ABSTRACT & COMMENTARY
Association Between Maternal Characteristics, Abnormal Serum Aneuploidy Analytes, and Placental Abruption
By John C. Hobbins, MD
Professor, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora
Dr. Hobbins reports no financial relationships relevant to this field of study.
A study using data from the California State Prenatal Screening Program has indicated a strong relationship between abnormal first and second trimester analyte values, as well as maternal characteristics, with placental abruption. This has stimulated a discussion of the possible benefit of retaining this type of biochemistry screening for prediction of other pregnancy complications.
Blumenfeld YJ, et al. Association between maternal characteristics, abnormal serum aneuploidy analytes, and placental abruption. Am J Obstet Gynecol 2014;211:144.e1-9. doi:10.1016/j.ajog.2014.03.027.
The incidence of placental abruption is thought to be about 1 in 100 pregnancies, but this number has been derived mostly from hospital records. The true incidence is higher because many pregnancies complicated by small placental separations uneventfully continue on, leaving little incentive to document at the time of delivery that it ever happened. Recently, there has been a major focus on the prediction of preeclampsia. Almost as a byproduct of this investigation, a study by Blumenfeld et al has linked serum analytes, along with maternal characteristics, with the later emergence of placental abruption.1
The authors mined information from the California Prenatal Screening Program database between 2009 and 2010. After excluding pregnancies complicated by aneuploidy, neural tube defects, abdominal wall defects, and placenta previa, 137,915 pregnancies remained — 1017 of whom were diagnosed to have an abruption. Each patient in the database had pregnancy-associated plasma protein-A (PAPP-A) and human chorionic gonadotropin (hCG) drawn between 10/0 weeks and 13/6 weeks and a full quad screen (estriol, inhibin-A, hCG, and alpha-fetoprotein [AFP]) drawn in the second trimester.
The maternal variables showing increased rates of abruption were: maternal age > 34 years (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.2-1.6), hypertension (OR, 2.5; 95% CI, 1.6-3.8), preeclampsia (OR, 3.8; 95% CI, 3.1-4.8), pre-gestational diabetes (OR, 2.0; 95% CI, 1.2-3.3), previous preterm birth (OR, 2.6; 95% CI, 1.4-4.7) or inter-pregnancy interval < 6 months (OR, 1.8; 95% CI, 1.2-2.7). Curiously, obesity seemed to be a deterrent to abruption (OR, 0.6; 95% CI, 0.4-0.9).
Regarding the ability of analytes to predict abruption, the winners were low PAPP-A
(< 5th percentile; OR, 1.6; 95% CI, 1.3-2.0), high AFP (> 95th percentile; OR 2.3, 95% CI, 1.4-3.8), and high inhibin-A
(> 95th percentile; OR, 1.9; 95% CI, 1.4-2.4). The best performer among maternal characteristics was hypertension. However, if patients with this condition were excluded, then only patients of advanced maternal age, low PAPP-A, and high AFP remained significantly linked with abruption.
Commentary
Some of the maternal characteristics results, especially hypertension and preeclampsia, are not surprising, but maternal age and short inter-pregnancy interval are worth a few words. These two factors point toward an unready or no-longer-ready environment for proper placental implantation. Abruption occurs at the decidual/myometrial border where the early changes in spiral artery remodeling occur. If the placental building blocks are not laid down on solid bedrock or rich soil, then these placentas are prone to disruption later in pregnancy.
The analyte pattern in abruption is fascinating. PAPP-A is a placental growth hormone, low levels of which have been associated with later fetal growth restriction and other complications of pregnancy.2 AFP is produced by the fetus. The placenta’s job as a gatekeeper is to keep substances of higher molecular weight, like AFP, from entering the maternal circulation. One of the first clues for placental disruption waiting to happen may be the leaking across the placenta of small amounts of AFP. All it takes is a little bit since the concentration of AFP in the fetus is measured in mg/mL, in the amniotic fluid in ug/mL, but in the maternal circulation in ng/mL.
About one in 10-15 patients will have some bleeding or spotting in pregnancy, and the diagnosis of abruption is made often by exclusion. There are only three possible causes for vaginal bleeding: placenta previa, placental separation, or external cervical bleeding. The last condition is easy to exclude by a simple speculum exam and the first is diagnosed by a simple trans-abdominal or, better yet, a transvaginal sonogram. Abruption can be a slam dunk diagnosis if an extra membranous clot is seen, but about 50% of the time, the blood tracks extra-membranously to and through the cervix without leaving behind any traces. Under these circumstances, the diagnosis is made by the often-used "what else could it be" approach. In this scenario, an elevated AFP might point even more toward abruption.
We are frequently confronted with patients who have been diagnosed to have a "silent abruption," meaning there is an echo spared area at the uterine/placental interface, or, more commonly, at the edge of the placenta, but with no bleeding. In the former scenario, the echo-spared area generally represents dilated maternal basal veins and can be documented by the use of power or color Doppler. The latter often represents a marginal lake into which intervillous blood flows at such a slow velocity that it is not to be appreciated with standard color flow settings. However, this slow swirling flow can be seen by super-magnifying the area with 2-D ultrasound alone. Clots do not do this. Again, in these clinical settings, serum analytes may be adjunctively useful.
In his companion commentary, Odibo pointed out that the sequential screen and/or quad screen may not be around for long, since the standard aneuploidy screening tests are now being replaced by the more accurate cell-free DNA testing.3 Even the concept of screening for neural tube defects with AFP alone has been challenged. Why? Because second trimester ultrasound imaging of the fetal posterior fossa (to demonstrate or exclude a Chiari malformation) is a far superior screening and diagnostic method for open neural tube defects. To counter, AFP proponents point to its superior public health benefit, since ultrasound expertise is inconsistent throughout the country and not all patients have easy access to second trimester ultrasound exams. Drawing blood for AFP requires minimal resources and one gets the bonus of sometimes useful information about other conditions such as abruption, pre-eclampsia, and even placenta accreta (about 50% of patients with placenta accreta have elevated levels of AFP).4
To accentuate the latter point, the authors of another paper in the same issue of the journal, using pooled data, showed that ultrasound is less precise in detecting accreta than was earlier reported — now showing an 18% false negative rate.5 Any case of unanticipated placenta accreta could end in disaster, but if the AFP were elevated in the face of an equivocal or even a "negative" ultrasound diagnosis of accreta (with a 1 in 5 chance of being wrong), one might still wish to prepare for this at the time of delivery. Perhaps we should think twice before abandoning second trimester biochemistry screening altogether.
References
- Blumenfeld YJ, et al. Am J Obstet Gynecol 2014;211:144.e1-9. doi:10.1016/j.ajog.2014.03.027.
- Dugoff L, Society for Maternal-Fetal Medicine. Obstet Gynecol 2010;115:1052-1061. doi:10.1097/AOG.0b013e3181da93da.
- Odibo AO. Am J Obstet Gynecol 2014;211:89-90. doi:10.1016/j.ajog.2014.03.062.
- Zelop C, et al. Obstet Gynecol 1992;80:693-694.
- Bowman ZS, et al. Am J Obstet Gynecol 2014;211:177.e17. doi:10.1016/j.ajog.2014.03.029.
