Bleeding in Pregnancy

Context

Bleeding in the first trimester is common occurring in up to 30% of pregnancies and being responsible for 50,000 admissions per annum to hospital in the UK. [1]

50-80% of patients presenting with first trimester vaginal bleeding will go on to have normal pregnancies. 

1 in 80 of pregnancies are ectopic and require prompt diagnosis and management.

Antepartum haemorrhage (APH) has an incidence of 3.5% of all pregnancies. Antenatal screening has reduced maternal mortality from placenta praevia, yet there remains considerable fetal and maternal morbidity and mortality associated with APH. [2,3]

10% of births are of Rh-positive babies to Rh-negative mothers. Consideration and appropriate use of anti-D immunoglobulin is highly cost effective and avoids considerable morbidity and mortality. [4]

Definition

First trimester: 1-12 weeks
Second trimester: 13-28 weeks
Third trimester: 29-40 weeks

Miscarriage is the loss of a pregnancy before 23 completed weeks. Early miscarriage is more precisely defined as pregnancy loss in the first 12 weeks and late miscarriage as pregnancy loss thereafter. Approximately 20% of pregnancies miscarry. [5]

Ectopic pregnancy occurs where a fertilized ovum is implanted in any tissue other than the uterine endometrium.

Antepartum haemorrhage (APH) is defined as vaginal bleeding occurring from the 24th week of pregnancy and prior to the birth of the baby.

Rhesus D antigen is found on the surface of RBC and is capable of inducing intense antigenic reactions.  Individuals without the antigen are determined rhesus negative and are homozygous recessive.

Bleeding in pregnancy can be due to:

• Miscarriage
• Gestational trophoblastic disease (GTD) is an umbrella term for a group of rare pregnancy-related disorders, which include molar pregnancies as well as malignant conditions such as choriocarcinoma. Molar pregnancy (also called a hydatidiform mole) is the most common type of GTD. In molar pregnancy, the placenta overgrows; the embryo does not form correctly and is not viable. Molar pregnancies can have abnormally elevated BHCG. Vaginal bleeding can contain fluid filled cysts. Molar pregnancies are benign. However, there is a small risk that the molar cells could become cancerous if they are not all removed. This is usually done by surgical suction curettage.
• Lesions of the lower genital tract
  • Cervical ectropion
  • Cervical carcinoma
  • Sexually transmitted diseases
• APH
  • Placental abruption
  • Placenta Praevia
  • Vasa Praevia
• Ectopic pregnancy
• Premature labour
• Placental abruption

There are many identified causative factors and associations. Although none can be translated to provide definitive risk stratification serum βhCG and USS provide valuable information.

Miscarriage

Miscarriage is the loss of a pregnancy before 23 completed weeks. Early miscarriage is more precisely defined as pregnancy loss in the first 12 weeks and late miscarriage as pregnancy loss thereafter.

Since 1997 the RCOG has encouraged the use of the term ‘miscarriage’ rather than (spontaneous) abortion.

Subdivision of miscarriage

Miscarriage is subdivided as follows:

Threatened miscarriage: bleeding or cramping in a continuing pregnancy. [6]  The cervical os is closed. An ultrasound scan is required to confirm fetal heart activity.

Complete miscarriage: all the fetal material has passed and the uterus is empty. [6] The cervical os will be closed and where there has not previously been an US scan, one should be performed together with serum βhCG to confirm pregnancy failure. [7]

Incomplete miscarriage: there is retained products of conception within the uterus and the os remains open. The patient is at risk of haemorrhage and infection.

Early embryonic/fetal demise (previously known as missed/anembryonic pregnancy/blighted ovum): a non-viable pregnancy at 12 weeks where the products of conception have not been passed.

Miscarriage with infection (previously referred to as septic): this is secondary to either a spontaneous miscarriage or induced termination. Presentation is with fever and foul-smelling discharge.

