Effects of prenatal alcohol and cigarette exposure on offspring substance use in multiplex, alcohol-dependent families.

paper Cited Public

Authors: O'Brien, Jessica W; Hill, Shirley Y
Year: 2014
Journal: Alcoholism, clinical and experimental research
PMID: 25581650
DOI: 10.1111/acer.12569
PMCID: PMC4293090

BACKGROUND: Prenatal exposures to alcohol, cigarettes, and other drugs of abuse are associated with numerous adverse consequences for affected offspring, including increased risk for substance use and abuse. However, maternal substance use during pregnancy appears to occur more often in those with a family history of alcohol dependence. Utilizing a sample that is enriched for familial alcohol dependence and includes controls selected for virtual absence of familial alcohol dependence could provide important information on the relative contribution of familial risk and prenatal exposures to offspring substance use. METHODS: A sample of multigenerational families specifically ascertained to be at either high or low risk for developing alcohol dependence (AD) provided biological offspring for a longitudinal prospective study. High-risk families were selected based on the presence of 2 alcohol-dependent sisters. Low-risk families were selected on the basis of minimal first and second-degree relatives with AD. High-risk (HR = 99) and Low-risk offspring (LR = 110) were assessed annually during childhood and biennially in young adulthood regarding their alcohol, drug, and cigarette use. At the first childhood visit, mothers were interviewed concerning their prenatal use of substances. RESULTS: High-risk mothers were more likely to use alcohol, cigarettes, and other drugs during pregnancy than low-risk control mothers, and to consume these substances in greater quantities. Across the sample, prenatal exposure to alcohol was associated with increased risk for both offspring cigarette use and substance use disorders (SUD), and prenatal cigarette exposure was associated with increased risk for offspring cigarette use. Controlling for risk status by examining patterns within the HR sample, prenatal cigarette exposure remained a specific predictor of offspring cigarette use, and prenatal alcohol exposure was specifically associated with increased risk for offspring SUD. CONCLUSIONS: Women with a family history of SUD are at increased risk for substance use during pregnancy. Both familial loading for alcohol dependence and prenatal exposure to alcohol or cigarettes are important risk factors in the development of offspring substance use. An inadequate assessment of family history may obscure important interactions between familial risk and prenatal exposures on offspring outcomes.

Figure 1

This pedigree illustrates the high density of alcohol dependence seen in the high-risk families in this study. Families were selected through women in the second generation depicted here. Solid circles (females) or squares (males) indicated affected (alcohol dependence) status by the time of the last follow up. In this pedigree, ‘exposed’ refers to prenatal alcohol exposure. Third generation offspring from this pedigree were first seen at an average age of 10.2 ± 2.2 years and were 31.3 ± 2.9 years of age at last follow up.

LLM interpretation

This image is a pedigree chart for Family W1429 illustrating the inheritance of alcohol dependence across three generations. Solid black shapes indicate affected individuals (squares for males, circles for females), showing a high density of the condition across all three generations. Specific individuals in the third generation are labeled as "Exposed," referring to prenatal alcohol exposure.

Figure 2

Mothers of High-Risk offspring (n=99) were significantly more likely than Low-Risk mothers to use substances during pregnancy, including alcohol, cigarettes, and other abusable drugs.

LLM interpretation

This grouped bar chart compares the percentage of "Yes" responses for maternal substance use during pregnancy between High-Risk (red) and Low-Risk (blue) groups. Across all categories—Alcohol Use, Cigarette Use, Drug Use, and Any Substance Use—the High-Risk group shows substantially higher percentages of use than the Low-Risk group. The y-axis represents "Percent Yes" from 0 to 100, with the largest disparity visible in the "Any Substance Use" category.

Figure 3

Across the sample, prenatal alcohol exposure was significantly associated with offspring substance use disorders. Exposure level was determined by conducting a median split of total number of alcoholic drinks consumed during pregnancy (median = 48 alcoholic drinks across pregnancy).

