Aetiology
The majority of miscarriages (around 80%) occur in the first trimester.[11][12] Approximately 1% to 2% of all second trimester pregnancies miscarry before 24 weeks.[13] The aetiology can be divided into embryonic and/or maternal factors, although it is more likely to be multi-factorial.
A woman who has experienced multiple miscarriages discusses with a GP how best to approach conversations around the cause of miscarriage and the importance of avoiding blame.
Embryonic factors:
The majority of first-trimester miscarriages (6 to 12 weeks) are attributable to primary embryonic disease, disorder, or damage[17]
Up to 80% of early pregnancy tissue from first-trimester miscarriages is chromosomally abnormal.[18] Early pregnancy tissue from recurrent miscarriages demonstrates higher frequencies of chromosomal anomalies.[19] Although skewed X chromosome inactivation was thought to be a specific genetic aetiological factor, studies have refuted this.[20][21] A study found that miscarriage appeared to be twice as likely in couples who had a first-degree female relative that had experienced spontaneous miscarriage compared with couples who had a third-degree female relative that had experienced spontaneous miscarriage. Therefore, positive family history for spontaneous miscarriage may be a causal factor for recurrent spontaneous miscarriage; however, further studies are required.[22]
Embryonic malformations, especially of the central nervous system, are frequent in spontaneously miscarried pregnancies.
Maternal factors:
Many second-trimester miscarriages (13 to 22 weeks) are due to maternal genital tract dysfunction or systemic illness. It has been suggested that the overwhelming majority of cases are associated with ascending infection from the lower genital tract. If confirmed in local and regional outcome data, it highlights the need for a significant shift in preventative and pre-emptive strategies.[23]
Maternal exposure to high doses of toxic agents, irradiation or chemotherapy, major endocrinopathies, immunological diseases, and trans-placental infections have all been implicated.[8] Asymptomatic bacterial vaginosis may have an important role in second-trimester miscarriage.[24][25] Large sub-mucous fibroids compromise early embryonic angiogenesis and micro-haemodynamics. The antiphospholipid antibody syndrome may underlie both first- and second-trimester recurrent miscarriage.[26] Cervical incompetence, insufficiency, or weakness account for most recurrent second-trimester miscarriages. Previous consecutive pregnancies might have been delivered prematurely.
One review of published articles on herbal/ traditional medicines ingested by pregnant women found that some may have abortifacient properties, including aloe vera, bitter lemon, and celery.[27] It remains unclear how the use of these substances, combined with substance interactions and patient heterogeneity, might affect the outcome of early pregnancies. It is clear, therefore, that further studies are required.
Using a predictive model incorporating nuchal translucencies, pregnancy-associated plasma protein A, and maternal characteristics in singleton pregnancies between 11 and 14 weeks (comparing 2396 women who had chorionic villus sampling to 33,856 who did not, at the same gestational age), the risk of miscarriage was increased in pregnancies resulting from ovulation induction, fetuses with high nuchal translucency, and in women with pre-existing diabetes mellitus.[28]
The severity, ongoing therapy, and other confounding factors of a particular maternal disorder may be more important than the existence of the disease itself.
In practice, the most common causes of second-trimester miscarriage are cervical incompetence, weakness, or insufficiency following invasive fetal diagnostic procedures; trans-placental fetal viral infection; trans-placental fetal bacterial infection; severe rhesus isoimmunisation.
Pathophysiology
The pathophysiology is unclear. Vaginal bleeding originates from the decidual implantation site or from the placenta. The onset of bleeding may follow or precede fetal demise. Immunogenic, hypoxic, and vascular causes lead to a final common pathway of severe villous or placental dysfunction resulting in embryonic or fetal demise. A possible hypothesis is that local bleeding of variable severity accompanies all miscarriages, but its persistence is revealed, concealed, or followed by fetal demise. This hypothesis is consistent with findings of abnormal vascular development at the maternal-embryonic interface.[29][30] Local dysfunction of implantation-modulating factors as well as systemic abnormalities have also been demonstrated.[31] The two major directions of current research appear to be the assessment of natural killer cell activity and impaired decidualisation.[32][33]
Classification
World Health Organization classification of the stages of spontaneous miscarriage[1]
Classified into the following categories:
Threatened miscarriage: a threat of miscarriage that exists when unprovoked vaginal bleeding, with or without lower abdominal pain, occurs in a pregnancy of 20-24 weeks (gestation depends on country), and where pregnancy may continue.
Inevitable miscarriage: a miscarriage deemed inevitable when specific clinical features indicate that a pregnancy is in the process of physiological expulsion from within the uterine cavity (pregnancy will not continue and will proceed to incomplete or complete miscarriage).
Incomplete miscarriage: a miscarriage in which early pregnancy tissue is partially expelled. It is possible that many incomplete miscarriages are unrecognised missed miscarriages.
Complete miscarriage: a miscarriage in which early pregnancy tissue is completely expelled.[Figure caption and citation for the preceding image starts]: The natural course of miscarriageFrom: Ankum WM, Wieringa-de Ward M, Bindels PJE. BMJ 2001 Jun 2;322(7298):1343-6. [Citation ends].
Other types of miscarriage
Missed miscarriage (early embryonic/fetal demise):[5]
A miscarriage with ultrasound features consistent with a non-viable or non-continuing pregnancy, even in the absence of clinical features. Missed miscarriage is usually an incidental finding because there is rarely any indication that anything was wrong with the pregnancy. Some women do recall a transient and/or brownish vaginal discharge, or a vague reduction in symptoms of early pregnancy.
Recurrent miscarriage:[3]
The spontaneous loss of ≥3 consecutive pregnancies before 20-24 completed weeks (gestation depends on country) is regarded as recurrent miscarriage.
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