Causative factors

Causative factors include [8]:

• Chromosomal abnormalities
• Increasing maternal age
• Smoking
• Alcohol
• Uterine abnormalities
• Maternal infection
• Co-morbidity

Presentation

• Vaginal bleeding ranging from ‘occasional spotting’ to significant haemorrhage or cervical shock
• Abdominal pain

The psychological aspect of miscarriage is often overlooked in busy emergency departments. For patients and their partners, miscarriage can be distressing and lonely. Please consider that your patient maybe finding it emotionally difficult to sit in a crowded waiting area. They may feel embarrassed if they are bleeding heavily and they are likely to be in pain. Addressing these needs may make a huge difference to their experience. Offer analgesia, sanitary towels, blankets and if possible, a place of privacy. Your patient may not need admission, or Early Pregnancy Unit services may not immediately be available, or ultrasound imaging at the time may not be clinically appropriate. When explaining this to patients, remember they may feel that faster management could save their pregnancy. [9]

This ‘wait’ understandably can cause more distress.

In terms of language to use, patients and their partners are sensitive to the words we use. If you’re not sure what term to use, mirror what the patient uses (baby, fetus, pregnancy).

The miscarriage association has a good practice guide for the emergency department.

Ectopic Pregnancy

An ectopic pregnancy occurs where a fertilized ovum is implanted in any tissue other than the uterine endometrium. The Royal College of Obstetricians and Gynaecologists estimate that the rate of ectopic pregnancy is 11.1 in 1000. The image below shows the potential sites of an ectopic pregnancy.

Patients presenting with abdominal pain and/or vaginal bleeding and a positive urinary βhCG in early pregnancy should be considered to have an ectopic pregnancy until proven otherwise.

Special note: Cornual implantation

Patients with cornual implantation may rupture after 12 weeks with catastrophic blood loss. These patients sometimes present with symptoms of gastroenteritis.

No single sign or combination of signs is diagnostic. Half of identified ectopics are in women with no known risk factors.

Risk factors for ectopic pregnancy include:

• Previous ectopic pregnancy – the risk of recurrence of ectopic pregnancy is about 18.5%.         
• History of pelvic inflammatory disease.
• Previous pelvic surgery (including sterilization [rare], tubal reconstruction surgery, caesarean section).
• Black ethnicity – black women are at increased risk compared to white women. 
• Assisted reproduction techniques, especially in vitro fertilization.
• Cigarette smoking.
• Maternal age over 35 years
• Intrauterine contraception (IUC) – the overall risk of ectopic pregnancy when using IUC is reduced compared to using no contraception. However, if pregnancy does occur with IUC in situ, the risk of an ectopic pregnancy is increased and, in some studies, half of pregnancies that occurred were ectopic.

No single sign or combination of signs is diagnostic. Half of identified ectopics is in women with no known risk factors.

On assessment THINK ECTOPIC for patients with a uterus of childbearing age who present with:

• Abdominal or pelvic pain
• Shoulder tip pain
• Collapse/syncope/faint
• Diarrhoea/ GI upset
• UTI symptoms
• Changes in menstrual cycle
• PV Bleeding
• Rectal pressure

Do a pregnancy test for all patients with a uterus of childbearing age who present with the above. [10]

Human Chorionic Gonadotropin (βhCG)

Human chorionic gonadotropin (βhCG) is detected in urine as early as one week before an expected menstrual period.

It usually remains elevated for several weeks after a pregnancy has ended.

Serum βhCG is definitive.

βhCG is typically lower in ectopic pregnancies than intra-uterine pregnancies for gestational age and in ectopics rises more slowly. This is however not diagnostic. [11,12]

Levels above 1000-2000 IU/L in the absence of sonographic signs of pregnancy is considered presumptive evidence of an ectopic pregnancy.

The gynaecologists manage some patients with known ectopic pregnancy expectantly. Usually falling βhCG levels suggest spontaneous involution. It is still possible for these ectopic pregnancies to rupture, and a high index of suspicion should be maintained when these women present to the ED with abdominal pain and/or vaginal bleeding. [13]

Vaginal bleeding occurring from the 24th week of pregnancy and prior to the birth of the baby is termed antepartum haemorrhage (APH). There are a number of causes of bleeding in late pregnancy:

Placenta praevia

Placenta praevia occurs when the placenta is implanted wholly or in part into the lower segment of the uterus. If the cervical os is completely covered it is considered a major praevia (complete) and if not, then it is considered a minor praevia (marginal).

