Pregnancy loss (miscarriage): Terminology, risk factors, and etiology

INTRODUCTION — Pregnancy loss, also referred to as miscarriage or spontaneous abortion, is generally defined as a nonviable intrauterine pregnancy up to 20 weeks gestation. Early pregnancy loss, which occurs in the first trimester, is the most common type. The nonspecific symptoms of vaginal bleeding and uterine cramping associated with pregnancy loss can occur in normal, ectopic, and molar pregnancies, which can be a source of frustration for patients and clinical confusion for care providers.

This topic will review the terminology, risk factors, and etiology for pregnancy loss up to 20 weeks gestation. Related topics on clinical presentation of individuals with pregnancy loss, treatment options, and management protocols, as well as related content on vaginal bleeding in pregnancy, stillbirth at ≥20 weeks gestation, ectopic pregnancy, and molar pregnancy are presented separately.

Content specific to pregnancy loss:

●(See "Pregnancy loss (miscarriage): Clinical presentations, diagnosis, and initial evaluation".)

●(See "Pregnancy loss (miscarriage): Counseling and comparison of treatment options and discussion of related care".)

●(See "Pregnancy loss (miscarriage): Description of management techniques".)

Content related to vaginal bleeding in pregnant individuals:

●(See "Evaluation and differential diagnosis of vaginal bleeding before 20 weeks of gestation".)

●(See "Stillbirth: Incidence, risk factors, etiology, and prevention".)

●(See "Ectopic pregnancy: Clinical manifestations and diagnosis".)

●(See "Hydatidiform mole: Epidemiology, clinical features, and diagnosis".)

In this topic, we will use the term "patient" to describe genetic females. We recognize that not all people capable of pregnancy identify as female and we encourage the reader to consider the specific counseling needs of transgender men and gender nonbinary individuals.

TERMINOLOGY OF PREGNANCY LOSS

Commonly used wording — A variety of terms are used to describe nonviable pregnancies, which can lead to confusion for clinicians and patients. We take the following approach to terminology:

●Abortion – This refers to pregnancy loss up to 20 weeks (sometimes called spontaneous abortion) or pregnancy termination at any gestational age.

In common parlance, induced abortion is also used to indicate a pregnancy terminated without an intent to result in a live fetus. In this scenario, the use represents a procedure (medical or surgical) and not a diagnosis. (See "Overview of pregnancy termination".)

Terminology for induced abortions include:

•Medication abortion – This wording refers to abortion performed "primarily with medications, including mifepristone, misoprostol, and misoprostol-alone," regardless of the "setting, context, gestational duration, or legal status" [1]

•Procedural abortion – This wording refers to abortion performed "primarily with instrumentation, including uterine aspiration (manual or electric), dilation and curettage, dilation and evacuation, or dilation and extraction," regardless of the "setting, context, pregnancy duration, or legal status" [1].

●Anembryonic pregnancy – Anembryonic pregnancy refers to a nonviable pregnancy with a gestational sac that does not contain a yolk sac or embryo [2]. This terminology includes pregnancies in which an embryo may have been present but has since been resorbed. Anembryonic pregnancy contrasts with "embryonic or fetal demise" in which an embryo or fetus is visualized but cardiac activity is not present.

An anembryonic pregnancy may be diagnosed with highest diagnostic certainty when [2,3] (see "Pregnancy loss (miscarriage): Ultrasound diagnosis"):

•There is no embryo seen on endovaginal scanning in a gestational sac with mean sac diameter ≥25 mm or

•There is no embryo on follow-up endovaginal scan

•≥11 days after scan showing gestational sac with yolk sac, but no embryo, or

•≥2 weeks after a scan showing gestational sac without yolk sac or embryo

●First-trimester (early) pregnancy loss – Although there is no consensus regarding terminology, first-trimester, or early pregnancy loss (EPL), is described by several national organizations as a nonviable, intrauterine pregnancy within the first trimester (up to 12 6/7 weeks from the last menstrual period) [4,5]. However, at least one organization uses 10 0/7 weeks of gestational age as the cutoff, which can make study comparisons challenging [6]. EPL is broad terminology that includes pregnancies with an empty gestational sac (sometimes referred to as an anembryonic pregnancy) and pregnancies with an embryo or fetus without cardiac activity. The ultrasound criteria for diagnosis of pregnancy loss are presented in related content. (See "Pregnancy loss (miscarriage): Ultrasound diagnosis".)

