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January 25, 2019
SON OF NIH, BETHESDA
May Describes Prevalence of Fetal Alcohol’s Harms

Dr. Philip May
Dr. Philip May

No matter what country or continent you travel to, people enjoy their alcohol, which can have a harmful effect on a fetus if you happen to be a pregnant woman.

It has been known since the early 1980s that there is no safe level of alcohol consumption if you are pregnant. Nonetheless, women who are pregnant sometimes drink, and in some cultures— for example, in parts of rural South Africa—weekend bingeing of perhaps 3 to 8 drinks a night can yield a devastating harvest: up to 10 percent of the children born to drinking mothers in small towns outside of Cape Town were shown to qualify for a diagnosis of fetal alcohol syndrome (FAS) and up to 28 percent for a diagnosis within the full continuum of fetal alcohol spectrum disorders (FASD).

The work was done by a team led by Dr. Philip May, a restless son of Bethesda whose dad, Dr. Everette L. May, had spent 35 years in NIH’s intramural program; he worked in the Laboratory of Medicinal Chemistry in the 1960s and 1970s at what was then NIAMD, having begun employment at NIH in 1941.

The son returned to NIH recently to give NIAAA’s 23rd annual Mark Keller Honorary Lecture on the prevalence of FASD, a topic May has explored on three continents.

Born and raised in Bethesda and the Shenandoah Valley, where the family had a farm, May had “a yearning to get out and explore…I was fairly independent, and tenacious.” He describes himself as a “shoe-leather epidemiologist, which means direct inquiry among the people you are studying. It’s not common today, but it’s what I special­ize in. Taking science to the population.”

In a 90-minute talk, May, now at UNC’s Gillings School of Global Public Health, described his journey, stopping often to credit the far-seeing leadership at NIAAA, which supported him when “I was an unknown professor at the University of New Mexico.”

FAS was first recognized in 1973, and even then, it was known to be a disorder of degree; some babies born to drinking mothers were categorized as suffering “fetal alcohol effects,” which means that they might not exhibit the classic dysmorphology of FAS, but did show behavioral and learning problems characteristic of the syndrome.

May had joined the Public Health Service in 1970, and by the time he began a 33-year career as a professor at UNM, he was well-grounded in the conduct of public health. Using “active case ascertainment” methods, he and his team found a prevalence of FASD of 2 percent in some of the heaviest-drinking tribes of the Southwest Plains.

By the time he contrib­uted to a 1996 Institute of Medicine report on FAS, the spectrum nature of the disorder had begun to take shape. It included growth deficiency and its victims were highly dysmorphic, especially if the mother’s heaviest drinking had taken place during the first 30 to 90 days of gestation.

Subcategories emerged. PFAS, or partial fetal alcohol syndrome, included more than one facial phe­notype; children with PFAS were more normal in their physical growth and development. There was ARND (alco­hol-related neurodevelopmental disorder), where there is much less dysmorphia, and ARBD (alcohol-related birth defects), which are rarely seen and where isolated major physical anomalies are present that can be linked to alcohol exposure.

“There’s not just one phenotype,” May said, “but multiple ones. The signs vary. Children can look very different [from one another] and still have FASD.

“The mother and the fetus have exactly the same blood alcohol concentration” when a pregnant mom drinks, May explained. “The elimination of alcohol and its metabolites from the fetus is much slower, though.”

QFT is critical: quantity, frequency and (gestational) timing of the alcohol exposure.

The severity of FAS seems to increase, May said, with advancing maternal age; with each subsequent pregnancy; and with a mother’s smaller body mass. It turns out that a high BMI, or obesity, is somehow protec­tive against the syndrome.

Interestingly, twins born to a drinking mother are not equally affected. “We don’t know the specific genetic, or epigenetic, mechanism, although concordance is higher with identical (monozygotic) twins,” May noted.

May’s first RO1 grant enabled him to study FAS in tribes of the Northern Plains. He found that the close personal contact of case management “made for healthier babies, in part because our staff members became their friends and were able to assist them in lowering their drinking.”

May went to South Africa in the mid-1990s at the government’s invitation. One local South African pediatrician had suspected very high rates of FAS, as much as 10 percent. May thought that was impossible.

But in a prevalence study among 450 first-graders conducted between 1997 and 1998, May and colleagues found, to their astonishment, that the South African pedia­trician’s estimate was true.

“That was absolutely unheard of,” he said. “No one thought it was possible.”

Subsequent studies of nearly 11,000 first-graders in two South African commu­nities turned up total rates of 24 percent qualifying for a diagnosis within the contin­uum of FASD. “These are unbelievable rates,” May said.

The big challenge is to diagnose a FASD early, to help address the newborns’ disabil­ities, May said. Children with FASD can be diagnosed as early as 9 months, “and for sure by 18 months if a combination of physical dysmorphology and developmental testing is used. It’s really going to help a lot of individ­ual cases. Cognitive testing at age 5 and later, if widely implemented, could help a lot of kids’ lives.”

Interventions include a focus on skills building, including extra tutoring in language and literacy. Exercise and music are important—especially if they can be linked—as a form of cognitive stimulation. Adequate nutrition is also important, although it has yet to be demonstrated whether multivitamins alone are beneficial, or if targeting with particular nutrients such as choline, omega-3 fatty acids and iron is the most efficacious.

May (c) is joined by NIAAA and NIDDK alumni (from l) Dr. Faye Calhoun, Dr. Ken Warren, J. Harrison Ager and Dr. Enoch Gordis.
May (c) is joined by NIAAA and NIDDK alumni (from l) Dr. Faye Calhoun, Dr. Ken Warren, J. Harrison Ager and Dr. Enoch Gordis.

PHOTOS: CHIA-CHI CHARLIE CHANG

Other takeaways included:

  • There is an effect of male drinking on fetuses, an issue that will be studied further.

  • Kids exposed to alcohol solely via breast milk are also affected—they tend to have lower birthweight, lower verbal IQ and more anomalies.

  • FASD affects boys and girls similarly, but girls tend to be in worse shape by age 7, both mentally and physically; it appears that more males miscarry, or are victims of SIDS than females.

  • Prevalence studies in the U.S., ongoing since 2006, reveal no particular ethnic or racial distribution of FASD—it’s a demo¬cratic malady in May’s studies to date. “It affects just as many upper-income families as lower-income ones,” he noted.

  • Contrary to what one might expect, general cognitive abilities in affected children are generally in the normal range. It may not be a major cause of mental retar¬dation as it was previously believed to be, but there are a host of behavioral problems found in children with FASD in the general population of the U.S., including mood regulation, lack of inhibition, aggression and attention problems. “An FAS child would have a real problem with this talk, which is over 1 hour long,” May quipped.

  • Alcohol use in pregnancy is a principal cause of developmental delay and behav¬ioral problems in children. The U.S. rate of FASD is quite conservatively estimated in May’s active case ascertainment studies in 4 regions of the country to be between 2-6.5 percent.

“Most people like alcohol, especially the population in general who are now of child¬bearing age. And current norms encourage or allow alcohol use more than in the past two or three generations,” said May. “You just don’t know—maybe one or a few drinks a night during particularly sensitive times in pregnancy could reduce your child’s IQ somewhat. Repeated nights of drinking have been demonstrated to affect not only brain structure and development, but also are linked with a variety of behavioral problems. There is too frequently an attitude-behavior disconnect with a significant number of people today.”

He concluded on a hopeful note: “These children with FASD do mature. They can get better with early recognition and remediation.”

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