LLM interpretation

This line graph shows the percent survival of offspring without substance use disorders (SUD) from age 13 to 30, categorized by prenatal alcohol exposure levels. The "High Alc Exposure" group shows a steep decline in survival compared to the "Low Alc Exposure" and "No Alc Exposure" groups, which maintain higher survival rates. The x-axis represents age and the y-axis represents percent survival.

Figure 4

Across the sample, prenatal alcohol exposure was significantly associated with offspring cigarette use in childhood and adolescence. Exposure level was determined by conducting a median split of total number of alcoholic drinks consumed during pregnancy (median = 48 alcoholic drinks across pregnancy).

LLM interpretation

This line graph shows the "Percent Survival" (representing the percentage of offspring who have not started smoking) from age 8 to 18, categorized by prenatal alcohol exposure level. The x-axis represents age in years, and the y-axis represents the percentage of survival. The data shows a downward trend for all groups over time, with the "High Alc Exposure" group (green line) showing the steepest decline and lowest survival rate compared to the "Low Alc Exposure" (purple line) and "No Alc Exposure" (blue line) groups.

Figure 5

Across the sample, prenatal cigarette exposure was significantly associated with offspring cigarette use in childhood and adolescence. Exposure level was determined by conducting a median split of total number of cigarettes consumed during pregnancy (median = 2700 cigarettes across pregnancy).

LLM interpretation

This line graph shows the "Percent Survival" (representing the proportion of offspring who have not started smoking) across ages 8 to 18, categorized by prenatal cigarette exposure levels. The x-axis represents age and the y-axis represents percent survival. A clear dose-response pattern is visible, where the "High Cig Exposure" group shows the steepest decline in survival, followed by the "Low Cig Exposure" group, with the "No Cig Exposure" group maintaining the highest survival rate.

Figure 6

Among offspring from multiplex, alcohol dependent families, prenatal alcohol exposure was significantly associated with offspring substance use disorders. Exposure level was determined by conducting a median split of total number of alcoholic drinks consumed during pregnancy (median = 48 alcoholic drinks across pregnancy).

LLM interpretation

This line graph shows the "Percent Survival" (representing the absence of substance use disorders) over time for high-risk offspring based on prenatal alcohol exposure levels. The x-axis tracks age from 13 to 30, while the y-axis measures the percentage of the population remaining free of SUD. The "High Alc Exposure" group shows a significantly steeper decline in survival compared to the "Low Alc Exposure" and "No Alc Exposure" groups, which maintain higher survival rates through age 30.

Figure 7

Among offspring from multiplex, alcohol dependent families, prenatal cigarette exposure were significantly associated with offspring cigarette use during childhood and adolescence. Exposure level was determined by conducting a median split of total number of cigarettes consumed during pregnancy (median = 2700 cigarettes across pregnancy).

LLM interpretation

This line graph shows the "Percent Survival" (representing the percentage of offspring who have not yet started smoking) across ages 8 to 18 for three groups: No Cig Exposure, Low Cig Exposure, and High Cig Exposure. The "High Cig Exposure" group shows a steeper and earlier decline in survival compared to the other two groups, starting around age 12. The "No Cig Exposure" and "Low Cig Exposure" groups follow a similar, more gradual decline, with the "No Cig Exposure" group maintaining the highest survival rate until age 17.