•Embryonic demise – Embryonic demise is diagnosed with the highest diagnostic certainty when a pregnancy with a visible embryo ≥7 mm is without cardiac activity. This terminology applies to pregnancies measuring less than 10 weeks by ultrasound.

•Fetal demise – Fetal demise is used if a fetus (ie, pregnancy measuring 10 weeks of gestation or greater) without cardiac activity is visualized.

●Miscarriage – Synonymous with pregnancy loss. Preferred terminology by patients in one survey study [7].

●Recurrent pregnancy loss – Recurrent pregnancy loss is defined as spontaneous loss of two or more pregnancies. (See "Recurrent pregnancy loss: Definition and etiology".)

●Second-trimester pregnancy loss – Early second-trimester pregnancy loss is one that occurs after 13 0/7 and up to 19 6/7 weeks of gestation [8]. The 19 6/7 week cutoff for stillbirth is arbitrary and not related to any physiologic differences between pregnancies less than 20 weeks versus greater than 20 weeks [9]. By convention, nonviable pregnancies of 20 weeks gestation or more are typically referred to as stillbirth or fetal death.

●Septic abortion (miscarriage) – Septic abortion refers to any abortion, spontaneous or induced, that is complicated by uterine infection. (See "Septic abortion: Clinical presentation and management".)

●Stillbirth or fetal death – Pregnancy loss that occurs at 20 0/7 weeks gestation or later, or at a weight of 350 grams or greater, is generally referred to as a stillbirth or fetal death, although differing criteria exist globally [10]. (See "Stillbirth: Incidence, risk factors, etiology, and prevention", section on 'Definitions'.)

●Nonspecific terminology – The terms below are historical and, in part, reflect the development and subsequently improved accuracy of ultrasound technology. We do not use these phrases as they are not clearly standardized, do not always convey the information required for clinical decision-making, and have contributed to patient confusion, particularly if used interchangeably.

•Blighted ovum – Blighted ovum is a historical phrase that is no longer preferred and has been replaced by "anembryonic pregnancy," as discussed above. Nonviability can result from multiple causes, not just the ovum.

•Incomplete miscarriage – "Incomplete miscarriage" and "incomplete abortion" are historical terms typically used to indicate that there is persistent pregnancy tissue in the uterus after a diagnosis of pregnancy loss. Other wording that is more specific is preferred; one example is "persistent empty gestational sac despite initial diagnosis of nonviability (insert number of weeks) weeks ago."

•Inevitable miscarriage – Inevitable miscarriage or abortion has been used to describe a miscarriage that cannot be avoided because the cervix is open, bleeding is heavy or increasing, and abdominal cramping is present. However, it can be difficult to differentiate between an open external or internal cervical os, particularly in parous individuals, and this phrase is no longer preferred.

•Missed abortion – "Missed abortion" has been used to describe a nonviable pregnancy in the absence of symptoms. These individuals are now described as having asymptomatic pregnancy loss. (See "Pregnancy loss (miscarriage): Clinical presentations, diagnosis, and initial evaluation", section on 'Asymptomatic or incidental'.)

•Threatened miscarriage – "Threatened miscarriage" or "threatened abortion" has been used in reference to a patient experiencing bleeding in early pregnancy but without a clear diagnosis of pregnancy loss. We find this definition imprecise and more accurately conveyed as bleeding in early pregnancy.

Language preferred by patients — In a study of 145 United States English-speaking patients being treated for first-trimester pregnancy loss, patients preferred the terms "miscarriage" and "early pregnancy loss" rather than "early pregnancy failure" or "spontaneous abortion," which they believed to be less clear [7]. It is unclear how primary spoken language and culture influence terminology preference.

Terminology versus billing codes — Continued use of imprecise terminology is problematic because available codes are not easily aligned with the clinically relevant pregnancy loss categories in use. Since these billing codes are generally required to document a clinical encounter in an electronic medical record, it is often impossible to document the relevant subcategory of pregnancy loss, making quality monitoring or other evaluation activities difficult (table 1).

INCIDENCE — Pregnancy loss is the most common complication in early pregnancy.

