregnancy is expelled; bleeding into the decidua basalis and tissue necrosis causes uterine contractions to expel the pregnancy.[20]

A chemical pregnancy refers to a pregnancy that was detected by testing but ends in miscarriage before or around the time of the next expected period.[21]

Chromosomal abnormalities are found in more than half of embryos miscarried in the first 13 weeks;[22] half of embryonic miscarriages (25% of all miscarriages) have an aneuploidy (abnormal number of chromosomes). Common aneuploidies found in miscarriages include autosomal trisomy (22-32%), monosomy X (5-20%), triploidy (6-8%), tetraploidy (2-4%), or other structural chromosomal abnormalities (2%).[20] Chromosomal problems due to a parent's genes may also cause miscarriage. 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.[23] Genetic problems are more likely to occur with older parents; this may account for the higher rates observed in older people.[24]

Progesterone deficiency may be another cause. Those 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.[23] There is no evidence that progesterone given in the first trimester reduces the risk of miscarriage, and luteal phase progesterone deficiency may or may not be a contributing factor to miscarriage.[25][26]

Second trimester

Second trimester losses may be due to uterine malformation, growths in the uterus (fibroids), or cervical problems.[23] These conditions also may contribute to premature birth.[18]

One study found that 19% of second trimester losses were caused by problems with the umbilical cord. Problems with the placenta also may account for a significant number of later-term miscarriages.[27]

Unlike in first-trimester miscarriages, second-trimester miscarriages are less likely to be cause by a genetic abnormality; chromosomal aberrations are found in a third of cases.[20]

Induced miscarriage

If a pregnant person does not want to give birth, doctors may induce a therapeutic abortion.[28] In places where induced abortion is illegal or carries heavy social stigma, those who wish to end the pregnancy may attempt self-induced abortion, sometimes called "induced miscarriage" or "self-induced miscarriage".

Risk factors

Multiple pregnancy

Pregnancies with more than one fetus are at increased risk for miscarriage. This risk increases with the number of fetuses in the pregnancy.[23]

Intercurrent diseases

Several intercurrent diseases in pregnancy can potentially increase the risk of miscarriage, including diabetes, polycystic ovarian syndrome (PCOS), hypothyroidism, certain infectious diseases, and autoimmune diseases. The risk of miscarriage is increased in those with poorly controlled insulin-dependent diabetes mellitus, but there is no significant increase in risk with well-controlled diabetes.[29] PCOS may increase the risk of miscarriage, but this is disputed.[30] Two studies suggested treatment with the drug metformin significantly lowers the rate of miscarriage in women with PCOS,[31][32] but the quality of these studies has been questioned.[33] A 2006 review of metformin treatment in pregnancy found insufficient evidence of safety, and did not recommend routine treatment with the drug.[34] In 2007 the Royal College of Obstetricians and Gynaecologists also recommended against use of the drug to prevent miscarriage.[33]

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.[23] The presence of anti-thyroid autoantibodies is associated with an increased risk with an odds ratio of 3.73 and 95% confidence interval 1.8–7.6.[35] Some research suggests autoimmunity in general as a possible cause of recurrent or late-term miscarriages. Autoimmune disease occurs when the body's own immune system acts against itself. Therefore, in the case of an autoimmune-induced miscarriages the woman's body attacks the growing fetus or prevents normal pregnancy progression.[36][37] Further research also has suggested that autoimmune disease may cause genetic abnormalities in embryos which in turn may lead to miscarriage.[38] As an example, Celiac disease increases the risk of miscarriage by an odds ratio of approximately 1.4.[39]

Diseases transmitted vertically (through the placenta to the fetus), such as rubella or chlamydia, can increase the risk of miscarriage.[23]Mycoplasma genitalium infection is associated with increased risk of preterm birth and miscarriage.[40]

Smoking

Tobacco (cigarette) smokers have an increased risk of miscarriage.[41] There is an increased risk regardless of which parent smokes, though the risk is higher when the gestational parent smokes. [42]

Age

Further information: Advanced maternal age

The age of the pregnant person is a significant risk factor. Miscarriage rates increase steadily with age, with more substantial increases after age 35.[43]

Morning sickness

Nausea and vomiting of pregnancy (NVP, or morning sickness) are associated with a decreased risk. Several proximate causes have been proposed for this relationship, but none are widely agreed upon.[44] NVP is generally interpreted as a defense mechanism which discourages the mother's ingestion of foods that are harmful to the fetus; according to this model, a lower frequency of miscarriage would be an expected consequence of the different food choices made by a women experiencing NVP.

