By Katharine Sanderson of Nature magazine

Babies who were exposed to certain organic pollutants in the womb are at a highly increased risk of neural tube defects leading to conditions such as spina bifida, according to researchers in China.

Neural tube defects, in which the spinal cord, the brain or their coverings fail to develop completely, arise very early in pregnancy and affect more than 320,000 infants worldwide every year. They can lead not just to spina bifida, in which the spinal covering does not close completely, but also to severe cranial abnormalities such as anencephaly, which often leads to stillbirth, and other conditions.

Previous studies have linked certain pollutants, in particular polycyclic aromatic hydrocarbons (PAHs), from sources such as indoor coal stoves, smoking and vehicle exhausts, to neural tube defects. But most of the evidence has been anecdotal, based on mothers saying they had been exposed to certain pollutants, or has relied on tests of the mother's blood alone.

Now an interdisciplinary team of researchers in China has shown the risk of a newborn or fetus having a neural tube defect is much higher when certain organic pollutants are found in the placenta, which shows what is actually reaching the fetus, rather than just what is circulating in the mother's blood stream.

"We only see the high levels of pollutants in the placenta, but we don't know if it's a true causal relationship," cautions reproductive health scientist Aiguo Ren of the Institute of Reproductive and Child Health at Peking University in Beijing, one of the authors of the new study.

Still, these defects happen in the first few weeks of pregnancy and the more information there is available on their causes, the more chance there is of reducing their occurrence. The new study also discovered one indication of a true link, the so-called 'dose-response relationship'.

Working on the relationship

With Ren, environmental scientist Tong Zhu, also at Peking University, investigated levels of PAHs and other pollutants in the placentas associated with 80 fetuses or newborns with neural tube defects between 2005 and 2007. They matched these fetuses to healthy newborns from the same area, giving a control group of 50 healthy placenta samples.

In all those studied, the risk of a defect was 4.5 times greater where the levels of PAHs were above the average of 597 nano-grams per gram of lipid. As the amount of PAHs in the placenta rises, that risk rises also, to over 11 times the risk of a defect in the cases with the highest levels of PAHs.

This 'dose-response relationship' is important as it is one indication that the link is real, and not merely an artifact of the data.

"It's not that we didn't know that this could be a problem," says Judith Rankin, a maternal and perinatal epidemiologist at Newcastle University, UK, who was not involved in the study. She notes, however, that in this study the researchers are using actual biomarkers in the blood rather than asking the mothers what they have been exposed to.

To ensure that the link between PAHs and neural tube defects is clear, the team also took account of other factors that affect the incidence of the defects, such as folic acid supplementation, which decreases risk, and smoking, which increases it.

h2. Persistent pesticides

Ren and Zhu's team also looked at other pollutants, including pesticides like DDT and flame retardants such as polybrominated diphenyl ethers.

DDT was banned or restricted for use as a pesticide in many countries from 1970 onwards, and in China, pesticides containing DDT were banned in 1983. But the team saw DDT and its metabolites in placentas they studied, and found a similar relationship between DDT levels and the risk of certain fetal defects seen with PAHs.

"I did not expect these results," says Ren. DDT is a very persistent molecule and the levels seen may result from residues in the environment from past use, the team suggests.

In the case of these mothers, the source of the PAHs in their placentas is probably indoor coal stoves and passive smoking. Although exposure to these sources could be more tightly controlled, it cannot be banned outright, says Zhu. But women could be advised to minimize their exposure during early pregnancy.

"There are still many things we don't know," says Zhu. In particular, the mechanism that causes the defects, and conclusive proof that the pollutants are to blame, he says.

Ren and Zhu now want to do more work to unravel the mechanisms at work, and also look at the genes of both mothers and fetuses in cases of neural tube defects to see if there are any genetic problems that might compound the risk presented by pollutants.

The problems aren't restricted to China, Ren adds: "Exposure to indoor air pollution is a problem in many other developing countries."

This article is reproduced with permission from the magazine Nature. The article was first published on July 18, 2011.