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This coronal T2 image (top) of a fetus diagnosed with an aberrant pulmonary vein shows agenesis of the corpus callosum, abnormal and retarded gyration, malrotation of both hippocampi, and associated signal abnormalities of the developing white matter at 28 weeks. The brain of a fetus (bottom) with Fallot’s tetralogy shows bilateral germinolytic cysts in the caudothalamic groove at 25 weeks.

Induction Effect
Declines in mean birth weight and gestational age are linked to an increase in labor induction.
PAGE 6
D R . G REGOR K ASPRIAN

HT May Benefit Postmenopausal Cognition, Memory
Three new studies contradict past results.
B Y M I C H E L E G. S U L L I VA N

Preterm Triggers
Low HDL cholesterol and high homocysteine levels may be keys to preterm delivery.
PAGE 10

Mid-Atlantic Bureau

Trump the Triad
Education and professional teamwork can prevent the female athlete triad.
PAGE 16

Fetal Cardiac, Brain Defects Are Linked
BY AMY ROTHMAN SCHONFELD

Contributing Writer

N E W O R L E A N S — Fetal MRI shows that almost 60% of fetuses with cardiac defects also have brain abnormalities, according to the findings of an imaging study conducted in Vienna. A total of 57 pregnant women whose fetuses had cardiac malformations identified by ultrasound were studied. The findings were presented by Dr. Gregor Kasprian at the American Society of Neuroradiology. The fetuses had a variety of cardiac malformations, including: Fallot’s tetralogy (nine cases); transposition of the great vessels (three); ventricle septum defect with or without associated cardiac malformations (nine); rhabdomyoma (three); aortic stenosis at the isthmus (three); arteriovenous canal (three); cardiomegaly (unilateral or bilateral) (three); or other pathologies such as an aneurysm, cardiac teratoma, missing inferior vena cava, and double-outlet right ventricle. In some cases, it was too early to classify the defect. When these fetuses then underwent fetal MRI between 20 and 38 gestational weeks (with a 1.5-T superconducting system using ultrafast T2-weighted, T1weighted, diffusion-weighted, and

echo-planar sequences in three orthogonal section planes), brain pathology was found in 33 cases (59%), said Dr. Kasprian, a radiologist at the Medical University of Vienna. This rate is generally higher than that reported using prenatal ultrasonography The study was carried out under the auspices of the Fetal MRI Work Group, led by Dr. Daniela Prayer, also of the Medical University of Vienna. Eighteen fetuses demonstrated brain malformations, such as commissural anomalies (three cases), holoprosencephaly (one), See Defects page 7

C H I C A G O — Hormone therapy might preserve cognition and memory in postmenopausal women, and even attenuate some of the cognitive deficits that occur in Alzheimer’s disease, new research suggests. Controversy exists over the possible cognitive benefits of hormone therapy in older women, Dr. Mary Tierney said at the International Conference on Alzheimer’s Disease. “While preclinical and observational studies have shown a positive effect of estradiol on the brain and cognitive function, randomized con-

trolled trials using conjugated equine estrogens have shown no treatment effects in women at risk for Alzheimer’s disease, or in women who have the illness.” These concerns, plus her own hypothesis that the “minidoses” of hormones used in many randomized trials might be too low to offer protective benefit, prompted Dr. Tierney of the Sunnybrook Health Sciences Centre, Toronto, and her colleagues to undertake a new study. The 2-year trial randomized 142 women aged 61-87 years to either placebo or to 1 mg estradiol daily plus 0.35 mg progestin 3 days per week. The primary outcome was the See Cognition page 6

I MAGES

COURTESY

Health Politics
Sen. John McCain proposes to replace the tax exclusion for employee health benefits with a tax credit.
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First-Trimester Lamotrigine Use Linked to Oral Clefts
BY ROBERT FINN

San Francisco Bureau

VITAL SIGNS Median Income for Ob.Gyns.
$300,000 Actual $250,000 $237,191 $233,066
E LSEVIER G LOBAL M EDICAL N EWS

$280,629

M O N T E R E Y, C A L I F. — Women who take the anticonvulsant lamotrigine during their first trimester of pregnancy have a 10-fold greater risk of having a baby with nonsyndromal cleft lip, cleft palate, or both, according to a peer-reviewed study. Among 684 women enrolled in the North American AntiEpileptic Drug (AED) Pregnancy Registry who reported taking lamotrigine monotherapy during their first trimester, there were 16 infants born with major malfor-

mations, Dr. Lewis B. Holmes said at the annual meeting of the Teratology Society. This translates to a rate of 2.3%, compared with a baseline rate of 1.6% in unexposed newborn infants (Neurology 2008;70:2152-8). Although this difference in combined major malformation rates was not statistically significant, the investigators observed a significantly increased risk when they restricted the analysis to oral clefts. Three of the infants had an isolated cleft palate, one had an isolated cleft lip, and one had bilateral cleft lip and palate, for an overall See Lamotrigine page 7

