Miscarriage

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For usage in law, see Miscarriage of justice.
Miscarriage
Classification and external resources

A human embryo at about six weeks after conception, i.e. eight weeks from the last menstrual period (LMP)
ICD-10 O03
ICD-9 634
DiseasesDB 29
MedlinePlus 001488
eMedicine topic list
MeSH D000022

A miscarriage is the natural death of an unborn human while it is still an embryo or fetus in its mother's womb. Such a death takes place in the early stages of prenatal development prior to fetal viability (the stage of potential independent survival). The danger of a miscarriage is the most common complication of early pregnancy in humans.[1]

Terminology

Miscarriage is the accepted formal term for early pregnancy loss before fetal viability.[2] Those born before 24 weeks of gestation rarely survive.[3] 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.[3][4][5] A fetus that died before birth after this gestational age may be referred to as a stillbirth.[3] Under UK law, all stillbirths should be registered,[6] although this does not apply to miscarriages.

The medical terminology applied to women's experiences during early pregnancy has changed over time.[7] Before the 1980s, health professionals used the phrase "spontaneous abortion" for a miscarriage and "induced abortion" for a willful termination of the pregnancy (abbreviated to TOP).[7][8] When terminations of pregnancy needed to be hidden, suspicion sometimes surrounded miscarriage, complicating an already sensitive language issue.[9] Research suggests that some women dislike the term abortion for miscarriage, some are indifferent and some prefer it.[10] These preferences may reflect cultural differences, but more research would be needed to clarify this.[10]

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 "abortion" because they argued this would more respectful to women's feelings and help ease a distressing experience.[11][12][13] The change was being formally recognized by the profession in England in the late 1990s.[14] 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.[15] The preferred terminology for "missed abortion" is delayed or silent miscarriage.[15][16]

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.[7] in countries where pregnancy termination remains illegal doctors may still not distinguish between "spontaneous" and "induced" abortions in clinical practice.

Signs and symptoms

The most common symptom of a miscarriage is bleeding;[17] 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.[18] Symptoms other than bleeding are not statistically related.[17]

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.

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.

Psychological

Although a woman generally physically recovers from a miscarriage quickly, some struggle to recover emotionally.[19] A questionnaire (GHQ-12 General Health Questionnaire) study following women having miscarried showed that more than half (55%) of them 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.[20]

A cemetery for miscarried babies

Besides the feeling of loss, a lack of understanding by others is often important. People who have not experienced it themselves may find it difficult 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 the miscarriage cease to be mentioned in conversations, often because the subject is too painful. This may make the woman feel particularly isolated. 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.[21]

Interaction with pregnant women and newborn children may understandably be painful for parents who have experienced miscarriage. Sometimes this makes interaction with friends, acquaintances, and family very difficult.[22]

Some women gain emotional support and feel less alone in their grief through miscarriage self-help and support groups, and for others, online forums or message boards for pregnancy loss play a role in coping and recovery.[19]

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%).[23][24]

First trimester

Most clinically apparent miscarriages (two-thirds to three-quarters in various studies) occur during the first trimester.[25][26] 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."[27]

Chromosomal abnormalities are found in more than half of embryos miscarried in the first 13 weeks.[28] 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.[29] Genetic problems are more likely to occur with older parents; this may account for the higher rates observed in older women.[30]

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.[29] No study has shown that general first-trimester progesterone supplements reduce the risk however, (when a mother might already be losing her baby),[31] and even the identification of problems with the luteal phase as a contributing factor has been questioned.[32]

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.[29] These conditions also may contribute to premature birth.[25]

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.[33]

Risk factors

Pregnancies involving more than one fetus are considered at increased risk.[29]

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.[34] 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.[35] Two studies suggested treatment with the drug metformin significantly lowers the rate of miscarriage in women with PCOS,[36][37] but the quality of these studies has been questioned.[38] A 2006 review of metformin treatment in pregnancy found insufficient evidence of safety, and did not recommend routine treatment with the drug.[39] In 2007 the Royal College of Obstetricians and Gynaecologists also recommended against use of the drug to prevent miscarriage.[38]
  • 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.[41][42] Further research also has suggested that autoimmune disease may cause genetic abnormalities in embryos which in turn may lead to miscarriage.[43]

Smoking

See also: Smoking and pregnancy

Tobacco (cigarette) smokers have an increased risk of miscarriage.[44] An increase in the rates also is associated with the father being a cigarette smoker.[45] 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

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.[46]

