Pregnancy Loss (Miscarriage) - Terminology, Risk Factors, and Etiology - UpToDate

8/3/22, 22:36 Pregnancy loss (miscarriage): Terminology, risk factors, and etiology - UpToDate
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Pregnancy loss (miscarriage): Terminology, risk factors,

and etiology
Authors: Sarah Prager, MD, MAS, Elizabeth Micks, MD, MPH, Vanessa K Dalton, MD, MPH
Section Editors: Robert L Barbieri, MD, Courtney A Schreiber, MD, MPH, Deborah Levine, MD
Deputy Editor: Kristen Eckler, MD, FACOG
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2022. | This topic last updated: Sep 24, 2021.
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): Comparison of treatment options and discussion of

related care".)
● (See "Pregnancy loss (miscarriage): Management techniques".)
https://www.uptodate.com/contents/pregnancy-loss-miscarriage-terminology-risk-factors-and-etiology/print?search=miscarriage&topicRef=5442&sour… 1/27
Content related to vaginal bleeding in pregnant individuals:
● (See "Overview of the etiology and evaluation of vaginal bleeding in pregnancy".)
● (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. However, 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, abortion is also used to indicate a pregnancy terminated

iatrogenically 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".)
● Anembryonic pregnancy – Anembryonic pregnancy refers to a nonviable pregnancy with

a gestational sac that does not contain a yolk sac or embryo [1]. 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 when [1,2]:
• 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
weeks from the last menstrual period) [3,4]. However, at least one organization uses 10
weeks of gestational age as the cutoff, which can make study comparisons challenging [5].
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 a pregnancy with a visible embryo ≥7 mm

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 [6].
● 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 and prior to 20+0 weeks of gestation [7]. The 20 week cutoff is arbitrary
and not related to any physiologic differences between pregnancies less than 20 weeks
versus greater than 20 weeks [8]. 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 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 [9]. (See "Stillbirth: Incidence, risk factors, etiology,
and prevention", section on 'Definition'.)
● 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 [6]. 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 [10,11].
● Second trimester – The incidence of second-trimester loss up to 20 weeks gestation is

less than 1 percent [12].
● 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) [11]. 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.
Increasing age — Extremes of age increase the risk of pregnancy loss, with age >35 years
being the most significant risk factor because of the strong association with fetal chromosomal
abnormalities ( table 2) [10,13]. 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 [10].
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). (See 'Chromosomal abnormalities' below.)
While the impact of increasing paternal age is somewhat less clear, pregnancy loss risk does
appear to rise with increasing paternal age ( figure 1) [14]. 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 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) [10]. 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 [15].
Medical conditions in parents
Maternal — Various causes of maternal morbidity, such as endocrinopathies, cardiovascular

disease, and metabolic disorders, are associated with pregnancy loss [16]. 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 [17]. Untreated
syphilis leads to a 21 percent increased risk of fetal loss and stillbirth [18]. 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 [19-21]. However, maternal infection with HIV or
toxoplasmosis does not appear to be associated with an increased risk of pregnancy loss
[22,23].
• (See "Syphilis in pregnancy".)
• (See "Parvovirus B19 infection during pregnancy".)
• (See "Zika virus infection: Evaluation and management of pregnant women", 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) [24]. (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 [25]. 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 [26,27].
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 [28-32]. 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 [28].
● Inherited thrombophilias – The effect of inheritable thrombophilias on pregnancy loss

risk is unclear as the body of evidence conflicts. The available date 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 [33]. 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 [34].
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 LactMed toxicology data network
site. 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 [35,36]. (See "Safety of rheumatic disease medication use
during pregnancy and lactation", section on 'NSAIDs'.)
Receipt of an mRNA Covid-19 vaccine either before conception or during pregnancy does not
appear to increase the risk of pregnancy loss [37-39]. (See "COVID-19: Overview of pregnancy
issues", section on 'Vaccination in people planning pregnancy and pregnant or recently
pregnant people'.)
Substance use — Substance use during pregnancy is 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. In general,
smoking, caffeine, and alcohol consumption appear to increase the risk of pregnancy loss in a
dose-related fashion [40-46]. Some studies have reported increased risks with exposure to
cocaine or methamphetamines [43]. Marijuana use in pregnancy does not appear to increase
the risk of pregnancy loss, although it does negatively impact neonatal development [47].
● (See "Substance use during pregnancy: Screening and prenatal care".)
● (See "Alcohol intake and pregnancy", section on 'Perinatal outcomes'.)
● (See "Cigarette and tobacco products in pregnancy: Impact on pregnancy and the
neonate", section on 'Miscarriage'.)
● (See "Substance use during pregnancy: Overview of selected drugs".)
● (See "Caffeine: Effects on reproductive outcomes in females", section on 'Pregnancy loss

