TERATOLOGY AND HAZARDS TO PRENATAL DEVELOPMENT

 

TERATOLOGY AND HAZARDS TO PRENATAL DEVELOPMENT

The environment can affect the embryo or fetus in many well-documented ways.

 

General Principles

A teratogen is any agent that can potentially cause a birth defect or negatively alter cognitive and behavioral outcomes. (The word comes from the Greek word tera, meaning “monster.”) So many teratogens exist that practically every fetus is exposed to at least some teratogens. For this reason, it is difficult to determine which teratogen causes which problem. In addition, it may take a long time for the effects of a teratogen to show up. Only about half of all potential effects appear at birth.

The field of study that investigates the causes of birth defects is called teratology. Some exposures to teratogens do not cause physical birth defects but can alter the developing brain and influence cognitive and behavioral functioning, in which case the field of study is called behavioral teratology.

The dose, genetic susceptibility, and the time of exposure to a particular teratogen influence both the severity of the damage to an embryo or fetus and the type of defect:

· Dose. The dose effect is rather obvious—the greater the dose of an agent, such as a drug, the greater the effect.

· Genetic susceptibility. The type or severity of abnormalities caused by a teratogen is linked to the genotype of the pregnant woman and the genotype of the embryo or fetus (Lidral & Murray, 2005). For example, how a mother metabolizes a particular drug can influence the degree to which the drug effects are transmitted to the embryo or fetus. The extent to which an embryo or fetus is vulnerable to a teratogen may also depend on its genotype (Marinucci & others, 2009). Also, for unknown reasons, male fetuses are far more likely to be affected by teratogens than female fetuses.

· Time of exposure. Teratogens do more damage when they occur at some points in development than at others (Weiner & Buhimschi, 2009). Damage during the germinal period may even prevent implantation. In general, the embryonic period is more vulnerable than the fetal period.

Figure 3.5 on the next page summarizes additional information about the effects of time of exposure to a teratogen. The probability of a structural defect is greatest early in the embryonic period, when organs are being formed (Hill, 2007). Each body structure has its own critical period of formation. The critical period for the nervous system (week 3) is earlier than for arms and legs (weeks 4 and 5).

 

After organogenesis is complete, teratogens are less likely to cause anatomical defects. Instead, exposure during the fetal period is more likely instead to stunt growth or to create problems in the way organs function. To examine some key teratogens and their effects, let’s begin with drugs.

Prescription and Nonprescription Drugs

Many U.S. women are given prescriptions for drugs while they are pregnant—especially antibiotics, analgesics, and asthma medications. Prescription as well as nonprescription drugs, however, may have effects on the embryo or fetus that the women never imagine (Weiner & Buhimschi, 2009).

Prescription drugs that can function as teratogens include antibiotics, such as streptomycin and tetracycline; some antidepressants; certain hormones, such as progestin and synthetic estrogen; and Accutane (which often is prescribed for acne) (Bayraktar & others, 2010; Teichert & others, 2010).

Antidepressant use by pregnant women has been extensively studied (Pedersen & others, 2009; Reis & Kallen, 2010; Simoncelli, Martin, & Berard, 2010). A recent study revealed that the offspring of pregnant women who redeemed prescriptions for more than one type of SSRIs (selective serotonin reuptake inhibitors) early in pregnancy had an increased risk of heart defects (Pedersen & others, 2009). In this study, negative effects on children’s heart functioning increased when their mothers took these two SSRIs early in pregnancy: sertraline and citalopram. However, a recent research review by the American Psychiatric Association and the American College of Obstetricians and Gynecologists indicated that although some studies have found negative outcomes for antidepressant use during pregnancy, failure to control for various factors that can influence birth outcomes, such as maternal illness or problematic health behaviors, make conclusions about a link between antidepressant use by pregnant women and birth outcomes difficult (Yonkers & others, 2009). Later in the chapter, we will further discuss depression during pregnancy.

Nonprescription drugs that can be harmful include diet pills and high dosages of aspirin (Norgard & others, 2006). However, recent studies indicated that low doses of aspirin pose no harm for the fetus but that high doses can contribute to maternal and fetal bleeding (James, Brancazio, & Price, 2008; Marret & others, 2010).

Psychoactive Drugs

Psychoactive drugs are drugs that act on the nervous system to alter states of consciousness, modify perceptions, and change moods. Examples include caffeine, alcohol, and nicotine, as well as illicit drugs such as cocaine, methamphetamine, marijuana, and heroin.

Caffeine

People often consume caffeine by drinking coffee, tea, or colas, or by eating chocolate. A recent study revealed that pregnant women who consumed 200 or more milligrams of caffeine a day had an increased risk of miscarriage (Weng, Odouli, & Li, 2008). Taking into account such results, the Food and Drug Administration recommends that pregnant women either not consume caffeine or consume it only sparingly.

