Clinical Review
UPDATE ON OBSTETRICS
The drive to do more and do it faster continues, leading to notable advances in prenatal diagnosis and fetal therapy, but is not sustainable over...
What this EVIDENCE means for practice
Be alert and ready to act if an infectious threat is noted in your obstetric population. Get your flu shot. Give it to your obstetric patients. And don’t forget that ACOG also supports the administration of one dose of the tetanus, diphtheria, and pertussis vaccine during each pregnancy.
How much prenatal screening is too much?
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Dugoff L; Society for Maternal-Fetal Medicine. First- and second-trimester maternal serum markers for aneuploidy and adverse obstetric outcomes. Obstet Gynecol. 2010;115(5):1052–1061.
Martin A, Krishna I, Martina B, et al. Can the quantity of cell-free fetal DNA predict preeclampsia: a systematic review. Prenatal Diagn. 2014;34(7): 685–691.
Audibert F, Boucoiran I, An N, et al. Screening for preeclampsia using first-trimester serum markers and uterine artery Doppler in nulliparous women. Am J Obstet Gynecol. 2010;203(4):383.e1–e8.
Myatt L, Clifton RG, Roberts JM, et al. First-trimester prediction of preeclampsia in nulliparous women at low risk. Obstet Gynecol. 2012;119(6):1234–1242.
The placenta of a normal pregnancy secretes small amounts of a variety of biomarkers such as alpha-fetoprotein (AFP), human chorionic gonadotropin, unconjugated estriol, inhibin A, pregnancy-associated placental protein A (PAPP-A), soluble fms-like tyrosine kinase, and placental growth factor.
The association between abnormal maternal serum biomarkers and abnormal pregnancy outcomes has been known since the 1970s, when elevated AFP was noted in pregnancies with fetal open neural tube defects. Shortly thereafter, low levels of AFP were associated with fetuses with trisomy 21.
One theory is that the abnormality in pregnancy leads to abnormal regulation at the level of the fetal-placental interface and over- or under-secretion of the various biomarkers. An offshoot of this theory is the idea that abnormal placentation (ie, preeclampsia, fetal growth restriction, accreta) also may be reflected in elevated or suppressed secretion of placental biomarkers, which could be used to screen for these conditions during pregnancy.
PAPP-A is a placental serum marker that is a component of first-trimester genetic screening. It is a marker of placental function, and low levels have been associated with fetal growth restriction, preterm birth, preeclampsia, and fetal loss. Another first-trimester marker associated with adverse outcomes is cell-free fetal DNA. This DNA, found in the maternal blood, is a product of placental apoptosis, and elevated levels have been demonstrated in women who develop preeclampsia.
Although many of the biomarkers listed here are not available specifically as a clinical screening test in the United States, the link to common genetic screens makes it tempting to try to add prediction of preeclampsia and other information to an existing test. If specific numbers are reported on the genetic screen for the different markers, that information is already there, and some companies may flag abnormally high or low levels.
However, although the association between abnormal pregnancy outcomes and abnormal biomarkers is well established in the literature, the clinical predictive value is not—nor is there always an effective intervention available. One could argue that low-dose aspirin, which is already recommended for patients with a prior delivery before 34 weeks due to preeclampsia, or more than one prior pregnancy with preeclampsia, could be recommended for patients identified on early screens to be at increased risk for preeclampsia. This approach should be tested in randomized clinical trials before universal adoption.
What this EVIDENCE means for practice
Although it is tempting to use associations to predict adverse events, the clinical value of doing so has not yet been proven. Exercise caution before potentially causing concern for both you and your patient.
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