●First trimester – The incidence of early pregnancy loss (EPL) has been estimated to be high as 31 percent by logistic regression, though that incidence decreases to approximately 10 percent when considering only losses occurring in clinically recognized pregnancies [11,12].

●Second trimester – The incidence of second-trimester loss up to 20 weeks gestation is less than 1 percent [13].

●Data limitations – The true incidence of pregnancy loss is difficult to ascertain as many losses occur prior to clinically recognized pregnancy. We think about pregnancy loss as occurring at two different time points: after implantation but before clinical recognition or after clinical recognition (defined as diagnosed by a clinician or by standard pregnancy testing) [12]. A fertilized egg that does not implant is technically not a pregnancy, per accepted medical definitions of pregnancy. (See "Clinical manifestations and diagnosis of early pregnancy", section on 'Diagnosis'.)

RISK FACTORS — Common risk factors for pregnancy loss include increasing maternal age, medical conditions, medication and/or substance use, and environmental exposures.

Maternal age and genetic anomaly — Extremes of age increase the risk of pregnancy loss. Maternal age >35 years is the most significant risk factor because of the strong association of advancing maternal age with fetal chromosomal abnormalities (table 2) [11,14]. In a national prospective cohort study of over 421,000 pregnancies, the risk of miscarriage (after excluding induced abortions) was lowest (10 percent) in individuals age 25 to 29 years and rose to a high of 57 percent for people age ≥45 years [11]. The early pregnancy loss rates by other age subgroups were 17 percent (<20 years), 11 percent (20 to 24 years), 11 percent (30 to 34 years), 17 percent (35 to 39 years), and 33 percent (40 to 44 years).

While the impact of increasing paternal age is somewhat less clear, pregnancy loss risk does appear to rise with increasing paternal age (figure 1) [15]. These issues are presented in greater detail separately.

●(See "Effects of advanced maternal age on pregnancy", section on 'Early pregnancy issues'.)

●(See "Effect of advanced paternal age on fertility and pregnancy".)

Prior pregnancy loss — Prior pregnancy loss also increases the risk of subsequent pregnancy loss, independent of maternal age. In the above prospective cohort study of over 421,000 pregnancies, after adjusting for maternal age, the risk of miscarriage increased among those whose prior pregnancy ended in a miscarriage (adjusted odds ratios [OR] of miscarriage for one prior miscarriage: 1.54, 95% CI 1.48-1.60; two prior miscarriages: 2.21, 95% CI 2.03-2.41; three prior miscarriages: 3.97, 95% CI 3.29-4.78) [11]. In addition, at least one study has reported that patients who experienced pregnancy loss were more likely to have a mother who also had a history of pregnancy loss, which suggests a potentially inheritable component [16].

Medical conditions in parents

Maternal — Various causes of maternal morbidity, such as endocrinopathies, cardiovascular disease, and metabolic disorders, are associated with pregnancy loss [17]. These may also be considered modifiable risk factors, as well-controlled maternal conditions are far less likely to result in loss. While any medical condition that negatively impacts maternal health can have potential reproductive consequences, some of the more common conditions that increase the risk of pregnancy loss are discussed below.

●Infection – Bacterial, protozoan, and viral infectious agents have been associated with increased risk of miscarriage; the exact mechanisms are not fully known [18]. Untreated syphilis leads to a 21 percent increased risk of fetal loss and stillbirth [19]. As compared with uninfected pregnant individuals, maternal viral infections have been associated with fetal loss rates nearly 8 percent for parvovirus B19, nearly 6 percent for Zika virus, and 2.5 percent for cytomegalovirus [20-22]. However, maternal infection with HIV or toxoplasmosis does not appear to be associated with an increased risk of pregnancy loss [23,24].

•(See "Syphilis in pregnancy".)

•(See "Parvovirus B19 infection during pregnancy".)

•(See "Zika virus infection: Evaluation and management of pregnant patients", section on 'Potential consequences of vertical transmission'.)

•(See "Cytomegalovirus infection in pregnancy".)

●Diabetes – The effects of type 1 and 2 diabetes on early pregnancy can be extreme, even resulting in lethal fetal anomalies or pregnancy loss. Euglycemia in the preconception and periconception time periods brings this risk back to baseline. (See "Pregestational (preexisting) diabetes: Preconception counseling, evaluation, and management".)