Alcohol

Heavy drinking by pregnant women can be devastating to offspring. Fetal alcohol spectrum disorders (FASD) are a cluster of abnormalities and problems that appear in the offspring of mothers who drink alcohol heavily during pregnancy. The abnormalities include facial deformities and defective limbs, face, and heart (Klingenberg & others, 2010). Most children with FASD have learning problems and many are below average in intelligence with some that are mentally retarded (Dalen & others, 2009). Recent studies revealed that children and adults with FASD have impaired memory development (Coles & others, 2010; Pei & others, 2008). Another recent study found that children with FASD have impaired math ability linked to multiple regions of the brain (Lebel & others, 2010). Although many mothers of FASD infants are heavy drinkers, many mothers who are heavy drinkers do not have children with FASD or have one child with FASD and other children who do not have it.

What are some guidelines for alcohol use during pregnancy? Even drinking just one or two servings of beer or wine or one serving of hard liquor a few days a week can have negative effects on the fetus, although it is generally agreed that this level of alcohol use will not cause fetal alcohol syndrome. The U.S. Surgeon General recommends that no alcohol be consumed during pregnancy. And research suggests that it may not be wise to consume alcohol at the time of conception. One study revealed that intakes of alcohol by both men and women during the weeks of conception increased the risk of early pregnancy loss (Henriksen & others, 2004).

Nicotine

Cigarette smoking by pregnant women can also adversely influence prenatal development, birth, and postnatal development (Blood-Siegfried & Rende, 2010). Preterm births and low birth weights, fetal and neonatal deaths, respiratory problems, sudden infant death syndrome (SIDS, also known as crib death), and cardiovascular problems are all more common among the offspring of mothers who smoked during pregnancy (Feng & others, 2010; Landau, 2008; Lazic & others, 2010). Maternal smoking during pregnancy also has been identified as a risk factor for the development of attention deficit hyperactivity disorder in offspring (Knopik, 2009; Pinkhardt & others, 2009). A recent research review also indicated that environmental tobacco smoke was linked to increased risk of low birth weight in offspring (Leonardi-Bee & others, 2008).

Cocaine

Does cocaine use during pregnancy harm the developing embryo and fetus? The most consistent finding is that cocaine exposure during prenatal development is associated with reduced birth weight, length, and head circumference (Smith & others, 2001). Also, in other studies, prenatal cocaine exposure has been linked to lower arousal, less effective self-regulation, higher excitability, and lower quality of reflexes at 1 month of age (Lester & others, 2002); to impaired motor development at 2 years of age and a slower rate of growth through 10 years of age (Richardson, Goldschmidt, & Willford, 2008); to deficits in behavioral self-regulation (Ackerman, Riggins, & Black, 2010); to impaired language development and information processing (Beeghly & others, 2006), including attention deficits (especially in sustained attention) in preschool and elementary schoolchildren (Accornero & others, 2006; Ackerman, Riggins, & Black, 2010); and to increased likelihood of being in a special education program that involves support services (Levine & others, 2008).

Some researchers argue that these findings should be interpreted cautiously (Accornero & others, 2006). Why? Because other factors in the lives of pregnant women who use cocaine (such as poverty, malnutrition, and other substance abuse) often cannot be ruled out as possible contributors to the problems found in their children (Hurt & others, 2005). For example, cocaine users are more likely than nonusers to smoke cigarettes, use marijuana, drink alcohol, and take amphetamines.

Despite these cautions, the weight of research evidence indicates that children born to mothers who use cocaine are likely to have neurological, medical, and cognitive deficits (Field, 2007; Mayer & Zhang, 2009). Cocaine use by pregnant women is never recommended. Methamphetamine

Methamphetamine, like cocaine, is a stimulant, speeding up an individual's nervous system. Babies born to mothers who use methamphetamine, or "meth," during pregnancy are at risk for a number of problems, including high infant mortality, low birth weight, and developmental and behavioral problems (Forester & Merz, 2007). A recent study also found memory deficits in children whose mothers used methamphetamine during pregnancy (Lu & others, 2009).

Marijuana

An increasing number of studies find that marijuana use by pregnant women also has negative outcomes for offspring. For example, a recent study found that prenatal marijuana exposure was related to lower intelligence in children (Goldschmidt & others, 2008). Another study indicated that prenatal exposure to marijuana was linked to marijuana use at 14 years of age (Day, Goldschmidt, & Thomas, 2006). In sum, marijuana use is not recommended for pregnant women. Heroin

It is well documented that infants whose mothers are addicted to heroin show several behavioral difficulties at birth (Steinhausen, Blattmann, & Pfund, 2007). The difficulties include withdrawal symptoms, such as tremors, irritability, abnormal crying, disturbed sleep, and impaired motor control. Many still show behavioral problems at their first birthday, and attention deficits may appear later in development. The most common treatment for heroin addiction, methadone, is associated with very severe withdrawal symptoms in newborns (Binder & Vavrinkova, 2008).