#	Section	Preview
20	Results — Prenatal Exposures and Offspring Outcomes	Separate Cox Regression survival analyses were conducted to assess the effects of prenatal exposure…
21	Results — Prenatal Exposures and Offspring Outcomes	For each substance used during pregnancy, a median for the entire group of mothers reporting any use…
22	Results — Prenatal Alcohol Exposure	Survival analysis revealed that offspring substance use disorder outcome was influenced by prenatal…
23	Results — Prenatal Cigarette Exposure	Offspring cigarette use, but not substance use disorder, was influenced by prenatal use of…
24	Results — Analyses within the High-Risk Group: Prenatal Alcohol Exposure	Among HR offspring, level of prenatal alcohol exposure was significantly associated with offspring…
25	Results — Analyses within the High-Risk Group: Prenatal Cigarette Exposure	Among HR offspring, level of prenatal cigarette exposure was associated with increased risk for…
26	Discussion	The current study sought to characterize maternal substance use during pregnancy in a sample of…
27	Discussion	Across High and Low-Risk participants, prenatal exposure to either alcohol or cigarettes increased…
28	Discussion	These findings are an important contribution to the extant literature on the etiology of substance…
29	Discussion	history of SUD support a causal influence of prenatal exposure on offspring substance use (Ernst et…
30	Discussion	psychiatric disorders (Hill et al., 2000) and body mass index (BMI) (Hill et al., 2005). The present…
31	Discussion	The current study has demonstrated more specific effects of prenatal exposures within the High-Risk…
32	Discussion	exposure to nicotine is associated with increased numbers of nicotinic binding sites in the brain…
33	Discussion	In addition to disentangling the relative contributions of direct and indirect effects of prenatal…
34	Discussion — Study Limitations	Retrospective collection of data on maternal substance use during pregnancy has been considered less…
35	Discussion — Study Limitations	A limitation of this study is that we were unable to assess the direct effect of prenatal exposure…
36	Discussion — Study Limitations	Women who use substances during pregnancy may be more likely to continue to drink, smoke, or use…
37	Discussion — Study Limitations	Use of ultra-high-risk AD families can be viewed as either a strength or weakness of our findings.…
38	Discussion — Study Limitations	This study compared maternal substance use during pregnancy between women at ultra-high familial…