Exercise

A study of more than 92,000 pregnant people found that most types of exercise (with the exception of swimming) correlated with a higher risk of miscarrying prior to 18 weeks. Increasing time spent on exercise was associated with a greater risk: 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 more than 7 hours per week of exercise. However, the study found none of these risks to be statistically significant. High-impact exercise was especially associated with the increased risk. No relationship was found between exercise rates after the 18th week of pregnancy. The majority of miscarriages had already occurred at the time pregnant people were recruited for the study, and no information on nausea during pregnancy or exercise habits prior to pregnancy was collected.[45]

Caffeine

Caffeine consumption also has been correlated to miscarriage rates, at least at higher levels of intake. However, such higher rates have been found to be statistically significant only in certain circumstances. A 2007 study of more than 1,000 pregnant people found that those who reported consuming 200 mg or more of caffeine per day experienced a 25% rate of miscarriage, 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 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.[46] 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 rates (the study did not include women who drank more than 200 mg per day past early pregnancy).[47] A prospective cohort study in 2009 found that light or moderate caffeine consumption (up to 300 mg per day) had no effect on pregnancy or miscarriage rates.[48]

Other

Transvaginal ultrasonography showing an abnormal mass in the gestational sac, next to a normal embryo (at bottom right) of a gestational age of 7 weeks with visible heartbeat. Masses like these are presumed to increase the risk of miscarriage.

Sexual intercourse during the first trimester has often been assumed by doctors to be a cause of miscarriage. However the association has never been proved or disproved.[49]

Cocaine use increases the rate of miscarriage.[41] Physical trauma, exposure to environmental toxins, and use of an intrauterine device at the time of fertilization have also been linked to increased risk.[50]

Loop electrosurgical excision procedure (LEEP) is one of the most commonly used approaches to treat high grade cervical dysplasia. A cohort study came to the result that those with a time interval from LEEP to pregnancy of less than 12 months compared with 12 months or more were at significantly increased risk for spontaneous abortion, with risk of spontaneous abortion of 18% compared with 4.6%, respectively.[51] On the other hand, no increased risk was identified for preterm birth after LEEP.[51]

Antidepressants, especially paroxetine and venlafaxine, can cause a miscarriage.[52][53]

Diagnosis

Bleeding during early pregnancy is the most common symptom of both impending miscarriage and of ectopic pregnancy. Pain does not strongly correlate with the former, but is a common symptom of ectopic pregnancy.[14] Typically, in the case of 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.[54][55]

A miscarriage may be confirmed via obstetric ultrasound and by the examination of the passed tissue. When looking for microscopic pathologic symptoms, one looks for the products of conception. Microscopically, these include villi, trophoblast, fetal parts, and background gestational changes in the endometrium. When chromosomal abnormalities are found in more than one miscarriage, genetic testing of both parents may be done.[56]

Ultrasound criteria

A review article in The New England Journal of Medicine based on a consensus meeting of the Society of Radiologists in Ultrasound in America (SRU) has suggested that miscarriage should be diagnosed only if any of the following criteria are met upon ultrasonography visualization:[57]

In addition, signs upon ultrasonography that are suggested to be suspicious for miscarriage, but not diagnostic of it, include:[57]

Classification

The clinical presentation of a "threatened miscarriage" describes any bleeding 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.

An anembryonic pregnancy (also called an "empty sac" or "blighted ovum") is a condition where the gestational sac develops normally, while the embryonic part of the pregnancy is either absent or stops growing very early. This accounts for approximately half of miscarriages. All other miscarriages are classified as embryonic miscarriages, meaning that there is an embryo present in the gestational sac. Half of embryonic miscarriages have aneuploidy (an abnormal number of chromosomes).[20]

An inevitable miscarriage occurs when the cervix has already dilated,[58] but the fetus has yet to be expelled. This usually will progress to a complete miscarriage. The fetus may or may not have cardiac activity.

Transvaginal ultrasonography after an episode of heavy bleeding in an intrauterine pregnancy that had been confirmed by a previous ultrasononography. There is some widening between the uterine walls, but no sign of any gestational sac, thus in this case being diagnostic of a complete miscarriage.

A complete miscarriage is when all products of conception have been expelled; these may include the trophoblast, chorionic villi, gestational sac, yolk sac, and fetal pole (embryo); or later in pregnancy the fetus, umbilical cord, placenta, amniotic fluid, and amniotic membrane. The presence of a pregnancy test that is still positive as well as an empty uterus upon transvaginal ultrasonography does, however, fulfill the definition of pregnancy of unknown location. Therefore, there may be a need for e.g. follow-up pregnancy tests to ensure that there is no remaining pregnancy, including an ectopic pregnancy.

Transvaginal ultrasonography, with some products of conception in the cervix (to the left in the image) and remnants of a gestational sac by the fundus (to the right in the image), indicating an incomplete miscarriage.