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.[47] NVP is generally interpreted as a defense mechanism against the ingestion by the mother 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.[48]

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.[49] 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).[50] 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.[51]

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.[52]

Cocaine use increases the rates.[44] Physical trauma, exposure to environmental toxins, and use of an IUD during the time of conception have also been linked to increased risk.[53]

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.[54] On the other hand, no increased risk was identified for preterm birth after LEEP.[54]

Antidepressants, especially paroxetine and venlafaxine, can lead to a miscarriage.[55][56]

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.[57] When chromosomal abnormalities are found in more than one miscarriage, genetic testing of both parents may be done.[57]

Ultrasound criteria

A study in The New England Journal of Medicine has suggested that miscarriage should be diagnosed only if any of the following criteria are met upon ultrasonography visualization:[58]

  • 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:[58]

  • 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,[59] 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.
  • A complete miscarriage is when all products of conception have been expelled. Products of conception 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.
  • An incomplete miscarriage occurs when some tissue has been passed, but some remains in utero.[60]
  • 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.

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

  • A 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,[61] 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%.[61] 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:[62]

  • 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
O03.0-O06.4
O02.1
O20.0

Prevention

Prevention of miscarriage is mainly based on avoiding or mitigating any risk factors of it. Currently there is no known way to prevent an impending miscarriage. Identifying the cause of the miscarriage may help prevent it from happening again in a future pregnancy. In recurrent miscarriage, various tests are indicated to identify any underlying cause. Vitamin supplementation has not been found to be effective to prevent miscarriage.[63]

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.[17] 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.[64][65]

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,[66] the prevailing opinion is that this is of no proven benefit.[67]

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.[68] This path avoids the side effects and complications possible from medications and surgery,[69] but increases the risk of mild bleeding, need for unplanned surgical treatment, and incomplete miscarriage.[68]
  • 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.[68]
  • Surgical treatment (most commonly vacuum aspiration, sometimes referred to as a D&C or D&E) 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.[68] 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. D&C, however, has a higher risk of complications, 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.

In delayed miscarriage

In delayed miscarriage (also called missed abortion), the Royal Women's Hospital recommendations of management depend on the findings in ultrasonography:[70]

  • Gestational sac greater than 30-35mm, embryo larger than ~25mm (corresponding to 9+0 weeks of gestational age): Surgery is recommended. It poses a high risk of pain and bleeding with passage of products of conception. Alternative methods may still be considered.
  • Gestational sac 15-35mm, embryo smaller than 25mm (corresponding to between 7 and 9+0 weeks of gestational age): Medication is recommended. Surgery or expectant management may be considered.
  • Gestational sac smaller than 15-20mm, corresponding to a gestational age of less than 7 weeks: Expectant management or medication is preferable. The products of conception may be difficult to find surgically with a considerable risk of failed surgical procedure.

In incomplete miscarriage

In incomplete miscarriage, the Royal Women's Hospital recommendations of management depend on the findings in ultrasonography:[70]

  • Retained products of conception smaller than 15mm: Expectant management is generally preferable. There is a high chance of spontaneous expulsion.
  • Retained products of conception measuring between 15 and 20mm: Medical or expectant management are recommended. Surgery should only be considered upon specific indication.
  • At retained products of conception measuring over 35 to 50mm, the following measures are recommended:
  • Administration of misoprostol to hasten passage of products of conception.
  • Admission to inpatient care for observation for a few hours or overnight until the majority of the products of conception has passed and bleeding subsided.
  • After apparent failure of misoprostol, a gynecologic examination should be done prior to considering surgical evacuation of the uterus or the patient leaving the hospital.

Epidemiology

Determining the precise prevalence of miscarriage is not possible, because miscarriages occur before pregnancies become established and before women are aware they are pregnant.[71] In addition, women with bleeding in early pregnancy may attend for medical care more often than women not experiencing bleeding.[71] 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.[71] 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.[71] 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.[71]

The prevalence of miscarriage increases with the age of the mother[71][72] and the father.[73][74] 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.[72]

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 for it in non-human animals. For example, in sheep, it may be caused by crowding through doors, or being chased by dogs.[75] In cows, spontaneous abortion may be caused by contagious disease, such as Brucellosis or Campylobacter, but often can be controlled by vaccination.[76] Other diseases are also known to make animals susceptible. Spontaneous abortion occurs in pregnant prairie voles when their mate is removed and they are exposed to a new male,[77] an example of the Bruce effect, although this effect is seen less in wild populations than in the laboratory.[78] 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 abort.[79]

Later cardiovascular disease

There is a significant association between miscarriage and later development of coronary artery disease, but not of cerebrovascular disease.[80] The association does not imply causation, but may be a result of an underlying factor that increases the risk of both.