Name	Type
Adolescent Psychiatric Disorders local	phenotype
Age of study entry local	phenotype
alcohol	phenotype
alcohol abuse	phenotype
alcohol dependence	phenotype
Alcohol Use Disorder	phenotype
alcohol use disorders	phenotype
Altered density of nicotinic acetylcholine receptors local	phenotype
Altered reward system local	phenotype
antisocial personality disorder	phenotype
Axis I psychopathology local	phenotype
bipolar disorder	phenotype
Birth outcomes local	phenotype
body mass index	phenotype
brain	anatomy
child/adolescent local	cohort
Childhood smoking local	phenotype
cigarettes	phenotype
cigarette/tobacco local	drug
cigarette/tobacco use local	phenotype
cocaine	phenotype
Concurrent report local	cohort
Control families	cohort
Current Substance Use local	phenotype
disadvantaged prenatal care local	phenotype
drug	drug
drug and alcohol problems in adolescence and adulthood local	phenotype
drug dependence	phenotype
early alcohol use	phenotype
Early-onset cigarette smoking local	phenotype
educational attainment	phenotype
Familial background factors local	phenotype
Familial history of substance use disorders local	phenotype
familial risk	cohort
family history of alcoholism	phenotype
Family history of substance use disorder local	phenotype
Father (married into target pedigree family) local	cohort
first-degree relatives	cohort
General sample local	cohort
High familial risk women local	cohort
High-risk adolescents	cohort
High-Risk background local	cohort
high-risk families	cohort
High-risk mothers local	cohort
High-Risk mothers local	cohort
high-risk offspring	cohort
High-Risk participants local	cohort
high-risk sample	cohort
Hollingshead Four-Factor Index of Socioeconomic Status local	phenotype
HR group local	cohort
HR mothers local	cohort
illicit drugs	phenotype
income	phenotype
Increased alcohol preference local	phenotype
Increased behavior related to drug reinforcement local	phenotype
Increased drug self-administration local	phenotype
lifetime alcohol use	phenotype
lower socioeconomic status	phenotype
Low familial risk women local	cohort
Low-risk control families local	cohort
Low-risk mothers local	cohort
Low-Risk mothers local	cohort
Low Risk offspring local	cohort
Low-Risk offspring local	cohort
Low-Risk participants local	cohort
Low-risk women local	cohort
LR mothers local	cohort
major depressive disorder	phenotype
marijuana	phenotype
maternal multiplex families local	cohort
Maternal Prenatal Substance Use local	phenotype
Maternal Report of Prenatal Use local	phenotype
maternal smoking	phenotype
midbrain	anatomy
Midbrain morphological and neurochemical alterations local	phenotype
mothers	cohort
mothers with substance use disorders local	phenotype
multiplex alcohol dependent families local	cohort
multiplex families	cohort
nicotine	drug
nicotine self-administration	phenotype
Nicotinic binding sites local	phenotype
Number of first- and second-degree relatives with alcohol dependence local	phenotype
offspring	cohort
offspring alcohol problems	phenotype
Offspring alcohol-use problems local	phenotype
offspring cigarette use local	phenotype
Offspring cigarette use local	phenotype
Offspring Cigarette Use local	phenotype
Offspring Drinking Behavior local	phenotype
Offspring drug use local	phenotype
Offspring Follow-up Cohort local	cohort
offspring of alcoholics	cohort
Offspring preference for alcohol local	phenotype
Offspring smoking	phenotype
offspring smoking outcome local	phenotype
Offspring substance use local	phenotype
Offspring Substance Use local	phenotype
Offspring Substance Use Disorder local	phenotype
Offspring substance use disorders local	phenotype
Offspring substance use outcomes local	phenotype
offspring SUD local	phenotype
offspring SUD outcomes local	phenotype
opioid	drug
other drugs	drug
Other drugs of abuse local	drug
other drug use	phenotype
Parental SUD	phenotype
polysubstance abuse	phenotype
Postpartum Substance Use local	phenotype
prenatal alcohol exposure	phenotype
prenatal cigarette exposure local	drug
prenatal cigarette exposure local	phenotype
Prenatal cigarette exposure local	drug
Prenatal cigarette exposure local	phenotype
Prenatal Cigarette Exposure local	drug
prenatal drug exposure	drug
prenatal exposure local	drug
Prenatal exposure to cigarettes local	phenotype
prenatal exposure to other drugs local	drug
Prenatally exposed animals local	cohort
Prenatal nicotine exposure	drug
prenatal other drug exposure local	phenotype
Prenatal substance use local	phenotype
proband pair local	cohort
Prospective report local	cohort
psychiatric disorders	phenotype
Retrospective report local	cohort
risk group status local	cohort
rodents	cohort
schizophrenia	phenotype
sedatives	drug
SES	phenotype
sex	phenotype
socioeconomic status	phenotype
spouses	cohort
stimulants	drug
substance abuse	phenotype
substance use	phenotype
SUD	phenotype
Target pedigree family local	cohort
Teen outcomes local	phenotype
third generation offspring local	cohort
tobacco use	phenotype
Ultra-high Familial Risk Cohort local	cohort
Ultra-high familial risk women local	cohort
Ultra-high-risk AD families local	cohort
Unexposed control animals local	cohort
women	cohort
Young adult cohort	cohort
young adults	cohort

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In this knowledge base

Title	Year	PMID
Meta-Analyses of Externalizing Disorders: Genetics or Prenatal Alcohol Exposure?	2018	29063614
Differentiating the Effects of Familial Risk for Alcohol Dependence and Prenatal Exposure to Alcohol on Offspring Brain Morphology.	2017	28084631

External

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Prenatal substance exposure and child health: Understanding the role of environmental factors, genetics, and brain development.	Gu Z et al.	—	2024	→
Factors to be considered as part of a holistic assessment for fetal alcohol spectrum disorder: A scoping review.	Reid N et al.	—	2023	→
Reducing the risk of prenatal alcohol exposure and FASD through social services: promising results from the FAR SEAS pilot project.	Okulicz-Kozaryn K et al.	—	2023	→
Alcohol use during pregnancy: findings from a gender-based violence survey in Mongolia.	Erdenetuya B et al.	—	2022	→
Brain morphology predictors of alcohol, tobacco, and cannabis use in adolescence: A systematic review.	Boer OD et al.	—	2022	→
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