Introduction
Teratogen is broadly defined as an environmental agent capable of causing abnormal prenatal variation in form or function. In other words, it can be any environmental factor that can produce a permanent abnormality in structure or function of an embryo or fetus or restriction of growth of an infant (Gilbert-Barness, 2010). In prenatal life, exposure to teratogens may even lead to death of the embryo or fetus. It is estimated that approximately 15% of all congenital structural abnormalities observed in a child are due to exposure to some kind of teratogens during the prenatal life (Brent, 2001). A larger number of such infants either have growth retardation or functional abnormalities (Gilbert-Barness, 2010).
It is generally suspected that medications/ drugs are teratogenic agents, but it can be anything. Teratogens are not only medications; according to Robinson and Linden, it can be anything e.g., infectious (syphilis, toxoplasmosis, or cytomegalovirus infection); physical (heat or radiation); maternal (maternal diabetes, phenylketonuria); or paternal (cumulative exposures resulting in DNA damage) (Robinson, 1993).
Some researchers are of the opinion that it is inappropriate to label a particular agent as teratogenic without knowing the dose of the agent, the route of exposure, and the stage of pregnancy when the exposure occurred (Brent, 2001). Most structural defects found in an infant caused by teratogenic exposures occur during the embryonic period at a time when critical developments are taking place in terms of organ formation and development (Gilbert, 2003). The table below provides a description of the teratogenic agents with their effects and possible time of risk.
The above listed teratogenic agents are capable of causing certain damages to the life of an individual both in prenatal and post natal life (Nwoke, 2008).
Teratogenic agents affect the genes by damaging them. One researcher observed that thousands of babies are born deformed or mentally retarded every year; and the deformity or retardation is the result of events that occur in the mother’s life. The author has classified such events as teratogens (Santrock, 2006).
How agents like drugs exert teratogenic effects?
Though drugs are designed to become more permeable to the blood brain barrier, they still inevitably cross the placenta and enter the fetal brain (Bercovici, n.d.). The effect of drugs on cognitive and neuro development can occur in two ways. In one way, drug specific actions on the developing brain of the fetus alter brain neurotransmitter levels, change receptor levels, and ultimately alter the brain circuitry. Various molecular changes occur during this process after prenatal drug exposure which may have functional consequences later in life. Another way a prenatal drug exposure can affect the cognitive neurodevelopment is via perinatal complications. If the mother was under antidepressant, anxiolytics or antiepileptic treatment, the neonate may exhibit withdrawal symptoms even when the mother’s drug exposure was within a therapeutic dose. Withdrawal symptoms can include respiratory and sleep difficulties, apnea, or cyanosis that can probably lead to a low Apgar score (Bercovici, n.d.). Holst et al. assessed the neonatal risk factors associated with developmental disability in later life and found that intrapartum asphyxia was a strong predictor of developmental disabilities in childhood. The authors described asphyxia as Apgar scores of less than 7 at 1 minute and less than 10 at 10 minutes. Many of the new borns prenatally exposed to selective serotonin reuptake inhibitors (SSRIs) or benzodiapines in the last trimester of pregnancy had reduced Apgar scores as compared to unexposed children, which may have put them at risk for developmental disabilities in later life. The authors also describe low birth weight and early gestation as a strong predictor of delays in development (Holst, 1989).
Examples of teratogens
A prime example of a teratogen widely used in skin care products (products to treat acne) is the vitamin A derivative, isotretinoin, which can cause hearing and visual loss and intellectual impairment in exposed fetuses (Parisi, 2011).
Stress as a teratogenic agent
Autistic disorder is a severe neurodevelopmental disorder evident since early childhood. Quite a few studies have suggested the importance of genetic factors in autism; the same studies have also indicated that environmental factors too play a role (Campbell, 2006; Folstein, 1991; Muhle, 2004). Environmental factors in the form of stress or stressful life events that distress an expectant mother can increase the risk of autistic disorder in a child. Two studies have reported on the association between an increased risk of autism in the child and prenatal exposure to stressful events. Ward (1990) compared data from prenatal records of 59 mothers of autistic children to records of a matched sample of 59 mothers of healthy children. He found that the mothers of autistic children reported having experienced significantly more family problems during their pregnancies with the AD children. A total of 19 women here were mothers of autistic children, but only 2 of the control mothers experienced discord during their pregnancies with their children (p < 0.05). In a similar study, Beversdorf et al. (2005) found that 188 mothers of autistic disorder children reported having experienced significantly more stressful life events–such as job loss or death of husband–during their pregnancies (44.7 events per 100 responses) than did 202 mothers of typically developing children (only 25.9 events per 100 responses; p = 0.0007).
Natural calamity as a teratogen
One study (Kinney, 2008) actually used natural disasters like hurricanes and severe tropical storms to investigate whether autism in children is associated with the mother’s exposure to stressful events during sensitive periods of gestation. The most destructive storms affecting Louisiana between 1980 and 1996 were identified using National Weather Service data. Mothers in Orleans Parish (which is geographically identical to New Orleans) were particularly likely to be vulnerable to storms’ effects because much of New Orleans is below sea level and subject to severe flooding and a high proportion of New Orleans residents are near or below the poverty line, and have fewer resources to cope with the storms’ effects. Interestingly, prevalence of autism was found to increase significantly, in a dose-response fashion, with the severity of prenatal storm exposure, from the control cohort that had no exposure to either storm factor (prevalence of 4.49 cases per 10,000 births), to the cohort exposed to one or the other storm factor (AD prevalence of 6.06), to lastly the cohort exposed to both storm factors (prevalence of 13.32 cases per 10,000 births). The increase in the risk of autistic disorder with storm exposure was particularly large for children who had been exposed to storms in specific periods near the middle and end of gestation.