●Obesity – Obesity is more strongly and consistently associated with pregnancy loss than either type 1 or 2 diabetes. A 2008 meta-analysis of 16 studies demonstrated that a body mass index greater than 25 was associated with a nearly 70 percent increased odds of pregnancy loss up to 20 weeks gestation after spontaneous or assisted conception (OR 1.67, 95% CI 1.25-2.25) [25]. (See "Obesity in pregnancy: Complications and maternal management", section on 'Early pregnancy loss'.)

●Thyroid disease – Both hyper- and hypothyroidism have been associated with increased risk of pregnancy loss, with at least one study reporting a doubling of risk [26]. These topics are covered in detail elsewhere.

•(See "Hypothyroidism during pregnancy: Clinical manifestations, diagnosis, and treatment", section on 'Pregnancy complications'.)

•(See "Hyperthyroidism during pregnancy: Clinical manifestations, diagnosis, and causes", section on 'Pregnancy complications'.)

●Stress – Both acute and chronic stress can increase the risk of pregnancy loss [27,28]. Stress is multifactorial and can be difficult to separate out from other risks. Chronic stress can lead to increased cortisol levels, decreased immunity, and may increase susceptibility to infection and other maternal conditions, all of which can then increase the risk of pregnancy loss [29-33]. If a person has an otherwise stable life, a short period of stress, such as a busy time at work or acute illness in a loved one, is unlikely to have a major impact. However, racial/ethnic, financial or other disparities, risk of violence, significant periods of housing or food insecurity in the past or present, or other long-term life stressors can negatively impact health in many ways, including increasing the risk of pregnancy loss [29].

●Inherited thrombophilias – The effect of inheritable thrombophilias on pregnancy loss risk is unclear as the body of evidence conflicts. The available data are covered in detail elsewhere. (See "Inherited thrombophilias in pregnancy", section on 'Adverse pregnancy outcome risk'.)

●Pregnancy with intrauterine device (IUD) in place – While IUDs are some of the most effective contraceptive methods, device failures do occur. Though pregnancy with an IUD in place is relatively rare, for those patients who choose to continue their pregnancies, the risk of pregnancy loss appears to be higher for individuals who elect to leave the IUD in place rather than have it removed [34]. These issues are presented in greater detail in a related topic. (See "Intrauterine contraception: Management of side effects and complications" and "Intrauterine contraception: Management of side effects and complications", section on 'Pregnancy'.)

Paternal — After controlling for maternal age and medical comorbidities, preconception paternal medical conditions may modestly increase the risk of pregnancy loss. In a retrospective cohort study of an insurance database covering 958,804 pregnancies in the United States, compared with men with no components of metabolic syndrome (MetS), the risk of pregnancy loss increased for men with one (relative risk [RR] 1.10, 95% CI 1.09-1.12), two (RR 1.15, 95% CI 1.13-1.17), or three or more (RR 1.19, 95% CI 1.14-1.24) MetS components after stratifying for maternal and paternal age [35]. (See "Effect of advanced paternal age on fertility and pregnancy".)

Medications and drug exposure

Medication — Information regarding the impact of specific drugs on the risk of miscarriage is available at the United States National Library of Medicine Drugs and Lactation Database.

●Challenges of risk assessment – The role of medication and substance use on pregnancy loss risk is challenging to assess as the impact varies by agent, dose, and timing of exposure. Numerous therapeutic medications are considered teratogenic in pregnancy, and some teratogenic effects can also result in an increased risk of pregnancy loss. Alternately, medications may be associated with pregnancy loss even in the absence of teratogenicity. As an example of the complicated nature of medication and risk of pregnancy loss, the nonsteroidal anti-inflammatory drugs (NSAIDs) aspirin and indomethacin are used for specific obstetric indications (preeclampsia prevention and treatment of acute preterm labor) while other NSAIDs, including ibuprofen and diclofenac, may increase risk of pregnancy loss [36,37]. (See "Safety of rheumatic disease medication use during pregnancy and lactation", section on 'NSAIDs'.)

●Psychiatric medications – Psychiatric drugs, including antidepressants and antipsychotics, are presumed to cross the placenta. The impact by drug group is presented in related content.

•(See "Antenatal use of antidepressants and the potential risk of teratogenicity and adverse pregnancy outcomes: Selective serotonin reuptake inhibitors".)

