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miscarriages

Posted on: April 11, 2015


miscarriage is the natural death of an embryo or fetus in the womb. It takes place in the early stages of prenatal development prior to fetal viability (the stage of potential independent survival). Among women who know they are pregnant, the miscarriage rate is roughly 15-20% and it is the most common complication of early pregnancy in humans.

CAUSES

Among women who know they are pregnant, the miscarriage rate is roughly 15-20%. 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%).

First trimester

Most clinically apparent miscarriages (two-thirds to three-quarters in various studies) occur during the first trimester. The National Institutes of Health report that “around half of all fertilized eggs die and are lost (aborted) spontaneously, usually before the woman knows she is pregnant.”

Chromosomal abnormalities are found in more than half of embryos miscarried in the first 13 weeks. 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 a woman suffering repeated miscarriages, or if one of the parents has a child or other relatives with birth defects. Genetic problems are more likely to occur with older parents; this may account for the higher rates observed in older women.

Progesterone deficiency may be another cause. 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. No study has shown that general first-trimester progesterone supplements reduce the risk however, (when a mother might already be losing her baby), and even the identification of problems with the luteal phase as a contributing factor has been questioned.

Second trimester

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

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.

Risk factors

Multiple pregnancy

Pregnancies of more than one fetus, i.e. twins, triplets, etc., are considered at increased risk. The more fetuses in the womb, the higher the risk

Intercurrent diseases

Several intercurrent diseases in pregnancy can potentially increase the risk of miscarriage, including:

  • Diabetes mellitus; The risk of miscarriage is increased in women with poorly controlled insulin-dependent diabetes mellitus. This 1998 prospective study found that the risk increased by 3.1% (over the background risk of about 16%) for each standard deviation in glycosylated haemoglobin above the normal range. The risk was not found to be significantly increased in women with good glycaemic control in early pregnancy.
  • Polycystic ovary syndrome, which may increase the risk of miscarriage, but this is disputed. Two studies suggested treatment with the drug metformin significantly lowers the rate of miscarriage in women with PCOS, but the quality of these studies has been questioned. A 2006 review of metformin treatment in pregnancy found insufficient evidence of safety, and did not recommend routine treatment with the drug. In 2007 the Royal College of Obstetricians and Gynaecologists also recommended against use of the drug to prevent miscarriage.
  • Hypothyroidism; 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. 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.
  • Vertically transmitted infections; Certain vertically transmitted infections (such as rubella and chlamydia) increase the risk.
  • Autoimmune disease; Some research suggests autoimmunity 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. Further research also has suggested that autoimmune disease may cause genetic abnormalities in embryos which in turn may lead to miscarriage. As an example, Celiac disease increases the risk of miscarriage by an odds ratio of approximately 1.4.

Smoking

Tobacco (cigarette) smokers have an increased risk of miscarriage. An increase in the rates also is associated with the father being a cigarette smoker. 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.

Age

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

Several other factors have been correlated with higher rates in some research, but whether they cause the 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 may introduce bias) rather than prospective (beginning the study before the women became pregnant), or both. A greater correlation has been shown in the following categories, however.

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. 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 women 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 women were recruited for the study, and no information on nausea during pregnancy or exercise habits prior to pregnancy was collected.

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 women found that those who reported consuming 200& mg or more of caffeine per day experienced a 25% 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 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. 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). 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.

Other

Sexual intercourse during the first trimester has often been said or assumed by doctors to be a cause of miscarriage. However the association has never been proved or disproved. Physical trauma, exposure to environmental toxins, and use of an IUD during the time of conception have also been linked to increased risk.

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 women 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. On the other hand, no increased risk was identified for preterm birth after LEEP.

Antidepressants, especially paroxetine and venlafaxine, can lead to a miscarriage.

DIAGNOSIS

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. As many as half the embryos miscarried have a chromosomal abnormality. When chromosomal abnormalities are found in more than one miscarriage, genetic testing of both parents may be done.

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:

  • Crown-rump length of at least 7& mm and no heartbeat.
  • Mean gestational sac diameter of at least 25& mm and no embryo.
  • Absence of embryo with heartbeat at least 2 weeks after an ultrasound scan that showed a gestational sac without a yolk sac.
  • Absence of embryo with heartbeat at least 11 days after an ultrasound scan that showed a gestational sac with a yolk sac.

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

  • Crown-rump length of less than 7& mm and no heartbeat.
  • Mean gestational sac diameter of 16-24& mm and no embryo.
  • Absence of embryo with heartbeat 7-13 days after an ultrasound scan that showed a gestational sac without a yolk sac.
  • Absence of embryo with heartbeat 7-10 days after a scan that showed a gestational sac with a yolk sac.
  • Absence of embryo at least 6 weeks after last menstrual period.
  • Amniotic sac seen adjacent to yolk sac, and with no visible embryo.
  • Yolk sac of more than 7& mm.
  • Small gestational sac compared to embryo size (less than 5& mm difference between mean sac diameter and crown-rump length).

