Saturday, September 18, 2021

Congenital Infection of the Neonate Case File

Posted By: Medical Group - 9/18/2021 Post Author : Medical Group Post Date : Saturday, September 18, 2021 Post Time : 9/18/2021
Congenital Infection of the Neonate Case File
Eugene C. Toy, MD, Edward Yeomans, MD, Linda Fonseca, MD, Joseph M. Ernest, MD

Case 12
A 17-year-old primigravida presents in labor with no prenatal care. By her LMP, she is 39 weeks’ gestation, but bedside ultrasound reveals a symmetrically grown fetus with normal amniotic fluid volume, estimated fetal weight of 2300 g, and estimated gestational age of 34 weeks. She denies medical problems or drug usage prior to or during pregnancy. Her vital signs are normal and she rapidly progresses from 6 cm dilation to spontaneous vaginal delivery of a 2390 g male infant with Apgar score of 7/8. On examination of the neonate, the pediatrician estimates the gestational age to be 39 to 40 weeks and notes hepatosplenomegaly and a petechial rash over the infant’s trunk and extremities.

➤ What is the most likely diagnosis?
➤ What is your next step?
➤ What are potential complications of the patient’s disorder?


ANSWERS TO CASE 12:
Congenital Infection of the Neonate

Summary: This 17-year-old primigravida with a negative medical history delivered a symmetrically growth-restricted infant at term with evidence of thrombocytopenia and hepatosplenomegaly after a pregnancy with no prenatal care.

➤ Most likely diagnosis: Congenital cytomegalovirus infection.
➤ Next step: Evaluate patient for acute, chronic infection.
➤ Potential complications: Potential infectivity to other patients, staff; risk of recurrence in subsequent pregnancy; long-term effects to neonate.


ANALYSIS
Objectives
  1. Recognize the prenatal patient at risk for delivering an infant with a congenital infection.
  2. Understand noninvasive and invasive testing appropriate to evaluate the potentially infected prenatal patient.
  3. Describe the labor management of the patient at risk for a congenitally infected neonate.
  4. Discuss the risk of recurrence of congenital infection in subsequent pregnancies.

Considerations
While most pregnant patients who deliver congenitally infected infants have had no identifiable risk factors before delivery, specific situations occur that do pose additional risk. In addition to routine testing at the initial prenatal visit for hepatitis B, syphilis, gonorrhea, Chlamydia, HIV, and rubella, careful history at that time may reveal risk factors for, or prior infection with, other potential pathogens including group B β-hemolytic Streptococcus (GBS), herpes simplex virus (HSV), hepatitis C, and toxoplasmosis. During pregnancy, a nondescript viral type illness may indicate the presence of toxoplasmosis, parvovirus, hepatitis B or C, or CMV that, depending on the trimester, could pose devastating effects on the fetus.

The congenitally infected fetus may demonstrate impaired growth in a symmetrical fashion, as opposed to the asymmetrically growth-restricted infant whose impaired growth is due to placental inadequacy. The congenitally infected fetus may also demonstrate anomalies including hydrops, intracranial calcifications, ventriculomegaly or hydrocephalus, cardiac anomalies, and bony abnormalities.

At delivery, the neonate that is small for gestational age without obvious prenatal etiology, has consistently low Apgar scores at 5 and 10 minutes with no evidence of intrapartum cause, and/or has a rash or petechiae should be brought to the attention of the pediatrician for further evaluation for potential congenital infection. An ongoing discussion between the obstetrician and pediatrician should ensue to determine if isolation of neonate or mother is warranted, and if further maternal testing would assist the pediatrician in determining the underlying cause of the neonate’s appearance at birth.

APPROACH TO
Congenital Infection of the Neonate
If not previously performed at her first prenatal visit, the patient whose previous child has been affected with a congenital infection should be evaluated for the potential for recurrence. The development of maternal antibodies to rubella and parvovirus protect future fetuses and make the recurrence of toxoplasmosis and hepatitis B unlikely. Hepatitis C and HSV become much less likely to recur with the presence of maternal antibodies, and the potential for antibiotic-induced eradication of syphilis, gonorrhea, Chlamydia, and Listeria makes recurrence of these infections potentially preventable. Antibiotic prophylaxis to reduce vaginal colonization with GBS reduces the risk of neonatal infection with this bacteria, and antenatal and intrapartum prophylaxis with appropriate antivirals reduces the risk of vertical transmission with HIV.