•(See "Teratogenicity, pregnancy complications, and postnatal risks of antipsychotics, benzodiazepines, lithium, and electroconvulsive therapy".)

●COVID-19 vaccine – Receipt of an mRNA COVID-19 vaccine either before conception or during pregnancy does not appear to increase the risk of pregnancy loss [38-41]. (See "COVID-19: Overview of pregnancy issues", section on 'Vaccination in people planning pregnancy and pregnant or recently pregnant people'.)

Substance use — In general, smoking, caffeine, and alcohol consumption appear to increase the risk of pregnancy loss in a dose-related fashion [42-48]. However, studies of substance use during pregnancy are almost always confounded with other factors that lead to poor health status and increased risk of pregnancy loss, and thus it is difficult to assess the independent impact of the drug(s) in epidemiologic studies. To significantly reduce the risks of confounding and reverse causality, a Mendelian-randomization study that used genetic variants associated with smoking initiation confirmed a 30 percent increased risk of pregnancy loss per standard deviation increase in the prevalence of smoking initiation (odds ratio 1.31, 95% CI 1.25-1.37) [49]. Significant associations were not reported for caffeine or alcohol consumption, showing them to be likely confounders and not causally related. The use of non-modifiable genetic data strengthens the causal association of smoking and pregnancy loss.

●(See "Cigarette and tobacco products in pregnancy: Impact on pregnancy and the neonate", section on 'Pregnancy loss (miscarriage)'.)

●(See "Caffeine: Effects on reproductive outcomes in females", section on 'Pregnancy loss (miscarriage)'.)

●(See "Alcohol intake and pregnancy", section on 'Perinatal outcomes'.)

Some studies have reported increased risks with exposure to cocaine or methamphetamines [45]. Marijuana use in pregnancy does not appear to increase the risk of pregnancy loss, although it does negatively impact neonatal development [50].

●(See "Substance use during pregnancy: Screening and prenatal care".)

●(See "Substance use during pregnancy: Overview of selected drugs".)

Environmental factors and exposures — Exposure to toxins and pollutants and other environmental factors may increase the risk of pregnancy loss by causing cell death, altering growth of normal tissues, or interfering with normal cellular differentiation or other processes. Exposure to ionizing radiation is definitively associated with pregnancy loss [51], while excessive lead, arsenic, and air pollution exposure appear to increase the risk. Some of these exposures can be avoided, but many occur where one lives or works and may not be avoidable. The role of specific agents and their impact on reproductive outcomes are discussed in more detail in related topics.

●(See "Overview of occupational and environmental risks to reproduction in females".)

●(See "Occupational and environmental risks to reproduction in females: Specific exposures and impact".)

In addition, work type or schedule (eg, night time shift work) may increase risk of pregnancy loss [52]. (See "Working during pregnancy".)

Race and ethnicity — Studies have consistently reported an increased risk of pregnancy loss in Black, Indigenous, and other people of color compared with White persons [53,54]. As an example, one prospective cohort study reported pregnancy loss between 10 and 20 weeks was nearly twice as common among Black American women compared with White American women (adjusted hazard ratio 1.57, 95% CI 1.27-1.93) [53]. However, this difference more likely reflects the impact of the cumulative stressors of systemic racism, social determinants of health, and unavoidable occupational and/or environmental exposure to potential toxins than a true biologic difference. (See "Racial and ethnic inequities in obstetric and gynecologic care and role of implicit biases", section on 'Examples of inequities in reproductive health'.)

Subchorionic hematoma — Subchorionic hemorrhage or hematoma is associated with increased risk of pregnancy loss, particularly when it amounts to 25 percent or more of the volume of the gestational sac (image 1A-B) [55]. In a meta-analysis of seven comparative studies, pregnant individuals with subchorionic hematoma had double the odds of pregnancy loss compared with those without (18 versus 9 percent, OR 2.18, 95% CI 1.29-3.68) [56].

RISK REDUCTION — Multiple agents have been studied to reduce the risk of miscarriage.

●Not helpful

•Prenatal vitamins – A meta-analysis of over 40 studies concluded that use of prenatal vitamins in the preconception, periconception, and early pregnancy time frames does not prevent early pregnancy loss [57]. It is unclear if folic acid specifically can reduce the risk of miscarriage, though supplementation does appear to reduce the risk compared with no supplementation [58,59], and multivitamins plus iron and folic acid have been associated with a reduced risk for stillbirth [57]. (See "Nutrition in pregnancy: Dietary requirements and supplements", section on 'Micronutrients'.)

