A baby boy was stillborn at the 39^th week of gestation, weighing 2.44 kg.  His mother, a 19-year-old married woman, had no notable complications throughout her pregnancy, and she took iron, calcium, and folic acid during pregnancy for about a month. She reported taking some herbal medicines before her pregnancy to increase fertility. She had been married for 5 years, and this was her second pregnancy. Her first pregnancy ended in a miscarriage at 12 weeks gestation for unknown causes.

During the verbal autopsy interview, the mother reported that she experienced blurring of vision and weakness until her third month of pregnancy. She attended two ANC visits with a qualified private physician. The first ANC visit occurred during the 25^th gestational week, during which the doctor reported that the baby was fine. Due to her financial situation, she could not afford regular check-ups, despite the doctor’s recommendations.

During the second ANC visit at the 35^th week of gestation, she complained of low-back pain and body aches.  In addition, she underwent several blood tests, including hemoglobin (11.3 gm/dl), random blood sugar (4.2 mmol/l), serum total thyroid stimulating hormone (2.15 IU/ml), blood grouping (A+), and routine urine examination, which showed no abnormalities. An ultrasonogram revealed a single live pregnancy of 35+ weeks gestation with cephalic presentation. The amniotic fluid was adequate (approximately 16 ml). Other ultrasonogram findings included antero‐fundal placenta with maturity grade II, fetal heart rate of 150 bpm, and fetal weight of approximately 2.3 kg. The mother was prescribed paracetamol, iron, calcium, and vitamin supplements.

One night during the 39^th gestational week, the mother noted not feeling any fetal movement. The following morning, she consulted with her physician, who examined her and performed ultrasonography. The results of the ultrasonogram revealed a case of intrauterine fetal death with adequate liquor and placental maturity grade III. She was immediately referred to a tertiary care hospital.

The mother was admitted to the hospital at 1:15 p.m. Upon admission, her blood pressure was 120/70 mmHg, and her pulse was 80 bpm. She did not show signs of anemia on general examination, and her temperature was normal. She was prescribed mifepristone to initiate labor and two antibiotics – ceftriaxone and metronidazole. On the third day of admission, at 11:40 PM, the baby was delivered stillborn by spontaneous vaginal delivery without any additional complications for the mother.

Uncovering the Cause

As the family had experienced adverse outcomes in their previous pregnancy, they expressed interest in knowing the cause of this baby’s death. After obtaining consent from the family, a minimally invasive tissue sampling (MITS) procedure was performed approximately an hour after delivery. PCR testing for multiple pathogens in the CHAMPS laboratory using the Taqman Array Card (TAC) were positive for Cytomegalovirus (CMV).

The site pathology report revealed severe destruction of cells in the liver and both right and left preterm lungs. In the placenta, mild intra-amniotic infection (acute deciduitis and subchorionitis), chronic terminal villous infarction, villous stromal karyorrhexis, and maternal villous malperfusion (distal villous hypoplasia, increased syncytial knots) were found.

The available clinical data and verbal autopsy alone were insufficient to make a reasonable inference on cause of death. The mother did not recognize any complications during her pregnancy, labor, and delivery, and without the diagnosis of CMV, the cause of death would have remained obscure. Most people infected with CMV are asymptomatic, and routine screening, which includes a panel of tests to detect infections in pregnant women, is not commonly practiced. This means that the mother was never diagnosed with CMV during her pregnancy. However, the detection of CMV through the minimally invasive tissue sampling (MITS) performed by CHAMPS allowed for a specific diagnosis of Congenital CMV infection.

Pathology Images 

Unfortunately, histopathological evaluation was limited because samples from this case were technically inadequate (Technical adequacy requires the presence of at least 2 full cores of target tissue for evaluation). Hyaline membrane disease illustrated with CHAMPS Pathology Image

Family Follow-Up 

CHAMPS results provided much-needed answers for the family of the stillborn child and demonstrate the importance of routine screening for CMV.  After learning about her baby’s cause of death, the mother was under regular follow-up through the CHAMPS sites’ follow-up system The mother was completely healthy at the first follow-up visit and remained healthy at subsequent visits. A CMV-infected person, although healthy, is a lifelong carrier, and the virus can reactivate in immunocompromised conditions. Although unlikely, CMV could be an issue in her future pregnancies.   As such, the mother was advised to consult with a specialist before planning her subsequent pregnancy and to receive regular antenatal check-ups. The family was also educated about the possible future risks and precautions that should be taken.

Public Health Implications

The disease burden of CMV is not well studied or documented in many countries, including in the country where this case occurred. However, CMV is known to be a common infection worldwide and is known for causing congenital anomalies. According to the U.S. Centers for Disease Control and Prevention (CDC), Cytomegalovirus is the most common infectious cause of birth defects, and almost 1 in every 200 babies is born with Congenital CMV infection in the United States. Babies infected with CMV often show no symptoms, but about one-fifth of those infected will show immediate symptoms or have immediate or chronic neuro-developmental health problems like hearing or vision loss, intrauterine growth restriction, enlarged liver and spleen, retinitis, vision loss, microcephaly, seizures, intellectual disability and lack of coordination or weakness. Congenital CMV infection can be diagnosed both intrapartum (based on amniotic fluid to test for chromosomal abnormalities and fetal infections) and within 2-3 weeks of birth by testing the baby’s urine, saliva, or blood. Available antiviral drugs can reduce the severity of the effects in the long run, but early and timely diagnosis of the mother and child is necessary for recognizing the need for treatment and for the best outcome.

Having a vaccine that could effectively prevent CMV infection would be an enormous step forward. In the meantime, routine screening tests for CMV should be a common practice among obstetricians, particularly when infections are suspected in pregnant mothers. Awareness and health education can provide accurate and accessible information to empower individuals to protect themselves and reduce the spread of CMV in their communities. Increasing the availability of screening facilities and subsequent treatments for cytomegalovirus (CMV) infection is an important public health need.

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