• The incidence is 0.48% with a resulting mortality of 0.03%. [14]
• The exact pathophysiology is unknown; uterine scarring (such as previous c-section), multiparity, multiple gestations and advanced maternal age are all associated risk factors.
• Bleeding is a result of contractions, cervical effacement and dilatation separating the placenta from the uterus.
• Prior to labour this may be self-limiting.
• Painless PV bleeding in the second or third trimester is the classical sign. However, abdominal pain can also occur. Placenta praevia may also be suspected later in pregnancy if the foetus is found to be in a breech or a transverse position.
• Antenatal screening at 20 weeks enables detection and expectant management.
• It is rare to have an undiagnosed placenta praevia present to the ED.
• Women who have had a bleed will be managed as in patients from 34 weeks. Asymptomatic women may be managed as outpatients with close monitoring. [15]

Placental abruption

Placental abruption is the complete or partial premature separation of a normally implanted placenta from the uterus causing haemorrhage.

• Bleeding may be concealed in up to 20% of placental abruption.
• Placental abruption should be considered when the pain is continuous. (Labour should also be considered if the pain is intermittent.)
• Abdominal examination may show fundal tenderness. A tense or ‘woody’ feel to the uterus indicates a significant abruption.
• Foetal distress is indicative of abruption and foetal death is common where separation is more than 50%. [16]
• DIC occurs in 10%, which can cause long-term renal failure.
• Increased maternal age, smoking, use of cocaine, hypertension, multiple pregnancy, high parity, prolonged rupture of membranes, low body mass index (BMI), pregnancy following assisted reproductive techniques, and trauma are all risk factors.

Vasa praevia

Vasa praevia is a condition in which the fetal blood vessels run freely and unsupported through the membranes, over the cervix across the internal os beneath the presenting part, unprotected by placenta or umbilical cord. [17]

• The incidence is approximately 1/2500 deliveries and undiagnosed is associated with a perinatal mortality of 56%. [17,18]
• Risk factors include placenta praevia, multilobed placenta, velamentous insertion of the umbilical cord, multiple pregnancies and IVF pregnancies.
• The fetal blood vessels may be ruptured at amniotomy, spontaneous rupture of membranes or during cervical dilatation.
• Painless PV bleeding and foetal heart activity abnormalities are common. Pulsating vessels on vaginal examination are indicative, however PV examination is normally contraindicated because of the possibility of placenta praevia.
• Targeted screening of high-risk pregnancies is suggested. [19]  Routine screening is not cost effective and undetected ‘low risk’ pregnancies may present to the ED.

Placenta accreta

Placenta accreta is abnormal adherence of the placenta to the uterus. It is strongly associated with previous caesarean sections and can be identified on US. It is usually a post partum phenomenon although rarely may cause spontaneous uterine rupture and massive intraperitoneal haemorrhage. [20]

Points to note:

• Vasa praevia and uterine rupture are rare
• placenta accreta is increasing in incidence with increasing caesarean section rate.
• No definite cause can be identified in at least half of cases of APH.

• Around 30% of domestic abuse begins during pregnancy, while 40 to 60% of women experiencing domestic abuse are abused during pregnancy. [21]
• While only one in five survivors of domestic violence will call the police, 80% will seek help from health services. [22]
• NICE recommends that all pregnant women should be asked about domestic violence as part of their social history. This is not limited to those who only present following trauma.
• It is therefore important in the emergency department we enquire about DV in a private and in a sensitive manner.

Therapeutic Interventions

Initial Resuscitation is generic. Specific interventions are directed at the cause of bleeding and are dealt with individually.

The majority of patients presenting to the ED with vaginal bleeding in pregnancy will not require resuscitation. Those that do require a multidisciplinary approach and involvement of senior obstetricians, paediatricians, anaesthetists, intensivists and haematologists should be sought early. Locally devised multidisciplinary protocols for massive obstetric haemorrhage should be in place.

An ABC approach to management is advocated.

Suspected ectopic pregnancy: requires definitive management by the gynaecology team.

Suspected cervical shock: remove products of conception from the os with the aid of a speculum and sponge forceps.

Continued haemorrhage: consider administration of ergometrine and oxytocin. (to promote uterine contraction)

Delivery of the baby: in severe APH where fetal heart activity is detected, caesarean delivery of the baby should proceed. Where no fetal activity is identified vaginal delivery is advocated.