•Progesterone supplementation – Progesterone supplementation for patients with first-trimester vaginal bleeding has not been associated with increased live birth rates and is not advised for routine use [60-62].

●Helpful in some individuals

•Low-dose aspirin – Low-dose aspirin (81 mg) was associated with reduced risk of pregnancy loss in one study of patients with one to two prior pregnancy losses [63]. While low-dose aspirin may have a role for patients with prior loss, it is not advised for routine use in individuals who have never been pregnant or not experienced miscarriage. A detailed discussion of the study and the authors approach is presented in related content. (See "Pregnancy loss (miscarriage): Counseling and comparison of treatment options and discussion of related care", section on 'Role of low-dose aspirin to reduce risk of pregnancy loss'.)

Patients with recurrent miscarriage, defined as two to three prior losses, are discussed elsewhere. (See "Recurrent pregnancy loss: Management".)

ETIOLOGY — Common etiologies of pregnancy loss at any gestational age include chromosomal abnormalities, maternal anatomic abnormalities, and trauma. For individuals with second-trimester loss, additional possible etiologies must be considered.

Chromosomal abnormalities — Chromosomal abnormalities, including aneuploidy, partial deletion, or duplication, are present in up to 70 percent of pregnancy losses before 20 weeks, though the prevalence varies by gestational age [64-69].

●Impact of gestational age at loss – In a study that evaluated 80 patients with pregnancy loss at <20 weeks gestation with chromosomal microarray analysis, genetic abnormalities were reported in 9 percent of pre-embryonic losses (from implantation to less than 6 weeks), 69 percent of embryos between 6 0/7 weeks and 9 6/7 weeks, and 33 percent of fetuses between 10 0/7 weeks and 19 6/7 weeks [66]. The use of chromosomal microarray likely increased the ability to identify chromosomal abnormalities in earlier preclinical losses that previously were undetected by karyotype. This study challenged historic teaching that earlier gestational age was associated with increased risk of chromosomal abnormality. While embryonic losses are still more likely to result from chromosomal abnormalities compared with later fetal losses, this relationship does not appear to be valid for pre-embryonic losses (defined as no visible embryo on ultrasound evaluation). (See "Prenatal diagnosis of chromosomal imbalance: Chromosomal microarray".)

●Overall frequency of aneuploidy – In a study of 1000 consecutive patients age ≥18 years with pregnancy loss up to 22 weeks, evaluation of fetal ploidy status using cell-free fetal DNA (cffDNA) reported 45 percent euploid, 41 percent aneuploid, 4 percent with multiple aneuploidies, and 11 percent inconclusive [70]. Use of cffDNA to test patients with pregnancy loss is investigational and not routinely performed but presents a promising use of this technology.

Maternal anatomic anomalies — Anatomic anomalies, such as uterine leiomyomas (fibroids), polyps, adhesions, or septa, may be associated with pregnancy loss based on their size and position in relation to the developing pregnancy. These may not be identified prior to experiencing pregnancy loss but, once diagnosed, can often be surgically or medically addressed before another pregnancy is attempted.

While not all studies support fibroids as contributing factors to pregnancy loss, different study populations may be one factor contributing to discrepant outcomes (recurrent pregnancy loss versus routine obstetric patients). The impact of fibroids on pregnancy loss likely varies by other clinical aspects as well, such as distortion of the uterine cavity and/or blood supply. (See "Uterine fibroids (leiomyomas): Issues in pregnancy", section on 'Early pregnancy loss'.)

●In a study of 104 women with recurrent pregnancy loss of multiple types, the most common structural diagnoses that likely contributed to the loss were intrauterine adhesions (15 percent), fibroids (14 percent), uterine septum (3 percent), and endometrial polyps (2 percent) [71]. For intrauterine adhesions, the number of adhesions was not reported. No diagnosis was identified in 18 percent of patients.

●A 2017 meta-analysis of five studies including over 21,000 routine obstetric patients reported no association between uterine leiomyomas and pregnancy loss [72].

