NICHD Research Seeks Clues into the Causes of Alcohol- and Drug-Related Birth Defects
According to the Centers for Disease Control and Prevention (CDC), birth defects occur in one of every 33 babies and are the leading cause of infant death. These problems, present at birth, are caused by genetics, the environment, and other known and unknown causes. Environmental causes of birth defects include chemical and other exposures that occur during pregnancy, including exposure to alcohol and drugs.
The NICHD is aware that the term "birth defects" carries negative undertones and that the term does not reflect the many abilities and talents of those impacted by these problems. Communities are discussing alternative terms for describing these birth problems. Until a consensus is reached, and with the goal of highlighting research on this important topic, this spotlight uses the term to describe health problems present at birth.
Research shows that there is no safe level of alcohol use during pregnancy; even a very small amount can have negative effects on the developing fetus. For this reason, health care providers recommend that women avoid drinking alcohol and eating foods or taking medications that may contain alcohol, such as certain cough syrups, if there is a chance they might be pregnant.
Drug exposure during pregnancy is not limited to illegal drugs, such as cocaine, but includes prescription and over-the-counter drugs and supplements that might disrupt the development of the fetus.
Health care providers recommend that women who are thinking about pregnancy avoid exposure to alcohol and drugs up to 3 months before starting to try to get pregnant. This and other aspects of preconception care can help to promote a healthy pregnancy.
Factors that affect pregnancy and fetal development are central to the NICHD's research. The Institute supports and conducts research to understand the ways in which exposures to alcohol and drugs may affect pregnancy, a developing fetus, and development throughout the lifespan. Some of this research is done in partnership with other NIH Institutes whose sole focus is on alcohol and drugs, such as the National Institute on Alcoholism and Alcohol Abuse (NIAAA) and the National Institute on Drug Abuse (NIDA), while other efforts are handled solely by NICHD organizational units.
Within this context, some NICHD research is currently examining:
- Effects of alcohol consumption on fetal development and infant health
- Effects of exposure to different classes of drugs on fetal development and on later development
- Mechanisms by which alcohol causes birth defects
- Effects of alcohol on maternal health, including placental effects
- Patterns of alcohol consumption and drug use during pregnancy
Recent and ongoing research by NICHD scientists and NICHD-funded researchers on alcohol- and drug-related birth defects is described below. Select a link to learn more:
Research on Alcohol- and Drug-Related Birth Defects
Research on the Mechanisms that Cause These Birth Defects
Research on Patterns of Alcohol Consumption During Pregnancy
Research on Alcohol- and Drug-Related Birth Defects
Absence of Eye Malformations in Alcohol-Exposed Children Who Do Not Develop Fetal Alcohol Syndrome (FAS)
The effects of alcohol consumption during pregnancy on the fetus have been known for some time. Such consumption can cause fetal alcohol spectrum disorders (FASDs), which include physical abnormalities and problems with behavior and learning that last throughout a person's life. FAS, which is characterized by more serious growth deficits, neurological defects, and body malformations, including problems with the structure of the head and face, is at the severe end of the FASD spectrum. Previous studies have found some eye abnormalities resulting from prenatal alcohol exposure, but no studies have investigated the effects of heavy alcohol consumption on the eye development of children who do not have FAS.
Recent findings from a study conducted by researchers in the NICHD Division of Intramural Population Health Research (DIPHR) aimed to address this issue and prospectively tracked the children of women who drank alcohol heavily during their pregnancies. Heavy alcohol consumption was defined as two or more ounces (or 48 grams or more) of alcohol per day. This level of alcohol intake per day has been linked to adverse effects on the developing fetus, including effects on the central nervous system. The participants in the study were from the NICHD University of Chile Alcohol in Pregnancy Study. The children in the study were examined and observed for a period of up to 9 years. None of the children developed FAS even though all had been prenatally exposed to alcohol. The study included a control cohort of children who were not prenatally exposed to alcohol.