(miscarriage)'.)
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 [48], 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 [49]. (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 [50,51]. 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 disparities in obstetric
and gynecologic care and role of implicit biases", section on 'Examples of racial and ethnic
disparities in obstetric and gynecologic 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) [52]. 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) [53].
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 [54]. 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 [55,56], and multivitamins plus iron and folic acid
have been associated with a reduced risk for stillbirth [54]. (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 [57-59].
● 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 [60].
While low-dose aspirin may have a role for patients with prior loss, it is not advised for
https://www.uptodate.com/contents/pregnancy-loss-miscarriage-terminology-risk-factors-and-etiology/print?search=miscarriage&topicRef=5442&so… 10/27
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): 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 are present in up to 70 percent

of pregnancy losses before 20 weeks, though the prevalence varies by gestational age [61-65].
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
weeks and 9+6 weeks, and 33 percent of fetuses between 10+0 weeks and 19+6 weeks [63]. The
use of chromosomal microarray likely increased the ability to identify 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).
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 'Miscarriage'.)
● 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) [66]. 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 [67].
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 [68,69], though the data on IPV directly resulting in pregnancy loss are more
mixed [70,71]. 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 [72].
Known and suspected etiologies of second-trimester pregnancy loss include [72]:
• Infection, including chorioamnionitis and maternal viral infection [73]
• Chronic stressors, including contributions from racial/ethnic, financial or other

disparities, chronic food or housing insecurity, and other long-term life stressors [28]
• 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
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) [50].
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 5th to 6th 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 10th to 12th 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: Miscarriage (The Basics)" and "Patient education:
Bleeding in early pregnancy (The Basics)")
● Beyond the Basics topics (see "Patient education: Miscarriage (Beyond the Basics)")
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 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): 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 an earlier version of this topic review.
Use of UpToDate is subject to the Terms of Use.
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25. Maraka S, Ospina NM, O'Keeffe DT, et al. Subclinical Hypothyroidism in Pregnancy: A
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36. Li DK, Ferber JR, Odouli R, Quesenberry C. Use of nonsteroidal antiinflammatory drugs
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37. Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons. N Engl J Med
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38. Zauche LH, Wallace B, Smoots AN, et al. Receipt of mRNA Covid-19 Vaccines and Risk of
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39. Kharbanda EO, Haapala J, DeSilva M, et al. Spontaneous Abortion Following COVID-19
Vaccination During Pregnancy. JAMA 2021; 326:1629.
40. Avalos LA, Roberts SC, Kaskutas LA, et al. Volume and type of alcohol during early
pregnancy and the risk of miscarriage. Subst Use Misuse 2014; 49:1437.
41. Henriksen TB, Hjollund NH, Jensen TK, et al. Alcohol consumption at the time of conception
and spontaneous abortion. Am J Epidemiol 2004; 160:661.
42. Pineles BL, Park E, Samet JM. Systematic review and meta-analysis of miscarriage and
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43. Ness RB, Grisso JA, Hirschinger N, et al. Cocaine and tobacco use and the risk of
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44. Chen LW, Wu Y, Neelakantan N, et al. Maternal caffeine intake during pregnancy and risk of
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45. Lee SW, Han YJ, Cho DH, et al. Smoking Exposure in Early Pregnancy and Adverse
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46. Sundermann AC, Zhao S, Young CL, et al. Alcohol Use in Pregnancy and Miscarriage: A
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124:202.
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early pregnancy loss. Ultrasound Obstet Gynecol 2015; 45:89.
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66. Young BK. A multidisciplinary approach to pregnancy loss: the pregnancy loss prevention
center. J Perinat Med 2018; 47:41.
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130:1065.
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violence in New Zealand. Aust N Z J Obstet Gynaecol 2008; 48:391.
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pregnancy, miscarriage, induced abortion, and stillbirth among a national sample of
Bangladeshi women. BJOG 2007; 114:1246.
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sectional study among women of childbearing ages, Sivas, Turkey. Women Health 2014;
54:425.
71. Nelson DB, Grisso JA, Joffe MM, et al. Violence does not influence early pregnancy loss.
Fertil Steril 2003; 80:1205.
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Clin North Am 2014; 41:87.
73. Allanson B, Jennings B, Jacques A, et al. Infection and fetal loss in the mid-second trimester
of pregnancy. Aust N Z J Obstet Gynaecol 2010; 50:221.
Topic 5439 Version 61.0
GRAPHICS
Clinical scenario and ICD-10 diagnosis
ICD-10 diagnosis
Clinical scenario
Code Definition
Complete EPL: Complete spontaneous passage of O03.9* Complete or unspecified spontaneous