$200,000

$221,980

Adjusted*

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2003

2004

2005

2006

2007

*Adjusted for inflation to 2000 dollars. Source: Medical Group Management Association

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AMA Apologizes for Past Racial Discrimination
A national minority physicians’ group wants to use the apology as a springboard for three initiatives.
B Y M A RY E L L E N S C H N E I D E R

Ne w York Bureau

frican American physicians are looking for action to back up the words of apology recently tendered by the American Medical Association for more than a century of racial inequity and bias. In accepting the AMA’s apology, the National Medical Association (NMA), which represents minority physicians, urged the AMA leadership to work with them on three initiatives: recruiting more African American physicians, reducing health disparities among minorities, and requiring medical schools and licensing boards to make cultural competency mandatory for medical students, residents, and practicing physicians. “We really want to use this apology as a springboard,” said Dr. Nedra H. Joyner, chair of the NMA board of trustees and an otolaryngologist in Chicago. These changes will be critical to reversing racial health disparities that have led to poorer health outcomes in African Americans, she said. “Talk is cheap,” said Dr. Carl Bell, professor of public health and psychiatry at the University of Illinois at Chicago. Dr. Bell said that while he is hopeful that the AMA will take some meaningful action

A

to reduce health disparities, he is unimpressed by the apology alone. Instead, he would like the AMA to take a stand on issues that would advance minority health in the United States. For example, he wants to see the AMA push for single-payer national health insurance, be stronger in challenging the pharmaceutical industry, do a better job of promoting public health, and support research into minority health and mental health issues. Dr. Warren A. Jones, who was the The AMA needs first African Amerito take a stand on can president of the issues that would American Academy advance minority of Family Physihealth in the U.S. cians, agreed that further action will DR. BELL be needed but called the AMA’s apology “appropriate” and “timely.” This is not an apology of convenience, he said, but a signal of a change in the mind-set of the AMA leadership. The AMA now has an opportunity to ensure that cultural competency becomes a tool in the medical armamentarium in the same way as the stethoscope or the scalpel, he said. “Now is the time for the AMA to put its resources where its mouth is,” said Dr. Jones, executive director of the Mississippi Institute for Improvement of Geographic Minority Health. The AMA offered the apology in July to coincide with the release of a historic paper in its flagship journal that examined race relations in organized medicine

(JAMA 2008;300:306-13). The paper, which chronicles the origins of the racial divide in AMA history, was prepared by an independent panel of experts convened by the AMA in 2005. The panel reviewed archives of the AMA, the NMA, and newspapers from the time to provide a history from the founding of the AMA through the civil rights movement. The paper notes a number of instances where the AMA leadership fostered racial segregation and bias. For example, in 1874 the AMA began restricting delegations to the organization’s national convention to state and local medical societies. This move effectively excluded most African American physicians because many medical societies, especially those in the South, openly refused membership to them. Later, in the 1960s, the AMA rejected the idea of excluding medical societies with discriminatory practices. During the civil rights era, the AMA was seen as obstructing the civil rights agenda, the paper noted. In 1961, the AMA refused to defend eight African American physicians who were arrested after asking to be served at a medical society luncheon in Atlanta. In its review, the independent panel applauded AMA for its willingness to explore its history. But the researchers also noted that the legacy of inequality continues to negatively affect African American physicians and patients. For example, in 2006 African Americans made up 2.2% of physi-

cians and medical students, less than in 1910 when 2.5% were African American. In a commentary to accompany the history, Dr. Ronald M. Davis, immediate past president of the AMA, acknowledged the “stain left by a legacy of discrimination” and outlined what AMA is doing to eliminate prejudice within the organization and improve the health of minority patients ( JAMA 2008;300:323-5). Dr. Davis said that the AMA leadership felt it was important to offer the apology because it demonstrates the “current moral orientation of the organization” and lays down a marker to compare current and future actions. ‘Now is the time Within the orgafor the AMA to nization, AMA has put its resources in place a number where its of policies that exmouth is.’ plicitly prohibit discrimination in DR. JONES membership and support funding for “pipeline” programs to engage minority individuals to enter medical school. In addition, in 2004, the AMA joined the NMA and the National Hispanic Medical Association to form the Commission to End Health Care Disparities. That group has been working to expand the “Doctors Back to School” program, which brings minority physicians into schools to encourage students to consider careers in medicine. The ultimate goal is to have as much diversity among physicians as in the general population, where African Americans make up about 12% of the U.S. population, Dr. Davis said. “Obviously, we have a long way to go,” he said. ■

