Assessment of Toxicogenomic Risk Factors in Etiology of Preterm Delivery

Abstract

Worldwide, preterm birth accounts for more than 60% of prenatal morbidity and mortality and is the leading cause of neonatal deaths. Globally, every year, around 13 million babies are born preterm, with rates being highest in the low and middle-income group. India is leading all the nations in PTD, as reported by WHO. PTD is considered as a major pregnancy complication. PTD continues to be a major clinical and public health problem and is regarded as a syndrome with multiple causes. Environmental stressors such as heavy metal, Organochlorine pesticides have a long history of widespread use all around the world. Because of high stability, extremely low biodegradability and long half life, these compounds are typically very persistent in the environment, and are known to accumulate in soil, food, blood, fatty tissue etc. Humans, being at the top of the food chain are most vulnerable to health effects as the level of the toxic chemicals is several folds higher through the process of bio-magnifications. The problem gets compounded in women because of increased adipose tissue in them and high liposolubility of these OCPs. Pesticide toxicity is of utmost concern during pregnancy as studies have revealed that mother and fetus are more vulnerable to their toxic effects. OCPs are metabolized by xenobiotic metabolizing enzymes such as CYP P450 and GSTs. Polymorphism in xenobiotic metabolizing genes may cause improper metabolism of xenobiotics which may cause high free radical generation, increased oxidative stress, improper cytokines release and also increased inflammation. OCPs levels are also correlated significantly with increased expression of COX-2 gene. The mechanisms underlying the etiology and onset of preterm birth is not clearly understood. Still more than 40-50% cases of preterm delivery are 'idiopathic'. So, it is very essential to assess the etiological factors and the mechanisms by which they result in preterm birth in order to make further research in targeted interventions to prevent preterm labor.

Maternal plasma lipids are involved in the pathogenesis of preterm birth

“…5 ) suggest that CYP4F/A enzymes, the enzyme catalyzing this conversion, have reduced activities in preterm delivery. Polymorphisms in CYP4F/A genes, which impair enzyme functions, previously showed associations with preterm birth [ 41 ]. Thus, we speculate that polymorphisms or other forms of deactivation of CYP4F/A genes may play a role in preterm births.…”

Maternal plasma lipids are involved in the pathogenesis of preterm birth

“…The accumulation of fatty acids and reduction of suberic acid in preterm maternal blood samples (Fig 5) suggest that CYP4F/A enzymes, the enzyme catalyzing this conversion, have reduced activities in preterm delivery. Polymorphisms in CYP4F/A genes, which impair enzyme functions, previously showed associations with preterm birth [41]. Thus, we speculate that polymorphisms or other forms of deactivation of CYP4F/A genes may play a role in preterm births.…”

Which One Is Better for Tocolysis in Pre-Term Labor?: Oral Nifedipine vs Transder-Mal Nitroglycerin Patch

“…[8] Preterm birth accounts for 7-12% of pregnancies and causes up to 70-80% of infant morbidity and mortality, making it a severe public health concern. [9] Practically speaking, due to the recent rapid developments in feto-maternal medicine, survival outcomes are better in births that occur after 34 weeks of gestation. [10] One of the best ways to lower preterm morbidity and death is to use tocolytics.…”