An incomplete miscarriage occurs when some products of conception have been passed, but some remains inside the uterus.[59] However, an increased distance between the uterine walls on transvaginal ultrasonography may also simply be an increased endometrial thickness and/or a polyp. The use of a Doppler ultrasound may be better in confirming the presence of significant retained products of conception in the uterine cavity.[60] In cases of uncertainty, ectopic pregnancy must be excluded using techniques like serial beta-hCG measurements.[60]

A 13-week fetus without cardiac activity located in the uterus (delayed or missed miscarriage)

A missed miscarriage is when the embryo or fetus has died, but a miscarriage has not yet occurred. It is also referred to as delayed miscarriage or silent miscarriage.[61][62]

A septic miscarriage occurs when the tissue from a missed or incomplete miscarriage becomes infected, which carries the risk of spreading infection (septicaemia) and can be fatal.[20]

Recurrent pregnancy loss (RPL) or recurrent miscarriage is the occurrence of multiple consecutive miscarriages; the exact number used to diagnose recurrent miscarriage varies.[20] If the proportion of pregnancies ending in miscarriage is 15% and assuming that miscarriages are independent events,[63] then the probability of two consecutive miscarriages is 2.25% and the probability of three consecutive miscarriages is 0.34%. The occurrence of recurrent pregnancy loss is 1%.[63] A large majority (85%) of those who have had two miscarriages will conceive and carry normally afterward.

The physical symptoms of a miscarriage vary according to the length of pregnancy, though most miscarriages cause pain or cramping. The size of blood clots and pregnancy tissue that are passed become larger with longer gestations. After 13 weeks' gestation, there is a higher risk of placenta retention.[64]

Prevention

Prevention of miscarriage centers on decreasing risk factors.[8] This may include good prenatal care, avoiding drugs and alcohol, preventing infectious diseases, and avoiding radiation.[8] Identifying the cause of the miscarriage may help prevent future pregnancy loss, especially in cases of recurrent miscarriage. Often there is little a person can do to prevent a miscarriage.[8] Vitamin supplementation has not been found to be effective to prevent miscarriage.[65]

Management

It is estimated about half of early miscarriages will complete on their own; in other cases, medication treatment or aspiration of the products of conception can be used to remove remaining tissue.[66] Emergency care may become necessary in cases of very heavy bleeding or fever.

While bed rest has been advocated to prevent miscarriage, and in one study possibly helped when small subchorionic hematoma had been found on ultrasound scans,[67] the prevailing opinion is that this is of no proven benefit.[68]

There is not good evidence that the use of Rho(D) immune globulin after a spontaneous miscarriage is needed and a Cochrane review recommends that local practices be followed.[69] In the UK, Rho(D) immune globulin is recommended in Rh-negative people after 12 weeks gestational age and before 12 weeks gestational age in those who need surgery or medication to complete the miscarriage.[70]

Methods

No treatment is necessary for a diagnosis of complete miscarriage (so long as ectopic pregnancy is ruled out). In cases of an incomplete miscarriage, empty sac, or missed abortion there are three treatment options: watchful waiting, medical management, and surgical treatment. With no treatment (watchful waiting), most miscarriages (65–80%) will pass naturally within two to six weeks.[71] This treatment avoids the possible side effects and complications of medications and surgery,[72] but increases the risk of mild bleeding, need for unplanned surgical treatment, and incomplete miscarriage. Medical treatment usually consists of using misoprostol (a prostaglandin) to contract the uterus, pushing the products of conception out of the cervix. This works within a few days in 95% of cases.[71] Surgical treatment for a miscarriage can be used to complete the removal of pregnancy tissue, and shortens the duration and severity of bleeding and pain. Vacuum aspiration or sharp curettage can be used, though vacuum aspiration is lower-risk and more common.[71]

Delayed and incomplete miscarriage

In delayed or incomplete miscarriage, management depends on the amount of material left in the uterus as measured with ultrasonography. Treatment can include surgical removal of the retained pregnancy with vacuum aspiration or misoprostol.[73]

Prognosis

Psychological

A cemetery for miscarried fetuses, stillborn babies, and babies who have died soon after birth.