gestational tissue. abortion without complication
Incomplete EPL: Ultrasound or other evidence of O03.4* Incomplete spontaneous abortion

retained pregnancy tissue, with history of or without complication
ongoing vaginal bleeding. No cardiac activity or
other evidence of viability.
Incomplete EPL: Fetal or embryonic demise has O02.1 Missed abortion

occurred, and gestational tissue remains in the
uterus. Typically with little or no vaginal bleeding
and evidence that the nonviable gestation has
remained in the uterus for a period of time
Vaginal bleeding with evidence of embryonic or O20.0 Threatened abortion

fetal viability, such as fetal cardiac activity.
ICD: International Statistical Classification of Diseases and Related Health Problems, 10th revision; EPL:
early pregnancy loss.
* Refer to ICD-10 for coding when complications are present.
Courtesy of Sarah Prager, MD, MAS, Elizabeth Micks, MD, MPH, and Vanessa Dalton, MD, MPH.
Graphic 120361 Version 3.0
Maternal age-related risk for common fetal trisomies across pregnancy
Down Edwards Patau

Maternal syndrome/trisomy syndrome/trisomy syndrome/trisomy
age 21 risk (1:n) 18 risk (1:n) 13 risk (1:n)
(years)
CVS Amnio Term CVS Amnio Term CVS Amnio Term
18 1150 1210 1495 2520 3150 9010 6985 7945 13,700
19 1145 1205 1490 2515 3145 8985 6970 7930 13,670
20 1135 1200 1475 2510 3135 8960 6955 7905 13,635
21 1125 1185 1460 2500 3125 8930 6925 7875 13,580
22 1110 1165 1440 2490 3110 8885 6890 7835 13,510
23 1090 1150 1415 2470 3090 8825 6840 7780 13,410
24 1065 1120 1380 2450 3060 8745 6770 7700 13,275
25 1030 1085 1340 2415 3020 8630 6675 7590 13,090
26 975 1030 1285 2375 2970 8480 6545 7445 12,840
27 925 975 1220 2320 2900 8280 6375 7250 12,500
28 855 900 1140 2245 2805 8010 6145 6990 12,050
29 770 825 1045 2145 2680 7660 5850 6655 11,470
30 685 730 935 2020 2525 7215 5475 6225 10,735
31 590 630 815 1865 2330 6655 5015 5700 9830
32 490 535 695 1675 2095 5990 4475 5085 8770
33 400 430 570 1460 1825 5220 3870 4400 7585
34 310 345 455 1225 1535 4380 3235 3680 6345
35 240 260 350 990 1235 3530 2615 2975 5130
36 180 195 265 765 955 2725 2055 2335 4030
37 130 145 195 565 710 2025 1580 1800 3100
38 95 105 145 410 510 1455 1210 1375 2370
39 71 79 110 290 360 1035 930 1060 1825
40 52 60 85 205 255 735 730 830 1430
41 40 46 66 150 185 530 590 670 1160
42 32 38 54 110 140 395 495 560 970
43 27 31 45 87 110 310 425 485 840
44 22 26 39 70 88 250 380 435 745
45 19 23 34 60 74 215 350 395 685
46 18 21 31 52 65 185 325 370 640
47 16 19 29 47 59 170 310 355 610
48 15 18 27 44 55 155 300 340 590
49 15 18 26 41 52 150 290 330 570
The table shows the expected prevalence of 3 common autosomal trisomies (21, 18, and 13) individually
(first 3 boxed columns) and together (last boxed column). Within each of these groups, the prevalence is
shown at 3 different times in gestation. These include at the time of CVS at approximately 11 to 13 weeks
of gestation, amniocentesis at approximately 15 to 18 weeks of gestation, and at term. Each row of the
table shows these results for a given maternal age (eg, the row "35 years" includes women age 35.0
through 35.9, average 35.5 years) at the expected date of delivery. For example, consider a 32.4-year-old
woman being counseled prior to a CVS procedure who has no specific indications of an abnormality
other than age (eg, no abnormal ultrasound findings or pregnancy history of aneuploidy). The chance
that the CVS will identify a fetus with Down syndrome is 1:490, with trisomy 18 is 1:1675, and with
trisomy 13 is 1:4475. Together, these pose a current combined risk of 1:350. However, her chance of
having a term birth with Down syndrome (1:696), trisomy 18 (1:5990), or trisomy 13 (1:8770) is lower.
Together, these pose a term risk of 1:580.
CVS: chorionic villus sampling; amnio: amniocentesis.
References:
1. Morris JK, Savva GM. The risk of fetal loss following a prenatal diagnosis of trisomy 13 or trisomy 18. Am J Med Genet 2008;
146A:827.
2. Morris JK, Mutton DE, Alberman E. Revised estimates of the maternal age specific live birth prevalence of Down's syndrome.
J Med Screen 2002; 9:2.
3. Savva GM, Morris JK, Mutton DE, Alberman E. Maternal age-specific fetal loss rates in Down syndrome pregnancies. Prenat
Diagn 2006; 26:499.
4. Savva GM, Walker K, Morris JK. The maternal age-specific live birth prevalence of trisomies 13 and 18 compared to trisomy
21 (Down syndrome). Prenat Diagn 2010; 30:57.
Risk of fetal loss (including early pregnancy loss, ectopic pregnancy, and stillbirt
according to maternal age at conception
Risk of fetal loss from spontaneous abortion, ectopic pregnancy, and stillbirth according to maternal age at
conception.
Reproduced with permission from: Nybo Andersen AM, Wohlfahrt J, Christens P, et al. Maternal age and fetal loss: population based
register linkage study. BMJ 2000; 320(7251):1708-12. Copyright © 2000 BMJ Publishing Group Ltd.
Distinction between subchorionic hematoma and