Trauma — Significant trauma can cause pregnancy loss. While the developing embryo is relatively protected within the uterus in early pregnancy, trauma that results in direct impact to the uterus can cause pregnancy loss. This can be due to violent trauma (gunshot wounds, penetrating injuries) or iatrogenic trauma, as with chorionic villus sampling and amniocentesis. (See "Chorionic villus sampling".)

A history of intimate partner violence (IPV) is consistently associated with higher incidence of pregnancy loss [73,74], though the data on IPV directly resulting in pregnancy loss are more mixed [75,76]. The association may be attributable to physical violence, psychological harm, or a combination of factors, both known and unknown. (See "Intimate partner violence: Diagnosis and screening" and "Intimate partner violence: Epidemiology and health consequences".)

Specific to second-trimester loss — Individuals experiencing second-trimester pregnancy loss are a heterogeneous group, and the underlying pathology overlaps with obstetric complications such as preterm delivery and preterm premature rupture of membranes. Frequently, second-trimester pregnancy loss has more than one cause, and often no etiology is identified [77].

Known and suspected etiologies of second-trimester pregnancy loss include [77]:

•Infection, including chorioamnionitis and maternal viral infection [78]

•Chronic stressors, including contributions from racial/ethnic, financial or other disparities, chronic food or housing insecurity, and other long-term life stressors [29]

•Uterine malformation

•Cervical insufficiency

•Fetal malformation or syndromes such as anencephaly, trisomies, renal agenesis, or hydrops

•Thrombophilias

•Abruption

•Premature preterm rupture of membranes

•Preterm labor

RESOURCES FOR PATIENTS AND CLINICIANS

●Planned Parenthood – How do I know if I am having a miscarriage?

●American College of Obstetricians and Gynecologists – FAQ Early Pregnancy Loss

●Royal College of Obstetricians & Gynaecologists – Early miscarriage

●Early pregnancy loss resources – An educational resource for both clinicians and patients supported by a grant through the University of California San Francisco

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pregnancy loss (spontaneous abortion)".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Pregnancy loss (The Basics)" and "Patient education: Coping after pregnancy loss (The Basics)" and "Patient education: Bleeding in early pregnancy (The Basics)")

●Beyond the Basics topic (see "Patient education: Pregnancy loss (Beyond the Basics)")

PATIENT PERSPECTIVE TOPIC — Patient perspectives are provided for selected disorders to help clinicians better understand the patient experience and patient concerns. These narratives may offer insights into patient values and preferences not included in other UpToDate topics. (See "Patient perspective: Pregnancy loss".)

SUMMARY AND RECOMMENDATIONS

●Terminology – A variety of terms are used to describe nonviable pregnancies, which can lead to confusion for clinicians and patients. Although there is no consensus regarding terminology, we prefer the terms "early pregnancy loss" (EPL) for nonviable, intrauterine pregnancies within the first trimester (up to 12 6/7 weeks from the last menstrual period) and "pregnancy loss" for any non-viable pregnancy up to 20 weeks gestation. (See 'Terminology of pregnancy loss' above.)

●Incidence – Pregnancy loss is the most common complication in early pregnancy. The incidence of first-trimester pregnancy loss is as high as 31 percent, though that incidence decreases to approximately 10 percent when considering only losses occurring in clinically recognized pregnancies. (See 'Incidence' above.)

●Risk factors – Common risk factors for pregnancy loss include increasing maternal age, prior pregnancy loss, medical conditions, medication and/or substance use, and environmental exposures. (See 'Risk factors' above.)

●Risk reduction – While prenatal vitamins and progesterone supplementation have not been shown to reduce risk of pregnancy loss, low-dose aspirin (81 mg) may be helpful in individuals with one to two prior pregnancy losses. (See 'Risk reduction' above and "Pregnancy loss (miscarriage): Counseling and comparison of treatment options and discussion of related care", section on 'Role of low-dose aspirin to reduce risk of pregnancy loss'.)

●Etiologies – Etiologies common to pregnancy loss of any gestational age include chromosomal abnormalities, maternal anatomic abnormalities, and trauma. Individuals with second-trimester loss are a heterogeneous group and additional possible etiologies must be considered. (See 'Etiology' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Togas Tulandi, MD, MHCM, and Haya Al-Fozan, MD, who contributed to earlier versions of this topic review.