Every year, around one million pregnancies in the United States terminate in miscarriage. Furthermore, around 20,000 pregnancies terminate in stillbirth at or after 20 weeks, with approximately 50% of these instances remaining unexplained.
A recent research published in Reproductive Sciences investigates probable placental disorders that might be to blame for these episodes of unexplained infant death.
Introduction
Miscarriage occurs in around 10-25% of pregnancies between five and twenty weeks of gestation. The incidence of unexplained pregnancy loss (EPL) is uncertain, with some studies indicating a 10% frequency and others reporting a 50% prevalence. The most prevalent cause of fetal mortality, according to the Centers for Disease Control and Prevention (CDC), is likewise unknown.
Placental illness is common in failed pregnancies and may be caused by avoidable reasons in up to 67% of instances. However, dysmorphic chorionic villi (DCVs) are not included as a placental defect in these circumstances.
Trophoblast inclusions (TIs) and invaginations are examples of DCVs. Despite the fact that TIs are detected in various genetic disorders and are seldom identified in normal placental tissue, DCVs have not been included in earlier classifications.
What did the study reveal?
The current investigation included approximately 1,200 EPLs from 922 individuals from a tertiary clinical database. All EPLs died between the ages of six and 43 weeks of pregnancy. Over 900 of these were miscarriages, with the remainder being stillbirths before delivery.
Miscarriages occurred at a rate of around 45% in the first trimester, 35% in the second trimester, and 20% in the third trimester, respectively.
Each case’s placental tissue was analyzed for any abnormalities. Approximately 92% of these tissues had a disease process, which included over 90% of miscarriages and practically all stillbirths.
DCVs were shown to be the most common illness cause in unexplained miscarriages (86%). The most frequent pathology among unexplained stillbirths was a tiny placenta, which was detected in 33% of cases.
Other causes of fetal loss included cord accidents, infection, maternal immune system rejection, placental abruption, fetomaternal hemorrhage, and maternal intervillous thrombosis.
Approximately 85% of tiny placentas were in the first percentile or below. DCVs were found in 63% of stillbirths with tiny placentas.
One in every six unexplained stillbirths had a large placenta, with 46% also having DCVs. In 31% of unexplained stillbirths and 15% of cord accidents, DCVs were found. TIs were found in around 75% of DCVs, whereas invaginations were found in 25% of DCVs.
At a median of nine and 13 weeks, early trimester losses were more typically linked with thrombotic villi and DCVs, respectively. Other anomalies were mostly noticed after 33 weeks. When compared to the other two trimesters, third-trimester EPLs had the most diversified etiology.
Over 230 people had multiple losses, with some suffering up to six. Approximately 83% of these individuals had the same pathology in two or more of their losses, with approximately 95% of them being DCVs.
What are the consequences?
For 99% of EPLs, placental disease was identified as a probable underlying cause. Almost of EPLs were effectively identified after combining two extended placental pathology categories. This has clinical implications because placental histopathology is already incorporated into the stillbirth process.
Many pregnancy losses were unexplained and, as a result, possibly avoidable in the absence of these categories. Furthermore, pinpointing placental disease as a key cause of pregnancy loss demonstrates that these occurrences follow a U-shaped curve, with the 20-week marker seen as artificial rather than objective. In reality, the majority of placental losses occur at ten weeks, followed by 39 weeks.
While DCVs are frequently connected with early losses, subsequent losses are predominantly related with tiny placentas and, to a lesser extent, cord accidents. All tiny placentas do not imply that the pregnancy would end in miscarriage; nonetheless, the likelihood of stillbirth increases dramatically if placental weight falls more than one standard deviation below the norm. The recent study found that a tiny placenta was responsible for around 30% of unexplained stillbirths.
Although not yet clinically confirmed, identifying a fetus with a tiny placenta, when combined with other clinical risk factors, may enable an earlier delivery, thereby preventing prenatal stillbirth.”
Future research is needed to identify whether and how certain genetic disorders are linked to the occurrence of DCVs and TIs, especially because TIs and invaginations are more prevalent in cases of placenta percreta, increta, and accreta, as well as fetal growth limitation. These diseases are not more common in women with pregnant hypertension, gestational diabetes, or pre-eclampsia.
More study into how genetic changes enable TIs and invaginations to occur by influencing trophoblast layer differentiation may reveal probable implications of the same process on fetal development, including the existence and driving effects of particular mutations.