unfused amnion in patient with vaginal bleeding at
13 weeks' gestational age
Transabdominal sagittal sonogram of uterus reveals subchorionic

hematoma (H) extending posteriorly around chorion (arrows) and
lifting edge of anterior placenta (P). Appearance should not be
confused with that of unfused amnion. Amnion is the thin
membrane continuous along anterior placental edge, but limited by
umbilical cord insertion; subchorionic bleeding leads to edge of
placenta.
Reproduced with permission from Trop I, Levine D. Hemorrage During Pregnancy:

Sonography and MR Imaging. AJR Am J Roentgenol 2001; 176:607. Copyright 2001
American Roentgen Ray Society.
Subchorionic bleeding in fetus at 5.5 weeks' gestational

age
(A) Transverse transvaginal sonogram reveals intrauterine gestational sac

with yolk sac. Note small amount of blood (arrow) adjacent to gestational sac.
(B) Transvaginal sagittal sonogram obtained 2 weeks after (A) because of

vaginal bleeding shows subchorionic hematoma (arrow) with debris.
Collection could be mistake for second gestational sac with embryonic
demise.
Reproduced with permission from Trop I, Levine D. Hemorrage During Pregnancy: Sonography
and MR Imaging. AJR Am J Roentgenol 2001; 176:607. Copyright 2001 American.
Contributor Disclosures
Sarah Prager, MD, MAS No relevant financial relationship(s) with ineligible companies to
disclose. Elizabeth Micks, MD, MPH No relevant financial relationship(s) with ineligible companies to
disclose. Vanessa K Dalton, MD, MPH Grant/Research/Clinical Trial Support: Agency for Healthcare
Research and Quality [Contraception]; American Association of Obstetrician and Gynecologists Foundation
[Contraception]; Laura and John Arnold Foundation [Contraception]; Blue Cross Blue Shield of Michigan
Foundation [Contraception]; Michigan Department of Health and Human Services [Perinatal health];
National Institutes for Health [Perinatal depression]. Consultant/Advisory Boards: Bayer [Expert witness
IUD litigation]; Merck [HPV vaccination]; Bind [Insurance benefit design]. Other Financial Interest: Medical
Letter Contributing Editor [Women's health]. All of the relevant financial relationships listed have been
mitigated. Robert L Barbieri, MD No relevant financial relationship(s) with ineligible companies to
disclose. Courtney A Schreiber, MD, MPH Patent Holder: Penn, Saul [Medical management of nonviable
pregnancy]. Grant/Research/Clinical Trial Support: Bayer [Contraception];Medicines360
[Contraception];VeraCept [Contraception]. Consultant/Advisory Boards: Danco Pharmaceuticals [Early
pregnancy loss];Medicines360 [Consultant]. Other Financial Interest: American Board of Obstetrics and
Gynecology. All of the relevant financial relationships listed have been mitigated. Deborah Levine, MD No
relevant financial relationship(s) with ineligible companies to disclose. Kristen Eckler, MD, FACOG No
relevant financial relationship(s) with ineligible companies to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.
Conflict of interest policy