Incompatible Blood Types

Incompatibility between the mother's and father's blood types poses another risk to prenatal development. Blood types are created by differences in the surface structure of red blood cells. One type of difference in the surface of red blood cells creates the familiar blood groups—A, B, 0, and AB. A second difference creates what is called Rh-positive and Rh-negative blood. If a surface marker, called the Rh-factor, is present in an individual's red blood cells, the person is said to be Rh-positive; if the Rh-marker is not present, the person is said to be Rh-negative. If a pregnant woman is Rh-negative and her partner is Rh-positive, the fetus may be Rh-positive. If the fetus' blood is Rh-positive and the mother's is Rh-negative, the mother's immune system may produce antibodies that will attack the fetus. This can result in any number of problems, including miscarriage or stillbirth, anemia, jaundice, heart defects, brain damage, or death soon after birth (Moise, 2005).

Generally, the first Rh-positive baby of an Rh-negative mother is not at risk, but with each subsequent pregnancy the risk increases. A vaccine (RhoGAM) may be given to the mother within three days of the first child's birth to prevent her body from making antibodies that will attack any future Rh-positive fetuses in subsequent pregnancies. Also, babies affected by Rh incompatibility can be given blood transfusions before or right after birth (Flegal, 2007).

Environmental Hazards

Many aspects of our modern industrial world can endanger the embryo or fetus. Some specific hazards to the embryo or fetus include radiation, toxic wastes, and other chemical pollutants (O'Connor & Roy, 2008).

X-ray radiation can affect the developing embryo or fetus, especially in the first several weeks after conception, when women do not yet know they are pregnant (Urbano & Tait, 2004). Women and their physicians should weigh the risk of an X-ray when an actual or potential pregnancy is involved (Baysinger, 2010; Menias & others, 2007). However, a routine diagnostic X-ray of a body area other than the abdomen, with the woman's abdomen protected by a lead apron, is generally considered safe (Brent, 2009).

Environmental pollutants and toxic wastes are also sources of danger to unborn children. Among the dangerous pollutants are carbon monoxide, mercury, and lead, as well as certain fertilizers and pesticides.

Maternal Diseases

Maternal diseases and infections can produce defects in offspring by crossing the placental barrier, or they can cause damage during birth. Rubella (German measles) is one disease that can cause prenatal defects. Women who plan to have children should have a blood test before they become pregnant to determine if they are immune to the disease (Coonrod & others, 2008).

Syphilis (a sexually transmitted infection) is more damaging later in prenatal development—four months or more after conception. Damage includes eye lesions, which can cause blindness, and skin lesions.

Another infection that has received widespread attention is genital herpes. Newborns contract this virus when they are delivered through the birth canal of a mother with genital herpes (Hollier & Wendel, 2008). About one-third of babies delivered through an infected birth canal die: another one-fourth become brain damaged. If an active case of genital herpes is detected in a pregnant woman close to her delivery date, a cesarean section can be performed (in which the infant is delivered through an incision in the mother's abdomen) to keep the virus from infecting the newborn (Sellner & others, 2009).

AIDS is a sexually transmitted infection that is caused by the human immunodeficiency virus (HIV), which destroys the body's immune system. A mother can infect her offspring with HIV/AIDS in three ways: (1) during gestation across the placenta, (2) during delivery through contact with

maternal blood or fluids, and (3) postpartum (after birth) through breast

feeding. The transmission of AIDS through breast feeding is especially a problem in many developing countries (UNICEF, 2010). Babies born to HIV-infected mothers can be (1) infected and symptomatic (show HIV symptoms), (2) infected but asymptomatic (not show HIV symptoms), or (3) not infected at all. An infant who is infected and asymptomatic may still develop HIV symptoms up until 15 months of age.

The more widespread disease of diabetes, characterized by high levels of sugar in the blood, also affects offspring (Huda, Brodie, & Sattar, 2010; Oostdam & others, 2009). A recent large-scale study revealed that from 1999 to 2005 twice as many women and five times as many adolescents giving birth had diabetes (Lawrence & others, 2008).

A research review indicated that when newborns have physical defects they are more likely to have diabetic mothers (Eriksson, 2009). Women who have gestational diabetes also may deliver very large infants (weighing 10 pounds or more), and the infants are at risk for diabetes themselves (Gluck & others, 2009).

Other Parental Factors

So far we have discussed a number of drugs, environmental hazards, maternal diseases, and incompatible blood types that can harm the embryo or fetus. Here we will explore other characteristics of the mother and father that can affect prenatal and child development, including nutrition, age, and emotional states and stress.

