Prenatal cocaine exposure

During the 1980s and 1990s, a surge occurred in the use of crack cocaine in US cities: Reporting on the effects of PCE may have been affected by publication bias, a disproportionate publication of studies indicating more severe outcomes as the crack epidemic emerged. Scientific studies that reported PCE to have significant effects were more likely to be published than those that did not. Between 1980 and 1989, 57% of studies showing cocaine has effects on a fetus were accepted by the Society for Pediatric Research, compared with only 11% of studies showing no effects. Findings that other factors such as prematurity were behind symptoms that cocaine-exposed babies showed did not "fit within the narrative of what had become a national scare" and were given less attention. Ideas about severe effects of PCE may have been more readily embraced because they "fit in with cultural stereotypes". At the time, the proposed mechanism by which cocaine harmed fetuses was as a stimulant— cocaine was predicted to disrupt normal development of parts of the brain that dealt with stimulation, resulting in problems such as bipolar disorder and attention deficit disorder. Reports from the mid-1980s to early '90s raised concerns about links between PCE and slowed growth, deformed limbs, defects of the kidneys and genitourinary and gastrointestinal systems, neurological damage, small head size, atrophy or cysts in the cerebral cortex, bleeding into the brain's ventricles, and obstruction of blood supply in the central nervous system. After the early studies that reported that PCE children would be severely disabled, came studies that purported to show that cocaine exposure in utero has no important effects. Almost every prenatal complication originally thought to be due directly to PCE was found to result from confounding factors such as poor maternal nutrition, use of other drugs, depression, and lack of prenatal care. More recently, the scientific community has begun to reach an understanding that PCE does have some important effects, but that they are not as severe as was predicted in the early studies. The effects of PCE are subtle, but they exist. Most people who were exposed to cocaine in utero are normal or close to it. ==Pathophysiology==

Cocaine, a small molecule, can cross the placenta into the bloodstream of the fetus. In fact, it may be present in a higher concentration in the amniotic fluid than it is in the mother's bloodstream. The skin of the fetus can absorb the chemical directly from the amniotic fluid until the 24th week of pregnancy. Cocaine can also show up in breast milk and affect the nursing baby. The severity of effects depends on how much of the drug is used, how often, and the stage in the development of the fetus. Cocaine prevents the reuptake of the neurotransmitters dopamine, serotonin, and norepinephrine. The euphoria experienced by cocaine users is thought to be largely due to the way it prevents these neurotransmitters from being reabsorbed by the presynaptic neuron that released it. Cocaine causes vasoconstriction (narrowing of blood vessels) in both mother and fetus, which can cause hypoxia in the fetus. Constricting blood vessels causes tissues to receive insufficient blood flow, killing cells, but this effect is less pronounced with cocaine than with nicotine. The reduction in blood flow to the uterus limits the delivery of oxygen and nutrients to the fetus. Cocaine also constricts the blood vessels in the fetus, which is potentially linked to slowed fetal growth and abnormal development of the genitourinary, cardiovascular, digestive, and musculoskeletal systems. Cocaine causes changes in the mother's blood pressure that are thought to be the cause of strokes in the fetus; one study found that 6% of cocaine-exposed infants had had one or more strokes. Such prenatal strokes may be the cause of neurological problems found in some cocaine-exposed infants after birth. Blood vessel contraction can also cause premature labor and premature birth. Cocaine has also been found to enhance the contractility of the tissue in the uterus, another factor that has been suggested as a possible mechanism for its contribution to increased prematurity rates. Increased contractility of the uterus may also be behind the increased likelihood of placental abruption (the placenta tearing away from the uterine wall), which some findings have linked with PCE. ==Diagnosis==

Cocaine use during pregnancy can be discovered by asking the mother, but sometimes women will not admit to having used drugs. Mothers may lie for fear of prosecution or having their children taken away, but even when they are willing to tell the truth, their memories may not be very accurate. Determining the purity of the drug they have taken also may not be possible. More reliable methods for detecting cocaine exposure involve testing the newborn's hair or meconium (the infant's earliest stool). Hair analysis, however, can give false positives for cocaine exposure, and a newborn may not have enough hair to test. The newborn's urine can be tested for cocaine and metabolites, but it must be collected as soon as possible after birth. It is not known how long after exposure the markers will still show up in a newborn's urine. The mother's urine can also be tested for drugs, but it cannot detect drugs used too far in the past or determine how much or how often the drugs were used. Tests cannot generally detect cocaine use over a week prior to sample collection. Mothers are more honest about cocaine use when their urine is also tested, but many users still deny it. Both maternal and neonatal urine tests can give false negatives. ==Effects and prognosis==

As of 2014, studies had returned widely varying reports of the effects of PCE; some claimed the physical disabilities are severe and generalized, others find specific effects, and others none at all. It has been suggested that some birth defects could be due to cocaine's disruption of blood vessel growth. Like birth defects, small head size, and stroke are risks in PCE. ==Epidemiology==

Of all cocaine users, women of childbearing age comprise 15–17%. An estimated 0.6 to 3% of pregnant women in the developed world use cocaine. However, the real prevalence of cocaine use by pregnant women is unknown. ==Legal and ethical issues ==

