Pathogenesis (development of disease)
Threatened preterm birth. or premature birth, is the result and final course of many different underlying pathologies (abnormal and pathological processes and conditions in the body). The most important causes are infections and disorders of placental (placental) function due to decreased uteroplacental (uterine and placental) blood flow. The manner in which the balance between relaxed (relaxed) and contractile myometrium (uterine musculature), rigid (rigid, stiff, firm) cervix (uterine cervix), and resistant membranes is affected is only partially understood. For example, in ascending infection, bacterial endotoxins (decay products of bacteria that can trigger numerous physiological responses in humans) lead to the release of cytokines (proteins that regulate cell growth and differentiation), particularly interleukin-1 and tumor necrosis factor (TNF), via activation of macrophages (phagocytes). Through various mechanisms, these induce the formation of prostaglandins in the chorium (tree-like branched placental villi) and decidua (endometrium during pregnancy), which ultimately lead to remodeling processes in the cervix and thus to cervical ripening, or cervical insufficiency, structural changes in the membranes with loss of resistance, and thus to premature rupture of the membranes and preterm labor. Reduced blood flow to the placenta results, in a simplified manner, in the formation of oxygen radicals, which can lead to the activation of cytokines and an activation of corticotropin-releasing hormone (CRH), which can lead to contraction of the muscles and premature labor. In other causes, such as chronic stress, the release of CRH from the trophoblast is of particular importance. It stimulates the formation of prostaglandins and that of oxytocin receptors.
Etiology (Causes)
Threatened preterm birth should be understood as the final stage of various diseases or pathophysiological causes, the consequence of which may be preterm labor, premature rupture of the membranes, and/or remodeling processes in the cervix (cervical insufficiency). The most common causes are:
- Infections
- Ascending (ascending) infections
- Systemic infections
- Urinary tract infections; women with asymptomatic bacteriuria also have an increased preterm birth rate, which, with intervention, resulted in a significant reduction in the preterm birth rate before 37+0 weeks gestation
- Chorioamnionitis (inflammation of the inner egg skin and outer layer of amniotic membranes around the embryo or fetus/unborn child).
- Pathology of the uteroplacental (utero-uterine) unit caused by hypoxia (deficiency in oxygen supply to the tissues) and ischemia (decreased blood flow), e.g. Preeclampsia, eclampsia, HELLP syndrome (H = hemolysis/dissolution of erythrocytes (red blood cells) in the blood), EL = elevated liver enzymes, LP = low platelets (thrombocytopenia/decrease in platelets), diabetes mellitus, placenta praevia (malposition of the placenta (placenta) near the cervix), abruptio placentae (premature placental abruption).
- Fetal pathology
- Malformations
- Chromosomal abnormalities
- Uterine pathology
- Cervical insufficiency (weakness of the cervix)
- Myomas (guat-like muscular growths).
- Uterine malformations
- Condition after surgery, e.g., extended conization (surgery on the cervix in which a cone of tissue (cone) is excised from the cervix and subsequently examined microscopically), myoma removal (removal of a muscular growth) with opening of the cavum uteri (uterine cavity), condition after instrumental abortion
- Multiple pregnancies
Biographical causes
- Genetic predisposition to a risk of preterm birth
- Twin and family studies have shown that the influence of genes for pregnancy before the end of 37 weeks could be 30-40 percent.
- Gene variants (EBF1, EEFSEC, AGTR2, WNT4, ADCY5, and RAP2C) that influence the length of pregnancy and gene variants (EBF1, EEFSEC, and AGTR2) that could also be responsible for preterm births.
- Uterine malformations (malformations of the uterus).
- Gynecologic and obstetrical history.
- Condition after abortion (miscarriage)
- Condition after spontaneous preterm birth
- Pregnancy interval < 12 months
- Condition after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) (preterm birth rate 10.1% vs. 5.5% for pregnancy by natural means).
- Condition after surgery, e.g., extended conization (surgery on the cervix in which a cone of tissue (cone) is cut out of the cervix and then examined microscopically), myoma removal (removal of a muscular growth) with opening of the cavum uteri (uterine cavity), condition after instrumental abortion
- History of cancer: a study of this examined women who, between the ages of 15 and 39, had cancer
- (melanoma/skin cancer (21%)/melanoma in situ (10%), thyroid carcinoma (19%), and breast carcinoma/breast cancer (14%), as well as Hodgkin lymphoma (7%), gynecologic tumors (5%), and non-Hodgkin lymphoma (4%)). Of these, approximately one in four each received chemotherapy or radiation. The prevalence ratio (PR), i.e., the quotient of the prevalence in cancer patients and healthy persons, was
- For preterm birth was 1.52 (95% confidence interval between 1.34 and 1.71),
- For low birth weight at 1.59 (95% confidence interval between 1.38 and 1.83).
- For women with gynecologic tumors, at 2.58 (PR: 2.58; 95% confidence interval between 1.83 and 3.63)
- For preterm delivery and low birth weight after chemotherapy without radiotherapy (radiotherapy), at 2.11 and 2.36, respectively
- Multiple pregnancies (approximately 10% of all preterm births).
- Age
- Mother: < 18 and > 35 years; > 40 years (regardless of confounding factors).
- Father: > 45 years of age → children were born on average 0.12 weeks earlier than those born to younger fathers; risk of preterm birth was increased by 14%.
- Socioeconomic factors (preterm birth; birth before completion of 37 weeks’ gestation (SSW: 37+0) or birth weight <2,500 g).
- Low socioeconomic status
- Low schooling and education
- Unmarried pregnant women
- Working pregnant women
Behavioral causes
- Nutrition
- Malnutrition
- Malnutrition
- Micronutrient deficiency (vital substances): e.g. folic acid deficiency – see micronutrient therapy.
- Pleasure food consumption
- Alcohol (> 20 g/day)
- Tobacco (smoking)
- Drug use
- Physical activity
- High physical load
- Psycho-social situation
- Chronic stress
- Overweight (BMI ≥ 25; obesity).
- Underweight
Causes due to disease
- Anemia (anemia)
- Diabetes mellitus
- Hypertension (high blood pressure)
- Infections
- Ascending (ascending) infections.
- Bacterial vaginosis (2.4 times higher risk).
- Urinary tract infections
- Systemic infections: e.g. influenza (flu): preterm birth (< 37 weeks gestation) 3.9-fold risk compared to pregnant women without influenza
- Insomnia (sleep disturbances) – especially in sleep apnea (cessation of breathing during sleep) led to preterm birth before 37 weeks of gestation
- Kidney disease
- Periodontitis (disease of the periodontium).
- Thyroid disease
- Pregnancy disorders: Preeclampsia, eclampsia, HELLP syndrome (H = hemolysis/dissolution of erythrocytes (red blood cells) in the blood), EL = elevated liver enzymes, LP = low platelets (thrombocytopenia/decrease in platelets), diabetes mellitus, placenta praevia (malposition of the placenta (placenta) near the cervix), abruptio placentae (premature placental abruption).
- Uterine fibroids – benign tumors arising from the muscles of the uterus.
Medication
- Oxytocin
- Prostaglandins
Other causes
- Gemini (twin pregnancy)
- Vaginal bleeding (bleeding from the vagina): in early and late pregnancy.
- Polyhydramnios (amount of amniotic fluid > 2l).
- Shortened cervix (≤ 25 mm before the 24th SSW).
