Perinatology Consult #2 - September 2010

Perinatology Notes

September 2010

Patient comes in with a tragic pregnancy history and infertility for a prepregnancy consultation. Patient’s pregnancy history is as follows. She is gravida 5, para 2-1-2-2. Her first pregnancy was in 2003. Her son was found to be lagging in growth at 20 weeks, more severe by 30 weeks, but she delivered at term weighing 5 pounds 0 ounces. He had thick meconium and a nuchal cord. Apgars were 2 and 7, and he spent 5 days in the Neonatal Intensive Care Unit. She was told that the placenta was small and the umbilical cord was thin. No pathology was done. Her son is 7 years old.

In 2005 her daughter was delivered at 38 weeks. She weighed 6 pounds 3 ounces and the placenta was noted to have a partial abruption that occurred during labor. She was also told the placenta had “2 sacs”, which probably means a chorion-amnion separation. Again, no pathology was performed.

The patient’s next pregnancy occurred in 2007. This resulted in an in utero fetal demise at 21 weeks. Patient had a positive test for anticardiolipin antibody following delivery, but retesting 6 weeks later was negative. The pathology on the placenta and cord showed hypercoiling and a disrupted placenta. No mention was made of a Kleihauer-Betke.

Again in 2007 patient had an 18 week fetal demise, where a cord stricture was noted on pathology. Additional testing showed she is heterozygous for MTHRF. This placenta showed old blood in the amniotic fluid which, of course, could have occurred after the demise, and there was also 2.5 cc of fetal blood in her circulation, which is well within normal limits. Patient had been treated with a single baby aspirin a day during that pregnancy because of the history of anticardiolopin antibody, even though testing for this was negative after this pregnancy. She had a consultation with a perinatologist after that loss which included a complete workup of protein S and C, antithrombin III, factor II, HSV, IgG and IgM, which was only positive in IgG, CMV, and toxo, all negative. The only positive result was the heterozygosity for MTHFR. Again, anticardiolipin antibody was negative.

In 2008, patient had a laparoscopy showing endometriosis and scarring from her previous surgery for cyst removal. This was a 20 cm mucinous cystadenoma removed intact before any of their pregnancies. The right tube and ovary were removed. After this, she has had difficulty with infertility, as mentioned earlier. In 02/2009 she got pregnant on her first cycle of Clomid and IUI. This resulted in a very early loss.


Patient’s past medical history is significant for palpitations, which have been worked up extensively with a normal echo and Holter monitor. She reports that these have decreased. She is on oral contraceptive pills and feels that her periods are getting shorter and shorter. She has long been at her ideal weight. She is planning a mid-October attempt with IVF.


The patient is a healthy, 34-year-old woman in no respiratory distress. She is alert, well-oriented, well-nourished, and well-hydrated. She has no unusual skin rashes, joint deformities, or edema. Her mood and affect are appropriate.

Patient has done a great deal of research. She feels that given her first child’s small size and small placenta, she may have issues with umbilical cords that could be recurrent and, it is true, there are a number of case studies regarding cord structure as a cause for recurrent fetal death. The most recent one I found was in Obstetrics and Gynecology, 2005, Vol. 105, pp. 1235-1239. The first author is Amy French. Your patient has found a Dr. Jason Collins who runs a Pregnancy Institute in Louisiana and has many ideas of care for patients with previous cord accidents. I am not familiar with his work.

The patient may well have a genetic problem. Her husband was reportedly only 5 pounds at term birth, so he was somewhat growth-delayed. Patient does have a chromosomal abnormality, but it appears to be a common normal variant. I made arrangements for her to see a genetic counselor as well.

Her family history does not include any diabetes, thromboses, or hypertension. There is no Lupus in the family.

I feel that the number of losses and problems with pregnancy justify a fairly extensive workup. I took the liberty of drawing a TSH, a vitamin D level, a hemoglobin A1c, a CBC with platelets, lupus anticoagulant, beta 2 glycoprotein, plasminogen inhibitor A, a FANA, and a homocysteine level. I will call the patient with these results next week. I, sadly, have no certain explanation for her losses.

I recommend that she start omega-3 at 1000 mg a day, vitamin D at 1000 mg a day, and folic acid to override her MTHFR heterozygous gene mutation. I would like to see her get about 2 mg of folic acid a day total and told her to continue the baby aspirin.

If she should achieve pregnancy with IVF, clearly high-risk prenatal care from the beginning is important. She reports talking to several people online who have started Lovenox at the day of embryo transfer with IVF. I have no objection to this, although there is clearly no data to support it. I am sure her RE would not object to it either. I would start her on 40 mg SQ of Lovenox since she has never had a thrombosis, nor does she have any first degree relatives who have had thromboses.

My additional recommendations would include nuchal translucency at 11-13 weeks. In addition, a sequential test at 16 weeks, to additionally screen for placental problems. These proteins can give warning of placental problems, particularly low PAAP-A and beta-hCG, as well as elevated maternal serum AFP. A targeted ultrasound at 20 weeks would be the next ultrasound, although an interim study looking at the cord for hypercoiling and constriction will probably be wanted by your patient. Clearly, previable cord constriction as a source of stillbirth is not a preventable problem. If we do see a stricture of the umbilical cord or alterations in the placental architecture, she will be exceedingly anxious and probably want daily fetal monitoring. I would be reluctant to do this before viability, which in our setting is 23 weeks. It think it would be important to follow her very closely with ultrasounds every 3 to 4 weeks for growth and intense fetal surveillance when she gets to viability. Hopefully, her next baby will be very well grown and have a completely different pattern than her previous pregnancy losses. Time will tell.


ANA (antinuclear antibody) – Positive 1:40 with speckled pattern

Beta 2 Glycoprotein 1 -

IgA: 69.46 U/mL
IgM: 4.84 U/mL
IgG: 3.72 U/mL

Note from Mayo Clinic Lab for IgA, IgM, and IgG interpretation:
<10.0 U/mL = negative
10.0 – 14.9 U/mL = borderline
>15 U/mL = positive


Cardiolipin Antibody
Plasminogen INH1 ACT
Lupus Anticoagulant

[Note:  This visit cost $3526!!!  My insurance company must hate me - this is just a drop in the bucket compared to all the other expenses I've racked up these last few years!]