Ophthalmologic examination of the children's eyes over the study period of up to 9 years did not show any differences between children who had been exposed to alcohol and those who had not. Eye examinations included measures to evaluate eye structure and function, including visual acuity, light refraction, amount of eyelid drooping, eye corner structure, and the spacing between the upper and lower eyelids. The findings suggest that children with heavy prenatal alcohol exposure, who do not develop FAS, have normal eye development during early childhood. The findings also suggest that it is not be useful to use presence of eye abnormalities as a way to diagnose children suspected of having prenatal alcohol exposure-related effects. For details on this finding, visit PubMed ID: 18571671.
Exposure to Alcohol and Commercial Cigarettes Before and During Pregnancy and the Risk of Birth Defects
Few studies have simultaneously examined the effects of alcohol consumption and cigarette smoking during pregnancy, although both are known to damage a developing fetus. In a study co-funded by the NICHD, the March of Dimes, and the California Tobacco-Related Diseases Research Program, researchers from the NICHD's DIPHR did just this. They examined the effects of prenatal exposure to tobacco smoke and alcohol. In the study, the researchers examined 1,355 cases, which included live-born infants, still-born fetuses (fetal death at greater than 20 weeks gestation), and electively terminated fetuses, with birth defects. Control cases included 700 live-born infants with no birth defects or other abnormalities. Women completed computer-based questionnaires during a 4-month periconceptional time, which was defined as from 2 months before conception to 2 months after conception.
In the study, maternal intake of alcohol less than 1 day per week was associated with about twice the risk of neural tube defects (NTDs), heart artery abnormalities, and cleft lip, with or without cleft palate (CLP), as compared with nondrinkers. Cleft lip and CLP are types of head and face abnormalities commonly seen in infants who have FAS. More frequent alcohol consumption during pregnancy led to higher rates of NTDs and CLP. Maternal smoking of cigarettes was not associated with an increased risk of NTDs or heart defects. Unexpectedly, smoking was associated with a lower risk of NTDs and a lower risk of certain types of heart defects. The results of this study suggested that maternal alcohol intake increases the risk for neural tube, heart, and facial birth defects. Although smoking cigarettes did not contribute to any of the birth defects that were evaluated in the study, smoking during pregnancy is known to increase the risk of miscarriage, stillbirth, preterm birth, low birth weight, Sudden Infant Death Syndrome, lung problems, learning problems, and other short- and long-term health problems. For details on this finding, visit PubMed ID: 18481814.
Effects of Cocaine Exposure During Pregnancy on Child Development
As reported in a previous NICHD spotlight, researchers supported by the NICHD's Pregnancy and Perinatology (PP) Branch and NIDA examined the effects of prenatal exposure to cocaine on child development, specifically on the child's stress response system. The researchers found decreased cortisol response to stress in children who were exposed to cocaine in the womb compared to similarly aged children who were not exposed. Decreased cortisol response can lead to increased sensitivity to stress, pain, and fatigue.
While previous studies focused only on infants, this study collected data on 743 children from birth to age 11, testing the cortisol response to stress in samples of saliva. This allowed the scientists to weigh environmental factors such as poverty, violence, and parental influence. The most significant decrease in cortisol response was detected in children who were both exposed to cocaine prior to birth and exposed to domestic violence at any time since birth. The findings of decreased cortisol response in children exposed to drugs prenatally not only confirm similar findings from past studies but also show how these negative effects may persist well into childhood. For more information, visit http://www.ncbi.nlm.nih.gov/pubmed/20400094.