Table 12–1 lists various agents responsible for congenital infection, the baseline population risk of congenital infection, the method to confirm diagnosis, and risk of congenital infection with an acute infection during pregnancy if no treatment is offered (or available). While routine screening is obtained for many of these infectious agents, others will be detected only with a high index of suspicion. Table 12–2 lists reasons why a potential agent that causes congenital infection may come to the attention of the obstetrician and necessitate further testing.

CMV Infection
Cytomegalovirus (CMV) is the most common congenital infection worldwide. It is found in many secretions, and daycare centers are common locations of acquisition of the infection. Primary infection with CMV is associated with a higher viral load and a risk factor for congenital infection. After the primary infection, the virus can be dormant and have periodic reactivation. Viral shedding occurs despite the presence of IgG antibody. Pregnant women are often asymptomatic; however, 10% to 15% of infected women

congenital infection and detection methods

develop a mono-like illness with fatigue, lymphadenopathy, elevated liver function tests, fever, and pharyngitis.

Primary infection, associated with higher viral load, is associated with a 40% to 50% fetal transmission, and can lead to significant morbidity and mortality. Reactivation is associated with only a 1% risk of vertical transmission. With such a high prevalence of CMV infection, thankfully, most neonates are asymptomatic. Only 5% manifest the severe congenital syndrome of IUGR, microcephaly, intracranial calcifications, mental retardation, sensorneural deficits, hepatosplenomegaly, and jaundice. Nevertheless, some of the asymptomatic neonates will develop learning disabilities or neurological deficits later in childhood.

The diagnosis of maternal infection with CMV is established with paired acute and convalescent titers. CMV-specific IgM antibody is diagnostic of acute infection; also a fourfold rise in IgG titer is likewise diagnostic. Viral culture is not generally helpful. Suspicion of fetal infection is raised by IUGR, microcephaly, cerebral calcifications, ascites, hyperechoic bowel, and oligohydramnios. Amniotic fluid assay for PCR of the CMV DNA is considered the test of choice.

evaluation for infection

The treatment of a pregnant woman infected by CMV is supportive. In situations where a primary infection that is discovered, the patient should be offered amniocentesis testing. Counseling should be careful since although the transmission with primary infection is high, the likelihood of a normal neonate is also very high. There is currently no vaccine. Antiviral therapy has not been shown to decrease vertical transmission. Some limited data suggest that CMV-specific IgG may decrease vertical transmission, although more studies are needed. The focus on congenital CMV is currently prevention. Antiviral therapy to the infected neonate may decrease the risk of later sequelae.

Other Infections
When an agent that may cause congenital infection has been identified during a pregnancy, it is important to determine if therapy is indicated and if specific prenatal evaluations should be avoided to minimize infectious risk to the fetus. Table 12–3 lists infectious agents, whether therapy is available, and the risk of congenital infection if optimal therapy is administered. Table 12–4 lists those infectious agents and activities that may affect the risk of vertical transmission. The patient will often inquire about the safety of lactation and the possibility of congentital infection. Aside from maternal HIV infection or cracked/bleeding nipples where blood-borne pathogens may be an issue, breast-feeding is safe.

When a fetus is suspected of having acquired a congenital infection, the potential effects of that infection should be discussed with the parents. While there are many determinants of the severity of fetal infection including the nature of the infectious agent, general rules are that primary maternal infections and earlier trimester of acquisition seem to be most important.

Once the neonate is delivered and the pediatricians have determined the presence of a congenital infection, the parents should be informed about the risk of recurrence and activities they may undertake to reduce or prevent recurrence. Table 12–5 lists various agents and the effects of congenital infection and risk of recurrence in subsequent pregnancies.

risk of congenital infection


Congenital Infection of the Neonate


effects of congenital infection and risk of recurrence


Comprehension Questions

12.1 A 27-year-old G2P1 woman at 8 weeks’ gestation is seen for her first prenatal visit. Her first pregnancy was complicated by a neonate with congenital toxoplasmosis. Which of the following statements dealing with recurrence is the most appropriate?
A. “You should have your housecats tested for toxoplasmosis.”
B. “The risk of recurrence is extremely low.”
C. “We will need to retest you for toxoplasmosis antibodies.”
D. “You will need prophylactic antibiotics near term.”