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Pregnancy loss (miscarriage): Terminology, risk factors,

Pregnancy loss, also referred to as miscarriage or spontaneous abortion, is generally defined as

Content specific to pregnancy loss:

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

● (See "Pregnancy loss (miscarriage): Comparison of treatment options and discussion of

● (See "Pregnancy loss (miscarriage): Management techniques".)

Content related to vaginal bleeding in pregnant individuals:

● (See "Overview of the etiology and evaluation of vaginal bleeding in pregnancy".)

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

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

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

TERMINOLOGY OF PREGNANCY LOSS

● Abortion – This refers to pregnancy loss up to 20 weeks (sometimes called spontaneous

In common parlance, abortion is also used to indicate a pregnancy terminated

● Anembryonic pregnancy – Anembryonic pregnancy refers to a nonviable pregnancy with

An anembryonic pregnancy may be diagnosed when [1,2]:

• There is no embryo on follow-up endovaginal scan

● First-trimester (early) pregnancy loss – Although there is no consensus regarding

• Embryonic demise – Embryonic demise is a pregnancy with a visible embryo ≥7 mm

● Miscarriage – Synonymous with pregnancy loss. Preferred terminology by patients in one

● Recurrent pregnancy loss – Recurrent pregnancy loss is defined as spontaneous loss of

● Second-trimester pregnancy loss – Early second-trimester pregnancy loss is one that

● Septic abortion (miscarriage) – Septic abortion refers to any abortion, spontaneous or

• Incomplete miscarriage – "Incomplete miscarriage" and "incomplete abortion" are

• Inevitable miscarriage – Inevitable miscarriage or abortion has been used to describe

• Threatened miscarriage – "Threatened miscarriage" or "threatened abortion" has

Language preferred by patients — In a study of 145 United States English-speaking patients

Terminology versus billing codes — Continued use of imprecise terminology is problematic

Pregnancy loss is the most common complication in early pregnancy.

● Second trimester – The incidence of second-trimester loss up to 20 weeks gestation is

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

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

Medical conditions in parents

Maternal — Various causes of maternal morbidity, such as endocrinopathies, cardiovascular

• (See "Syphilis in pregnancy".)

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

• (See "Cytomegalovirus infection in pregnancy".)

• (See "Hypothyroidism during pregnancy: Clinical manifestations, diagnosis, and

• (See "Hyperthyroidism during pregnancy: Clinical manifestations, diagnosis, and

● Inherited thrombophilias – The effect of inheritable thrombophilias on pregnancy loss

Medications and drug exposure

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

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

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

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

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

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

Subchorionic hematoma — Subchorionic hemorrhage or hematoma is associated with

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

• Prenatal vitamins – A meta-analysis of over 40 studies concluded that use of prenatal

• Progesterone supplementation – Progesterone supplementation for patients with

● Helpful in some individuals

Common etiologies of pregnancy loss at any gestational age include chromosomal

Chromosomal abnormalities — Chromosomal abnormalities are present in up to 70 percent

Maternal anatomic anomalies — Anatomic anomalies, such as uterine leiomyomas (fibroids),

Specific to second-trimester loss — Individuals experiencing second-trimester pregnancy loss

Known and suspected etiologies of second-trimester pregnancy loss include [72]:

• Infection, including chorioamnionitis and maternal viral infection [73]

• Chronic stressors, including contributions from racial/ethnic, financial or other

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

• Premature preterm rupture of membranes