Miscarriage (Abortion): Causes

Pathogenesis (development of disease)

In miscarriage, a multifactorial event is present. Several factors can be distinguished, such as maternal (maternal), genital, and extragenital factors, as well as immunologic, fetoplacental, or andrologic (male-related) factors. Chromosomal disorders of the embryo or fetus are present in 50-70% of all spontaneous abortions. Another frequent cause of spontaneous abortions is the wind egg (synonyms: wind mole or abortive egg): undeveloped egg without embryo development (trophoblast (cell layer in the womb, which is essential for the supply of the embryo) conditionally capable of development, embryoblast perishes prematurely).

The earlier an abortion occurs, the more likely the presence of embryonic chromosomal aberration. A distinction is made between different stages of abortion:

  • Abortus imminens (threatened abortion).
  • Abortus incipiens (incipient abortion).
  • Abortus incompletus (incomplete abortion).
  • Abortus completus (complete abortion)

In addition, there are Missed abortion (restrained abortion; miscarriage in which the fetus is dead but not spontaneously expelled from the uterus (womb)), Abortus febrilis (febrile miscarriage) and Abortus habitualis (habitual abortion; three or more miscarriages diagnosed by a doctor).

Etiology (causes)

Biographic causes

  • Genetic abnormalities – “errors” on chromosomes such as in trisomy, where one chromosome is present three times instead of normally twiceNote: As the number of miscarriages increases, the proportion of chromosomally abnormal fetuses decreases.
    • Approximately 4-5% of couples with 2 or more abortions have a balanced chromosomal abnormality (translocation, inversion) in one partner
    • Congenital thrombophilic factors (tendency to thrombosis) as a cause of habitual abortions (recurrent spontaneous abortions, RSA):
      • Factor V Leiden(FVL) mutation.
      • Prothrombin(PT)-G20210A mutation
      • Protein S deficiency
  • Anomalies of the genitalia of women such as uterine anomalies (malformations of the uterus):
    • Uterus arcuatus (lat. arcuatus “bent”) – slightest expression of the uterus septus (see below).
    • Uterus bicornis (partial fusion of Müller ducts): this conditions a common cervix (cervix) with uterine horns separated to varying degrees. Pregnant women must be at high rates for preterm abortions, preterm births and breech presentation (BEL).
    • Uterus didelphys (lack of fusion of the two Müller ducts): this causes duplicity of the corpus uteri (uterine body) and cervix uteri. In case of pregnancy, an increased risk of positional anomalies and preterm birth is to be expected.
    • Uterine septum (complete fusion of the Müller ducts with incomplete resorption of the middle septum, resulting in a varying length and shape of the septum (septum); most common uterine malformation): This results in an externally normal-shaped uterus with an externally broadly expansive smooth fundus (broad part of the uterus lying between the tubal openings) with sagittal median septum. Three forms can be distinguished according to the length of the septum:
      • Uterus subseptus (septum extends into the cavum/uterine cavity) [increased likelihood of miscarriage].
      • Uterus septus (septum extends to the cervix).
      • Uterus septus completus (septum extends into the cervix).
    • Uterus unicornis (maldevelopment in a Müller duct): this may result in the presence of a rudimentary horn. In the case of implantation in this horn, the probability of a disturbed pregnancy or tubargravidität (tubaria; tubal pregnancy) is very high.
  • Birth history: one or more premature abortions.
  • Male: sperm (semen) alterations/ abnormalities.
  • Age – older age of the woman; from the age of 40 years, the frequency of chromosomal abnormalities increases more than tenfold.
  • Occupations – occupational groups with occupational contact with carcinogens; flight attendants.
  • Socioeconomic factors: low socioeconomic status.

Behavioral causes

  • Nutrition
    • Micronutrient deficiency (vital substances) – see Prevention with micronutrients.
  • Consumption of stimulants
    • Coffee – Women who consumed 200 mg (the equivalent of one cup of coffee) or more of caffeine per day during pregnancy had twice the risk of miscarriage (abortion) as women who did not consume caffeine.
    • Alcohol
    • Tobacco (smoking)
  • Physical activity
    • Too much exercise early in pregnancy – Pregnant women who exercise more than seven hours per week have a three-and-a-half times higher risk of losing their baby than women who avoid physical exertion; the most dangerous sports are: jogging, ball sports or tennis; swimming is safe; after the 18th week of pregnancy, no increased risk of miscarriage was detectable
    • Regular lifting of objects weighing more than 20 kg.
  • Psycho-social situation
    • Stress
    • Shift work before pregnancy
  • Overweight (BMI ≥ 25; obesity) -.
    • After spontaneous conception, ovulation induction (drug-assisted. Triggering ovulation), IVF treatment and after egg donation → increased risk of miscarriage.
    • Risk factor for stillbirth and infant mortality; increase in risk for stillbirth if woman’s body mass index (BMI) increases between pregnancies:
      • 2 to 4 kg/m2 increased risk by 38%.
      • ≥ 4 kg/m2 increased the risk by 55%.