Classification

The clinical presentation of a threatened miscarriage 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:

  • An empty sac is a condition where the gestational sac develops normally, while the embryonic part of the pregnancy is either absent or stops growing very early. Other terms for this condition are blighted ovum and anembryonic pregnancy.
  • An inevitable miscarriage describes a condition in which the cervix has already dilated open, but the fetus has yet to be expelled. This usually will progress to a complete miscarriage. The fetal heart beat may have been shown to have stopped, but this is not part of the criteria.
  • complete miscarriage is when all products of conception have been expelled. Products of conceptionmay 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 any ectopic one.
  • An incomplete miscarriage occurs when some products of conception have been passed, but some remainsin utero. 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 power Doppler may be better in confirming the presence of significant retained products of conception in the uterine cavity. In cases of uncertainty, there is a need to exclude an ectopic pregnancy, such as by serial beta-hCG measurements.

    • 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 orsilent miscarriage.

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

    • septic miscarriage occurs when the tissue from a missed or incomplete miscarriage becomes infected. The infection of the uterus carries risk of spreading infection (septicaemia) and is a grave risk to the life of the woman.
    • Recurrent pregnancy loss(RPL) or recurrent miscarriage is the occurrence of three consecutive miscarriages. If the proportion of pregnancies ending in miscarriage is 15% and assuming that miscarriages are independent events, 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%. A large majority (85%) of women who have had two miscarriages will conceive and carry normally afterward.

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

      • At up to six weeks only small blood clots may be present, possibly accompanied by mild cramping or period pain.
      • At 6 to 13 weeks a clot will form around the embryo or fetus, and the placenta, with many clots up to 5& cm in size being expelled prior to completion of the process. The process may take a few hours or be on and off for a few days. Symptoms vary widely and may include vomiting and loose bowels, possibly due to physical discomfort.
      • At more than 13 weeks the fetus may be passed easily from the uterus, however the placenta is more likely to be fully or partially retained in the uterus, resulting in an incomplete miscarriage. The physical signs of bleeding, cramping, and pain may be similar to an early stage abortion, but sometimes more severe and labor-like.

      ICD10 codes

      • Habitual abortion
      • Incomplete abortion
      • Missed abortion
      • Threatened abortion
      N96<br> O03.0-O06.4<br> O02.1<br> O20.0

EPIDEMIOLOGY

Determining the precise prevalence of miscarriage is not possible, because a large number of miscarriages occur before pregnancies become established and before women are aware they are pregnant. In addition, women with bleeding in early pregnancy may attend for medical care more often than women not experiencing bleeding. Some studies have attempted to account for this by recruiting women who are planning pregnancies and testing for very early pregnancy, although these would also not be representative of the wider population. 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. 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.

The prevalence of miscarriage increases with the age of the mother and the father. In a Danish register-based study where the prevalence of miscarriage was 11%, the prevalence rose from 9% in women at 22 years of age to 84% by 48 years of age.

SIGNS AND SYMPTOMS

The most common symptom of a miscarriage is vaginal bleeding. 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 women who seek clinical treatment for bleeding during pregnancy, about half will miscarry. Symptoms other than bleeding are not statistically related.

Miscarriage may be detected during an ultrasound exam, or through serial human chorionic gonadotropin (HCG) testing. Women pregnant from assisted reproductive technology methods, and women with a history of aborting, may be monitored closely and so detection is sooner than women without such monitoring.

It is estimated about half of early miscarriages will be fully expelled naturally. Several medical options exist for managing documented nonviable pregnancies that have not been expelled naturally, such as medicinal treatment or a dilation and curettage (D&C) procedure. An ERPC, or evacuation of retained products of conception, may be performed to remove the remains of a pregnancy and the placental tissue from the uterus.>

MANAGEMENT

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. 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.

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 seeking emergency medical attention is recommended.

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

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:

  • With no treatment (watchful waiting), most of these cases (65-80%) will pass naturally within two to six weeks. This path avoids the side effects and complications possible from medications and surgery, but increases the risk of mild bleeding, need for unplanned surgical treatment, and incomplete miscarriage.
    • Medical management usually consists of using misoprostol (a prostaglandin, brand name Cytotec) to encourage completion of the natural process. About 95% of cases treated with misoprostol will complete within a few days.
    • Surgical treatment is the fastest way to complete the process. It also shortens the duration and heaviness of bleeding, and avoids the physical pain associated with the miscarriage. In cases of repeated spontaneous abortions, D&C is also the most convenient way to obtain tissue samples for karyotype analysis (cytogenetic or molecular), although it is also possible to do with expectant and medical management, including the following techniques:
    • Vacuum aspiration, sometimes referred to as dilation and evacuation (D&E), uses aspiration to remove uterine contents through the cervix.
    • Dilation and curettage (D&C), which involves dilation (widening/opening) of the cervix and surgical removal of part of the lining of the uterus and/or contents of the uterus by scraping and scooping (curettage). D&C has a higher risk of complications compared to non-surgical treatment, including risk of injury to the cervix (e.g. cervical incompetence) and uterus, perforation of the uterus, and potential scarring of the intrauterine lining (Asherman’s syndrome). This is an important consideration for women who would like to have children in the future and want to preserve their fertility and reduce the chance of future pregnancy complications.
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