What are the potential causes of 2nd trimester pregnancy loss in a female of childbearing age with no known medical history?

Causes of Second Trimester Pregnancy Loss

Second trimester pregnancy loss (14-24 weeks gestation) results from identifiable causes in approximately 40-50% of cases, with the most common etiologies being placental abnormalities, cervical insufficiency, antiphospholipid syndrome, chromosomal abnormalities, and maternal medical conditions. 1, 2, 3

Major Etiologic Categories

Placental and Vascular Causes (Most Common)

Placental pathology represents the leading identifiable cause of second trimester loss:

• Placental abruption affects approximately 1% of pregnancies and is a significant cause of second trimester loss, with central abruption carrying worse outcomes than marginal separation 1
• Placenta previa occurs in 1 in 200 pregnancies and can lead to loss through hemorrhage 1
• Vasa previa (1 in 2,500-5,000 deliveries) carries high fetal mortality risk if undiagnosed 1
• Placental causes account for 19-27% of second trimester losses, with higher rates (27%) in women experiencing recurrent losses 4

Cervical Insufficiency

• Cervical incompetence is identified in approximately 8% of women with second trimester loss using strict diagnostic criteria 2
• This represents a mechanical cause where the cervix dilates painlessly in the second trimester without contractions 5

Immunologic Factors

Antiphospholipid syndrome (APS) is the most common treatable immunologic cause:

• APS is present in 18-33% of women with second trimester loss, making it one of the most frequently identified causes 2, 3
• Women with JAK2V617F mutations in myeloproliferative neoplasms show particularly high rates (92%) of second trimester complications including miscarriage and stillbirth 6
• Prior vascular events increase second trimester complications 4-fold 6

Chromosomal and Fetal Abnormalities

• Fetal chromosomal abnormalities are less common in second trimester compared to first trimester losses, but still represent 18-27% of cases 4
• Common aneuploidies are less frequent in recurrent second trimester loss 4
• Idiopathic hydrops and multiple congenital anomalies not fitting known syndromes suggest overlooked genetic causes requiring investigation 4
• Congenital anomalies account for 3-4% of pregnancies and increase risk of poor outcomes 6

Uterine Anatomic Abnormalities

• Uterine anomalies are identified in approximately 4% of second trimester losses 2
• These include septate uterus, bicornuate uterus, and other müllerian duct abnormalities 5

Maternal Medical Conditions

Several maternal conditions significantly increase second trimester loss risk:

• Gestational hypertension and preeclampsia are associated with second trimester complications 1
• Gestational diabetes increases pregnancy complication risk including loss 1
• Hypothyroidism is present in 2% of second trimester loss cases 2
• Maternal schizophrenia is associated with increased stillbirth risk 1
• Advanced maternal age (≥35 years) significantly increases miscarriage risk (OR 1.85) 1
• Low serum AMH levels are associated with higher miscarriage risk (OR 1.91), with even higher risk in women over 35 with diminished ovarian reserve (OR 2.05) 1

Infection

• Maternal infections account for approximately 3% of second trimester losses 2
• Premature rupture of membranes complicated by infection can lead to pregnancy loss 1

Premature Labor and Membrane Rupture

• Threatened preterm labor is a recognized cause of second trimester loss 1
• Premature rupture of membranes particularly when complicated by infection 1

Important Clinical Considerations

Dual Pathology

• 5% of women with second trimester loss have dual pathology, requiring comprehensive evaluation rather than stopping after identifying one cause 2

Recurrence Risk Patterns

Women with prior second trimester loss face substantially elevated recurrence risks:

• Overall recurrence rate is approximately 4% in the general population 4
• Women with previous second trimester loss or stillbirth face 7-8% recurrence risk compared to 4% in women without such history 4
• Prior pregnancy loss increases subsequent pregnancy complication risk 3.86-fold 7, 8
• Women with recurrent losses are more likely to have maternal (20% vs 11%) or placental (27% vs 19%) causes 4
• Recurrences are more likely to occur in the second trimester (52% vs 37%) 4

Male Fetal Vulnerability

• Male fetuses have higher susceptibility to impaired placental implantation, leading to increased spontaneous miscarriage rates when pregnancy complications occur 7
• This sex-dimorphic effect means male fetuses with placental dysfunction are more likely to miscarry early rather than progress to later complications 7

Idiopathic Cases

• 50-60% of second trimester losses remain unexplained despite thorough investigation 2, 3
• Idiopathic loss is a diagnosis by exclusion requiring high index of suspicion and modern diagnostic techniques 2

Critical Diagnostic Approach

Digital pelvic examination should be avoided until placenta previa, low-lying placenta, and vasa previa have been excluded by ultrasound to prevent catastrophic hemorrhage 1

• Transabdominal and transvaginal ultrasound are the diagnostic mainstays, with transvaginal ultrasound being both accurate and safe for evaluating cervical and placental causes 1
• Fetal anatomy scan at 18-22 weeks is recommended to evaluate for congenital malformations 6

Preventive Considerations for Subsequent Pregnancies

For women with prior second trimester loss:

• Initiate low-dose aspirin (75-100 mg daily) before 16 weeks gestation, which reduces preterm preeclampsia risk from 4.3% to 1.6% in high-risk patients 7
• Implement enhanced surveillance with first trimester uterine artery Doppler to identify placental vascular resistance abnormalities early 7
• Despite identifying causes in only 42.5% of cases, subsequent pregnancy outcomes show 60.9% live birth rates 3