Authors
Laura Torres-Arreola MD, M. Sc., Gertrud Berkowitz Ph. D., Luisa Torres-Sánchez M. Sc., Malaquías López-Cervantes Ph.D., Mariano E. Cebrián Ph.D., Marisela Uribe B.Sc., and Lizbeth López-Carrillo DR., Ph.D.

Title:
Preterm Birth in Relation to Maternal Organochlorine Serum Levels

Journal:
Annals of Epidemiology 13: 158-62. 2003.

Summary:
The reproductive toxicity of organochlorine pesticides such as beta-hexachlorocyclohexane (beta-HCH), hexachlorobenzene (HCB), and 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p-DDE) in animal studies and placental transfer in humans has been documented in many studies around the world. Chloro-organic compounds can influence female fertility at every phase of reproduction. They may induce hormonal disorders, preventing ovulation and pregnancy. They can also result in spontaneous abortions and preterm birth. Higher serum levels of p,p-DDE have been reported to increase risk of preterm birth and spontaneous abortion in humans, however, previous studies were based on small populations and generally lacked control of confounding factors. Preterm birth is an important determinant of infant mortality and represents a serious public health problem in Mexico.

The purpose of the present study was to evaluate the association between maternal p,p-DDE, beta-HCH, and HCB serum levels and preterm birth among women in Mexico. A case-cohort study included 233 mothers who were recruited at three large maternity hospitals in Mexico City in 1995. One hundred women with a preterm birth were selected for the case-study group. Preterm birth was defined as a term of less than 37 weeks of gestation with no weight criterion. Gestational age was calculated from the date of the last menstrual period. The control group consisted of 133 women with a full-term birth. Variables evaluated included maternal age, education, marital status, parity, history of previous abortions, preterm birth, low-birth weight, pre-pregnancy maternal weight, prenatal care, smoking, and calcium and iron supplementation during pregnancy.

p,p-DDE, beta-HCH and HCB levels were measured in maternal blood serum using gas chromatography. Venous blood for chemical analysis was obtained within 24 hours from time of delivery. Concentration of organochlorines was expressed as nanogram per milliliter (ng/ml) of serum and categorized by concentration intervals according to the distribution among controls. The lipid-adjusted levels of p,p-DDE, beta-HCH and HCB were analyzed using gravimetric determination and expressed in ppb lipid weight (ng/g). The association between p,p-DDE, beta-HCH and HCB serum levels and preterm birth was estimated using regression analysis after controlling for a range of important factors that can affect the term of delivery, including pre-pregnancy weight, history of previous preterm birth, prenatal care, and parity.

Overall, this study did not demonstrate any relation between maternal HCB level and preterm birth. However, a non-significant increased risk of preterm birth in relation to elevated p,p-DDE serum levels was observed (adjusted odds ratio (OR) = 1.67, 95% confidence interval (CI) = 0.84-3.31). There was also a suggestion of an increased risk of preterm birth among women in the group with the highest level of beta-HCH (OR = 1.85, 95% CI = 0.94-3.66, p-value test for trend = 0.08) compared with the lowest levels. The study also indicated that in the total population, women with a pre-pregnancy weight of less than 50 kg had a two-fold increased risk of preterm birth when compared to women with a pre-pregnancy weight of more than 60 kg (OR = 2.06, 95% CI = 1.02-4.16). Preterm birth had no association with smoking habits or calcium/iron supplementation during pregnancy.

Laura Torres-Arreola et al., suggest that among possible explanations of the results could be the ability of p,p-DDE to act as a potent androgen receptor antagonist and its ability to interfere with the binding of progesterone to its receptor, which may affect pregnancy duration. The present study does not rule out the possibility that some unknown factors such as other environmental toxicants (lead, other organochlorine chemicals) may be associated with risk of preterm birth among Mexican women.

Maternal exposure to chlorinated organic compounds has lead to concern that these chemicals can lead to adverse obstetrical outcomes such as intra-uterine growth restriction, low birth weight, and preterm birth. To demonstrate that a relationship between maternal exposures to chlorinated organic contaminants and adverse obstetrical outcomes, in the general population whose exposures are representative of background levels, would require the inclusion of many thousands of study subjects which would be prohibitively expensive and time consuming. Therefore, although studies such as the present one include women whose exposures are higher than those reported in contemporary studies for women with background exposure, they are important because they permit more manageable sample sizes to be studied over a shorter time frame. While results from such studies to not necessarily allow for extrapolation of adverse outcomes to populations with lower exposure levels, they do provide evidence that these chemicals can induce adverse health effects in human populations and demonstrate exposure scenarios where this is likely to occur. Such studies can also focus subsequent research attention on identifying the toxic agents responsible as well as the mechanism of action. This case cohort study is particularly important because it examined the relationship between exposure to several chlorinated organic compounds that despite decades since their use was banned in North America continue to be measured in human tissues and preterm birth. The rate of preterm births has increased and while there may be many explanations, the role of environmental contaminants cannot be excluded, is potentially preventable, and therefore must be explored.