Loss of intrauterine pregnancy within the first trimester, including detection of the empty gestational sac (sac without embryonic tissue) or gestational sac containing embryo or fetus without the heart activity, or loss of the gestational material vaginally, is interchangeably called early pregnancy loss (EPL), miscarriage or spontaneous abortion.
According to the World Health Organization, miscarriage is a spontaneous loss of an embryo or the fetus weighing below 500 g before 20-22nd gestational weeks. EPL is a commonly observed condition occurring in 10 to 15% of all clinically diagnosed pregnancies. The estimated annual number of miscarriages worldwide is 23 million. Approximately 10.8% of women have one miscarriage in their lifetime.
Definitions of early pregnancy loss
Biochemical pregnancy loss is a pregnancy confirmed with a positive pregnancy test only (without an ultrasound evaluation), which later becomes negative.
Missed abortus is a failure to detect the embryonic heartbeat in an intrauterine pregnancy despite the presence of a gestational sac or embryo.
Incomplete abortus is the pregnancy loss observed with vaginal bleeding and irregular structures within the uterine cavity.
Complete abortus is diagnosed with an empty uterine cavity following vaginal bleeding in a woman with a previously confirmed pregnancy.
Risk factors for miscarriages
Demographic factors: Obesity adversely affects the transformation of the endometrium (the inner layer of the uterus) to accommodate the placenta. Female body mass index (BMI) is associated with increased risk; the normal range of BMI (18.5 to 24.9 kg/m2) is the least risk-associated range. A population-based study from the UK reports that being underweight (BMI <18.5) increases miscarriage risk by 72% while being overweight or obese is not effective on the risk.
Lifestyle and environmental factors: Cigarette smoking is a modifiable risk factor for EPL. This risk is correlated with the amount of daily use; every cigarette smoked per day increases the miscarriage risk by 1%. Alcohol consumption is another modifiable factor associated with increased odds of miscarriage. Each additional weekly drink is associated with a 6% increased risk of EPL among alcohol consumers of five or fewer drinks per week. Effects of alcohol are prominent among regular drinkers (at least once a week to daily) and those who drink more than 14 units weekly. High caffeine intake is also among the considered factors.
Air pollution, organochlorides, and sprayed pesticide exposures are environmental factors increasing miscarriage and recurrent pregnancy loss rates.
Fetal chromosomal abnormalities: This factor accounts for approximately 50 to 60% of all cases. Autosomal trisomies are the most frequent chromosomal abnormalities; fetal trisomy 16 appears incompatible with life, being the most common trisomy in miscarried fetuses.
Maternal age: The frequency of clinically recognized EPLs significantly increases with the advancing age. Women who conceive at the age of 20 to 30 carry a 9 to 17% risk of miscarriage, while this risk doubles after the age of 35, reaching 40%, with a later increase to 80% at the age of 45. However, females younger than 20 also carry an increased risk for miscarriage.
Paternal age: According to a recent report, advanced paternal age is also a risk factor for miscarriage. Compared to the 25 to 29 years, males in the age group of 30 to 34 and 35 to 39 carry a 4% and 15% higher risk, while this number rises to 23% and 43% in the age groups of 40 to 44 and over 45, respectively.
Prior history of EPL: A history of miscarriage increases the risk by 10% for each lost pregnancy reaching 42% in women with three or more previous histories.
Complications and long-term health risks of miscarriage
Obstetric complications in subsequent pregnancies: Each previous EPL increases the risk of preterm birth. It could be associated with the miscarriage management methods, such as repeated uterine curettage causing cervical and endometrial damage. Endometrial damage may also cause abnormal placental implantation and lead to the development of placental abruption and placenta previa in subsequent pregnancies.
Long-term health risks: Recurrent miscarriages increase the risk of cardiovascular disease and venous thromboembolism, which could be an important reminder for lifestyle modifications. Miscarriage undeniably impacts maternal mental health, especially in societies that view the inability to deliver a baby as shameful or demeaning. Studies show that pregnancy loss is strongly linked with a post-traumatic disorder, anxiety (moderate to severe in 17%), depression (moderate to severe in 6%), and suicide rates.
Miscarriage or early pregnancy loss is a frequent obstetric condition affecting 10.8% of women at least once in their lifetime. EPL might be related to genetic predispositions and co-morbidities, as well as to demographic and lifestyle factors.
- Miscarriage is a loss of the pregnancy before the 22nd gestational week and accounts for 10 to 15% of all clinically diagnosed pregnancies.
- Miscarriage is associated with demographic (parental age, BMI, weight), lifestyle (smoking, alcohol consumption), and environmental (pollution, pesticide exposure) factors.
- Miscarriage might have long-term systemic and mental health risks for the mother, which should be considered by family members and patients.
American College of Obstetricians and Gynecologists' Committee on Practice Bulletins—Gynecology. (2018). ACOG Practice Bulletin No. 200: Early Pregnancy Loss. Obstet Gynecol.
Quenby, S., et al. (2021). Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss. Lancet.
ESHRE Guideline Group on RPL, et al. (2018). ESHRE guideline: recurrent pregnancy loss. Human Reproduction Open.
Maconochie, N., et al. (2017). Risk factors for first trimester miscarriage – results from a UK-population-based case-control study. Bjog.
Pineles, B.L., E. Park, and J.M. Samet. (2014). Systematic review and meta-analysis of miscarriage and maternal exposure to tobacco smoke during pregnancy. American Journal of Epidemiology.
Sundermann, A.C., et al. (2019). Alcohol Use in Pregnancy and Miscarriage: A Systematic Review and Meta-Analysis. Alcohol Clin Exp Res.
du Fossé, N.A., et al. (2020). Advanced paternal age is associated with an increased risk of spontaneous miscarriage: a systematic review and meta-analysis. Hum Reprod Update.