 

Maternal Diet and Nutrition

A developing embryo or fetus depends completely on its mother for nutrition, which comes from the mother’s blood (Shapira, 2008). The nutritional status of the embryo or fetus is determined by the mother’s total caloric intake, and her intake of proteins, vitamins, and minerals. Children born to malnourished mothers are more likely than other children to be malformed.

Being overweight before and during pregnancy can also put the embryo or fetus at risk, and an increasing number of pregnant women in the United States are overweight (Griffiths & others, 2010; Sullivan & others, 2010). A recent research review concluded that obesity during pregnancy is linked to increased maternal risks of infertility, hypertensive disorders, diabetes, and delivery by cesarean section (Arendas, Qui, & Gruslin, 2008). In this review, obesity during pregnancy included these increased risks to the fetus: macrosomia (newborn with excessive birth weight), intrauterine fetal death, stillbirth, and admission to the neonatal intensive care unit (NICU).

One aspect of maternal nutrition that is important for normal prenatal development is folic acid, a B-complex vitamin (Rasmussen & Clemmensen, 2010). A recent study of more than 34,000 women taking folic acid either alone or as part of a multivitamin for at least one year prior to conceiving was linked with a 70 percent lower risk of delivering from 20 to 28 weeks and a 50 percent lower risk of delivering between 28 to 32 weeks (Bukowski & others, 2008). Another recent study revealed that toddlers of mothers who did not use folic acid supplements in the first trimester of pregnancy had more behavior problems (Roza & others, 2010). Also, we indicated earlier in the chapter, a lack of folic acid is related to neural tube defects in offspring, such as spina bifida (a defect in the spinal cord) (Shookhoff & Ian Gallicano, 2010). The U.S. Department of Health and Human Services (2009) recommends that pregnant women consume a minimum of 400 micrograms of folic acid per day (about twice the amount the average woman gets in one day). Orange juice and spinach are examples of foods rich in folic acid.

Eating fish is often recommended as part of a healthy diet, but pollution has made many fish a risky choice for pregnant women. Some fish contain high levels of mercury, which is released into the air both naturally and by industrial pollution (Genuis, 2009). When mercury falls into the water it can become toxic and accumulate in large fish, such as shark, swordfish, king mackerel, and some species of large tuna (Mayo Clinic, 2009; Ramon & others, 2009). Mercury is easily transferred across the placenta, and the embryo’s developing brain and nervous system are highly sensitive to the metal (Gliori & others, 2006). Researchers have found that prenatal mercury exposure is linked to adverse outcomes, including miscarriage, preterm birth, and lower intelligence (Triche & Hossain, 2007; Xue & others, 2007).

Maternal Age

When possible harmful effects on the fetus and infant are considered, two maternal ages are of special interest: (1) adolescence, and (2) 35 years and older (Malizia, Hacker, & Penzias, 2009). The mortality rate of infants born to adolescent mothers is double that of infants born to mothers in their twenties. Adequate prenatal care decreases the probability that a child born to an adolescent girl will have physical problems. However, adolescents are the least likely of women in all age groups to obtain prenatal assistance from clinics and health services. Maternal age is also linked to the risk that a child will have Down syndrome (Allen & others, 2009; Ghosh & others, 2010). an individual with Down syndrome has distinctive facial characteristics, short limbs, and retardation of motor and mental abilities.

 

Emotional States and Stress

When a pregnant woman experiences intense fears, anxieties, and other emotions or negative mood states, physiological changes occur that may affect her fetus (Entringer & others, 2009; Leung & others, 2010). A mother’s stress may also influence the fetus indirectly by increasing the likelihood that the mother will engage in unhealthy behaviors, such as taking drugs and engaging in poor prenatal care.

High maternal anxiety and stress during pregnancy can have long-term consequences for the offspring. A recent research review indicated that pregnant women with high levels of stress are at increased risk for having a child with emotional or cognitive problems, attention deficit hyperactivity disorder (ADHD), and language delay (Taige & others, 2007).

Might maternal depression also have an adverse effect on prenatal development and birth? A recent study revealed maternal depression was linked to preterm birth and slower prenatal growth rates (Diego & others, 2009). In this study, mothers who were depressed had elevated cortisol levels, which likely contributed to the negative outcomes for the fetus and newborn.

Paternal Factors

So far, we have discussed how characteristics of the mother—such as drug use, disease, diet and nutrition, age, and emotional states—can influence prenatal development and the development of the child. Might there also be some paternal risk factors? Indeed, there are several. Men’s exposure to lead, radiation, certain pesticides, and petrochemicals may cause abnormalities in sperm that lead to miscarriage or diseases, such as childhood cancer (Cordier, 2008). The father’s smoking during the mother’s pregnancy also can cause problems for the offspring. In one study, heavy paternal smoking was associated with the risk of early pregnancy loss (Venners & others, 2003). This negative outcome may be related to secondhand smoke.