Research on the Mechanisms that Cause Birth Defects
Prenatal Alcohol Exposure Does Not Affect Maternal Oxidative Stress or Blood Vessel Constriction
Previous studies have been unable to determine, biologically, how alcohol causes FASDs. Some research suggests that heavy alcohol intake by the mother during pregnancy causes blood vessel to constrict (called vasoconstriction), which damages fetal cells. Vasoconstriction could also cause oxidative stress (an imbalance in the oxygen system that can disrupt normal cell signaling) and impair blood and tissue oxygenation, leading to additional cellular damage in the developing fetus. Researchers from the NICHD's DIPHR examined participants in the NICHD University of Chile Alcohol in Pregnancy Study to learn more.
Study participants included a cohort of 29 women who heavily consumed alcohol during pregnancy, e.g., two or more ounces of alcohol per day. The control cohort included 39 women who did not consume alcohol during their pregnancy. During the women's pregnancies, researchers collected urine samples and analyzed them for the presence of certain proteins that can indicate different levels of oxidative stress and blood vessel dilation/constriction.
The researchers found no differences in the levels of protein markers of oxidative stress and vasoconstriction between women who drank heavily during pregnancy and those who did not. The results suggest that maternal oxidative stress and vasoconstriction do not contribute to mechanisms that cause alcohol damage in the developing fetus. Researchers are continuing to investigate other mechanisms of alcohol's effect on the developing fetus. For details on this finding, visit PubMed ID: 18715278.
Prenatal Exposure to Alcohol Affects Growth-Associated Proteins in Infants and Children
Previous human and animal studies have shown that exposure to alcohol during pregnancy may interfere with both prenatal fetal and postnatal infant weight gain and height. In a study conducted by DIPHR, researchers examined the mechanism that allows alcohol to interfere with postnatal growth. In a prospective cohort study, the researchers assessed the growth of 69 children born to women who heavily consumed alcohol during pregnancy and 83 children born to women who did not drink during pregnancy. Heavy alcohol consumption was defined as four or more alcoholic drinks per day (48 grams or more of alcohol per day). (Please note that different studies use different definitions of alcohol use.)
In the study, the researchers collected blood from infants and children from 1 month to 5 years of age and measured the levels of several regulatory proteins, including insulin-like growth factor (IGF)-I, IGF-II, and leptin. IGF-I and IGF-II are proteins that regulate growth and development; among its many activities, the hormone leptin regulates appetite and metabolism. In children ages 3, 4, and 5, IFG-II levels were higher in those born to mothers who drank alcohol during pregnancy than in children who were not exposed to alcohol. IGF-I levels were also higher, and leptin levels were lower in exposed children ages 1 and 2.
Although the study did not identify how changes in these proteins might affect growth, the findings suggest that alcohol exposure during pregnancy affects the levels of several proteins that are critical in growth regulation. There are few known markers of prenatal alcohol exposure—this study was the first to identify IGF-II as a possible marker. For details on this finding, visit PubMed ID: 20847545.
Research on Patterns of Alcohol Consumption During Pregnancy
Researchers Develop a New Questionnaire for Assessing Alcohol Consumption During Pregnancy
Developing effective survey tools, such as questionnaires, to help study alcohol consumption during pregnancy is an important area of epidemiological research. Knowing the patterns of alcohol exposure, including alcohol type, intake amount, and intake frequency, that contribute to developmental effects can help identify and design the most effective interventions. In a study conducted by DIPHR, in collaboration with the NIAAA, the NIH Office of Research on Minority Health, and the NIH Office of Research on Women's Health, researchers aimed to create and evaluate the usefulness of a questionnaire for studying alcohol consumption in pregnant women.
The 506 pregnant women in the study were older than age 18 years and participated in the study while they were visiting their local prenatal care clinics in Washington, DC. Women answered questions about themselves and about their drinking habits using a computer-based questionnaire. Questions included specifics about alcohol intake during the 3 months before pregnancy and during pregnancy, including the amount that the women drank, the type of alcohol, and the pattern of drinking throughout the week.
After analyzing the answers, researchers were able to categorize women by their risk for alcohol consumption during the rest of pregnancy. They found that women who were at high risk for drinking alcohol during pregnancy were: aware that others were worried about their drinking; drank upon waking in the morning; felt that they needed to reduce the amount that they drank; and had a fracture or road injury in the last 5 years.