Some people struggle emotionally following a miscarriage.[3] A questionnaire for those who had experienced a miscarriage showed that more than half (55%) presented with significant psychological distress immediately, while 25% did at 3 months; 18% showed psychological symptoms at 6 months, and 11% at 1 year after miscarriage.[74]

Besides the feeling of loss, a lack of understanding by others can affect someone. People who have not experienced a miscarriage themselves may find it difficult to empathize, which can lead to unrealistic expectations of recovery. The pregnancy and the miscarriage may cease to be mentioned in conversations, often because the subject is too painful, causing feelings of isolation. Inappropriate or insensitive responses from medical professionals can add to the distress and trauma experienced, so in some cases attempts have been made to draw up a standard code of practice.[75]

Interaction with pregnant women and newborn children may understandably be painful for those who have experienced miscarriage. Sometimes this makes interaction with friends, acquaintances, and family very difficult.[76] People who have lost a desired pregnancy may find psychological comfort in memorializing their loss.[77]

Later cardiovascular disease

There is a significant association between miscarriage and later development of coronary artery disease, but not of cerebrovascular disease.[78] The association does not imply causation, but may be a result of an underlying factor that increases the risk of both.

Epidemiology

Among those who know they are pregnant, the miscarriage rate is roughly 10% to 20%, while rates among all fertilized zygotes is around 30% to 50%.[1][5][20]

Determining the precise rate is not possible as a large number of miscarriages occur before pregnancies become established and before the person is aware they are pregnant.[79] In addition, those with bleeding in early pregnancy may seek medical care more often than those not experiencing bleeding.[79] Some studies have attempted to account for this by recruiting people who are planning pregnancies and testing for very early pregnancy, although these would also not be representative of the wider population.[79] A systematic review found that the cumulative risk of miscarriage between 5 and 20 weeks of gestation varied from 11% to 22% in studies assessing miscarriage rates.[79] Up to the 13th week of pregnancy, the risk of miscarriage each week was around 2%, dropping to 1% in week 14 and reducing slowly between 14 and 20 weeks.[79]

The prevalence of miscarriage increases with the age of both parents.[79][80][81][82] In a Danish register-based study where the prevalence of miscarriage was 11%, the prevalence rose from 9% at 22 years of age to 84% by 48 years of age.[80] Another study found that when either parent was over the age of 40, the rate of known miscarriages doubled.[20]

Terminology

While miscarriage is a term for early pregnancy loss, it is also frequently known in medical literature as "spontaneous abortion".[83] Those fetuses born before 24 weeks of gestation rarely survive.[84] However, the designation "fetal death" applies variably in different countries and contexts, sometimes incorporating weight, and gestational age from 16 weeks in Norway, 20 weeks in the US and Australia, 24 weeks in the UK to 26 weeks in Italy and Spain.[84][85][86] A fetus that died before birth after this gestational age may be referred to as a stillbirth.[84] Under UK law, all stillbirths should be registered,[87] although this does not apply to miscarriages.

The medical terminology applied to experiences during early pregnancy has changed over time.[88] Before the 1980s, health professionals used the phrase "spontaneous abortion" for a miscarriage and "induced abortion" for a termination of the pregnancy.[88][89] In places where induced abortion is illegal or carries heavy social stigma, suspicion may surround miscarriage, complicating an already sensitive language issue.[90] Research suggests that some dislike the term spontaneous abortion for miscarriage, some are indifferent and some prefer it.[91] These preferences may reflect cultural differences.[91]

In the late 1980s and 1990s, doctors became more conscious of their language in relation to early pregnancy loss. Some medical authors advocated change to use of "miscarriage" instead of "spontaneous abortion" because they argued this would more respectful and help ease a distressing experience.[92][93][94] The change was being recommended by some by the profession in Britain in the late 1990s.[95] In 2005 the European Society for Human Reproduction and Embryology (ESHRE) published a paper aiming to facilitate a revision of nomenclature used to describe early pregnancy events.[61]

Historical analysis of the medical terminology applied to early pregnancy loss in Britain has shown that the use of "miscarriage" (instead of "spontaneous abortion") by doctors only occurred after changes in legislation (in the 1960s) and developments in ultrasound technology (in the early 1980s) allowed them to identify miscarriages.[88] in countries where pregnancy termination remains illegal doctors may still not distinguish between "spontaneous" and "induced" abortions in clinical practice.

Other animals

Miscarriage occurs in all animals that experience pregnancy, though in such contexts it is more commonly referred to as a "spontaneous abortion" (the two terms are synonymous). There are a variety of known risk factors in non-human animals. For example, in sheep, miscarriage may be caused by crowding through doors, or being chased by dogs.[96] In cows, spontaneous abortion may be caused by contagious disease, such as brucellosis or Campylobacter, but often can be controlled by vaccination.[97] Other diseases are also known to make animals susceptible to miscarriage. Spontaneous abortion occurs in pregnant prairie voles when their mate is removed and they are exposed to a new male,[98] an example of the Bruce effect, although this effect is seen less in wild populations than in the laboratory.[99] Female mice who had spontaneous abortions showed a sharp rise in the amount of time spent with unfamiliar males preceding the abortion than those who did not.[100]

See also

References

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