Neonatal death caused by complications of prematurity linked to maternal cervical insufficiency; possible role of anticardiolipin antibodies
September 5, 2023
A baby girl was born prematurely at about 25 weeks of gestation and died one day and 11 hours after her birth. Although the baby was born with an APGAR score of 9 and was crying, showing spontaneous movement, and had a regular heartbeat, she had difficulty breathing and could not be fed. She was immediately admitted to the NICU but unfortunately passed away while receiving treatment.
Her mother, a 20-year-old woman, had four previous pregnancies but no surviving children. In her first pregnancy, the baby died one day after delivery because of prematurity; subsequent pregnancies resulted in miscarriages. In the current pregnancy, the mother attended four antenatal care visits and had one ultrasound. She also received cervical cerclage—a procedure temporarily stitching the cervix closed during pregnancy to avoid preterm birth—at 14 weeks and 3 days gestational. Symptoms noted during her pregnancy included pelvic pain and foul-smelling discharge (leucorrhea).
Uncovering the Cause
The family consented to participate in CHAMPS and the MITS procedure performed. The placenta was not available to be sampled or examined. Results from microbiology and molecular testing of other MITS specimens through CHAMPS did not indicate any infectious etiology. Pathologists noted that lung samples showed signs of prematurity, aspiration of rare squamous cells without inflammation, and increased alveolar macrophages — findings compatible with intrauterine fetal stress. The CHAMPS Determination of Cause of Death (DeCoDe) panel determined that the baby’s extreme prematurity led to hyaline membrane disease, also known as respiratory distress syndrome, which caused the death. The premature labor was caused by maternal cervical insufficiency, despite the cerclage procedure.
DeCoDe panelists also noted the mother’s challenges with preterm delivery and recurrent pregnancy loss and recommended that she undergo further testing. Anatomical causes that can lead to recurrent pregnancy loss include congenital defects, such as having a septum in the uterus or a bicornuate uterus, or acquired conditions in the uterus such as fibroids or polyps. Procedures like transvaginal sonogram and hysterosalpingogram can detect anatomical problems. Women with recurrent pregnancy loss should also be tested for antiphospholipid antibody syndrome, including tests for anticardiolipin antibodies (IgG and IgM) and lupus anticoagulant, to rule out a medical explanation. Pathology examination of the placenta can show clotting or other findings suggestive of antiphospholipid antibody syndrome; such an examination could not be conducted for this death, however, as the placenta had been discarded before the baby enrolled in CHAMPS.
Unfortunately, histopathological evaluation was limited due to samples from this case are 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.
During the final session of family follow-up, the CHAMPS team learned that the mother had recently become pregnant again and suffered another miscarriage of a set of twins. The CHAMPS team gave the mother final results from the DeCoDe panel’s review in addition to information about recurrent miscarriages and how to get tested. The mother was referred to take an anticardiolipin antibody test, which came back positive. The mother planned to have a second test to confirm the diagnosis. Knowing she has this diagnosis will allow her to work closely with her obstetric care provider in the future and increase her chances for having a healthy baby.
Public Health Implications
Anticardiolipin antibodies are a specific type of a family of antiphospholipid antibodies – antibodies that attack certain types of fat. What causes a person to have antiphospholipid antibodies is unknown, but complications of having antiphospholipid antibodies during pregnancy have been studied. Women who have these antibodies are at higher risk during pregnancy for stroke, blood clots, high blood pressure, stillbirths, miscarriages, poor fetal growth and preterm birth. Some of these complications are thought to occur because the antibodies cause damage to the placenta, which in turn affects the fetus’ ability to grow or survive.
Access to health facilities that can provide high-risk pregnancy care and the needed medical testing is important for expectant women who have a history of miscarriages and stillbirths. Training for obstetric care providers should cover the importance of testing for potential causes for women experiencing unexplained fetal loss or recurring miscarriages.
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