Alcohol as a teratogen
Alcohol is one of the most dangerous teratogens. Maternal alcohol intake during pregnancy leads to a congenital syndrome termed as “fetal alcohol syndrome (FAS)”. This syndrome is preventable by abstinence from alcohol during pregnancy. It is the main cause of mental retardation and can lead to lifelong disabilities such as behavioral problems, learning difficulties, poor academic achievements, or inadequate social relationships. It is interesting to note that in a study on assessment of prevalence of FAS in Croatia, mothers who had alcohol during pregnancy mentioned about the beneficial effects of alcohol on pregnancy outcome and they believed that having red wine during pregnancy would prevent anemia or having beer towards the last few days of pregnancy would enhance breast milk flow. Such findings suggest that women are not appropriately informed or are not aware of the toxic effects of alcohol on the outcome of pregnancy and the growth and development of a healthy child (Petkovic, 2013).
Cocaine as a teratogen
Cocaine is also believed to be a uniquely dangerous teratogen. Findings of cocaine effects depend on contextual factors, such as the child’s history of prematurity, age at time of assessment, and the effects of prenatal exposure to other substances. So far nine studies have evaluated prenatal cocaine effects on the developmental test scores in infants, of which five studies have found no effect (Frank, 2001). In very low-birth-weight infants, Singer et al reported a negative association between prenatal cocaine exposure and developmental scores at 16 months corrected age. Griffith et al found that children exposed to cocaine in addition to other substances scored significantly lower than unexposed controls on a verbal reasoning scale of the IQ test. Two studies by Fetter et al and one by Swanson reported less optimal motor scores in the first seven months of life following prenatal cocaine exposure. Alessandri et al reported 4- to 8-month-old cocaine-exposed children to show less arousal, interest, joy, or sadness during the learning task. Similarly, Mayes et al found heavy prenatal cocaine use correlated with less optimal maternal behavior and with decreased readiness for interaction among infants at the age of six months (Frank, 2001).
DDT as a teratogen
Dichlorodiphenyltrichloroethane (DDT) was identified to be a potent insecticide decades back and was later known to be an insecticide of choice in households. It was widely used till about 1970, but later there were concerns about its toxic effects. This led to restrictions in its use in many countries. Dichlorodiphenyldichloroethylene (DDE) is a primary byproduct of (DDT). Few studies have shown high maternal serum DDE concentrations to be associated with an increased risk of fetal loss. Preclinical studies have confirmed that DDE is a neurodevelopmental toxicant. In one study, it was found that the maternal serum and breast milk DDE levels were related to hyporeflexia in a dose-dependent fashion in infants as assessed by the Brazelton Neonatal Behavioral Assessment Scale (BNBAS). In another study, increased maternal serum DDT levels were associated with poorer psychomotor development at 6, 12, and 24 months and mental development at 12 and 24 months in the CHAMACOS cohort. In a study in Spain, cord serum DDT levels were found to be associated with poorer performance in general cognitive, memory, quantitative, verbal, and executive function domains of the MCSA in 4- and 5-year-old children. However, these studies also showed that breast feeding may modulate some of the negative effects of DDT (Eskenazi, 2009).
Caffeine/ smoking as a teratogen
Researchers across the world have focused their attention on the effects of caffeine on pregnancy loss, congenital malformations, and fetal growth retardation because caffeine is the most widely used CNS stimulant in the world.
Bille et al. (2007) reported the association between oral clefts and maternal lifestyle in the first trimester of pregnancy. The study assessed 192 mothers who had given birth to a child with oral clefts. The authors reported first trimester smoking to be associated with an increased risk of clefting, OR = 1.5 (95% CI = 1.05 – 2.14). The authors also reported a finding that a habit of drinking five or more cups of tea per day in early pregnancy in mothers of 58 children to be associated with cleft palate, OR = 2.9, 95% CI (1.1–5.6). However, this study reported no significant association between caffeine consumption and oral clefts. But a recent study by Collier reported a significant association with maternal intake of 200mg of caffeine per day or more, among the mothers of 175 infants with cleft lip with or without cleft palate and other congenital anomalies (OR = 1.7; 95% CI = 1.0–2.9) (Collier, 2009).
Well known teratogen – thalidomide
A drug with devastating teratogenic effects is thalidomide. This was a drug used to treat morning sickness in pregnant women as well as anxiety and insomnia in the general population. It was withdrawn from the market after almost a decade of causing havoc. The drug was found to cause devastating birth defects that included major malformations such as missing arms and legs (Bercovici, n.d.).
Infectious agents as teratogens
Outbreaks of rubella in the years 1964 – 65 has recorded more than 20,000 infants to be born with malformations, including mental retardation, cataract or blindness, deafness, and serious congenital disorders. Another teratogenic agent – toxoplasmosis is transmitted to humans by animals, especially cats. Though it is harmless to adults, it can cause serious neurological problems in infants such as mental retardation, blindness, and cerebral palsy (Nwoke, 2008). HIV/AIDS in mothers too can prove to be teratogenic to offsprings. Caldwell and Rogers have indicated in their study that babies born to AIDS infected mothers can show or may not show symptoms of HIV/AIDS, but they develop the infection later in their lives (Caldwell, 1991).
Conclusion
In summary, teratogens are any agents that have a negative effect on the developing human beings. The adverse effects of the agents can be evident in prenatal or post natal life or even at infant or toddler stage. The teratogenic agent may be present in the woman’s body even before the conception takes place; and it can affect the unborn baby before birth, after birth, or anytime later in life. Even traditional beverages can have a negative impact on the growth and development of a child. Thus, it is necessary to be in a healthy and conducive environment, especially in the child - bearing years of life.
References
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