Causes due to disease

  • Anemia (anemia)
  • Autoimmunological diseases: Hashimoto’s thyroiditis (autoimmune disease leading to chronic inflammation of the thyroid gland) and antiphospholipid syndrome.
  • Chronic endometritis (inflammation of the uterus; in patients with repeated spontaneous abortions).
  • Endocrine disorders such as diabetes mellitus (diabetes), hyperthyroidism (hyperthyroidism), hypothyroidism (hypothyroidism).
  • Hormonal disorders such as.
    • Corpus luteum insufficiency (insufficient production of the corpus luteum hormone, which has the task of maintaining pregnancy),
    • Thyroid dysfunction (esp. latent hypothyroidism/ hypothyroidism)/manifest hyper- and hypothyroidism, and
    • Metabolic disorders associated with obesity, polycystic ovary syndrome (PCO syndrome), insulin resistance, and hyperandrogenemia
  • Immunological disorders
  • Infections mainly with the pathogens Chlamydia trachomatis, Toxoplasma gondii, cytomegalovirus, herpes virus, varicella zoster virus, measles virus, rubella virus, etc.
  • Consuming diseases – consuming diseases such as cancer or tuberculosis.
  • Myomas / benign neoplasm of women originating from the muscles (myoma) of the uterus (uterine) (submucosal fibroids).
  • Trauma (injuries)
  • Thrombophilia – genetic or acquired predisposition to thrombosis.

Laboratory diagnoses – laboratory parameters that are considered independent risk factors.

  • Hyperhomocysteinemia (homocysteine > 12 mmol/l) – elevated homocysteine levels are associated with an increased rate of miscarriage (recurrent abortions).
  • Vitamin B12 deficiency (vitamin B12 < 200 ng/l or 147.6 pmol/l).
  • Folic acid deficiency (folic acid < 2 ng/ml).
  • Lipoprotein (a) – elevated lipoprotein (a) levels are an independent risk factor for miscarriage

Medications

  • Antibiotics in early pregnancy
    • Azithromycin (macrolide antibiotic): adjusted odds ratio 1.65 (95% confidence interval of 1.34 to 2.02 based on 110 exposed cases significant)
    • Clarithromycin (macrolide antibiotic): adjusted odds ratio 2.35 (1.90-2.91, 111 exposed cases).
    • Quinolones (adjusted odds ratio 2.72; 2.27-3.27; 160 exposed cases).
    • Metronidazole: adjusted odds ratio 1.70 (1.27-2.26; 53 exposed cases).
    • Sulfonamides: adjusted odds ratio 2.01 (1.36-2.97; 30 exposed cases).
    • Tetracyclines (adjusted odds ratio 2.59 (1.97-3.41; 67 exposed cases).
  • Other antibiotics: Aminoglycosides, lincosamides.
  • Fluconazole (antifungal agent from the triazole derivatives group), oral.
    • Reproductive toxicity (48% ↑).
    • Single dose of 150 mg fluconazole first trimester (third trimester) of pregnancy showed an adjusted odds ratio for miscarriage of 2.23 (95% confidence interval 1.96-2.54
  • Nonsteroidal anti-inflammatory drugs (NSAIDs), excluding acetylsalicylic acid (ASA), double the risk of abortion; the risk was greatest with diclofenac, followed by naproxen, celecoxib, ibuprofen, and rofecoxib; other authors reached the opposite conclusion; except for indomethacin, whose use is associated with an increased risk of spontaneous abortion
  • Vaccinations with live vaccines such as against measles, mumps, rubella, yellow fever, varicella – chickenpox – should not be performed during pregnancy
  • Cytostatics – drugs such as cyclophosphamide or methotrexate to fight cancer can lead to abortions due to their teratogenicity – fertility damaging effect.

X-rays

Environmental pollution – intoxications (poisonings).

  • Occupational contact with carcinogens
  • Air pollutants: sulfur dioxide (SO2) levels correlate with the number of restrained abortions (Engl. missed abortion)
  • Phthalates (mainly as plasticizers for soft PVC)Note: Phthalates belong to the endocrine disruptors (synonym: xenohormones), which can harm health even in small amounts by changing the hormonal system.

Other causes