What are the effects of pesticides on neonates' health?

Pesticide use is universal today as part of the agricultural revolution that ushered in an era of bigger, better farming. However, generations after this practice began, scientists warned against these compounds' harmful effects on the soil, water, and air.

Children are naturally the most high-risk population for toxicity induced by most environmental pollutants. In fact, such diseases kill three million children before they turn five years of age, accounting for a third of global pediatric deaths annually.

A new study explores the impact of pesticide exposure in neonates, reviewing current literature while evaluating the research methods used in this area.

Introduction

Environment-induced teratogenic effects are particularly common during rapid development, including life in utero, infancy, and adolescence. This is due to the increased exposure to such toxins and the critical development points at potential risk for alteration by such exposures, altering the entire course of further growth and development.

Moreover, since children are at the beginning of their lives, the harm induced by such exposures has much more time to ripen, culminating in chronic diseases with very long latent periods like metabolic and endocrine disorders, neurodegenerative diseases, or cancers.

The impact of such compounds, called xenobiotics, on newborns, defined as infants within 28 days of life, is the subject of this paper, published in the journal Science of the Total Environment. These include heavy metals and organic compounds like pesticides, plasticizers, drugs, and dyes, among others.

Xenobiotic exposure in neonates occurs by exposure routes distinct from that of adults or older children, according to the World Health Organization (WHO). These include placental transfer and breast milk intake. These compounds, therefore, derive from the mother's body, and the buildup of xenobiotics in both maternal and fetal tissues is a crucial factor in determining the ultimate impact.

Some research showed a higher risk of premature birth, congenital anomalies, neurologic disorders, blood cancers, respiratory abnormalities, and endocrinopathies in xenobiotic-exposed newborns. The risk of exposure is measured using biomarkers.

Such markers must be identified, characterized, and accurately measured to tease out exposure risks. This covers their evaluation in various tissues and biological sources, including breast milk, saliva, blood, and urine, to understand how and when prenatal exposure is happening and to what extent.

Pesticides are a unique class of chemicals with biocidal properties and distinctive metabolic pathways in the human body. They belong to several structural classes, which indicates that they undergo several different routes of metabolism. Some such organic pesticides include organochlorine (OCs) and organophosphate (OPs) pesticides, carbamates, pyrethrins, and pyrethoids.

OCs include endosulfan, aldrin, DDTs, and HCBs. Newer, less toxic pesticides include succinate dehydrogenase inhibitors (SDHI; fungicides), nicotinic and diamide insecticides, or acetolactate synthase-based plant killers. With such a spectrum of compounds, sensitive and reliable analytical methods continue to be in great demand.

What did the review show?

OPs have been termed endocrine-disrupting chemicals, affecting reproductive hormones. Some evidence indicates lower estradiol and testosterone levels after early OP exposure. These compounds can also induce insulin resistance mediated by hyperglycemia after early exposure.

The accumulation of OCs in the placenta may increase the risk of low birth weight, along with a higher risk of being overweight at two years. Psychological and developmental impairment has been suggested as well, mediated by changes in thyroid function. For instance, higher levels of the thyroid-stimulating hormone (TSH) are linked by some research to higher blood OC levels, as well as to thyroxine levels in both mothers and children.

Neurologic disorders, including cognitive dysfunction, have also been linked to some OP and OC exposure. The results may include inattention, attention deficit and hyperactivity disorder (ADHD), autism spectrum disorder (ASP), and aggressive or depressive behavior in children.

With other pesticides, the evidence is lacking, though some scientists suggest developmental effects, reproductive system impairment, and liver toxicity via oxidative stress following neonicotinoid exposure. Many xenobiotics may also induce DNA damage, raising the issue of childhood cancers like neuroblastomas, brain cancers, and non-Hodgkin lymphoma following pesticide exposure of the parents.

Again, unlike adults, fetuses cannot metabolize pesticides with their immature organs. The mother's body thus deals with these compounds, in the liver primarily but also in the placenta. Cytochrome enzymes like YP1A2, CYP2C19, CYP2C9, and CYP3A4 are present at very low concentrations in the fetal liver; similarly, transporters and transferases are involved in detoxifying and eliminating these toxic compounds from the body.

Biomarkers may measure exposure, effect, or susceptibility to the potential toxin. Several types of samples have been studied, including blood, stool, urine, hair, and nails. While blood samples provide a snapshot of exposure, hair and nails are used to obtain a long-term picture of exposure.

Again, blood collection is invasive, while hair and nail clippings can be obtained non-invasively. However, the former is most reliable for measuring the original compounds' concentrations. Whole blood or dried blood spots may be used, the latter being far more convenient to obtain and handle.

Transportation, storage, and preservation must be carefully monitored for a reliable assay. Freezing is preferred except for nail, hair, and dried blood spot samples.

Careful sample preparation is also a must considering the heterogeneous nature of biological samples. This includes extraction, cleaning, and concentration of the sample before identifying and measuring the pesticides and/or metabolites.

Multiple methods have been used, and some are newly designed. In addition to targeted analysis seeking one or more specific compounds or classes of compounds, toxicity studies may require a broader sweep, such as a metabolomics approach. This involves an evaluation of the number and concentration of all the different metabolites in the sample, which is then analyzed using bioinformatics.

Sophisticated measuring techniques are used, including nuclear magnetic resonance (NMR) and mass spectroscopy, the latter often coupled with other methods like gas or liquid chromatography.

The resulting data exists as thousands of variables subjected to analysis by multiple types of processing algorithms: principal component analysis (PCA), hierarchical analysis (CA), heatmaps, molecular networks, partial least squares discriminant analysis (PLS-DA) or artificial neural networks (ANN) are some of them. The processing involves many other technical steps to refine the data, remove noise, correct for outliers and baseline variability, and so on.

The final results are interrogated using biological databases like KEGG, SMPDB, or HMDB. Such studies have shown an association between pesticide exposure and metabolic impairment due to oxidative stress, abnormal lipid, and fatty acid metabolism, perturbed mitochondrial metabolism, molecules that serve as neurotransmitter precursors, and pro-inflammatory molecules.

Metabolomics also suggests changes in pregnancy following pesticide exposure, possibly leading to low birth weight mediated by low thyroid hormone concentrations. Finally, it indicates a beneficial effect of an organic diet compared to one rich in pesticide-treated food in children aged 3-11 years.

What are the conclusions?

The researchers argue for a better understanding of the effects of pesticides on human health following exposure in fetal and neonatal life. This distinction is made based on the difference in the routes of exposure at this time, with the transplacental movement of pesticides and their metabolites playing a prominent role, along with the secretion of such compounds in breast milk.

This indicates that maternal exposure to pesticides "can have health-related consequences for fetuses during the perinatal period as well as breastfed neonates." Further research is required to understand how such compounds cross into fetal circulation and how they affect pediatric physiology.

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.