See also

References

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  2. ↑ Farquharson, RG; Jauniaux, E; Exalto, N; ESHRE Special Interest Group for Early Pregnancy, (SIGEP) (November 2005). "Updated and revised nomenclature for description of early pregnancy events.". Human reproduction (Oxford, England) 20 (11): 3008–11. doi:10.1093/humrep/dei167. PMID 16006453. 
  3. ↑ 3.0 3.1 3.2 Mohangoo, AD; Blondel, B; Gissler, M; Velebil, P; Macfarlane, A; Zeitlin, J; Euro-Peristat Scientific, Committee (2013). "International comparisons of fetal and neonatal mortality rates in high-income countries: should exclusion thresholds be based on birth weight or gestational age?". PLoS ONE 8 (5): e64869. doi:10.1371/journal.pone.0064869. PMID 23700489. 
  4. ↑ Li, Z; Zeki, R; Hilder, L; Sullivan, EA (2012). "Australia's Mothers and Babies 2010". Perinatal statistics series no. 27. Cat. no. PER 57. Australian Institute of Health and Welfare National Perinatal Statistics Unit, Australian Government. Retrieved 4 July 2013. 
  5. ↑ Royal College of Obstetricians and Gynaecologists UK (April 2001). "Further Issues Relating to Late Abortion, Fetal Viability and Registration of Births and Deaths". Royal College of Obstetricians and Gynaecologists UK. Retrieved 4 July 2013. 
  6. ↑ https://www.gov.uk/register-stillbirth | date=May 2013
  7. ↑ 7.0 7.1 7.2 Moscrop, A. (2013). "'Miscarriage or abortion?' Understanding the medical language of pregnancy loss in Britain; a historical perspective". Medical Humanities. doi:10.1136/medhum-2012-010284. PMID 23429567. 
  8. ↑ "Standard terminology for reporting of reproductive health statistics in the United States.". Public Health Report 103 (5): 464–71. 1988. PMC 1478116. PMID 3140271. 
  9. ↑ Gardner, RF (Jul 1, 1972). "Abortion and miscarriage.". British Medical Journal 3 (5817): 51. PMID 5039574. 
  10. ↑ 10.0 10.1 Chalmers, B (May 1992). "Terminology used in early pregnancy loss.". British journal of obstetrics and gynaecology 99 (5): 357–8. PMID 1622902. 
  11. ↑ Beard, RW; Mowbray, JF; Pinker, GD (1985). "Miscarriage or abortion". Lancet 2 (8464): 1122–3. doi:10.1016/S0140-6736(85)90709-3. PMID 2865589. 
  12. ↑ Hutchon, David J R; Cooper, Sandra (1998). "Terminology for early pregnancy loss must be changed". BMJ 317 (7165): 1081. doi:10.1136/bmj.317.7165.1081. PMC 1114078. PMID 9774309. 
  13. ↑ Hutchon, David J.R. (1998). "Understanding miscarriage or insensitive abortion: Time for more defined terminology?". American Journal of Obstetrics and Gynecology 179 (2): 397–8. doi:10.1016/S0002-9378(98)70370-9. PMID 9731844. 
  14. ↑ Hutchon, DJ; Cooper, S (Oct 17, 1998). "Terminology for early pregnancy loss must be changed.". BMJ (Clinical research ed.) 317 (7165): 1081. doi:10.1136/bmj.317.7165.1081. PMC 1114078. PMID 9774309. 
  15. ↑ 15.0 15.1 Farquharson, R. G.; Jauniaux, E; Exalto, N; ESHRE Special Interest Group for Early Pregnancy (2005). "Updated and revised nomenclature for description of early pregnancy events". Human Reproduction 20 (11): 3008–11. doi:10.1093/humrep/dei167. PMID 16006453. 
  16. ↑ Hutchon, DJ (June 1997). "Missed abortion versus delayed miscarriage.". British journal of obstetrics and gynaecology 104 (6): 753. PMID 9197887. 
  17. ↑ 17.0 17.1 17.2 Gracia, Clarisa R.; Sammel, Mary D.; Chittams, Jesse; Hummel, Amy C.; Shaunik, Alka; Barnhart, Kurt T. (2005). "Risk Factors for Spontaneous Abortion in Early Symptomatic First-Trimester Pregnancies". Obstetrics & Gynecology 106 (5, Part 1): 993–9. doi:10.1097/01.AOG.0000183604.09922.e0. PMID 16260517. 
