CMV in pregnancy

Background

• Infection with cytomegalovirus during pregnancy
• Infection can be primary infection, non-primary reinfection with another strain, or non-primary reactivation of latent virus
• Mainly of concern because of the risk of causing congenital CMV

Epidemiology

• Maternal seroconversion in about 2% of pregnancies
  • Higher in childcare workers
• Affects about 1 in 200 live births in US
• Risk of transmission to fetus is highest with maternal primary infection, and much lower for non-primary infection
  • Primary infection: 30% risk of congenital CMV
  • Non-primary:
    • Reinfection: 5% risk
    • Reactivation: 1% risk
• However, due to the much higher number of non-primary infections and reactivations, 75% of congenital CMV occurs in mothers who had non-primary infection
• Risk of transmission to fetus following primary infection increases with gestational age, but risk of neurological sequelae decreases substantially1

Maternal Serostatus	Trimester	Transmission to Fetus	Severity of Neurological Disease			Overall Probability (of any neurological disease)
			Severe	Mild/Transient	None
Primary	periconception	5%
	first	30%	5%	30%	65%	10%
	second	40%	0%	15%	85%	6%
	third	70%	0%	0%	100%	0%
	overall	40%	13%		78%
Reinfection	overall	5%				<1%
Reactivation	overall	1%				<1%

• Overall, 20% of infected babies will have permanent neurological sequelae2
  • 50% of those symptomatic at birth and 15% of those asymptomatic

Diagnosis

• Serology with IgM and IgG
  • IgM usually positive for 6 weeks after primary infection, but can remain positive for as long as 12 months
  • IgM has false positives, including from rheumatoid factor, EBV infection, lupus

IgG	IgM	Avidity	Interpretation
+	–	N/A	past infection, low risk for congenital infection
+	+	high	past infection, low risk for congenital infection
+	+	low	primary maternal infection within the past 3 months
–	–	N/A	either no infection, or repeat in 4 weeks

• Fetal infection is confirmed by amniocentesis sent for PCR
  • To minimized the risk of a false-negative result, it should be be done after 17 weeks gestation and at least 7 weeks after maternal infection

Management

• No clear benefit to use of CMV-targetted antivirals (ganciclovir or valganciclovir), and possible risk of gonadal dysgenesis and hematologic toxicity
• CMV hyperimmune globulin is promising but not yet in widespread use
• Counsel mother on risk of fetal infection and subsequent development of congenital CMV
• If they would terminate if CMV-positive due to those risks, then proceed with amniocentesis to diagnose

Prevention

• Prevention focusses on lifestyle or behavioural changes that can decrease the risk of primary or non-primary infection
  • Not sharing food, drink, utensils with young children
  • Not putting a child pacifier in the mouth
  • Avoiding saliva when kissing a child
  • Washing hands properly with soap and water after changing diapers, feeding children, or wiping children's nose or mouth
  • Not sharing toothbrushes
  • Cleaning surfaces and toys contaminated with children's urine or saliva
• Screening for CMV immunity is not routinely recommended, since 75% of infants with congenital CMV are born to infants with non-primary infection