Brain-Cardio Tie
Defects from page 1

Tenfold Increase in Risk
Lamotrigine from page 1

EDITORIAL A DV I S O RY B OA R D
ERIC J. BIEBER, M.D., Geisinger Health

posterior fossa pathologies (four), tuberous sclerosis (three), cortical malformations (three), and a combination of anomalies. For example, the coronal T2 image of a fetus aged 28 gestational weeks (see top figure, page 1) diagnosed with an aberrant pulmonary vein by fetal echocardiography shows agenesis of the corpus callosum, abnormal and retarded gyration, malrotation of both hippocampi, and associated signal abnormalities of the developing white matter. Widening of the internal or external CSF fluid spaces was seen in 12 fetal brains. This group included problems such as ventricular enlargement of more than 12 mm and widened subarachnoid spaces. One fetus showed hemorrhagic lesions and two others had germinolytic cysts (for an example of cysts in a fetus with Fallot’s tetralogy, see bottom figure, page 1, white arrows). Genetic analysis was conducted in 15 cases. Three cases had Di George syndrome and two cases had trisomy 13. The remaining 11 analyses were unremarkable. “This high frequency of brain abnormalities associated with congenital heart disease is higher than previously reported with ultrasounds,” said Dr. Kasprian. “This may be due to the higher sensitivity of fetal MRI to demonstrate brain lesions.” Dr. Kasprian said that he believes these brain abnormalities have a heterogenous etiology. He ascribed some to genetic defects, while others may be acquired as cerebral sequelae of altered cardiac hemodynamics or arise as a result of focal ischemia or hemorrhage. ■

prevalence rate of 7.3/1,000 infants. In comparison, the rate was 0.7/1,000 for unexposed controls, yielding a statistically significant relative risk of 10.4. “That’s a whopping increase,” said Dr. Holmes of Massachusetts General Hospital for Children, Boston. “You wonder if it’s a sample size [effect], but it’s certainly a point to be pursued in comparison to other databases.” Dr. Holmes examined data from five other pregnancy registries—an international registry maintained by GlaxoSmithKline, and national registries in the United Kingdom, Sweden, Denmark, and Australia. There was a combined total of 4 infants born with oral clefts among 1,623 lamotrigine-exposed women, for an overall rate of 2.5/1,000 and a relative risk of 3.6 vs. unexposed controls. “So a larger sample size is needed to see whether the rate of clefts is a 10-fold increase or as low as fourfold, or somewhere in between,” Dr. Holmes said. “But

this is the sort of thing that pregnancy registries were intended for, getting larger and larger samples.” (Women in North America can enroll in the AED registry by calling 888-233-2334 or by visiting www.AEDPregnancyregistry.org.) Other anticonvulsant drugs are associated with much greater increased risks of oral clefts. For example, the risk of oral clefts goes up 20-fold in women taking valproate, 21-fold in women taking carbamazepine, and 32-fold in women taking phenobarbital. The investigators noted one other fact about the five women in the North American Registry whose infants had oral clefts: All five had been taking folic acid supplementation at conception. Dr. Holmes disclosed that he receives financial support from the six sponsors of the North American AED Registry: Abbott Laboratories, Eisai Co., GlaxoSmithKline, Novartis, Ortho-McNeil, and Pfizer Inc. ■

System, Danville, Pa.
CONSTANCE J. BOHON, M.D., George-

town University, Washington EZRA C. DAVIDSON JR., M.D., Charles R. Drew University of Medicine and Science, Los Angeles BRUCE L. FLAMM, M.D., University of California, Irvine CHARLES B. HAMMOND, M.D., Duke University Medical Center, Durham, N.C. LUELLA V. KLEIN, M.D., Emory University, Atlanta
HAL C. LAWRENCE III, M.D.,

University of North Carolina, Chapel Hill CHARLES E. MILLER, M.D., University of Chicago E. ALBERT REECE, M.D., University of Maryland, Baltimore JAN LESLIE SHIFREN, M.D., Harvard Medical School, Boston CYRIL O. SPANN JR., M.D., Emory University, Atlanta Technical Consultant: LUIS E. SANZ, M.D., Virginia Hospital Center, Arlington, Va.