According to the researchers, the study validated the new computer-based questionnaire as a useful tool and effective way to identify women who are at risk for drinking during pregnancy. This low-cost screening tool could also help identify women who could be at risk and who might benefit from interventions seeking to lower prenatal alcohol exposure. For details on this finding, visit PubMed ID: 21649675.
NICHD University of Chile Alcohol in Pregnancy Study
Although the information above describes some of the findings from the NICHD University of Chile Alcohol in Pregnancy Study, this is a continuing prospective study designed to determine the effects of heavy alcohol exposure on the developing fetus and longer-term effects on children. Working with pediatricians, psychologists, and other investigators at the University of Chile in Santiago, DIPHR researchers will continue to collect and analyze data to learn as much as possible about this important group of participants.
Prenatal Alcohol and SIDS and Stillbirth (PASS) Network
The PASS Network is maintained through a partnership of the NICHD Pregnancy and Perinatology Branch (PPB), the NIAAA, and the National Institute on Deafness and Other Communication Disorders, to gain knowledge that can help women, families, physicians, and scientists find ways to improve pregnancy outcomes and infant health.
The PASS Network, which is comprised of different community-linked studies, has several objectives, including determining:
- The association between prenatal alcohol exposure and the risk for sudden infant death syndrome (SIDS), stillbirth (fetal death at greater than 20 weeks of gestation), FASD, and other adverse outcomes
- The role of the timing, pattern, and amount of prenatal alcohol exposure and other environmental factors in the risk for morbidity and mortality in early human life
- The role of genomic variation in modifying the risk for morbidity and mortality in early life associated with prenatal alcohol exposure
- The role of alcohol exposure during pregnancy and of interactions among alcohol exposure and environmental and genetic modifiers in altering autonomic activity of the fetus and infant, and neurologic, audiologic, and neurobehavioral outcomes in the infant
- The role of maternal alcohol exposure, as influenced by specific environmental and genetic factors, in impairing placental function and, thereby, possibly increasing the risk for fetal and/or infant morbidity and mortality
- The abnormalities in key neurotransmitter systems in the brains of fetuses and/or infants that convey risk for sudden death, and the role of prenatal alcohol exposure, as influenced by specific environmental and genetic factors
The Safe Passage Study is currently the main component of the PASS Network. The Study will enroll approximately 12,000 pregnant women from the United States and South Africa and will track the development of their infants through pregnancy and the infants' first year of life.
Obstetric and Pediatric Pharmacology (OPP) Branch
Surveys indicate that nearly two-thirds of all pregnant women take up to four drugs during pregnancy and labor. These drugs might be available by prescription or over-the-counter, or they could be categorized as nutritional supplements. The OPP Branch was established in 2004 as a way to promote and coordinate research to improve the safety and efficacy of pharmaceuticals used by women during pregnancy.
Surveys indicate that nearly two-thirds of all pregnant women take up to four drugs during pregnancy and labor. These drugs might be available by prescription or over-the-counter, or they could be categorized as nutritional supplements. In utero exposure to these drugs could have unpredictable or harmful effects to the unborn fetus. The OPP Branch supports research to evaluate and improve the safety and efficacy of drugs used by women during pregnancy.
An important research projects funded by the OPP Branch is the Obstetric-Fetal Pharmacology Research Units (OPRU) Network. This Network provides the expertise and infrastructure to recruit pregnant women for clinical trials to evaluate the impact of various drugs already prescribed for the pregnant women during their pregnancies. Visit http://opru.rti.org/Protocols/tabid/57/Default.aspx for more information on the types of trials conducted within the OPRU Network.
For more information on alcohol- and drug-related birth defects research at the NICHD, select one of the following links:
Originally Posted: June 27, 2012
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