Below are comments and questions from a reader who underwent combined first trimester screening for aneuploidy. Although the composite screening results did not place her at increased risk for having a baby with trisomy 21 (Down syndrome) or trisomies 18 and 13, she expressed some concern about the significance of the high free-?-hCG result. High free-?-hCG accompanied by low PAPP-A levels (which she did not have) are major determinants of risk for Down syndrome, regardless of the nuchal translucency result. Since I have gotten several queries about this, I thought it might be a good idea to post my thoughts, both in general and with specific attention to our reader’s medical history detailed as follows:
Fri Mar 28, 12:01:00 PM 2008, Anonymous said…
Hi Dr. Trofatter, This is a great blog, thank you! I've been searching for clues as to what else causes elevated free-?-hCG levels (besides trisomy 21) and have gotten only research papers and your blog. I would really appreciate it if you had a moment to look at my case.
My combined screenings came out as follows: singleton CRL 63.6mm, GA 12w6d Overall risk assessment: Trisomy 21 risk - 1 in 743 Trisomy 13/18 risk - 1 in 14,901 _______________________________
NT 1.2mm (Trisomy 21 risk 1 in 4764 on this basis alone) _______________________________ My stats are that I am a 33 year old (at term), Caucasian, 115 lbs maternal weight.
I know one poster already presented with a free-?-hCG of 2.59 MOM, but she also had a high level of PAPP-A, where as I do not. You also mention in the main article that hCG levels tend to diverge and PAPP-A levels converge... A midwife at my hospital called me back and assured me you're not allowed to pick one marker out of the screening to be alarmed, but she also couldn't tell me what else could cause such an elevated level of the hCG.
Since you mentioned these markers are produced by placental cells, perhaps it's of some interest that the ultrasound results also indicate a low anterior placenta, and they weren't sure if the umbilical cord had 2 or 3 blood vessels. Perhaps it is also of interest that I miscarried and had a D&C a couple months before this pregnancy? (I also had an elective abortion at age 19.) I was 9.5 weeks pregnant when I got into a car accident on 11 Nov. 2007. The next day the loss of the baby was confirmed (CRL correlated with fetal death at 9.5 weeks) and dilation commenced that day with the curettage the next morning. They told me to wait one cycle before trying again, and bingo presto, my LMP was 17-December-2007. This perhaps explains my weird implantation site (low anterior), but I have no idea if it explains anything else :(
Thanks *so* much for reading and have a good weekend!
Sun Mar 30, 04:38:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said...
To Anonymous Mar 28: In addition to high hCG levels in Down syndrome (and some other chromosomal abnormalities), sometimes folks just have bigger placentas that make more hCG! This is commonly seen in some diabetics and in multiple gestations. Elevated levels of hCG are also found with molar (or partial molar as would be the case with a baby present) pregnancies and choriocarcinoma. These latter conditions are called ‘gestational trophoblastic diseases’ and they are accompanied by uncontrolled proliferation of the placental trophoblasts and excretion of very high levels of hCG (much higher than yours). Also, in your situation, the hCG may be somewhat ‘artificially elevated’ because of your slight build (although the results are generally ‘corrected’ for maternal weight, there are some difficulties in interpretation at the high and low extremes). However, let me postulate another possible cause in your case (and bear in mind this is JUST a hypothesis)…
There is a possibility that because of the short interval between the previous pregnancy loss with the D&C and the conception of your current pregnancy that this baby implanted on a denuded (still healing) portion of the endometrium and had growth of the trophoblasts (placental cells) into the myometrium ( muscle of the uterus) rather than just the endometrium alone. Under normal circumstances, there is a balance between proliferation and invasion of the trophoblasts and your body's immune system which limits that growth and invasion. The myometrium is not able to control the growth of the trophoblasts as well as can be done in the endometrium. (We see this, routinely, with ectopic pregnancies that grow into and sometimes through the muscular wall of the fallopian tube).
My concern is that if this has occurred, it may increase your risk for a placenta accreta wherein the portion of the placenta that has invaded the myometrium does not detach normally following delivery. I don't know for sure in your case, but this is certainly a possibility and one of the reasons I recommend to women that they wait at least 2-3 months after a D&C to get pregnant again. Sometimes we can actually visualize a placenta accreta by ultrasound later in the pregnancy and you might ask your doctors to consider this option.
Anyway, despite my positing, the overwhelming odds are that both you and the baby are going to do just fine this pregnancy. So, good luck to you, thanks for reading, and let us know how things turn out. Dr T