Rhesus status and anti-D immunoglobulin

Administration of anti-D immunoglobulin to women at risk of Feto-maternal haemorrhage (FMH) reduces the risk of sensitisation.

Feto-maternal haemorrhage (FMH):

• Is most common in the third trimester, during childbirth and following events associated with FMH. Such events include medical interventions (chorionic villus sampling, amniocentesis, external cephalic version), terminations, late miscarriages, APH and abdominal trauma
• Can occur in the absence of an observed potentially sensitising event
• Causes alloimmunisation

Sensitisation:

• Has no effect on the mother and usually no adverse effect on the fetus in the primary pregnancy during which it occurs
• Is dependent on the volume of fetal blood entering the maternal circulation and the volume of the mother’s immune response
• Is greatest with the first pregnancy (with the same father) and reduced with subsequent pregnancies
• Once occurred is irreversible

The immune response is:

• Usually not detected in the first pregnancy
• Faster and greater in subsequent pregnancies
• Causes fetal anaemia which in utero leads to heart failure, hydrops foetalis and intrauterine death. Neonatally haemolytic disease of the newborn ensues causing kernicterus.

Use of Anti-D

Current guidelines state that Anti-D immunoglobulin should be administered as soon as possible and always within 72 hours of a sensitising event. [23] If this deadline has not been met, some protection may be offered if anti-D Ig is given up to 10 days after the sensitising event.

In pregnancies <12 weeks gestation, Anti-D is only indicated following ectopic or molar pregnancies, therapeutic termination of pregnancy and in cases of heavy or repeated uterine bleeding, or bleeding associated with abdominal pain, if these events occur as gestation approaches 12 weeks. The minimum dose is 250IU, and a Kleihauer test is not required.

For potentially sensitising events between 12 and 20 weeks, again the minimum dose is 250IU, and a Kleihauer test is not required.

After 20 weeks, a minimum dose of 500IU of Anti-D immunoglobulin and a Kleihauer test are both required.

If a patient requires Anti D but is declining this (for example some Jehovah’s witness may decline), offer for rhesus testing of the ‘father’ to establish if they are rhesus negative. If so, anti-D would not be required.

Administration of anti-D to rhesus-negative women is required with:

• Women who have heavy or repeated bleeding or where there is associated abdominal pain in the first trimester.
• Women having a spontaneous miscarriage or threatened miscarriage or who suffer from intermittent bleeding after the first trimester.
• Women having a therapeutic termination of pregnancy.
• Women having an ectopic pregnancy.
• Women who undergo intervention to remove products of conception.
• Women who have potentially sensitising events at any stage of pregnancy.

In these circumstances, the dose to administer is:

Before 20 weeks: 250 iu

After 20 weeks: 500 iu

Administer intramuscularly to the deltoid muscle as soon as possible after the sensitisation event.

After 20 weeks gestation a Kleihauer test should be performed to establish the size of the FMH and additional anti-D given as required. This would not be done in the ED.

As anti-D immunoglobulin is a blood product there will be a small number of patients with particular religious beliefs to whom this treatment is unacceptable.

There is no passive immunisation and no alternative treatment.

Administration of anti-D to rhesus-negative women is not required with

• Women who are already sensitised
• Women suffering a complete miscarriage before 12 weeks
• Women who have PV bleeding in the first 12 weeks and continue to have a viable pregnancy

Individuals who are already sensitied are identified through an indirect Coombs test.

• Failure to diagnose pregnancy. Every woman of reproductive age with lower abdominal pain or PV bleeding should have a pregnancy test.
• Failure to diagnose an ectopic pregnancy. Remember:Ectopic pregnancies can present with a range of presentations of women of reproductive age, including: Collapse/syncope/faint, Diarrhoea/ GI upset, UTI symptoms. Do a pregnancy test!
• Failure to recognise cervical shock. Cervical shock presents bradycardia and hypotension – remove what is causing the obstruction at the cervical OS.
• Failure to appreciate the extent of haemorrhage and consider concealed haemorrhage.
• Failure to prevent isoimmunisation.
• Failure to involve experienced specialists early.

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