History and exam

Key diagnostic factors

common

presence of risk factors

Key risk factors include older parental age, uterine malformation, bacterial vaginosis, and thrombophilias.

vaginal bleeding with or without clots

Patients with advanced maternal age, previous preterm delivery, multiple previous terminations, or multiple previous miscarriages report more intense vaginal bleeding in the first two trimesters of pregnancy than patients without these histories.[78]

Pregnancy loss in the first trimester is 18 times greater in patients who bleed moderately to severely than in patients who do not bleed.[79]

Other diagnostic factors

common

suprapubic pain

Cramp-like discomfort may signify the process of expulsion of the fetus.

Pain without vaginal bleeding does not suggest a miscarriage (but may suggest an ectopic pregnancy).

low back pain

Non-specific symptom in patients with miscarriage.

recent post-coital bleed

The odds of miscarriage double in women aged 18 to 55 years who report bleeding after sexual intercourse during pregnancy.[80]

uncommon

uterine structural abnormality

Sub-mucous fibroids co-existing with an ongoing pregnancy may increase the risk of bleeding in early pregnancy, although the risk is over-estimated.[81]

history of trauma

Trauma (e.g., motor vehicle accident) is uncommon during pregnancy; however, increased severity of abdomino-pelvic trauma leads to an increased risk of fetal loss. Caution should be exercised when ascertaining this from the history due to possible medico-legal implications. A cause-effect relationship is unlikely following a recent accidental or intentional suprapubic blunt trauma if there was unproven uterine hypoperfusion or maternal hypotension as a result.[65]

Risk factors

strong

older age

Eight-fold greater risk in women aged ≥45 years compared with women aged 20 to 24 years.[34]

Increasing ages of both parents also increases the risk.[35]

Advanced maternal age also seems to be closely associated with the occurrence of trisomy, identified in spontaneous miscarriages. Up to 60% of all spontaneous miscarriages are attributable to chromosomal abnormalities.[36]

uterine malformation

Congenital uterine malformations in women can result in early miscarriage depending on the severity and presence of associated chromosomal, vascular, or endocrine pathology.[37]

Acquired structural distortion with large sub-mucous fibroids may also result in pregnancy loss. One systematic review found that myomectomy for cavity-distorting myomas can reduce the risk of early pregnancy loss.[38]

bacterial vaginosis

Asymptomatic bacterial vaginosis may play an important role in second-trimester miscarriage.[39][40]

thrombophilia

Hyperhomocysteinaemia is a risk factor for recurrent miscarriage.[41]

Presence of anticardiolipin antibodies carries a 3- to 9-fold greater risk of fetal loss in low-risk pregnancies.[42] Women with a history of at least 3 prior miscarriages and no abnormality other than the presence of antiphospholipid antibodies are likely to have a future miscarriage.[42]

parental chromosomal anomaly

In approximately 2% to 5% of couples with recurrent miscarriage, one of the partners carries a balanced structural chromosomal anomaly (most commonly a balanced reciprocal or Robertsonian translocation).[43]

vitamin D deficiency

An extremely low 25(OH)D level (<20 ng/mL) was significantly associated with an increased risk of spontaneous pregnancy loss (SPL) in the first trimester (relative risk 2.24, 95% CI 1.15 to 4.37). Severe vitamin D deficiency could be detrimental to early embryonic development and increase the risk of early SPL.[44]

weak

previous spontaneous/induced miscarriage

The consequences of induced abortion on subsequent risk of miscarriage are unclear; one study demonstrated increased risk.[45] The risk is less likely if uterine evacuation was medical rather than surgical.[46]

Recurrent miscarriage of pregnancies affects 1% of couples trying to conceive.[43]

infertility/assisted conception

The cause remains unclear.[47][48]

Chromosomally defective fetuses may occur as a result of fertilisation by spermatozoa that carry abnormal chromosomes.[49]

non-steroidal anti-inflammatory drugs (NSAIDs)

According to a recent cohort study, NSAID use around conception was associated with an increased risk of miscarriage (<8 weeks) with a dose-response relationship (when used for more than 15 days).[50] In addition, women with lower body mass index could be especially vulnerable to the effects of NSAID use around the time of embryonic implantation, although this new observation must be confirmed in future studies.

An increased risk of miscarriage after NSAID use has been reported, with a consistently positive association with use in the weeks before miscarriage.[51][52]

However, it is unclear whether NSAID use or the primary indication for NSAID use is the risk factor.

caffeine

Effects of caffeine on early pregnancy are subject to many confounding factors, in view of widespread use.[53]

One meta-analysis of 14 studies concluded that each additional cup of coffee per day (approximately 100 mg/day caffeine intake) was associated with a 7% higher risk of pregnancy loss (95% CI 3% to 12%). However, the authors acknowledged the results may have been affected by residual confounding due to incomplete adjustment for smoking and pregnancy symptoms in some of the studies.[54]

alcohol

It is assumed that alcohol consumption is not safe in pregnancy. However, no consistently significant effects on miscarriage have been reported.[55] One study found that there was no increased risk in women who consumed 1 to 13 units of alcohol weekly.[56]

smoking

Risk is greater with current, rather than previous, history of smoking in mothers and a possible dose-response effect.[57]

Partnership of heavy-smoking fathers and non-smoking mothers also increases risk of early pregnancy loss.[58]

overweight/obesity

The role of obesity in reproductive health is becoming increasingly clear. The odds ratio (OR) for a risk of early miscarriage is significantly higher among obese patients (OR = 1.2 for early miscarriage, and OR = 3.5 for recurrent early miscarriages).[59]

thyroid dysfunction

The Endocrine Society clinical practice guideline suggests an increased incidence of miscarriage with maternal autoimmune thyroid disease hypothyroidism, although universal screening for thyroid disease in pregnancy is not, as yet, supported by adequate studies.[60] One study has shown that miscarriage rates are higher in pregnant women who are not treated with antithyroid peroxidase antibodies.[61] Good clinical practice, however, should ensure a maternal euthyroid state peri-conception.

diabetes mellitus

Poorly controlled diabetes with a high HbA1c in the first trimester is associated with miscarriage and fetal structural anomalies.[43]

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