Stillbirth
/Stillbirth is defined as fetal loss at 20 weeks’ gestation OR, if gestational age is unknown, then loss of a 350-gram fetus (which is the 50%tile weight at 20 weeks). Of note, this definition varies internationally. Stillbirth is synonymous with intrauterine fetal demise; some parent groups prefer the term stillbirth and recent research has started using this term instead. Its incidence is 1 in 160 deliveries in the United States, amounting to ~23,600 stillbirths reported annually in this country.
Potential causes of stillbirth:
Placental abruption: identified as the cause of stillbirth in 5-10% of cases
Genetic abnormalities: an abnormal karyotype can be found in ~6-13% of stillbirths
Infection: associated in 10-20% of stillbirths
Umbilical cord events: account for ~10% of stillbirths
The Stillbirth Collaborative Research Network published a study that evaluated 512 stillbirths and identified a probable cause in almost 61% of cases. A possible/probable cause was identified in 76.2% of cases. They discovered that the placental pathology had the highest diagnostic yield (aiding in almost 65% of the cases) followed by fetal autopsy (in 42% of the cases).
How to workup a cause of stillbirth:
Maternal Workup:
Medical history: diabetes, cHTN; autoimmune disease; thrombophilias, VTE; epilepsy
Exposure history: medications; infections; tobacco, alcohol or drugs
Obstetric history: recurrent pregnancy loss (RPL); fetal growth restriction
Family History:
Three-generation pedigree including stillborn infants and RPL
Liveborn infants w/ developmental delays or structural anomalies
Arrhythmias and sudden death (SIDS)
Maternal laboratory evaluation:
Syphilis testing
KB testing once diagnosis is made – and ideally before delivery because KB testing can be falsely elevated after delivery
Antiphospholipid antibody syndrome: One of the clinical criteria for diagnosis of APS is stillbirth: “One or more unexplained deaths of a morphologically normal fetus at or beyond the 10th week of gestation, with normal fetal morphology documented by ultrasound or by direct examination of the fetus.”
Check out our previous episode on this topic for more info.
Routine testing of inherited thrombophilias has NOT been shown to be helpful.
Other testing that is not helpful includes a full infectious serology panel
HbA1c should be obtained for patients with diabetes or suspected diagnosis of thereof.
Grief and Bereavement:
Patient support is two part: emotional support and clear communication of test results
Important to recognize their parenthood and acknowledge their grief, offer referrals to bereavement counselors and peer support groups, and communicate results of the workup in a timely manner.
A provider may feel at loss of words when approaching grief-stricken parents for consent on autopsy and further workup. At times, providers may not feel as though they’ve developed a strong enough rapport with the parent group so may not offer an autopsy to parents due to the concern that it may upset parents further. However, it is important to consider that the evaluation may provide answers and closure for these parents.
In fact, a study done by Rankin et al. estimated that parents who did not consent to a postmortem examination were approximately twice as likely to regret their decision compared tho those who chose to have this investigation performed.
Autopsy:
There are two types of autopsies: a partial and a complete autopsy.
A partial autopsy involves gross inspection of the fetus and placenta, ideally by a trained perinatal pathologist, and imaging studies. Approximately 20% of stillborn fetuses have dysmorphic features or skeletal abnormalities; of these, about 36% will have chromosomal abnormalities (Monosomy X, Trisomies).
Gross inspection would include measuring the weight of the fetus and the placenta, the head circumference and the length of the fetus, as well as obtaining frontal and profile photographs of the whole body, face, extremities, palms and any abnormalities.
Gross and microscopic evaluation of the placenta, as well as umbilical cord and membranes by a trained pathologist is the single most useful aspect of the stillbirth evaluation. Here the pathologist can evaluate for abruption, umbilical cord thrombosis, velamentous cord insertion, vasa previa, infection, and anemia
Cytogenetics Evaluation:
Usually done with karyotyping or microarray. Although new research studies are underway to evaluate if whole genome sequencing may yield better diagnostic utility, it is not currently part of the standard genetics workup in stillbirth evaluations.
The cytogenetic specimens are obtained with sterile techniques and instruments. Acceptable cytogenetics specimens include (place these specimens in a sterile tissue culture medium of lactated ringers solution and keep at room temperature. Do not place in formalin!):
Amniotic fluid obtained by amniocentesis at time of prenatal diagnosis. GOLD STANDARD
Internal fetal tissue specimen, such as costochondral junction or patella; skin is not recommended
Placental block (1x1cm) taken from below the cord insertion site below the unfixed placenta
Umbilical cord segment (1.5cm)
Techniques for cytogenetics evaluation include karyotyping which is fast and relatively inexpensive but can underestimate the contribution of genetic abnormalities because in up to 50% of karyotype attempts, cell culture is unsuccessful.
Chromosomal microarray can detect smaller deletions and duplications as well as aneuploidy. Compared to karyotype analysis, microarray analysis increases the diagnosis of a genetic cause to almost 42%.
Recently, there is new evidence to suggest that whole exome sequencing may further increase diagnostic yield in the evaluation of stillbirth.
In Future Pregnancies:
Offer aneuploidy screening, sonographic screening for fetal growth restriction after 28 weeks and antenatal fetal surveillance as detailed below.
Antenatal fetal surveillance:
For patients with a previous stillbirth at or after 32’0 weeks, once or twice weekly antenatal surveillance is recommended at 32’0 weeks or starting at 1—2 weeks before the gestational age of the prior stillbirth
For prior stillbirths that occurred earlier than 32 weeks gestation, individualized timing of antenatal surveillance should be considered.
Of note, antenatal fetal surveillance could lead to iatrogenic preterm deliveries based on false-positive test results. One study estimated a 1.5% rate of iatrogenic prematurity for interventions based on false-positive results, so this must be weighed in when deciding on type/frequency of surveillance.
Delivery: planned delivery at 39 0/7 weeks of gestation or as dictated by other maternal or fetal comorbid conditions.