and Engineering News
26 November 2001
of premature birth probed.
with a steady rise in premature births in the U.S., researchers
are beginning to put pressure on federal agencies and Congress to
take action. One possible cause may be exposure to chemicals that
somehow affect gestation times. To study this, scientists are seeking
changes in federal toxicology protocols that will give them the
data they need.
Last month, the Institute of Medicine (IOM) sponsored a meeting
on environmental causes of premature births. Speakers presented
evidence that industrial chemicals, pesticides, and air pollutants
could have contributed to the 23% rise in premature births in the
U.S. since the early 1980s. However, they said, the evidence is
not strong enough to blame premature births on environmental chemicals
in general or on specific substances.
noted that changes are needed in the Environmental Protection Agency's
and the National Toxicology Program's (NTP) chemical testing protocols
so that the effects, if any, of specific chemicals on premature
births can be identified. For example, in many rodent toxicity assays,
the offspring are removed from the womb before birth, giving no
indication if the compound could have affected gestation times.
1999 in the U.S., 11.8% of all babies, or about 440,000 infants,
were born prematurely--that is, before the end of the 37th week
of gestation. (The normal length of gestation is 40 weeks.) According
to data from the National Center for Health Statistics, in 1981,
9.4% of live births were premature. Part of the increase can be
attributed to the age of the women--women are becoming pregnant
at older ages now than in 1981--and to fertility treatments, which
often cause multiple births. But rates also rose among women under
35, from 10.8% in 1991 to 11.6% in 1999.
problem of premature births is so severe that researchers and the
March of Dimes hope to convince Congress to fund more studies in
this area. IOM is preparing a report on the meeting that it hopes
will raise Congressional awareness of the issue.
SOME scientific advances in understanding prematurity, no progress
has been made in lowering the rate of prematurity. "None of
the interventions used to try to reduce prematurity actually is
effective," Robert L. Goldenberg said at the meeting. Goldenberg
is a professor in the department of obstetrics and gynecology at
the University of Alabama, Birmingham. Illegal drugs, alcohol, and
tobacco use have been found to contribute little to the problem,
he explained. "The interventions which have been applied generally
to populations and to specific targeted high-risk populations, such
as home monitoring of fetal contractions, have not achieved any
real reduction in the preterm birth rate," he explained.
P. Longnecker, an epidemiologist at the National Institute of Environmental
Health Sciences (NIEHS), surveyed studies that attempted to gauge
the effects of environmental chemicals on preterm births. In three
studies of the effects of air pollution, sulfur dioxide and particulate
matter were associated with a modest increase in the risk of preterm
delivery, he said. But reaching definite conclusions from these
studies was not possible because data on personal exposures were
epidemiological study implicates arsenic in drinking water as a
cause of preterm births. But the levels in the arsenic study were
about two times greater than the most highly contaminated areas
of the U.S., Longnecker said. In occupational studies, maternal
exposures to solvents and paternal exposures to pesticides were
associated with preterm births, but only very general exposure data
were available in these papers.
of the strongest associations was found in a study by Longnecker.
He measured the levels of DDE--a metabolite of DDT--in stored sera
of mothers who gave birth between 1959 and 1966, when DDT was heavily
used in the U.S. In a sample group of 2,380 babies born to these
women, 361 were preterm and 221 were small for gestational age.
The greater the level of DDE in the mother's blood, the higher was
the risk for the infant [Lancet, 358, 110 (2001)]. "The findings
of our study strongly suggest that DDT use increases preterm births,"
Longnecker said. Because the current levels of DDE in U.S. women
are about 5% of what they were in the 1960s, DDT is probably not
a factor in the recent rise in premature births, he said. But in
the 25 countries where DDT is still used for malaria control, DDE
levels can greatly exceed the range observed in this study, he said,
and may cause early births or small babies. However, "none
of the substances studied thus far is yet firmly established as
a cause of preterm delivery," he concluded.
Wang, a professor of pediatrics at Boston University School of Medicine,
discussed her recent work on shortened gestation times associated
with benzene exposure. She studied 542 births to women working at
a Beijing petrochemical plant to determine if there was an interaction
between their genetic profile and susceptibility to benzene. She
found that benzene shortened the pregnancies of those women with
a genetic profile that prevented them from detoxifying benzene easily.
Although these women were more highly exposed to benzene than the
general population in the U.S., their exposures were low for an
occupational setting--about one-fifth of the limit set by the U.S.
Occupational Safety & Health Administration, she explained.
NEED FOR more data is obvious, but current federal testing guidelines
for toxic substances are often poorly designed for measuring chemicals'
effects on the length of gestation, said Carole A. Kimmel, senior
scientist at EPA's National Center for Environmental Assessment.
and NTP's prenatal developmental toxicity studies are usually done
in rats and rabbits. In both species, the pregnant animal is exposed
to a chemical beginning at day six of gestation and sacrificed before
the kits are born. So changes in the length of pregnancy can't be
detected, Kimmel said.
in two studies, the developmental neurotoxicity and the two-generation
toxicity protocol, a chemical's effect on the length of pregnancy
might be detected, Kimmel noted. In these tests, primarily done
in rats, chemical exposure begins at or before implantation and
continues through pregnancy and birth and into the postnatal period.
problem with nearly all of the tests is that chemicals' effects
on gestation length in rats may not be relevant to humans because
chemicals tend to lengthen, not shorten, a rat's gestation time.
"We may need better animal models so we can be sure what we
see in animals is relevant to humans," Kimmel explained.
research has to advance on multiple fronts before the causes of
the rise in preterm births can be nailed down. Areas mentioned at
the conference include studies on cellular mechanisms to see how
chemicals may affect uterine activity and research on the interaction
between chemicals, the immune system, and inflammatory responses.
Inflammation of the uterus is the proximate cause of many preterm
help solve this mystery of rising premature birth rates, some are
looking to Congress to direct NIEHS or EPA to spend more research
dollars on studying the causes of premature births. "Given
how little we know, a research initiative in that area would be
appropriate at this time," says Mary M. Gant, assistant to
the director for legislation at NIEHS. IOM's report on the meeting
will be sent to Congress in early 2002.