The harm to a child from PCE has implications for public policy and law. Some US states have pressed charges against pregnant women who use drugs, including assault with a deadly weapon, corruption of a minor, manslaughter, child abuse, and distribution of drugs to a minor. However, these approaches have generally been rejected in the courts on the basis that a fetus is not legally a child. Between 1985 and 2001, more than 200 women in over 30 US states faced prosecution for drug use during pregnancy. In South Carolina, a woman who used crack in her third trimester of pregnancy was sentenced to prison for eight years when her child was born with cocaine metabolites in its system. The Supreme Court of South Carolina upheld this conviction. As of 2013, all but one of the women prosecuted in the US for drug use while pregnant have won their cases on appeal. From 1989 to 1994, amid public outcry about cocaine babies, the Medical University of South Carolina tested pregnant women for cocaine, reporting those who tested positive to the police. The US Supreme Court found the policy to be unacceptable on constitutional grounds in 2001. Some advocates argue that punishment for crack-using pregnant women as a means to treat their addiction is a violation of their right to privacy. According to studies, fear of prosecution and having children taken away is associated with a refusal to seek prenatal care or medical treatment. Some nonprofit organizations aim to prevent PCE with birth control. One such initiative, Project Prevention, offers women addicted to cocaine money as an incentive to undergo long-term birth control or, frequently, sterilization—an approach which has led to public outcry from those who consider this practice to be eugenics. ==Social stigma==

Children who were exposed to crack prenatally faced social stigma as babies and school-aged children; some experts say that the "crack baby" stigma was more harmful than the PCE. The social stigma of the drug also complicated studies of PCE; researchers labored under the awareness that their findings would have political implications. In addition, the perceived hopelessness of 'crack babies' may have caused researchers to ignore possibilities for early intervention that could have helped them. The social stigma may turn out to be a self-fulfilling prophecy. ==Research==

Confounding factors A number of the effects that had been thought after early studies to be attributable to prenatal exposure to cocaine are actually due partially or wholly to other factors, such as exposure to other substances (including tobacco, alcohol, or marijuana) or to the environment in which the child is raised. PCE is very difficult to study because of a variety of factors that may confound the results: pre- and postnatal care may be poor; the pregnant mother and child may be malnourished; the amount of cocaine a mother takes can vary; she may take a variety of drugs during pregnancy in addition to cocaine; measurements for detecting deficits may not be sensitive enough; and results that are found may only last a short time. Studies differ in how they define heavy or light cocaine use during pregnancy, and the period of exposure during pregnancy on which they focus (e.g., first, second, or third trimester. Drug use by mothers puts children at high risk for exposure to toxic or otherwise dangerous environments, and PCE does not present much risk beyond these risk factors. PCE is clustered with other risk factors to the child, such as physical abuse and neglect, domestic violence, and prenatal exposure to other substances. Such environmental factors are known to adversely affect children in the same areas being studied concerning PCE. Most women who use cocaine while pregnant use other drugs too; one study found that 93% of those who use cocaine or opiates also use tobacco, marijuana, or alcohol. When researchers control for use of other drugs, many of the seeming effects of cocaine on head size, birth weight, Apgar scores, and prematurity disappear. Addiction to any substance, including crack, may be a risk factor for child abuse or neglect. Crack addiction, like other addictions, distracts parents from the child and leads to inattentive parenting. Mothers who continue to use drugs once their babies are born have trouble forming the normal parental bonds, more often interacting with their babies with a detached, unenthusiastic, flat demeanor. Conversely, low-stress environments and responsive caregiving may provide a protective effect on the child's brain, potentially compensating for negative effects of PCE. Many drug users do not get prenatal care, for a variety of reasons, including that they may not know they are pregnant. Many crack addicts get no medical care at all and have extremely poor diets, and children who live around crack smoking are at risk of inhaling secondary smoke. Cocaine using mothers also have a higher rate of sexually transmitted infections such as HIV and hepatitis. In some cases, it is not clear whether the direct results of PCE lead to behavioral problems or whether environmental factors are at fault. For example, children who have caregiver instability may have more behavioral problems as a result, or it may be that behavioral problems manifested by PCE children lead to greater turnover in caregivers. Other factors that make studying PCE difficult include unwillingness of mothers to tell the truth about drug history, uncertainty of dosages of street drugs, and high rates of attrition (loss of participants) from studies. Animal models One way to address problems with uncertainty about cocaine's effects due to confounding factors is to use animal models; these allow experimenters to study the effects at specific doses and times. Studies have used mice, other rodents, rabbits, and primates. However, differences between species' physiology and gestation times mean findings in animals may not apply to humans. Mice, rats, and rabbits have shorter gestational times, so experimenters must continue giving drugs after they are born to more closely model human gestation; however this introduces more differences. Animals and humans metabolize drugs at different rates, and drugs that are highly teratogenic in animals may not be in humans and vice versa. Animals cannot be used to measure differences in abilities such as reasoning that are only found in humans. Animal studies in various species have found that cocaine impacts brain structure, function, and chemistry, and causes long-term changes at the molecular, cellular, and behavioral levels. Animal Model Studies have shown that cocaine has the ability to cross the placenta and the blood brain barrier in the body. This is yet another example of the damage that can be done that can impact and effect the brain and body function and health overall. While the animal model is not as reliable for certain tests because we function differently, this test in particular gives us the idea of the level of damage that can be cause to the fetus of a pregnant women using cocaine during her pregnancy. In research studies on pregnant rats, injected cocaine did less damage to cells than injected nicotine, and more recovery occurred between doses. Adult rats that were exposed to cocaine prenatally have deficits in learning, memory, and motor skills, and may have abnormalities in dopamine processing. Animal research has also shown that offspring of males that used cocaine while their sperm were forming may go on to have abnormalities later in life. ==References==