12.2 The most common fetal presentation of parvovirus B19 infection is
which of the following?
A. Hypoplastic left heart
B. Skeletal dysplasia
C. Ventriculomegaly
D. Hydrops fetalis

12.3 A 24-year-old G1P1 woman is inquiring about whether it is acceptable for her to breast-feed. Breast-feeding is contraindicated in which of the following maternal infections?
A. HIV
B. Hepatitis B virus
C. Hepatitis C virus
D. Group B Streptococcus
E. Syphilis

12.4 Which of the following organisms cannot be completely eradicated from the pregnant woman with antibiotics?
A. Neisseria gonorrhea
B. Chlamydia trachomatis
C. Treponema pallidum
D. Group B Streptococcus


ANSWERS

12.1 B. Patients with a history of delivering a neonate with congenital toxoplasmosis develop antibodies to the parasite. These antibodies enable them to convey immunity to future pregnancies and can be reassured that recurrence of congenital infection is extremely rare. Testing cats for toxoplasmosis provides no useful information to aid with pregnancy management, and maternal antibody status will be positive (because of her history) and thus not necessary to evaluate.

12.2 D. Fetal parvovirus infection causes severe anemia and myocarditis, both of which may be responsible for congestive heart failure and hydrops. Structural anomalies are not associated with congenital parvovirus infection.

12.3 A. Because of the availability of clean water and infant formula, breast-feeding in developed countries is contraindicated in women who are HIV positive. In developing nations with poor or contaminated water supplies and erratic availability of appropriate formula, breastfeeding is sometimes recommended.

12.4 D. Group B Streptococcus resides in the vagina and rectum, and is rarely eradicated with antibiotics. Thus, during each pregnancy, even with a history of antibiotic therapy, reevaluation of the vaginal and rectal flora is indicated.


Clinical Pearls

See US Preventive Services Task Force Study Quality levels of evidence in Case 1
➤ The fetus with no structural anatomic abnormalities found to have nonimmune hydrops fetalis should be evaluated for congenital infection (Level II-3).
➤ The neonate with low Apgar score, growth restriction, and petechiae should be carefully evaluated by pediatrics for congenital infection (Level II-2).
➤ Maternal HIV rarely results in an infected neonate when antenatal and intrapartum evaluations and antiviral medications are appropriately administered (Level I).
➤ Invasive diagnostic procedures, such as amniocentesis, may be offered in all situations of maternal infection, after careful counseling with the parents regarding actual and theoretical risks (Level III).
➤ Cesarean section solely because of the presence of maternal infection is indicated only in selected cases of HIV and HSV (Level I).
➤ The most common congenital infection is cytomegalovirus (Level II-2).

REFERENCES

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2. Alexander JM, Sheffield JS, Sanchez PJ, et al: Efficacy of treatment for syphilis in pregnancy. Obstet Gynecol. 1999;93:5. 

3. Bialek SR, Armstrong GL, Williams IT. Hepatitis C virus. In: Long S, ed. Principles and Practice of Pediatric Infectious Diseases. 3rd ed. Philadelphia, PA: Churchill Livingstone; 2008. 

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5. Centers for Disease Control and Prevention: Achievements in public health: elimination of rubella and congenital rubella syndrome—United States, 1969- 2004. MWR. 2005;54:279-282. 

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17. Ouellet A, Sherlock R, Toye B, Fung KF. Antenatal diagnosis of intrauterine infection with coxsackievirus B3 associated with live birth. Infect Dis Obstet Gynecol. 2004;12(1):23-26. 

18. Pembrey Lucy, Newell Marie-Louise, Tovo Pier-Angelo, and the EPHN Collaborators. The management of HCV infected pregnant women and their children. J Hepatol. 2005;43:515-525. 

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