Having 5 or more children might put a woman at risk for shortened survival if
she later needs a heart transplant, according to new research presented here at
the International Society for Heart and Lung Transplantation 29th Annual Meeting
and Scientific Sessions.

"Pregnancy may represent an independent risk factor for yearly acute rejection
risk," said lead investigator Cheri Silverstein, MD, a clinical research fellow
in the Division of Cardiovascular Medicine at Vanderbilt University in
Nashville, Tennessee.

The risk for rejection appears to be independent of sensitization to fetal
antigens, Dr. Silverstein said.

Women who undergo orthotopic heart transplantation appear to be at increased
risk for rejection, compared with men, Dr. Silverstein said, and smaller studies
have suggested that a history of pregnancy in general, and 2 or more pregnancies
in particular, puts women at increased risk for elevated panel reactive
antibodies (PRA), a marker for rejection.

To determine whether cumulative pregnancies might increase the risk for
rejection requiring treatment within the first year, Dr. Silverstein and
colleagues gathered data from the United Network for Organ Sharing (UNOS)
database on all first transplants from 1995 to 2006 in patients 16 years and
older. They found data on rejection and prior pregnancy for 2644 women, and
compared the information with data on rejection for 10,172 men.

The authors used chi-square testing to evaluate the relation between the number
of pregnancies and sex with rejection, and multivariate logistic regression
analysis to assess the ability of the number of pregnancies to predict
rejection.

When they looked at the fraction of patients with rejection by number of
pregnancies, they found a clear and significant linear relationship, with
nulliparous women having virtually no risk, and women with 5 or more pregnancies
being at the highest risk (£q2 = 22.9; P = .0008).

In an analysis of rejection by sex, the investigators found that there was no
significant difference between men and women who had never been pregnant,
although there appeared to be a trend toward a higher fraction of women with
rejection.

"We suspect, but we can't determine, that this may represent some underreporting
of pregnancies, as opposed to number of children," Dr. Silverstein said.

In an analysis of class II PRA by pregnancy number in 536 women, reserachers
found a strong correlation with higher numbers of antibodies and higher numbers
of pregnancies (£q2 = 29.7; P = .003).

In logistic regression analysis, the only significant risk factor for rejection,
other than elevated PRA, was 5 or more pregnancies, which was associated with a
more than 2-fold risk for rejection requiring treatment in the first year (odds
ratio, 2.224; 95% confidence interval, 1.031 - 4.796).

Dr. Silverstein acknowledged that the study was limited by missing data and the
fact that the database did not contain information about patients surviving less
than 275 days, meaning that the investigators could not analyze any data about
hyperacute rejections or early adverse outcomes.

"There's no question that the incidence of presensitization and antibodies goes
up with pregnancy," Stuart D. Russell, MD, moderator of the session in which the
study was presented, told Medscape Transplantation. Dr. Russell, associate
professor of medicine and clinical chief of heart failure and transplantation at
Johns Hopkins University in Baltimore, Md, was not involved in the study.

"What's intriguing to me and to others is that there was another paper presented
here [that showed that] mortality among patients with peripartum cardiomyopathy
was significantly lower at 5 years, with the primary reason being noncompliance.
With all the caveats of the UNOS dataset, it makes one wonder whether there
might be a group of young women who get into a disastrous situation, and because
of that, they may have issues with compliance, as well as the fact that they're
presensitized and, by that fact alone, are at increased risk."

Dr. Silverstein and Dr. Russell have disclosed no relevant financial
relationships.

International Society for Heart and Lung Transplantation (ISHLT) 29th Annual
Meeting and Scientific Sessions: Abstract 568. Presented April 24, 2009.