| Gestational Period | What Happens | Possible Fetal Effects |
|---|---|---|
| 0–8 weeks | Maternal infection may be present, but fetal infection is difficult to demonstrate clinically | Very early infection could theoretically affect implantation/early development, but a characteristic "syphilitic embryopathy" pattern is not established |
| 9–12 weeks | Transplacental fetal infection is possible. T. pallidum has been demonstrated in fetal tissues from ~9–10 weeks | Early fetal loss is possible; placental infection/inflammation may begin |
| 13–15 weeks | Increasing placental vascular interface and fetal circulation | Fetal infection can become established; inflammatory injury rather than structural malformation predominates |
| 16–20 weeks | Important period for clinically apparent fetal disease | Hepatomegaly, placentomegaly, fetal anemia, ascites/hydrops, abnormal Dopplers may develop |
| 16–28 weeks | Historically described as the period in which transmission most commonly occurs | Increasing risk of fetal inflammatory disease, growth restriction, hepatosplenomegaly, hydrops and fetal death |
| 20–28 weeks | Fetal immune/inflammatory response becomes increasingly important | Hepatitis, anemia, hepatomegaly, placentitis, ascites, hydrops, bowel/intestinal abnormalities and skeletal abnormalities can become apparent |
| 28–40 weeks | Infection may remain clinically silent or progress | FGR, placental abnormalities, anemia, hepatosplenomegaly, hydrops, preterm delivery or stillbirth; neonate may be asymptomatic initially |
Syphilis should not generally be regarded like rubella, CMV or a teratogenic drug producing a predictable first-trimester malformation sequence.
The dominant mechanism is:
Maternal spirochetemia → placental infection/placentitis → transplacental passage of T. pallidum → fetal infection → fetal inflammatory response → organ injury
Thus, the classical fetal manifestations are largely inflammatory and destructive, rather than primary morphogenesis defects.
The fetal manifestations particularly include:
• Hepatomegaly
• Fetal anemia
• Placentomegaly/thickened placenta
• Ascites
• Hydrops
• FGR
• Abnormal fetal Dopplers
• Hepatitis
• Splenomegaly
• Bowel abnormalities
• Skeletal abnormalities, particularly long-bone changes
• Occasionally fetal demise
There are essentially three different fetal outcomes depending on when infection occurs:
Very early infection
→ fetal loss / early miscarriage may occur.
Mid-gestation infection
→ established fetal infection and inflammatory disease
→ hepatomegaly + anemia + placentomegaly ± hydrops
→ potentially severe fetal disease.
Late infection
→ fetal growth restriction, anemia, hepatosplenomegaly, placental disease, preterm birth or a neonate who may initially appear relatively normal.
Importantly, absence of ultrasound abnormalities does not exclude fetal infection. CDC notes that infants with congenital syphilis can be asymptomatic at birth.
Maternal syphilis acquired at 6–8 weeks → fetal anomalies at 12–14 weeks
Maternal infection
↓
Maternal spirochetemia
↓
Placental colonization / placentitis
↓
~9–10 weeks: fetal infection possible
↓
First trimester: fetal loss possible; fixed embryopathy not characteristic
↓
16–28 weeks: major window for clinically evident fetal infection
↓
Placental inflammation + fetal hepatitis
↓
Hepatomegaly + anemia + placentomegaly
↓
Ascites → hydrops → FGR / fetal distress / stillbirth