Pre-Conception Environmental Exposures and Preterm Births — Review of the Evidence
By: Manijeh, Mani
Tags: Preterm Birth, Pregnancy, Birth, Preconception Health, Premature Birth

By Manijeh “Mani” Berenji

Every year, an estimated 15 million babies are born preterm (which is defined as before 37 completed weeks of gestation) (1). Across 184 countries, the rate of preterm birth ranges from 5% to 18% of babies born and this number is rising every year (1). Preterm birth is the factor most strongly associated with neonatal mortality and long-term morbidity globally. (2–4). Preterm birth complications are the leading cause of death among children under 5 years of age, responsible for approximately 1 million deaths in 2015 (1,5).

Preterm birth is complex and occurs for a variety of reasons. Most preterm births happen spontaneously, but some are due to early induction of labor or caesarean birth, whether for medical or non-medical reasons. Although some risk factors for preterm birth have been identified, including maternal age, race/ethnicity, socioeconomic status, smoking during pregnancy, infection, and multiple gestations, these factors account for less than half of all cases, and underlying mechanisms remain largely unknown (2,4,6). The World Health Organization estimates that environmental factors account for 6% of the causes of adverse pregnancy outcomes such as preterm birth and has advised that there is a need for further research on the effect of the environment and chemicals on preterm birth (6,7).

The pre-conception period remains an important but largely unexplored critical window of exposure for perinatal and infant outcomes (6,8). Nutrition, stress, and environmental toxins (both from ambient environment as well as chemicals used to treat common medical ailments) can induce genetic changes which control long-term gene expression patterns from both maternal and paternal contributors (9). During early development, environmental stimuli determine not only short-term but also lifelong and trans-generationally heritable effects due to epigenetic imprinting (9,10). Such environmental-epigenetic mechanisms in the preconception period are likely associated with preterm birth (6,11–13).

Recently, studies have been conducted to explore the relationship between maternal/paternal pre-conception exposures and preterm birth. Zhang and colleagues conducted a preconception cohort study of subfertile couples comprising 419 mothers and 229 fathers and their 420 live-born singleton preterm babies (6). Pre-conception: urinary concentrations of metabolites of phthalates (a family of chemicals widely used in many consumer products and known reproductive toxicants in experimental animals) and phthalate substitutes were obtained from these mothers and fathers. The researchers measured maternal and paternal preconception urinary concentrations of di-(2-ethylhexyl) phthalate and di(isononyl)cyclohexane-1,2-dicarboxylate (a nonphthalate plasticizer substitute). Male and female participants provided 1 spot urine sample at study entry. Men provided an additional spot urine sample per cycle on the day when their female partner underwent the fertility procedure. Women provided up to 2 additional spot urine samples per fertility treatment cycle: one obtained during the follicular phase of the cycle (days 3–9) and the other on the day of the fertility procedure. Moreover, women provided 1 spot urine sample per trimester at a median of 6, 21, and 35 weeks’ gestation. After adjusting for covariates, maternal preconception urinary phthalate metabolite concentrations were associated with increased risk of preterm birth especially among male infants than female infants. However, there was little evidence of associations between paternal preconception phthalate metabolites or biomarkers of plasticizer substitutes and preterm birth.

As more preconception cohort studies are conducted, we will be able to gain a better understanding of prematurity and which babies are more at-risk of developing complications as a result. With such information, better interventions can be implemented to reduce infant morbidity and mortality (including essential care during child birth and in the postnatal period for every mother and baby; provision of antenatal steroid injections given to pregnant women at risk of preterm labor; antibiotics to treat newborn infections; and mother-to-baby with skin-to-skin contact and frequent breastfeeding) (1).