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Study finds high fetal death rate in sickle cell patients: rate pegged at 10% after first trimester.

SCOTTSDALE, ARIZ. -- Pregnant women with sickle cell trait may be at far greater risk for fetal harm than has been recognized, results of a large, retrospective study suggest.

Analysis of hospital records revealed that sickle cell patients had a fetal death rate of 10% after the first trimester. This figure was nearly three times higher than the 3.5% that Michelle Y. Taylor, M.D., and her colleagues at the University of Mississippi Medical Center in Jackson calculated for a control group of women with normal hemoglobin.

The sickle cell carriers also gave birth three weeks earlier on average: at 33 weeks' gestation, compared with 36 weeks' gestation in the control group. In turn, the babies of sickle cell carriers had a mean birth weight about 500 g less than the average for newborns from the control group.

"Further investigation in the form of a comprehensive prospective clinical trial is needed to confirm these findings and determine if there may be a benefit to antenatal surveillance or other interventions," Dr. Taylor said at the annual meeting of the Central Association of Obstetricians and Gynecologists.

A fellow in maternal fetal medicine at the hospital, Dr. Taylor received the association's Young Investigator's Award for the study.

Sickle cell trait is considered benign in pregnancy, according to Dr. Taylor, with anemia and genitourinary infections being the only added risks for most of these patients. In an interview she suggested that greater morbidity and mortality risks might not have been recognized previously because many of the women lose their babies before 20 weeks' gestation. The Mississippi study found 42% of fetal deaths happened between the 16th and 20th week.

"Late fetal losses are usually well documented," she said, speculating that some early losses could be undocumented miscarriages.

Reviewing hospital records from 2001 to 2005, the investigators found 236 pregnancies beyond the first trimester in which the woman was a sickle cell carrier.

After excluding 56 patients with incomplete records or major structural fetal abnormalities, the researchers compared 180 pregnancies (165 singleton and 15 twin) in sickle cell patients with 180 pregnancies (168 singleton and 12 twin) in the control group. The latter was drawn from the next African American woman with normal hemoglobin to give birth on the same day or the following day as each sickle cell patient.

The two groups were similar in age, gravidity, and parity. Yet the sickle cell cohort had 19 fetal deaths, while the control group had 7.

Placental pathology found acute ascending amniotic infection in half the samples from sickle cell patients but only 18% from the control group. Noting that meconium histiocytosis has been associated with intrauterine hypoxia, Dr. Taylor described meconium histiocytes as "almost universal" in the sickle cell carriers' placentas. They were found in the placentas of 91% of the study population vs. 13% of controls.

Intervillous sickling, ubiquitous in the sickle cell trait placentas and not unexpected, was not seen in the control placentas. What surprised the researchers, she said, was the observation of sickling within the decidual vasculature with stasis and infarction-"a phenomenon that had not previously been reported."

"Sickling in the placental vasculature and resultant intrauterine hypoxia may render these pregnancies more vulnerable to ascending amniotic infection and subsequent loss," she said.

In a discussion of the study, Curtis Lowery, M.D., questioned whether Dr. Taylor had identified "a wolf in sheep's clothing or a sheep." The study carries weight as the largest to date of sickle cell pregnancies, said Dr. Lowery, director of maternal fetal medicine at the University of Arkansas for Medical Sciences in Little Rock.

He wondered, however, about the extent to which the findings reflect Mississippi's high incidence of fetal death and the hospital's patient population. (In Dr. Taylor's words, "the sickest of the sick," are referred to the medical center in Jackson.)

Describing the study as "very, very interesting," Dr. Lowery said, "I would not change my counseling of patients with sickle cell trait based on a single retrospective paper. I do think it warrants further study. It is a good initial piece of work."


Southwest Bureau
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Author:MacNeil, Jane Salodof
Publication:OB GYN News
Date:Nov 15, 2005
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