  18. ↑ Everett, C. (1997). "Incidence and outcome of bleeding before the 20th week of pregnancy: Prospective study from general practice". BMJ 315 (7099): 32–4. doi:10.1136/bmj.315.7099.32. PMC 2127042. PMID 9233324. 
  19. ↑ 19.0 19.1 Gold, KJ; Boggs, ME; Mugisha, E; Palladino, CL (2012 Jan-Feb). "Internet message boards for pregnancy loss: who's on-line and why?". Women's health issues : official publication of the Jacobs Institute of Women's Health 22 (1): e67–72. doi:10.1016/j.whi.2011.07.006. PMID 21907592. 
  20. ↑ Lok, Ingrid Hung; Yip, Alexander Shing-Kai; Lee, Dominic Tak-Sing; Sahota, Daljit; Chung, Tony Kwok-Hung (2010). "A 1-year longitudinal study of psychological morbidity after miscarriage". Fertility and Sterility 93 (6): 1966–75. doi:10.1016/j.fertnstert.2008.12.048. PMID 19185858. 
  21. ↑ Miscarriage Standard Code of Practice
  22. ↑ David Vernon (2005). "Having a Great Birth in Australia". 
  23. ↑ Tabor, A; Alfirevic, Z (2010). "Update on procedure-related risks for prenatal diagnosis techniques.". Fetal diagnosis and therapy 27 (1): 1–7. doi:10.1159/000271995. PMID 20051662. 
  24. ↑ Agarwal, K; Alfirevic, Z (August 2012). "Pregnancy loss after chorionic villus sampling and genetic amniocentesis in twin pregnancies: a systematic review.". Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology 40 (2): 128–34. doi:10.1002/uog.10152. PMID 22125091. 
  25. ↑ 25.0 25.1 Rosenthal, M. Sara (1999). "The Second Trimester". The Gynecological Sourcebook. WebMD. Retrieved December 18, 2006. 
  26. ↑ Francis, O (1959). "An analysis of 1150 cases of abortions from the Government R.S.R.M. Lying-in Hospital, Madras". Journal of obstetrics and gynaecology of India 10 (1): 62–70. PMID 12336441. 
  27. ↑ Storck, Susan (2012-11-08). "Miscarriage". National Institute of Health. Retrieved 2013-09-01. 
  28. ↑ Kajii, T; Ferrier, A; Niikawa, N; Takahara, H; Ohama, K; Avirachan, S (1980). "Anatomic and chromosomal anomalies in 639 spontaneous abortuses". Human Genetics 55 (1): 87–98. doi:10.1007/BF00329132. PMID 7450760. 
  29. ↑ 29.0 29.1 29.2 29.3 29.4 29.5 "Miscarriage: Causes of Miscarriage". HealthCentral.com. Retrieved July 26, 2012. taken word-for-word from pp. 347–9 of: "What To Do When Miscarriage Strikes". The PDR Family Guide to Women's Health and Prescription Drugs. Montvale, NJ: Medical Economics. 1994. pp. 345–50. ISBN 1-56363-086-9. 
  30. ↑ "Pregnancy Over Age 30". MUSC Children's Hospital. Archived from the original on November 13, 2006. Retrieved December 18, 2006. 
  31. ↑ Wahabi, Hayfaa A; Abed Althagafi, Nuha F; Elawad, Mamoun; Al Zeidan, Rasmieh A (2007). "Progestogen for treating threatened miscarriage". In Wahabi, Hayfaa A. Cochrane Database of Systematic Reviews (12): CD005943. doi:10.1002/14651858.CD005943.pub2. PMID 22161393. 
  32. ↑ Bukulmez, Orhan; Arici, Aydin (2004). "Luteal phase defect: Myth or reality". Obstetrics and Gynecology Clinics of North America 31 (4): 727–44, ix. doi:10.1016/j.ogc.2004.08.007. PMID 15550332. 
  33. ↑ Peng, Hong Qi; Smith-Levitin, Michelle; Rochelson, Burton; Kahn, Ellen (2006). "Umbilical Cord Stricture and Overcoiling Are Common Causes of Fetal Demise". Pediatric and Developmental Pathology 9 (1): 14–9. doi:10.2350/05-05-0051.1. PMID 16808633. 
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